Elevated levels of liver methylglyoxal and d-lactate in early-stage hepatitis in rats.

PubMed

Wang, Wen-Chuang; Chou, Chu-Kuang; Chuang, Ming-Cheng; Li, Yi-Chieh; Lee, Jen-Ai

2018-02-01

Methylglyoxal (MGO) is highly cytotoxic and its levels are elevated in diabetes, nephropathy and atherosclerosis. However, it has never been studied in liver disease. For this reason, we aimed to assess the levels of MGO and its metabolite d-lactate in an early hepatitis model. Wistar rats were administered CCl 4 (0.75 mL/kg, i.p.) to induce hepatitis. In either CCl 4 -treated or untreated rats, alanine transaminase and aspartate transaminase levels did not change over the course of the study, indicating that significant liver damage did not occur following CCl 4 treatment. However, the levels of MGO and d-lactate were higher in the livers of CCl 4 -treated animals than in untreated animals (MGO: 128.2 ± 18.8 and 248.1 ± 64.9 μg/g protein, p < 0.01; d-lactate: 0.860 ± 0.040 and 1.293 ± 0.078 μmol/g protein, respectively p < 0.01). Furthermore, in untreated and treated animals, serum d-lactate levels were 57.65 ± 2.59 and 92.16 ± 16.69 μm and urine d-lactate levels were 1.060 ± 0.007 and 1.555 ± 0.366 μmol/mg UCr, respectively (p < 0.01). These data show that in this model of early-stage liver damage, the levels of MGO and its metabolite d-lactate are elevated and that d-lactate could be useful as a reference marker for the early stage of hepatitis. Copyright © 2017 John Wiley & Sons, Ltd.

Maternal consumption of a cafeteria diet during lactation in rats leads the offspring to a thin-outside-fat-inside phenotype.

PubMed

Pomar, C A; van Nes, R; Sánchez, J; Picó, C; Keijer, J; Palou, A

2017-08-01

The suckling period is a critical phase of development, in which maternal overnutrition may program the susceptibility of developing chronic diseases and disorders, such as obesity and metabolic alterations, in adult life. Here, we questioned whether the consumption of a cafeteria diet throughout lactation in rats affects the macronutrient composition of milk and whether it results in permanent metabolic effects in the offspring. Nursing rats were fed a control diet or a cafeteria diet during lactation. Milk was obtained at different time points of lactation. Offspring (males and females) were weaned onto a control diet until the age of 6 months. Circulating parameters were measured under ad libitum feeding and under 12-h fasting conditions at weaning and at 3 and 6 months of age. An oral glucose tolerance test (OGTT) was performed at 3 and 6 months of age. Rats fed a cafeteria diet during lactation consumed an unbalanced diet, with lower protein and higher fat content versus controls, which was reflected in the composition of the milk. The offspring of rats fed a cafeteria diet during lactation showed lower body weight and lower lean mass, but greater fat accumulation, compared with controls. They also displayed hyperleptinaemia, altered lipid profile and impaired response to an OGTT. Maternal consumption of a cafeteria diet throughout lactation in rats produces lasting effects in the metabolic health of their offspring, which are not associated with a higher body weight but with a greater fat accumulation, similarly to the thin-outside-fat-inside phenotype.

Galactagogue effects of Musa x paradisiaca flower extract on lactating rats.

PubMed

Mahmood, Azizah; Omar, Muhammad Nor; Ngah, Nurziana

2012-11-01

To investigate the potential of Musa x paradisiaca (M. x paradisiaca) flower extracts in promoting milk production of lactating rats and its effects on growth of the suckling pups. Galactagogue activity was evaluated in terms of quantity of milk produced from the rats treated with petroleum ether, ethanol or water extracts of the flower. Lactating rats (n = 5) of Spraque Dawley with six pups each were administered with the extracts in the amount of 500 mg/kg body weight, while the control rats were given an equivalent amount of distilled water. The rats were daily administered via oral feeding starting from Day 5 until Day 14 and the performance of milk production was measured along the experimental period by weight-suckle-weight method. Results were statistically analyzed using SPSS by means of ANOVA at 0.05 and was expressed as their mean?standard deviation. The rates of pups' growth were measured as the weight gain along the experimental period. The rats treated with aqueous extract produced higher milk than control and ethanol groups. Aqueous extract was identified to increase milk production by 25%, while petroleum ether extract by 18%. The mean of yields produced by the rats during suckling period for aqueous, petroleum ether, ethanol and control were 4.62±2.45, 4.37±1.93, 3.65±1.89 and 3.69±1.79, respectively. Growth rates of pups for the rats treated with control, aqueous, ethanol extract and petroleum ether were (1.85±0.49), (1.78±0.56), (1.65±0.46) and (1.56±0.42) g/pup, respectively. The present study reveals the potential of M. x paradisiaca flower to enhance milk production of nursing mothers which could be exploited for commercialization of the isolated extract. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Hyperthyroidism affects lipid metabolism in lactating and suckling rats.

PubMed

Varas, S M; Jahn, G A; Giménez, M S

2001-08-01

Two per thousand pregnant women have hyperthyroidism (HT), and although the symptoms are attenuated during pregnancy, they rebound after delivery, affecting infant development. To examine the effects of hyperthyroidism on lactation, we studied lipid metabolism in maternal mammary glands and livers of hyperthyroid rats and their pups. Thyroxine (10 microg/100 g body weight/d) or vehicle-treated rats were made pregnant 2 wk after commencement of treatment and sacrificed on days 7, 14, and 21 of lactation with the litters. Circulating triiodothyronine and tetraiodothyronine concentrations in the HT mothers were increased on all days. Hepatic esterified cholesterol (EC) and free cholesterol (FC) and triglyceride (TG) concentrations were diminished on days 14 and 21. Lipid synthesis, measured by incorporation of [3H]H2O into EC, FC, and TG, fatty acid synthase, and acetyl CoA carboxylase activities increased at day 14, while incorporation into FC and EC decreased at days 7 and 21, respectively. Mammary FC and TG concentrations were diminished at day 14; incorporation of [3H]H2O into TG decreased at days 7 and 21, and incorporation of [3H]H2O into FC increased at day 14. In the HT pups, growth rate was diminished, tetraiodothyronine concentration rose at days 7 and 14 of lactation, and triiodothyronine increased only at day 14. Liver TG concentrations increased at day 7 and fell at day 14, while FC increased at day 14 and only acetyl CoA carboxylase activity fell at day 14. Thus, hyperthyroidism changed maternal liver and mammary lipid metabolism, with decreased lipid concentration in spite of increased liver rate of synthesis and decreases in mammary synthesis. These changes, along with the mild hyperthyroidism of the litters, may have contributed to their reduced growth rate.

myo-Inositol metabolism during lactation and development in the rat. The prevention of lactation-induced fatty liver by dietary myo-inositol.

PubMed

Burton, L E; Wells, W W

1976-11-01

Effects of dietary myo-inositol deprivation were examined during prenatal and postnatal development and during lactation in the rat. The deficient diet contained no detectable myo-inositol while the supplemented diet contained 0.5% (w/w) myo-inositol while the supplemented diet ct contained 0.5% (w/w) myo-inositol at the expense of sucrose. Both diets contained 25% casein, adequate amounts of all known vitamins, choline, and essential fatty acids as well as 0.5% (w/w) phthalylsulfathiazole to depress myo-inositol contribution to the diet by microorganisms. Pregnant rats of the Holtzman strain were fed the respective diets during gestation and lactation, and pups were fed the corresponding diet after weaning until 3 months of age. There were no significant differen-es in body weight between experimental groups. Supplementation of the diet with myo-inositol significanly increased the levels of myo-inositol in plasma, liver, kidney, and intestine of pups at all ages examined, and significantly increased the levels of myo-inositol in the milk and mammary tissue during lactation. During lactation, the myo-inositol deprived dams developed severe fatty livers (31% w/w) characterized by diminished phosphatidyl-inositol (50%) and total phospholipid phosphorus (57%) levels as compared with controls. After weaning, the liver lipid content of the myo-inositol deprived dams returned to normal (4.5%). The data suggest that a possible threshold level of free myo-inositol (approximately 0.15 mumoles/g lipid-free tissue) was required to prevent fatty liver in lactating dams under these dietary conditions. Effects of the deficient diet on fertility were also examined. Based on sperm count and production of offspring, there were no differnences between the experimental and control males. Females of both groups showed equal ability to produce offspring.

Prolactin regulation of oxytocin neurone activity in pregnancy and lactation.

PubMed

Augustine, Rachael A; Ladyman, Sharon R; Bouwer, Gregory T; Alyousif, Yousif; Sapsford, Tony J; Scott, Victoria; Kokay, Ilona C; Grattan, David R; Brown, Colin H

2017-06-01

During lactation, prolactin promotes milk synthesis and oxytocin stimulates milk ejection. In virgin rats, prolactin inhibits the activity of oxytocin-secreting neurones. We found that prolactin inhibition of oxytocin neurone activity is lost in lactation, and that some oxytocin neurones were excited by prolactin in lactating rats. The change in prolactin regulation of oxytocin neurone activity was not associated with a change in activation of intracellular signalling pathways known to couple to prolactin receptors. The change in prolactin regulation of oxytocin neurone activity in lactation might allow coordinated activation of both populations of neurones when required for successful lactation. Secretion of prolactin for milk synthesis and oxytocin for milk secretion is required for successful lactation. In virgin rats, prolactin inhibits oxytocin neurones but this effect would be counterproductive during lactation when secretion of both hormones is required for synthesis and delivery of milk to the newborn. Hence, we determined the effects of intracerebroventricular (i.c.v.) prolactin on oxytocin neurones in urethane-anaesthetised virgin, pregnant and lactating rats. Prolactin (2 μg) consistently inhibited oxytocin neurones in virgin and pregnant rats (by 1.9 ± 0.4 and 1.8 ± 0.5 spikes s -1 , respectively), but not in lactating rats; indeed, prolactin excited six of 27 oxytocin neurones by >1 spike s -1 in lactating rats but excited none in virgin or pregnant rats (χ 2 2  = 7.2, P = 0.03). Vasopressin neurones were unaffected by prolactin (2 μg) in virgin rats but were inhibited by 1.1 ± 0.2 spikes s -1 in lactating rats. Immunohistochemistry showed that i.c.v. prolactin increased oxytocin expression in virgin and lactating rats and increased signal transducer and activator of transcription 5 phosphorylation to a similar extent in oxytocin neurones of virgin and lactating rats. Western blotting showed that i.c.v. prolactin did not affect

Maternal Nicotine Exposure During Late Gestation and Lactation Increases Anxiety-Like and Impulsive Decision-Making Behavior in Adolescent Offspring of Rat.

PubMed

Lee, Hyunchan; Chung, Sooyeon; Noh, Jihyun

2016-10-01

Prenatal nicotine exposure over an entire pregnancy has been associated with an increased prevalence of hyperactivity, anxiety-like behavior and depression-like behavior in mature rats. However, the effects of maternal nicotine exposure in late gestation and lactation on the psychology and behavior of adolescent rat offspring are unclear. Thus, we investigated the effect of nicotine exposure during late gestation and lactation on anxiety-like and impulsive decision-making behavior in adolescent offspring of rat. Female rats were orally exposed to nicotine which is within range of plasma level of human chronic smokers during the period of third last period of gestation and lactation. When the offspring were weaned, we observed alterations in the anxiety-like behavior and decision-making ability of adolescent rat offspring using light/dark box test and T-maze delay-based cost-benefit decision-making task. The maternal consumption of nicotine reduced both the time spent in the light compartment and the number of transitions compared to nicotine-free rats. Moreover, such nicotine exposed adolescent offspring rats showed impulsive decision making which chose the instant reward in a decision-making situation. We found that nicotine exposure during late gestation and lactation induces an increase in anxiety-like and impulsive decision-making behavior at this developmental stage. These findings suggest that maternal nicotine-exposed offspring are at an increased risk of developing anxious and impulsive behavior.

The metabolism of [3-(13)C]lactate in the rat brain is specific of a pyruvate carboxylase-deprived compartment.

PubMed

Bouzier, A K; Thiaudiere, E; Biran, M; Rouland, R; Canioni, P; Merle, M

2000-08-01

Lactate metabolism in the adult rat brain was investigated in relation with the concept of lactate trafficking between astrocytes and neurons. Wistar rats were infused intravenously with a solution containing either [3-(13)C]lactate (534 mM) or both glucose (750 mM) and [3-(13)C]lactate (534 mM). The time courses of both the concentration and (13)C enrichment of blood glucose and lactate were determined. The data indicated the occurrence of [3-(13)C]lactate recycling through liver gluconeogenesis. The yield of glucose labeling was, however, reduced when using the glucose-containing infusate. After a 20-min or 1-h infusion, perchloric acid extracts of the brain tissue were prepared and subsequently analyzed by (13)C- and (1)H-observed/(13)C-edited NMR spectroscopy. The (13)C labeling of amino acids indicated that [3-(13)C]lactate was metabolized in the brain. Based on the alanine C3 enrichment, lactate contribution to brain metabolism amounted to 35% under the most favorable conditions used. By contrast with what happens with [1-(13)C]glucose metabolism, no difference in glutamine C2 and C3 labeling was evidenced, indicating that lactate was metabolized in a compartment deprived of pyruvate carboxylase activity. This result confirms, for the first time from an in vivo study, that lactate is more specifically a neuronal substrate.

Fructose consumption during pregnancy and lactation induces fatty liver and glucose intolerance in rats

PubMed Central

Zou, Mi; Arentson, Emily J.; Teegarden, Dorothy; Koser, Stephanie L.; Onyskow, Laurie; Donkin, Shawn S.

2015-01-01

Nutritional insults during pregnancy and lactation are health risks for mother and offspring. Both fructose and low protein diets are linked to hepatic steatosis and insulin resistance in non-pregnant animals. We hypothesized that dietary fructose or low protein intake during pregnancy may exacerbate the already compromised glucose homeostasis to induce gestational diabetes and fatty liver. Therefore, we investigated and compared the effects of low protein or fructose intake on hepatic steatosis and insulin resistance in unmated controls and pregnant and lactating rats. Sprague-Dawley rats were fed either a control (CT), a 63% fructose (FR) or an 8% protein (LP) diet. Glucose tolerance test at day 17 of the study revealed greater (P < 0.05) blood glucose at 10 (75.6 vs. 64.0 ± 4.8 mg/dl) and 20 (72.4 vs. 58.6 ± 4.0 mg/dl) min after glucose dose and greater area under the curve (4302.3 vs. 3763.4 ± 263.6 mg·dl−1·min−1) for FR-fed dams compared with CT-fed dams. The rats were euthanized at 21 days postpartum. Both the FR- and LP-fed dams had enlarged (P < 0.05) livers (9.3, 7.1 vs. 4.8 ± 0.2 % body weight) and elevated (P < 0.05) liver triacylglycerol (216.0, 130.0 vs. 19.9 ± 12.6 mg/g liver weight) compared with CT-fed dams. FR induced fatty liver and glucose intolerance in pregnant and lactating rats, but not unmated control rats. The data demonstrate a unique physiological status response to diet resulting in the development of gestational diabetes coupled with hepatic steatosis in FR-fed dams, which is more severe than a LP diet. PMID:22935342

The hypothalamic paraventricular nucleus has a pivotal role in regulation of prolactin release in lactating rats.

PubMed

Kiss, J Z; Kanyicska, B; Nagy, G Y

1986-08-01

The affect of paraventricular nucleus (PVN) lesions on PRL secretory response to suckling was studied in adult female rats. Basal levels of PRL were similar in the control and lesioned groups. Substantial decreases in PRL levels occurred after separation of pups from their mothers in the control as well as lesioned animals. When mothers and pups were reunited, the circulating PRL concentrations of the control groups rose immediately from basal values of 50-100 micrograms/liter to reach peaks of 450-550 micrograms/liter. PVN lesions significantly decreased the suckling-induced rise of PRL levels. Furthermore, PVN lesions abolished the high amplitude, episodic pattern of PRL release in continuously lactating rats. These findings are consistent with the view that PVN neurons produce PRL releasing factor(s), which is (are) required for normal secretory patterns of PRL in lactating rats.

(13)C MR spectroscopy study of lactate as substrate for rat brain.

PubMed

Qu, H; Håberg, A; Haraldseth, O; Unsgård, G; Sonnewald, U

2000-01-01

In order to address the question whether lactate in blood can serve as a precursor for cerebral metabolites, fully awake rats were injected intravenously with [U-(13)C]lactate or [U-(13)C]glucose followed 15 min later by decapitation. Incorporation of label from [U-(13)C]glucose was seen mainly in glutamate, GABA, glutamine, aspartate, alanine and lactate. More label was found in glutamate than glutamine, underscoring the predominantly neuronal metabolism of pyruvate from [U-(13)C]glucose. It was estimated that the neuronal metabolism of acetyl CoA from glucose accounts for at least 66% and the glial for no more than 34% of the total glucose consumption. When [U-(13)C]lactate was the precursor, label incorporation was similar to that observed from [U-(13)C]glucose, but much reduced. Plasma analysis revealed the presence of approximately equal amounts of [1,2,3-(13)C]- and [1,2-(13)C]glucose, showing gluconeogenesis from [U-(13)C]lactate. It was thus possible that the labeling seen in the cerebral amino acids originated from labeled glucose, not [U-(13)C]lactate. However, the presence of significantly more label in [U-(13)C]- than in [2,3-(13)C]alanine demonstrated that [U-(13)C]lactate did indeed cross the blood-brain barrier, and was metabolized further in the brain. Furthermore, contributions from pyruvate carboxylase (glial enzyme) were detectable in glutamine, glutamate and GABA, and were comparatively more pronounced in the glucose group. This indicated that relatively more pyruvate from lactate than glucose was metabolized in neurons. Surprisingly, the same amount of lactate was synthesized via the tricarboxylic acid cycle in both groups, indicating transfer of neurotransmitters from the neuronal to the astrocytic compartment, as previous studies have shown that this lactate is synthesized primarily in astrocytes. Taking into consideration that astrocytes take up glutamate more avidly than GABA, it is conceivable that neuronal lactate metabolism was more

Bromocriptine modulates the expression of PTHrP receptor, Indian hedgehog, and Runx2 proteins in the growth plate of lactating rats.

PubMed

Wongdee, Kannikar; Thonapan, Natchayaporn; Saengamnart, Wasana; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

2013-09-01

In lactating rats, the endochondral bone growth is markedly enhanced, leading to the lengthening of long bone. This lactation-induced bone elongation could be abolished by a dopaminergic D2 receptor agonist bromocriptine, but how bromocriptine altered the expression of major chondroregulatory proteins in the growth plate cartilage was elusive. Here, we performed a quantitative immunohistochemical analysis to determine the expression of various peptides and transcription factors known to control the growth plate chondrocyte proliferation and differentiation [i.e., parathyroid hormone-related protein (PTHrP), PTHrP receptor, Indian hedgehog (Ihh), and runt-related transcription factor 2 (Runx2)], in bromocriptine-treated lactating rats. The results showed that bromocriptine markedly increased Ihh expression in hypertrophic chondrocytes during early and mid-lactation, while the expression of PTHrP receptor, but not its ligand PTHrP, was upregulated in the proliferative and hypertrophic zones during mid and late lactation. In contrast, the expression of Runx2, an important transcription factor for chondrocyte differentiation, was suppressed in the hypertrophic chondrocytes of bromocriptine-treated rats. In conclusion, bromocriptine increased Ihh and PTHrP receptor expressions and decreased Runx2 expression, which might, in turn, enhance chondrocyte proliferation and delay chondrocyte hypertrophy, thereby slowing down endochondral bone growth. This finding could explain how bromocriptine compromised the lactation-induced bone elongation.

Effects of maternal chronic alcohol administration in the rat: lactation performance and pup's growth.

PubMed

Murillo-Fuentes, L; Artillo, R; Carreras, O; Murillo, L

2001-08-01

A fostering/crossfostering analysis of the effects of maternal ethanol exposure on lactation performance and offspring growth was performed. Wistar rats were kept under one of the three experimental nutritional treatments: alcohol-treated (EG), pair-fed-treated (PFG) (as a nutritional control of alcohol-associated malnutrition), and control or normal diet (CG). Rats from the EG group were accustomed to increased amounts of ethanol (5% during the first week to 20% in the fourth week). The 20% ethanol level was maintained throughout three additional weeks and during gestational and lactational period. Daily food intake, fluid consumption, body weight and gestational parameters were studied in control (CG), pair-fed (PFG) and ethanol dams (EG). At birth, half the litters were fostered to other dams of the same treatment (GLG) and half were cross-fostered to dams of the opposite treatment (GG, LG). No cross-fostering analyses were performed on the pair-fed group. Offspring body weight was controlled throughout lactation. Liver, kidney and spleen weights as well as milk consumption were also studied at the end of lactation period. In dams, a significant reduction of body weight was described throughout the suckling period. No ethanol detrimental effects were observed on body weight at birth, but in spite of a normal birth weight, alcohol during lactation was responsible for a growth deficit. Milk consumption was significantly reduced in offspring exposed to ethanol during gestation and/or lactation. Curiously, prenatal alcohol exposure affects adversely the suckling behaviour in pups at the time of weaning. In our study, alcohol treatment and malnutrition affects liver and spleen weights. However, malnutrition decreases spleen weights more than alcohol treatment. In the case of the kidney weights the alcohol decreases kidney weight more than malnutrition. Collectively, the data from the present study show similar effects following pre/postnatal and postnatal alcohol

Choline deficiency impairs intestinal lipid metabolism in the lactating rat.

PubMed

da Silva, Robin P; Kelly, Karen B; Lewis, Erin D; Leonard, Kelly-Ann; Goruk, Sue; Curtis, Jonathan M; Vine, Donna F; Proctor, Spencer D; Field, Catherine J; Jacobs, René L

2015-10-01

Choline is a precursor to phosphatidylcholine (PC), a structural molecule in cellular membranes that is crucial for cell growth and function. PC is also required for the secretion of lipoprotein particles from liver and intestine. Choline requirements are increased during lactation when maternal choline is supplied to the offspring through breast milk. To investigate the effect of dietary choline on intestinal lipid metabolism during lactation, choline-supplemented (CS), phosphatidylcholine-supplemented (PCS) or choline-deficient (CD) diets were fed to dams during the suckling period. CD dams had lower plasma triacylglycerol, cholesterol and apoB in the fasted state and following a fat-challenge (P < .05). There was a higher content of neutral lipids and lower content of PC in the intestine of CD dams, compared with CS and PCS fed animals (P < .05). In addition, there was lower (P < .05) villus height in CD dams, which indicated a reduced absorptive surface area in the intestine. Choline is critical for the absorption of fat in lactating rats and choline deficiency alters intestinal morphology and impairs chylomicron secretion by limiting the supply of PC. Copyright © 2015 Elsevier Inc. All rights reserved.

Keratinocyte growth factor is a growth factor for mammary epithelium in vivo. The mammary epithelium of lactating rats is resistant to the proliferative action of keratinocyte growth factor.

PubMed Central

Ulich, T. R.; Yi, E. S.; Cardiff, R.; Yin, S.; Bikhazi, N.; Biltz, R.; Morris, C. F.; Pierce, G. F.

1994-01-01

Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor (FGF) family. KGF is secreted by stromal cells and affects epithelial but not mesenchymal cell proliferation. KGF injected intravenously was found to cause dramatic proliferation of mammary epithelium in the mammary glands of rats. KGF causes ductal neogenesis and intraductal epithelial hyperplasia but not lobular differentiation in nulliparous female rats. KGF causes ductal and lobular epithelial hyperplasia in male rats. KGF causes proliferation of ductal and acinar cells in the mammary glands of pregnant rats. On the other hand, the ductal epithelium of lactating postpartum rats is resistant to the proliferative action of KGF. The mammary glands of lactating rats did not express less KGF receptor mRNA than the glands of pregnant rats, suggesting that the resistance of the ductal epithelium to KGF during lactation is not related to KGF receptor mRNA down-regulation. The mammary glands of both pregnant and postpartum lactating rats express KGF mRNA with more KGF present in the glands of lactating rats. In conclusion, the KGF and KGF receptor genes are expressed in rat mammary glands and recombinant KGF is a potent growth factor for mammary epithelium. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8178937

Fructose intake during gestation and lactation differentially affects the expression of hippocampal neurosteroidogenic enzymes in rat offspring.

PubMed

Mizuno, Genki; Munetsuna, Eiji; Yamada, Hiroya; Ando, Yoshitaka; Yamazaki, Mirai; Murase, Yuri; Kondo, Kanako; Ishikawa, Hiroaki; Teradaira, Ryoji; Suzuki, Koji; Ohashi, Koji

2017-02-01

Neurosteroids, steroidal hormones synthesized de novo from cholesterol within the brain, stimulate hippocampal functions such as neuron protection and synapse formation. Previously, we examined the effect of maternal fructose on the transcriptional regulation of neurosteroidogenic enzymes. We found that the mRNA expression level of the steroidogenic acute regulatory protein (StAR), peripheral benzodiazepine receptor (PBR), cytochrome P450(11β), 11β-hydroxysteroid dehydrogenase (HSD), and 17β-HSD was altered. However, we could not determine whether maternal fructose intake played a role in the gestation or lactation period because the dam rats were fed fructose solution during both periods. Thus, in this study, we analyzed the hippocampi of the offspring of dams fed fructose during the gestation or lactation period. Maternal fructose consumption during either the gestation or lactation period did not affect the mRNA levels of StAR, P450(17α), 11β-HSD-2, and 17β-HSD-1. PBR expression was down-regulated, even when rats consumed fructose during the lactation period only, while fructose consumption during gestation tended to activate the expression of P450(11β)-2. We found that maternal fructose intake during gestation and lactation differentially affected the expression of hippocampal neurosteroidogenic enzymes in the offspring.

Effects of Hypergravity Exposure on Prolactin Levels in Pre-parturient , Parturient and Lactating Rat Dams

NASA Technical Reports Server (NTRS)

Baer. Lisa A.; Wade, Charles E.; Ronca, April E.; Sun, Sid (Technical Monitor)

2001-01-01

We analyzed the effects of 2.0-g, 1.75-g and 1.5-g hypergravity exposure on plasma concentrations of the lactotrophic hormone, prolactin (PRL), in female rats on pre-parturient (Gestation Day 20), parturient (Post-natal day 0) and lactating (P10) days. PRL levels have been found to be reduced in rat dams around the time of birth following exposure to gravitational loads varying from 2.16 to 3.14-g (Megory et. al., Aviation, Space and Environs 1129-1135, 1984). It has also been reported that at these high gravitational loads, neonatal mortality has been extremely high, suggesting a possible interaction between dam PRL concentration and neonatal outcome. We have previously reported no significant differences in PRL levels of parturient (PO) and lactating (P6 & P 15) dams when exposed to 1.5-g hypergravity, but did observe a slight elevation of PRL on PO and P 15, with a decrease on P6. In the present study, time-bred pregnant dams were exposed to either continuous 2.0-g, 1.75-g or 1.5-g centrifugation, beginning on Gestational day (G) 11 of the rats' 22-day pregnancy. We observed no significant differences in PRL concentrations between SC and any of the HG conditions. On G20 and PO, PRL concentrations of the 2.0-g and 1.5-g groups were slightly elevated as compared to SC. Similar to what we previously reported. PRL secretion was elevated in both HG and SC conditions on the day of birth relative to later during lactation, but on P10 it appeared to be reduced in HG relative to SC dams. These findings suggests that hypergravity slightly elevates plasma concentration of PRL in pre-parturient and lactating rat dams, with effects most pronounced during the periparturitional period and in a direction opposite to that observed following microgravity exposure.

Protocols for hyperlactatemia induction in the lactate minimum test adapted to swimming rats.

PubMed

de Araujo, Gustavo Gomes; Papoti, Marcelo; Manchado, Fúlvia de Barros; de Mello, Maria Alice Rostom; Gobatto, Claudio Alexandre

2007-12-01

The lactate minimum test (LACmin) has been considered an important indicator of endurance exercise capacity and a single session protocol can predict the maximal steady state lactate (MLSS). The objective of this study was to determine the best swimming protocol to induce hyperlactatemia in order to assure the LACmin in rats (Rattus norvegicus), standardized to four different protocols (P) of lactate elevation. The protocols were P1: 6 min of intermittent jumping exercise in water (load of 50% of the body weight - bw); P2: two 13% bw load swimming bouts until exhaustion (tlim); P3: one tlim 13% bw load swimming bout; and P4: two 13% bw load swimming bouts (1st 30 s, 2nd to tlim), separated by a 30 s interval. The incremental phase of LACmin beginning with initial loads of 4% bw, increased in 0.5% at each 5 min. Peak lactate concentration was collected after 5, 7 and 9 min (mmol L(-1)) and differed among the protocols P1 (15.2+/-0.4, 14.9+/-0.7, 14.8+/-0.6) and P2 (14.0+/-0.4, 14.9+/-0.4, 15.5+/-0.5) compared to P3 (5.1+/-0.1, 5.6+/-0.3, 5.6+/-0.3) and P4 (4.7+/-0.2, 6.8+/-0.2, 7.1+/-0.2). The LACmin determination success rates were 58%, 55%, 80% and 91% in P1, P2, P3 and P4 protocols, respectively. The MLSS did not differ from LACmin in any protocol. The LACmin obtained from P4 protocol showed better assurance for the MLSS identification in most of the tested rats.

Conjugated linoleic acid influences the metabolism of tocopherol in lactating rats but has little effect on tissue tocopherol concentrations in pups.

PubMed

Zeitz, Johanna O; Most, Erika; Eder, Klaus

2016-05-31

Conjugated linoleic acid (CLA) is known to affect the lipid metabolism in growing and lactating animals. However, potential effects on the metabolism of fat-soluble vitamins in lactating animals and co-occurring effects on their offspring are unknown. We aimed to investigate the effects of dietary CLA on concentrations of tocopherol in various tissues of lactating rats and their offspring and expression of genes involved in tocopherol metabolism. Twenty-eight Wistar Han rats were allocated to 2 groups and fed either a control diet (control group) or a diet containing 0.9 % of cis-9, trans-11 and trans-10, cis-12 (1:1) CLA (CLA group) during pregnancy and lactation. Feed intake of dams and body weight of dams and their pups were recorded weekly. Tocopherol concentrations in various body tissues were determined at day 14 of lactation in dams and 1, 7 and 14 days after birth in pups. Expression of selected genes involved in metabolism of tocopherol was determined in dams and pups. The data were statistically analysed by analysis of variance. Feed intake and body weight development of nursing rats and their pups was similar in both groups. In livers of CLA-fed dams, tocopherol concentrations decreased by 24 % but expression of TTPA and CYP3A1, involved in tocopherol transport and metabolism, were not influenced. In the dams' adipose tissue, gene expression of receptors involved in tissue tocopherol uptake, LDLR and SCARB1, but not of LPL, increased by 30 to 50 % and tocopherol concentrations increased by 47 % in CLA-fed compared to control dams. Expression of LPL, LDLR and SCARB1 in mammary gland was not influenced by CLA-feeding. Tocopherol concentrations in the pup's livers and lungs were similar in both groups, but at 14 days of age, adipose tissue tocopherol concentrations, and LDLR and SCARB1 expression, were higher in the CLA-exposed pups. We show that dietary CLA affects tissue concentrations of tocopherol in lactating rats and tocopherol metabolism in

Regulation of bone mineral loss during lactation

NASA Technical Reports Server (NTRS)

Brommage, R.; Deluca, H. F.

1985-01-01

The effects of varyng dietary calcium and phosphorous levels, vitamin D deficiency, oophorectomy, adrenalectomy, and simultaneous pregnancy on bone mineral loss during lactation in rats are studied. The experimental procedures and evaluations are described. The femur ash weight of lactating and nonlactating rats are calculated. The data reveals that a decrease in dietary calcium of 0.02 percent results in an increased loss of bone mineral, an increase in calcium to 1.4 percent does not lessen bone mineral loss, and bone mineral loss in vitamin D deficient rats is independent of calcium levels. It is observed that changes in dietary phosphorous level, oophorectomy, adrenalectomy, and simultaneous pragnancy do not reduce bone mineral loss during lactation. The analysis of various hormones to determine the mechanism that triggers bone mineral loss during lactation is presented.

Physiologically Based Pharmacokinetic Modeling of the Lactating Rat and Nursing Pup: a Multiroute Exposure Model for Trichloroethylene and its Metabolite, Trichloroacetic Acid

DTIC Science & Technology

1990-01-01

cumulated during pregnancy was described as a linear animal (allometrically scaled), was estimated by comput- process changing from 12.0% of body weight of...biochemical effects of TCE in neonatal pregnancy (Fisher et al., 1989) were used for repeated- rats born to dams exposed to TCE via drink- exposure...studies during lactation. Female cesarean-de- rived Fischer-344 rats, obtained from Charles Rivering water during pregnancy and lactation. Breeding

Differential effects of habitual chow-based and semi-purified diets on lipid metabolism in lactating rats and their offspring.

PubMed

Del Bas, Josep Maria; Caimari, Antoni; Ceresi, Enzo; Arola-Arnal, Anna; Palou, Andreu; Arola, Lluís; Crescenti, Anna

2015-03-14

Diet during pregnancy and lactation is a critical factor in relation to the health of dams and their offspring. Currently, control diets used in metabolic imprinting studies differ in composition and type, i.e. semi-purified diets (SD) or chow-based diets (ND). The aim of the present study was to determine whether two widely used control diets, a SD and a ND, that mainly differ in fat content (5·08 and 3·26 %, respectively) and its sources (soyabean oil for the SD and cereals and fish for the ND), fibre (6 and 15 %, respectively), and cholesterol (26 and 69 mg/kg diet, respectively) can influence the lipid metabolism of dams and their offspring. Wistar rats were fed either the SD or the ND during pregnancy and lactation. At weaning, SD-fed dams presented severe hepatic steatosis and increased levels of circulating TAG, NEFA and insulin. Importantly, the offspring presented an altered plasma lipid profile. In contrast, the ND allowed for a normal gestation and lactation process, and did not affect the metabolism of offspring. In parallel, virgin rats fed the SD showed no metabolic alterations. A higher intake of SFA and MUFA and a lower consumption of PUFA observed in SD-fed dams during the lactation period could contribute to explaining the observed effects. In conclusion, two different control diets produced very different outcomes in the lipid metabolism of lactating rats and their offspring. The present results highlight the importance of the assessment of the metabolic state of dams when interpreting the results of metabolic programming studies.

Iodine excess exposure during pregnancy and lactation impairs maternal thyroid function in rats

PubMed Central

Salgueiro, Rafael Barrera; Vitzel, Kaio Fernando; Pantaleão, Thiago; Corrêa da Costa, Vânia Maria

2017-01-01

Adequate maternal iodine consumption during pregnancy and lactation guarantees normal thyroid hormones (TH) production, which is crucial to the development of the fetus. Indeed, iodine deficiency is clearly related to maternal hypothyroidism and deleterious effects in the fetal development. Conversely, the effects of iodine excess (IE) consumption on maternal thyroid function are still controversial. Therefore, this study aimed to investigate the impact of IE exposure during pregnancy and lactation periods on maternal hypothalamus–pituitary–thyroid axis. IE-exposed dams presented reduced serum TH concentration and increased serum thyrotropin (TSH) levels. Moreover, maternal IE exposure increased the hypothalamic expression of Trh and the pituitary expression of Trhr, Dio2, Tsha and Tshb mRNA, while reduced the Gh mRNA content. Additionally, IE-exposed dams presented thyroid morphological alterations, increased thyroid oxidative stress and decreased expression of thyroid genes/proteins involved in TH synthesis, secretion and metabolism. Furthermore, Dio1 mRNA expression and D1 activity were reduced in the liver and the kidney of IE-treated animals. Finally, the mRNA expression of Slc5a5 and Slc26a4 were reduced in the mammary gland of IE-exposed rats. The latter results are in accordance with the reduction of prolactin expression and serum levels in IE-treated dams. In summary, our study indicates that the exposure to IE during pregnancy and lactation induces primary hypothyroidism in rat dams and impairs iodide transfer to the milk. PMID:28814477

Behavioral effects of bidirectional selection for behavior towards human in virgin and lactate Norway rats.

PubMed

Konoshenko, Maria Yu; Plyusnina, Irina Z

2012-06-01

Although numerous studies have demonstrated strong differences in behavioral, hormonal and neurobiological characteristics between male rats selected for elimination (tame) and enhancement (aggressive) of aggressiveness towards humans, few studies have examined changes in female behavior under this selection. The objective of the current work was to evaluate the effects of bidirectional selection for aggressiveness towards humans on behavioral profiles of virgin and lactating rats compared with the behavior in tame, aggressive and unselected (wild-type) females. The behavior of virgin females was studied using the light-dark box, the startle response test and the modified glove test. Tame females were less anxious and more tolerant towards humans than unselected and aggressive rats. Principal component analysis of all behavioral parameters produced three independent factors, explaining 66.37% of the total variability. The measures of behavior towards humans and the measures of anxiety mainly loaded on PC1 (first principal component) which separated the tame females from the unselected and aggressive ones. These data suggest the genetic correlation between the selected behavior towards humans and anxiety-related behavior in virgin rats. No significant effect of line was found for PC2 scores, associated with risk assessment behavior. Measurements of freezing behavior mainly loaded on PC3, and this component separated rats of different genetic groups from each other. The behavior of lactating rats was studied in maternal defense and pup retrieval tests. Females of selected lines did not significantly differ in behavioral measurements of these tests and were characterized by higher maternal motivation than unselected rats. It is suggested that long-term breeding of tame and aggressive rats in captivity has reduced the threshold for maternal behavior. Copyright © 2012 Elsevier B.V. All rights reserved.

Perfluorooctanoate: Placental and lactational transport pharmacokinetics in rats.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hinderliter, Paul M.; Mylchreest, E.; Gannon, S. A.

This study was conducted to develop a quantitative understanding of the potential for gestational and lactational transfer of perfluorooctanoate (PFOA) in the rat. Time-mated female rats were dosed by oral gavage once daily at concentrations of 3, 10, or 30 mg/kg/day of the ammonium salt of PFOA (APFO) starting on gestation (G) day 4 and continuing until sacrifice. On days 10, 15, and 21G, five rats per dose level were sacrificed and blood samples were collected 2h post-dose. Embryos were collected on day 10G, amniotic fluid, placentas, and embryos/fetuses were collected on days 15 and 21G, and fetal blood samplesmore » were collected on day 21G. Five rats per dose level were allowed to deliver and nurse their litters, and on days 3, 7, 14, and 21 post-partum (PP) milk and blood samples of maternal and pup were collected 2h post-dose. All samples were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS) for PFOA concentration. Concentrations of PFOA in maternal plasma and milk attained steady state during the sampling interval. The steady-state concentrations in maternal plasma were 10-15, 25-30, and 60-75 microg/mL in rats receiving 3, 10, and 30 mg/kg, respectively. Steady-state concentrations in milk were approximately 10 times less than those in maternal plasma. The concentration of PFOA in fetal plasma on day 21G was approximately half the steady-state concentration in maternal plasma. The milk concentrations appeared to be generally comparable to the concentrations in pup plasma. Pup plasma concentrations decreased from day 3PP to day 7PP, and were similar on days 7, 14, and 21PP at all dose levels. PFOA was detected in placenta (days 15 and 21G), amniotic fluid (days 15 and 21G), embryo (days 10 and 15G), and fetus (day 21G). These pharmacokinetics allow estimation of the dose to developing and nursing rat offspring following maternal exposure.« less

Effect of Intramuscular Protons, Lactate, and ATP on Muscle Hyperalgesia in Rats.

PubMed

Gregory, Nicholas S; Whitley, Phillip E; Sluka, Kathleen A

2015-01-01

Chronic muscle pain is a significant health problem leading to disability[1]. Muscle fatigue can exacerbate muscle pain. Metabolites, including ATP, lactate, and protons, are released during fatiguing exercise and produce pain in humans. These substances directly activate purinergic (P2X) and acid sensing ion channels (ASICs) on muscle nociceptors, and when combined, produce a greater increase in neuron firing than when given alone. Whether the enhanced effect of combining protons, lactate, and ATP is the sum of individual effects (additive) or more than the sum of individual effects (synergistic) is unknown. Using a rat model of muscle nociceptive behavior, we tested each of these compounds individually over a range of physiologic and supra-physiologic concentrations. Further, we combined all three compounds in a series of dilutions and tested their effect on muscle nociceptive behavior. We also tested a non-hydrolyzable form of ATP (α,β-meATP) alone and in combination with lactate and acidic pH. Surprisingly, we found no dose-dependent effect on muscle nociceptive behavior for protons, lactate, or ATP when given alone. We similarly found no effect after application of each two-metabolite combination. Only pH 4 saline and α,β-meATP produced hyperalgesia when given alone. When all 3 substances were combined, however, ATP (2.4μm), lactate (10mM), and acidic pH (pH 6.0) produced an enhanced effect greater than the sum of the effects of the individual components, i.e. synergism. α,β me ATP (3nmol), on the other hand, showed no enhanced effects when combined with lactate (10mM) or acidic pH (pH 6.0), i.e. additive. These data suggest that combining fatigue metabolites in muscle produces a synergistic effect on muscle nociception.

Effect of Intramuscular Protons, Lactate, and ATP on Muscle Hyperalgesia in Rats

PubMed Central

Gregory, Nicholas S.; Whitley, Phillip E.; Sluka, Kathleen A.

2015-01-01

Chronic muscle pain is a significant health problem leading to disability[1]. Muscle fatigue can exacerbate muscle pain. Metabolites, including ATP, lactate, and protons, are released during fatiguing exercise and produce pain in humans. These substances directly activate purinergic (P2X) and acid sensing ion channels (ASICs) on muscle nociceptors, and when combined, produce a greater increase in neuron firing than when given alone. Whether the enhanced effect of combining protons, lactate, and ATP is the sum of individual effects (additive) or more than the sum of individual effects (synergistic) is unknown. Using a rat model of muscle nociceptive behavior, we tested each of these compounds individually over a range of physiologic and supra-physiologic concentrations. Further, we combined all three compounds in a series of dilutions and tested their effect on muscle nociceptive behavior. We also tested a non-hydrolyzable form of ATP (α,β-meATP) alone and in combination with lactate and acidic pH. Surprisingly, we found no dose-dependent effect on muscle nociceptive behavior for protons, lactate, or ATP when given alone. We similarly found no effect after application of each two-metabolite combination. Only pH 4 saline and α,β-meATP produced hyperalgesia when given alone. When all 3 substances were combined, however, ATP (2.4μm), lactate (10mM), and acidic pH (pH 6.0) produced an enhanced effect greater than the sum of the effects of the individual components, i.e. synergism. α,β me ATP (3nmol), on the other hand, showed no enhanced effects when combined with lactate (10mM) or acidic pH (pH 6.0), i.e. additive. These data suggest that combining fatigue metabolites in muscle produces a synergistic effect on muscle nociception. PMID:26378796

Contribution of Intrinsic Lactate to Maintenance of Seizure Activity in Neocortical Slices from Patients with Temporal Lobe Epilepsy and in Rat Entorhinal Cortex.

PubMed

Angamo, Eskedar Ayele; ul Haq, Rizwan; Rösner, Jörg; Gabriel, Siegrun; Gerevich, Zoltán; Heinemann, Uwe; Kovács, Richard

2017-08-23

Neuronal lactate uptake supports energy metabolism associated with synaptic signaling and recovery of extracellular ion gradients following neuronal activation. Altered expression of the monocarboxylate transporters (MCT) in temporal lobe epilepsy (TLE) hampers lactate removal into the bloodstream. The resulting increase in parenchymal lactate levels might exert both, anti- and pro-ictogen effects, by causing acidosis and by supplementing energy metabolism, respectively. Hence, we assessed the contribution of lactate to the maintenance of transmembrane potassium gradients, synaptic signaling and pathological network activity in chronic epileptic human tissue. Stimulus induced and spontaneous field potentials and extracellular potassium concentration changes (∆[K⁺] O ) were recorded in parallel with tissue pO₂ and pH in slices from TLE patients while blocking MCTs by α-cyano-4-hydroxycinnamic acid (4-CIN) or d-lactate. Intrinsic lactate contributed to the oxidative energy metabolism in chronic epileptic tissue as revealed by the changes in pO₂ following blockade of lactate uptake. However, unlike the results in rat hippocampus, ∆[K⁺] O recovery kinetics and field potential amplitude did not depend on the presence of lactate. Remarkably, inhibition of lactate uptake exerted pH-independent anti-seizure effects both in healthy rat and chronic epileptic tissue and this effect was partly mediated via adenosine 1 receptor activation following decreased oxidative metabolism.

Contribution of Intrinsic Lactate to Maintenance of Seizure Activity in Neocortical Slices from Patients with Temporal Lobe Epilepsy and in Rat Entorhinal Cortex

PubMed Central

Angamo, Eskedar Ayele; Haq, Rizwan ul; Rösner, Jörg; Gabriel, Siegrun; Gerevich, Zoltán; Heinemann, Uwe

2017-01-01

Neuronal lactate uptake supports energy metabolism associated with synaptic signaling and recovery of extracellular ion gradients following neuronal activation. Altered expression of the monocarboxylate transporters (MCT) in temporal lobe epilepsy (TLE) hampers lactate removal into the bloodstream. The resulting increase in parenchymal lactate levels might exert both, anti- and pro-ictogen effects, by causing acidosis and by supplementing energy metabolism, respectively. Hence, we assessed the contribution of lactate to the maintenance of transmembrane potassium gradients, synaptic signaling and pathological network activity in chronic epileptic human tissue. Stimulus induced and spontaneous field potentials and extracellular potassium concentration changes (∆[K+]O) were recorded in parallel with tissue pO2 and pH in slices from TLE patients while blocking MCTs by α-cyano-4-hydroxycinnamic acid (4-CIN) or d-lactate. Intrinsic lactate contributed to the oxidative energy metabolism in chronic epileptic tissue as revealed by the changes in pO2 following blockade of lactate uptake. However, unlike the results in rat hippocampus, ∆[K+]O recovery kinetics and field potential amplitude did not depend on the presence of lactate. Remarkably, inhibition of lactate uptake exerted pH-independent anti-seizure effects both in healthy rat and chronic epileptic tissue and this effect was partly mediated via adenosine 1 receptor activation following decreased oxidative metabolism. PMID:28832554

Acute administration of cefepime lowers L-carnitine concentrations in early lactation stage rat milk.

PubMed

Ling, Binbing; Alcorn, Jane

2008-07-01

Our study investigated the potential for important in vivo drug-nutrient transport interactions at the lactating mammary gland using the L-carnitine transporter substrates, cefepime and L-carnitine, as proof-of-concept. On d 4 (n = 6/treatment) and d 10 (n = 6/treatment) of lactation, rats were administered cefepime (250 mg/h) or saline by continuous i.v. infusion (4 h). Serum and milk L-carnitine and cefepime concentrations were quantified by HPLC-UV. In whole mammary gland, organic cation/carnitine transporter (OCTN)1, OCTN2, OCTN3, amino acid transporter B(0,+) (ATB(0,+)), and L-carnitine transporter 2 expression were determined by quantitative RT-PCR and by western blot and immunohistochemistry when possible. Cefepime caused a 56% decrease in milk L-carnitine concentrations on lactation d 4 (P = 0.0048) but did not affect milk L-carnitine at lactation d 10 or serum L-carnitine concentrations at either time. The mean L-carnitine and cefepime milk:serum ratios (M/S) decreased from 9.1 +/- 0.4 to 4.9 +/- 0.6 (P < 0.0001) and 0.89 +/- 0.3 to 0.12 +/- 0.02 (P = 0.0473), respectively, between d 4 and d 10 of lactation. In both groups, OCTN2 (P < 0.0001), OCTN3 (P = 0.0039), and ATB(0,+) (P = 0.004) mRNA expression and OCTN2 protein (P < 0.0001) were higher in mammary glands at d 4 of lactation compared with d 10. Immunohistochemistry revealed OCTN1 and OCTN2 localization in the mammary alveolar epithelium and OCTN3 expression in the interstitial space and blood vessel endothelium. In conclusion, cefepime significantly decreased milk L-carnitine concentrations only at d 4 of lactation. Relative to d 10, enhanced expression of OCTN2 and ATB(0,+) in mammary glands at d 4 of lactation and higher M/S (L-carnitine and cefepime) suggests cefepime competes with L-carnitine for L-carnitine transporters expressed in the lactating mammary gland to adversely affect L-carnitine milk concentrations and these effects depend upon lactation stage.

The effect of methamphetamine exposure during pregnancy and lactation on hippocampal doublecortin expression, learning and memory of rat offspring.

PubMed

Jalayeri-Darbandi, Zahra; Rajabzadeh, Aliakbar; Hosseini, Mahmoud; Beheshti, Farimah; Ebrahimzadeh-Bideskan, Alireza

2018-06-01

The aim of this study was to evaluate the effect of methamphetamine (MA) exposure during pregnancy and lactation on doublecortin (DCX) expression in the hippocampus of rat offspring and also on learning/memory. Thirty-five pregnant Wistar rats were randomly divided into seven groups of 5 rats each: three experimental groups, each receiving 5 mg/kg body weight (BW) intraperitoneal (i.p.) injections of MA during pregnancy or/and lactation; three sham groups, each receiving saline injections; one control group, receiving no injection. After the interventions, two male pups (1 and 22 days old) were randomly selected from each mother, sacrificed and their brains subjected to DCX immunohistochemistry. One additional male pup from each mother was randomly selected and maintained for 60 days for testing in the Morris water maze and passive avoidance tests. MA administration during pregnancy was found to have significantly decreased the number of DCX-positive cells in the CA1, CA3 and DG regions of the hippocampus in the 1-day pups (P ≤ 0.05) and to have significantly decreased the number of DCX-positive cells in only two regions of the hippocampus, the CA1 and DG regions, in 22-day old pups. In comparison, exposure to MA during lactation was only associated with a significant decrease in the number of DCX-positive cells in the DG. Exposure to MA during pregnancy had significant impact on the intensity of DCX expression in the hippocampus of 1- and 22-day pups (P ≤ 0.05). There was no significant difference in memory/learning among the study groups. Our results indicate the administration of MA during pregnancy had a greater effect that during the lactation period on DCX expression in the hippocampus of rat offspring.

Detection of intracellular lactate with localized diffusion { 1H- 13C}-spectroscopy in rat glioma in vivo

NASA Astrophysics Data System (ADS)

Pfeuffer, Josef; Lin, Joseph C.; DelaBarre, Lance; Ugurbil, Kamil; Garwood, Michael

2005-11-01

The aim of this study was to compare the diffusion characteristic of lactate and alanine in a brain tumor model to that of normal brain metabolites known to be mainly intracellular such as N-acetylaspartate or creatine. The diffusion of 13C-labeled metabolites was measured in vivo with localized NMR spectroscopy at 9.4 T (400 MHz) using a previously described localization and editing pulse sequence known as ACED-STEAM ('adiabatic carbon editing and decoupling'). 13C-labeled glucose was administered and the apparent diffusion coefficients of the glycolytic products, { 1H- 13C}-lactate and { 1H- 13C}-alanine, were determined in rat intracerebral 9L glioma. To obtain insights into { 1H- 13C}-lactate compartmentation (intra- versus extracellular), the pulse sequence used very large diffusion weighting (50 ms/μm 2). Multi-exponential diffusion attenuation of the lactate metabolite signals was observed. The persistence of a lactate signal at very large diffusion weighting provided direct experimental evidence of significant intracellular lactate concentration. To investigate the spatial distribution of lactate and other metabolites, 1H spectroscopic images were also acquired. Lactate and choline-containing compounds were consistently elevated in tumor tissue, but not in necrotic regions and surrounding normal-appearing brain. Overall, these findings suggest that lactate is mainly associated with tumor tissue and that within the time-frame of these experiments at least some of the glycolytic product ([ 13C] lactate) originates from an intracellular compartment.

Body adiposity and bone parameters of male rats from mothers fed diet containing flaxseed flour during lactation.

PubMed

da Costa, C A S; da Silva, P C A; Ribeiro, D C; Pereira, A D D; Santos, A D S D; Maia, L D A; Ruffoni, L D G; de Santana, F C; de Abreu, M D C; Boueri, B F D C; Pessanha, C R; Nonaka, K O; Mancini-Filho, J; do Nascimento-Saba, C C A; Boaventura, G T

2015-12-07

Obesity and osteoporosis may have their origins in early postnatal life. This study was designed to evaluate whether flaxseed flour use during lactation period bears effect on body adiposity and skeletal structure of male rat pups at weaning. At birth, male Wistar rats were randomly assigned to control and experimental (FF) groups, whose dams were treated with control or flaxseed flour diet, respectively, during lactation. At 21 days of age, pups were weaned to assess body mass, length and composition by dual-energy X-ray absorptiometry. The animals were then sacrificed to carry out analysis of serum profile, intra-abdominal adipocyte morphology and femur characteristics. Differences were considered significant when P<0.05. The FF group displayed the following characteristics (P<0.05): higher body mass, length, bone mineral content, bone area and concentrations of osteoprotegerin, osteocalcin and high-density lipoprotein cholesterol; higher levels of stearic, α-linolenic, eicosapentaenoic and docosapentaenoic acids and lower levels of arachidonic acid and cholesterol; smaller adipocyte area; and higher mass, epiphysis distance, diaphysis width, maximal load, break load, resilience and stiffness of femur. Flaxseed flour intake during lactation period promoted adipocyte hypertrophy down-regulation and contributed to pup bone quality at weaning.

Effects of in utero and lactational exposure to triphenyltin chloride on pregnancy outcome and postnatal development in rat offspring.

PubMed

Grote, Konstanze; Hobler, Carolin; Andrade, Anderson J M; Grande, Simone Wichert; Gericke, Christine; Talsness, Chris E; Appel, Klaus E; Chahoud, Ibrahim

2007-09-05

The organotin compound (OTC) triphenyltin (TPT) is used extensively as a herbicide, pesticide and fungicide in agriculture as well as, together with tributyltin (TBT), in marine antifouling paints. We studied the effects of in utero exposure to 2 or 6 mg triphenyltinchloride (TPTCl)/kgb.w. on pregnancy outcome and postnatal development in rat offspring. Gravid Wistar rats were treated per gavage from gestational day 6 until the end of lactation. In the 6 mg TPTCl dose group gestational mortality in dams as well as an increased incidence of anticipated and delayed parturition was observed. Furthermore, treatment resulted in a significant increase in perinatal mortality, a decrease in lactational body weight gain as well as in delayed physical maturation of offspring. Similarily, exposure to 2mg TPTCl/kgb.w. resulted in a significant increase in perinatal mortality and in delayed eye opening. Lactational body weight gain and other landmarks of physical maturation were unaffected in the low dose group. We conclude, that in utero exposure to TPTCl at the described dose levels severely affected pregnancy outcome and perinatal survival of offspring. These results were unexpected, as in two earlier studies with pubertal rats TPTCl at the same dose levels no signs of general toxicity were observed.

Simulation of the pentose cycle in lactating rat mammary gland

PubMed Central

Haut, Michael J.; London, Jack W.; Garfinkel, David

1974-01-01

A computer model representing the pentose cycle, the tricarboxylic acid cycle and glycolysis in slices of lactating rat mammary glands has been constructed. This model is based primarily on the studies, with radioactive chemicals, of Abraham & Chaikoff (1959) [although some of the discrepant data of Katz & Wals (1972) could be accommodated by changing one enzyme activity]. Data obtained by using [1-14C]-, [6-14C]- and [3,4-14C]-glucose were simulated, as well as data obtained by using unlabelled glucose (for which some new experimental data are presented). Much past work on the pentose cycle has been mainly concerned with the division of glucose flow between the pentose cycle and glycolysis, and has relied on the assumption that the system is in steady state (both labelled and unlabelled). This assumption may not apply to lactating rat mammary glands, since the model shows that the percentage flow through the shunt progressively decreased for the first 2h of a 3h experiment, and we were unable to construct a completely steady-state model. The model allows examination of many quantitative features of the system, especially the amount of material passing through key enzymes, some of which appear to be regulated by NADP+ concentrations as proposed by McLean (1960). Supplementary information for this paper has been deposited as Supplementary Publication SUP 50023 at the British Museum (Lending Division) (formerly the National Lending Library for Science and Technology), Boston Spa, Yorks. LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1973) 131, 5. PMID:4154746

Differences in the ribosomes prepared from lactating and non-lactating bovine mammary gland

PubMed Central

Herrington, M. D.; Hawtrey, A. O.

1971-01-01

1. Ribosomes prepared from bovine lactating mammary gland are able to synthesize protein, whereas similar preparations from non-lactating glands are not. Washing the ribosome suspensions through a medium containing 0.5m-ammonium chloride enhanced their ability to incorporate phenylalanine into polyphenylalanine. 2. Ribosomes isolated from non-lactating bovine mammary gland, in contrast with those from rat liver and lactating mammary gland, contained significant amounts of extraneous nucleases. These enzymes could be removed by washing with a medium A buffer containing 0.5m-ammonium chloride. 3. Only those ribosomes from functionally active tissues were able to bind polyuridylic acid and phenylalanyl-tRNA. PMID:5165653

Postictal in situ MRS brain lactate in the rat kindling model.

PubMed

Maton, B M; Najm, I M; Wang, Y; Lüders, H O; Ng, T C

1999-12-10

To determine the temporal and spatial extent of the lactate (Lact) changes as correlated with seizure characteristics and EEG changes in the rat kindling model. Prior studies using MRS have detected cerebral Lact postictally in animal models of seizures and in patients with intractable focal epilepsy. We performed MRS in sham control rats (n = 4) and in rats stimulated in the right hippocampus at two different stages of the kindling and at three time points after the seizures: <2 hours (n = 8 and 5, stage 0 and stage 5), 2 to 3 hours (n = 5 and 6), and >3 hours (n = 4 and 2). Lact/creatine (Cr) and N-acetylaspartate (NAA)/Cr ratios were measured in six contiguous voxels (three left, three right) covering the hippocampi, anterior and posterior regions, and compared with EEG and ictal behavior. Lact/Cr ratios were measured at a very low level in the sham control rats and in the >3-hour group. In the <2-hour group, Lact/Cr increase was higher in stage-5 rats as compared with stage-0 rats (p = 0.001, unpaired t-test) and sham control rats when all the voxels were considered. Lact/Cr ratios were higher in the stimulated area as compared with all other brain areas in stage-0 rats (p = 0.05, paired t-test) but not in the stage-5 rats. Similar results with more inter-animal variability were measured in the 2- to 3-hour group. NAA/Cr ratios increased significantly after stage-0 kindling in the stimulated hippocampus but not after stage-5 kindling. Postictal Lact increase as assayed by MRS correlates with EEG and behavioral seizures and suggests that it would be an additional noninvasive technique for seizure localization during the presurgical evaluation of patients with intractable focal epilepsy.

The effects of pregnancy, lactation, and primiparity on object-in-place memory of female rats.

PubMed

Cost, Katherine Tombeau; Lobell, Thomas D; Williams-Yee, Zari N; Henderson, Sherryl; Dohanich, Gary

2014-01-01

Maternal physiology and behavior change dramatically over the course of pregnancy to nurture the fetus and prepare for motherhood. Further, the experience of motherhood itself continues to influence brain functioning well after birth, shaping behavior to promote the survival of offspring. To meet these goals, cognitive abilities, such as spatial memory and navigation, may be enhanced to facilitate foraging behavior. Existing studies on pregnant and maternal rats demonstrate enhanced cognitive function in specific spatial domains. We adopted a novel object-in-place task to assess the ability of female rats to integrate information about specific objects in specific locations, a critical element of foraging behavior. Using a longitudinal design to study changes in spatial memory across pregnancy and motherhood, an advantage in the object-in-place memory of primiparous female rats compared to nulliparous females emerged during lactation not during pregnancy, and was maintained after weaning at 42 days postpartum. This enhancement was not dependent on the non-mnemonic variables of anxiety or neophobia. Parity did not affect the type of learning strategy used by females to locate a cued escape platform on a dual-solution water maze task. Results indicate that the enhancement of object-in-place memory, a cognitive function that facilitates foraging, emerged after pregnancy during the postpartum period of lactation and persisted for several weeks after weaning of offspring. © 2013.

Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose-response model

EPA Science Inventory

A biologically-based dose response (BBDR) model for the hypothalamic-pituitary thyroid (BPT) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide deficiency on the HPT axis. Model calibrations, carried out by adjusting key model p...

[Behavioural studies during the gestational-lactation period in morphine treated rats].

PubMed

Sobor, Melinda; Timár, Júlia; Riba, Pál; Király, Kornél P; Al-Khrasani, Mahmoud; Gyarmati, Zsuzsanna; Fürst, Zsuzsanna

2013-12-01

Opioids impair the maternal behaviour of experimental animals. The effect of morphine on maternal behaviour in rat dams treated chronically with morphine during the whole pregnancy and lactation has not been yet analysed systematically. The aim of our work was to investigate the behavioural effects of moderate dose morphine administered constantly in the whole perinatal period in rats. Nulliparous female rats were treated with 10 mg/kg morphine s.c. once daily, from the day of mating. Maternal behaviour was observed, the effects of acute morphine treatment on the maternal behaviour and whether this effect could be antagonised by naloxone were also investigated. Physical and other behavioural (anxiety-like signals in elevated plus maze, changes in locomotor activity) withdrawal signs precipitated by naloxone were registered. After weaning sensitivity to the rewarding effect of morphine was measured by conditioned place preference and to the aversive effect of naloxone by conditioned place aversion tests. Antinociceptive test on tail-flick apparatus was performed to investigate the changes in morphine antinociceptive effects due to chronic morphine treatment. Maternal behaviour was significantly impaired in morphine-treated dams. This effect of morphine lasted c.a. 2-3 hours a day, it showed dose-dependency and was enhanced in MO-treated group (sensitisation). Only weak physical and no other behavioural (anxiety-like behaviour or hypolocomotion) withdrawal signs were precipitated by naloxone. The positive reinforcing effect of morphine and aversive effect of naloxone were markedly increased on conditioned place paradigm. Significant antinociceptive tolerance was not seen. Although human drug abuse can be hardly modelling under experimental circumstances, our constant, relatively moderate dose morphine treatment administered once daily during the whole pregnancy and lactation resulted in several subtle behavioural changes in dams. In perinatally opioid

Selective expression of neuropeptides in the rat mammary gland: somatostatin gene is expressed during lactation.

PubMed

Chen, A; Laskar-Levy, O; Koch, Y

1999-12-01

The existence of numerous neuropeptides in milk, in concentrations that exceed those in maternal plasma, is well established. It is still unclear whether these neuropeptides are produced by the mammary gland or that the gland concentrates them from the general circulation. In this study, we have examined the possibility that the genes of these neuropeptides are expressed in the rat mammary gland. RNA was extracted from the mammary glands of female rats during different stages of reproduction as well as from other tissues such as hypothalami, pancreas, pineal glands, small intestine, and ovaries. Following RT reaction, the resulting cDNA were amplified by radioactive PCR using specific oligonucleotide primers. We have used specific primers for the following neuropeptides: galanin, somatostatin, vasoactive intestinal peptide, TRH, GH-releasing hormone, cholecystokinin, neurotensin, oxytocin, and relaxin. We have also used primers for serotonin N-acetyl-transferase, the enzyme that is involved in melatonin biosynthesis. The ribosomal protein S-16 served as an internal control. Among all the neuropeptides that have been examined, somatostatin was the only one that was found to be expressed in the mammary gland. Somatostatin was expressed in the mammary gland of lactating rats, but not of virgin rats. Expression of the somatostatin gene was confirmed by Southern blot analysis and by sequencing of the PCR products. Immunohistochemical studies demonstrated somatostatin immunoreactivity in the epithelial cells that compose the secretory alveoli and in the secretory material. In addition, we have found that the mammary glands of the lactating rat express the PC-1 proteinase gene that process prosomatostatin to generate somatostatin-14, but do not express furin, the enzyme that is responsible for somatostatin-28 production. This finding substantiates previous studies that demonstrated that only somatostatin-14 is present in milk. The finding that most of the neuropeptides

Flaxseed oil during lactation changes milk and body composition in male and female suckling pups rats.

PubMed

Guarda, Deysla Sabino; Lisboa, Patricia Cristina; de Oliveira, Elaine; Nogueira-Neto, José Firmino; de Moura, Egberto Gaspar; Figueiredo, Mariana Sarto

2014-07-01

We have reported several changes in neonate or adult offspring after the maternal use of whole flaxseed or its components. However, it is unknown the use of higher oil intake in the neonatal period. Here we evaluated the effects of high maternal intake of flaxseed oil during lactation upon milk and body composition in male and female offspring. Lactating rats were divided into: (1) control (C, n=10), 7% soybean oil; (2) hyper 19% soybean oil (HS, n=10); and (3) hyper 17% flaxseed oil+2% soybean oil (HF, n=10). Dams and offspring were killed at weaning. HS and HF dams, male and female offspring presented lower body weight during lactation. HF mothers presented lower body and visceral fat masses. HF male offspring presented lower body and subcutaneous fat masses. HS and HF milk presented lower triglycerides (TG) and cholesterol. HF male and female offspring showed lower triglyceridemia and insulinemia, but no changes in glycemia and leptinemia. The higher intake of flaxseed oil during lactation reduced the body weight of mothers and offspring, decreases milk lipids and apparently increases insulin sensitivity in this critical period of life. Those changes may explain the previously reported programming effect of maternal flaxseed intake during lactation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Magnetic resonance lactate and lipid signals in rat brain after middle cerebral artery occlusion model

PubMed Central

Harada, Kuniaki; Honmou, Osamu; Liu, He; Bando, Michio; Houkin, Kiyohiro; Kocsis, Jeffery D.

2008-01-01

Proton magnetic resonance spectroscopy (1-H MRS) has revealed changes of metabolites in acute cerebral infarction. Although the drastic changes of lactate and N-acetyl-aspartate have been reported to be useful indicators of the ischemic damage in both humans and experimental animals, lipid signals are also detected by the short echo time sequence 1–5 days after ischemia. The objective of this study was to find a novel technique to isolate lactate signals from lipid signals in the ischemic brain. First, MRS was used to study the lipid and lactate components of a spherical phantom in vitro, and parameters were established to separate these components in vitro. Then, MR measurements were obtained from the brains of middle cerebral artery occlusion rats. All MR measurements were performed using a 7-T (300 MHz), 18.3-cm-bore superconducting magnet (Oxford Magnet Technologies) interfaced to a Unity INOVA Imaging System (Varian Technologies). T2-weighted images were obtained from a 1.0-mm-thick coronal section using a 3-cm field of view. It is well known that lipid has a shorter and lactate a longer T2 relaxation time. These distinct magnetic characteristics allowed us to separate the lactate signal from the lipid signal. Thus, adjustment of the echo time is essential to analyze the metabolites in acute cerebral infarction, which may be useful in both the clinic and laboratory. PMID:17196558

Renal structure and function evaluation of rats from dams that received increased sodium intake during pregnancy and lactation submitted or not to 5/6 nephrectomy.

PubMed

Marin, Evelyn Cristina Santana; Balbi, Ana Paula Coelho; Francescato, Heloísa Della Coletta; Alves da Silva, Cleonice Giovanini; Costa, Roberto Silva; Coimbra, Terezila M

2008-01-01

Adult rats submitted to perinatal salt overload presented renin-angiotensin system (RAS) functional disturbances. The RAS contributes to the renal development and renal damage in a 5/6 nephrectomy model. The aim of the present study was to analyze the renal structure and function of offspring from dams that received a high-salt intake during pregnancy and lactation. We also evaluated the influence of the prenatal high-salt intake on the evolution of 5/6 nephrectomy in adult rats. A total of 111 sixty-day-old rat pups from dams that received saline or water during pregnancy and lactation were submitted to 5/6 nephrectomy (nephrectomized) or to a sham operation (sham). The animals were killed 120 days after surgery, and the kidneys were removed for immunohistochemical and histological analysis. Systolic blood pressure (SBP), albuminuria, and glomerular filtration rate (GFR) were evaluated. Increased SBP, albuminuria, and decreased GFR were observed in the rats from dams submitted to high-sodium intake before surgery. However, there was no difference in these parameters between the groups after the 5/6 nephrectomy. The scores for tubulointerstitial lesions and glomerulosclerosis were higher in the rats from the sham saline group compared to the same age control rats, but there was no difference in the histological findings between the groups of nephrectomized rats. In conclusion, our data showed that the high-salt intake during pregnancy and lactation in rats leads to structural changes in the kidney of adult offspring. However, the progression of the renal lesions after 5/6 nephrectomy was similar in both groups.

The kinetics of transport of lactate and pyruvate into rat hepatocytes. Evidence for the presence of a specific carrier similar to that in erythrocytes.

PubMed Central

Edlund, G L; Halestrap, A P

1988-01-01

Time courses of L-lactate and pyruvate uptake into isolated rat hepatocytes were measured in a citrate-based medium to generate a pH gradient (alkaline inside), by using the silicone-oil-filtration technique at 0 degrees C to minimize metabolism. At low concentrations of lactate and pyruvate (0.5 mM), transport was inhibited by over 95% by 5 mM-alpha-cyano-4-hydroxycinnamate, whereas at higher concentrations (greater than 10 mM) a significant proportion of transport could not be inhibited. The rate of this non-inhibitable transport was linearly related to the substrate concentration, was less with pyruvate than with L-lactate, and appeared to be due to diffusion of undissociated acid. Uptake of D-lactate was not inhibited by alpha-cyano-4-hydroxycinnamate and occurred only by diffusion. Kinetic parameters for the carrier-mediated transport process were obtained after correction of the initial rates of uptake of lactate and pyruvate in the absence of 5 mM-alpha-cyano-4-hydroxycinnamate by that in the presence of inhibitor. Under the conditions used, the Km values for L-lactate and pyruvate were 2.4 and 0.6 mM respectively and the Ki for alpha-cyano-4-hydroxycinnamate as a competitive inhibitor was 0.11 mM. Km values for the transport of L-lactate and pyruvate into rat erythrocytes under similar conditions were 3.0 and 0.96 mM. The Vmax. of lactate and pyruvate transport into hepatocytes at 0 degrees C was 3 nmol/min per mg of protein. Carrier-mediated transport of 0.5 mM-L-lactate was inhibited by 0.2 mM-p-chloromercuribenzenesulphonate (greater than 90%), 0.5 mM-quercetin (80%), 0.6 mM-isobutylcarbonyl-lactyl anhydride (70%) and 0.5 mM-4,4'-di-isothiocyanostilbene-2,2'-disulphonate (50%). A similar pattern of inhibition of lactate transport is seen in erythrocytes. It is suggested that the same or a similar carrier protein exists in both tissues. The results also show that L-lactate transport into rat hepatocytes is very rapid at physiological temperatures and is

Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose response (BBDR) Model***

EPA Science Inventory

A biologically-based dose response (BBDR) model for the hypothalamic-pituitary thyroid (HPT) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide deficiency on the 1-IPT axis. Model calibrations, carried out by adjusting key model...

Effects of Hypergravity Exposure On Plasma Oxytocin Concentrations In Pregnant and Lactating Rat Dams

NASA Technical Reports Server (NTRS)

Baer, Lisa A.; Wade, Charles E.; Ronca, April E.; Dalton, Bonnie (Technical Monitor)

2002-01-01

Rat dams and offspring were exposed to 1.5-g, 1.75-g or 2.0-g hypergravity (hg) from Gestational day (G) 11 until Postnatal day (P) 10. To ascertain the role of maternal factors in reduced postnatal body weights of offspring developed in hg, the dams' lactational hormones were measured. Oxytocin (OT), the major hormone responsible for milk ejection, was reduced in hg dams whereas prolactin (Prl), involved in milk production, was unchanged. Video analyses of nursing behavior revealed that hg dams spent more time nursing relative to 1-g controls. We hypothesized impaired milk transfer from dam to pup, however pup body weight gains following a discrete suckling episode were comparable across conditions. Changes in lactational hormones and nursing behavior by dams exposed to hg do not account for reduced body masses of their offspring.

Lactate in the brain of the freely moving rat: voltammetric monitoring of the changes related to the sleep-wake states.

PubMed

Shram, Nataliya; Netchiporouk, Larissa; Cespuglio, Raymond

2002-08-01

Cortical lactate was monitored voltammetrically in freely moving rats equipped with polygraphic electrodes. Differential normal pulse voltammetric measurements were carried out using a lactate biosensor coated with lactate oxidase and cellulose acetate. Changes occurring in lactate level were in keeping with sleep-wake states. During slow wave sleep (SWS), the lactate level decreased significantly (-16.2%) vs. the spontaneous waking state (W) referenced to as 100%. During paradoxical sleep (PS), and still vs. W, it remained low (-9.0%) but this variation was not statistically significant. However, when this PS change was compared to the SWS variation, a significant increase in lactate level was then revealed (+8.5%). Finally, during the active waking (aW) triggered by a water puff stress, lactate level rose significantly in accordance with the animal activity (+53% compared to W). Long-term monitoring also allowed the determination of a circadian component in lactate production, the lowest and highest values being monitored during light and dark periods, respectively. The acrophasis of the circadian change occurred during the dark period, about 3 h after the light-off (+89%). It is suggested that during wakefulness astrocyte metabolism allows the transformation of the blood-borne glucose into lactate. The increase in this substrate observed during PS may fulfil the oxidative phosphorylation in order to supply the important ATP need of PS.

Effect of variation of trans-fatty acid in lactating rats' diet on lipoprotein lipase activity in mammary gland, liver, and adipose tissue.

PubMed

Assumpção, Renata Pereira; dos Santos, Flávia Duarte; de Mattos Machado Andrade, Priscila; Barreto, Giselle Freire; das Graças Tavares do Carmo, Maria

2004-09-01

Lactation is associated with an increase in lipoprotein lipase (LPL) activity in the mammary gland (MG) and a decrease in adipose tissue because lactation redirects circulating substrates to the MG for milk synthesis. We investigated the effects of different dietary contents of trans-fatty acid (TFA) on LPL activity in maternal tissues and fatty acid composition in milk. Lactating rats were fed semisynthetic isocaloric diets containing 7% soy oil (control), 7% partially hydrogenated vegetable oil (7%-PHVO), 5% PHVO plus 2% soy oil (5%-PHVO), or 3.5% PHVO plus 3.5% soy oil (3.5%-PHVO). On lactation day 14, animals were decapitated and MG, liver, and parametrial adipose tissue were extracted to determine total lipid contents, percentages of TFA, and LPL activity. Milk lipid composition was examined by gas chromatographic analysis of the gastric content of 14-d-old suckling pups. Maternal consumption of TFA increased dietary TFA incorporation in MG and liver and decreased it in parametrial adipose tissue. Diets with higher trans concentrations (7%-PHVO) significantly increased lipid content in the MG, and all groups fed trans-based diets showed significant increases in LPL activity in the MG. Although LPL increased in the MG, milk of rats fed TFA-based diets had significant decreases in the percentage of essential fatty acids. TFA intake during lactation alters maternal lipid metabolism and the percentage of essential fatty acids in milk; therefore, it is important to alert the population to avoid excessive intake of TFAs during lactation.

The “metabolic sensor” function of rat supraoptic oxytocin and vasopressin neurons is attenuated during lactation but not in diet-induced obesity

PubMed Central

Stevens, Wanida; Song, Zhilin; Johnson, Ginger C.; MacLean, Paul S.

2015-01-01

The oxytocin (OT) and vasopressin (VP) neurons of the supraoptic nucleus (SON) demonstrate characteristics of “metabolic sensors”. They express insulin receptors and glucokinase (GK). They respond to an increase in glucose and insulin with an increase in intracellular [Ca2+] and increased OT and VP release that is GK dependent. Although this is consistent with the established role of OT as an anorectic agent, how these molecules function relative to the important role of OT during lactation and whether deficits in this metabolic sensor function contribute to obesity remain to be examined. Thus, we evaluated whether insulin and glucose-induced OT and VP secretion from perifused explants of the hypothalamo-neurohypophyseal system are altered during lactation and by diet-induced obesity (DIO). In explants from female day 8 lactating rats, increasing glucose (Glu, 5 mM) did not alter OT or VP release. However, insulin (Ins; 3 ng/ml) increased OT release, and increasing the glucose concentration in the presence of insulin (Ins+Glu) resulted in a sustained elevation in both OT and VP release that was not prevented by alloxan, a GK inhibitor. Explants from male DIO rats also responded to Ins+Glu with an increase in OT and VP regardless of whether obesity had been induced by feeding a high-fat diet (HFD). The HFD-DIO rats had elevated body weight, plasma Ins, Glu, leptin, and triglycerides. These findings suggest that the role of SON neurons as metabolic sensors is diminished during lactation, but not in this animal model of obesity. PMID:26661099

Isoenzymes of protein kinase C in rat mammary tissue: changes in properties and relative amounts during pregnancy and lactation.

PubMed

Connor, K; Clegg, R A

1993-05-01

Protein kinase isoenzymes belonging to the protein kinase C (PK-C) family present in rat mammary tissue have been resolved from one another by chromatography on hydroxyapatite, and characterized. PK-C alpha is the predominant isoenzyme and is present at a constant level of activity throughout mammary-gland development and differentiation. In contrast, marked changes in the relative abundance of other mammary PK-C isoenzymes accompany the transition from pregnancy to lactation. The sensitivity of mammary PK-C alpha to Ca2+ is greater in tissue from pregnant than from lactating rats. This isoenzyme has other atypical properties consistent with its being more highly phosphorylated than PK-C alpha in rat brain and spleen. One of the protein kinase isoenzymes resolved from mammary tissue recognizes the peptide substrate used to assay AMP-activated kinase and may thus interfere in the determination of this activity. Another is fully active in the absence of Ca2+ and is more than 80% active in the absence of added lipid effectors. A 'housekeeping' role is proposed for PK-C alpha in mammary tissue, whereas the less abundant PK-C isoenzymes may be involved in mammary cell proliferation and differentiation.

[Use of diet containing yeast protein (Saccharomyces cerevisiae): effects upon pregnancy, lactation and development in rats].

PubMed

de Oliveira, S R; Bion, F M; Lopes, S M; Metri, A C

2001-03-01

The nutritive value of manioc flour (Manihot esculenta) enriched with yeast protein (Saccharomyces cerevisiae) added to a food mixture most frequently consumed by low-income populations was assessed in female Wistar rats (n = 30; 100-120 days old). Animals were divided into three groups, mated and had free access to diets and water. Diets were as follows: beans, rice, yeast-enriched manioc flour (BRYMF17); beans, rice, manioc flour (BRMF13); casein (17% protein) (CAS17). Body weight gains and food consumption were recorded during pregnancy and lactation. At the parturition, the number of pups per litter was recorded and offspring were uniformly distributed (7 pups per litter). Weight gains were determined until weaning (21 days). At weaning two youngs were selected from each litter and individually housed. Weight gains, food consumption and the length of the tail were measured until rats were 70 days old. Rats had their liver and brain removed for protein determination and wet and relative weights. Liver samples were histologically examined. Blood hemoglobin, hematocrit and proteins, as well as the Food Efficiency Ratio (FER), were determined. ANOVA and Tukey's test were used. The experimental diet had not significant effect on pregnant and lactating dams. Values for the investigated parameters were higher in experimental youngs than in their controls and lower than in the standard group. This yeast protein-enriched manioc flour proved to be valid in terms of dietary supplementation.

Intake and hedonics of calcium and sodium during pregnancy and lactation in the rat.

PubMed

Leshem, M; Levin, T; Schulkin, J

2002-03-01

These experiments sought to distinguish whether increased calcium intake during pregnancy and lactation in the rat is due to arousal of a specific calcium appetite, with altered taste hedonics, as occurs with sodium depletion, to reduced taste sensitivity, or to the hyperdipsia of reproduction. We find that, during pregnancy and lactation, CaCl(2) intake is not increased more (in fact less) than intakes of control tastants, MgCl(2) and quinine HCl, and multiparous dams do not have a greater calcium intake than primaparous dams. Changes in taste reactivity to CaCl(2) and to NaCl do not correlate with changes in intake of these minerals during pregnancy or lactation, suggesting that alterations in hedonics or sensitivity do not explain the increased intake of these minerals. Taken together with the increased intake of all the tastants, it may be that the increased intakes of calcium and sodium during reproduction are not due to respective specific appetites or to a general mineral appetite but rather to the reproduction-increased ingestion that may meet all the dam's increased mineral and nutrient requirements. Differences in the degree of increased intakes of tastes may be due to specific alterations in their transduction during reproduction.

Effect of maternal exposure to Tityus bahiensis scorpion venom during lactation on the offspring of rats.

PubMed

Martins, Adriana do Nascimento; Nencioni, Ana Leonor Abrahão; Dorce, Ana Leticia Coronado; Paulo, Maria Eliza F V; Frare, Eduardo Osório; Dorce, Valquíria Abrão Coronado

2016-01-01

Scorpion stings are a public health problem in Brazil and lactating women may be affected. We aimed to study the effects of Tityus bahiensis venom in the offspring of rats treated during lactation. Mothers received a subcutaneous injection of saline (1.0ml/kg) or venom (2.5mg/kg) or an intraperitoneal injection of LPS (lipopolysaccharide) (100μg/kg) on postnatal (PN) days 2 (PN2), 10 (PN10) or 16 (PN16). The offspring were evaluated during the childhood and adulthood. Pups showed a delay in physical and reflexological development, and a decrease in motor activity. Adults displayed low anxiety. There was an increase in the number of viable neuronal cells in hippocampal areas CA1 and CA4. The levels of IFN-γ (interferon-gamma) increased in the experimental groups. Several of the parameters analyzed showed important differences between the sexes. Thus, the scorpion venom affects the development in the offspring of mothers envenomed during the lactation. Copyright © 2015 Elsevier Inc. All rights reserved.

Adaptative decrease in expression of the mRNA for uncoupling protein and subunit II of cytochrome c oxidase in rat brown adipose tissue during pregnancy and lactation.

PubMed Central

Martin, I; Giralt, M; Viñas, O; Iglesias, R; Mampel, T; Villarroya, F

1989-01-01

Uncoupling-protein (UCP) mRNA expression is decreased to 15% of virgin control levels between days 10 and 15 of pregnancy, and remains at these low values during late pregnancy and lactation. Abrupt weaning of mid-lactating rats causes a slight but significant increase in UCP mRNA. Expression of mRNA for subunit II of cytochrome c oxidase (COII) decreased to half that of virgin control in late pregnancy and during lactation. Whereas COII mRNA expression is in step with the known modifications of brown-fat mitochondria content during the breeding cycle of the rat, UCP mRNA expression appears to be diminished much earlier than the mitochondrial proton-conductance-pathway activity. On the other hand, the reactivity of brown fat to increase expression of UCP and COII mRNAs in response to acute cold or noradrenaline treatment is not impaired during lactation. Images Fig. 1. Fig. 2. Fig. 3. PMID:2557014

Upregulation of GH, but not IGF1, in the hippocampus of the lactating dam after kainic acid injury

PubMed Central

Arellanes-Licea, Elvira C; Ávila-Mendoza, José; Ramírez-Martínez, Elizabeth C; Ramos, Eugenia; Uribe-González, Nancy; Arámburo, Carlos

2018-01-01

Lactation embodies a natural model of morphological, neurochemical, and functional brain plasticity. In this reproductive stage, the hippocampus of the female is less sensitive to excitotoxins in contrast to nulliparity. Growth hormone (GH) and insulin-like growth factor 1 (IGF1) are known to be neuroprotective in several experimental models of brain lesion. Here, activation of the GH–IGF1 pituitary–brain axis following kainic acid (7.5 mg/kg i.p. KA) lesion was studied in lactating and nulliparous rats. Serum concentrations of GH and IGF1 were uncoupled in lactation. Compared to virgin rats, the basal concentration of GH increased up to 40% but IGF1 decreased 58% in dams, and only GH increased further after KA treatment. In the hippocampus, basal expression of GH mRNA was higher (2.8-fold) in lactating rats than in virgin rats. GH mRNA expression in lactating rats increased further after KA administration in the hippocampus and in the hypothalamus, in parallel to GH protein concentration in the hippocampus of KA-treated lactating rats (43% vs lactating control), as detected by Western blot and immunofluorescence. Except for the significantly lower mRNA concentration in the liver of lactating rats, IGF1 expression was not altered by the reproductive condition or by KA treatment in the hippocampus and hypothalamus. Present results indicate upregulation of GH expression in the hippocampus after an excitotoxic lesion, suggesting paracrine/autocrine actions of GH as a factor underlying neuroprotection in the brain of the lactating dam. Since no induction of IGF1 was detected, present data suggest a direct action of GH. PMID:29321175

Voluntary exercise in pregnant rats improves post-lactation maternal bone parameters but does not affect offspring outcomes in early life.

PubMed

Rosa, B V; Blair, H T; Vickers, M H; Morel, P C; Cockrem, J F; Firth, E C

2012-12-01

The objectives of this study were to examine the effects of voluntary exercise during pregnancy on maternal post-lactation bone parameters and offspring growth. Pregnant Wistar rats were housed in conventional cages (control), or were housed in raised cages requiring them to rise to an erect, bipedal stance to obtain food/water, throughout pregnancy. Dual energy X-ray absorptiometry and peripheral quantitative computed tomography scans were performed pre-mating and post-weaning. Maternal stress was assessed by fecal corticosterone measurement. Offspring weights were assessed at postnatal days 1 and 25 (weaning). Changes in bone mineral over the pregnancy/lactation period were site-specific. Exercise did not affect loss of bone mineral from the lumbar spine, but did attenuate the loss of trabecular bone mineral from the tibial metaphysis and enhance the strength strain index and cross-sectional moment of inertia at the tibial diaphysis (P≤0.05) in dams in the exercised group. Fecal corticosterone did not differ between dam groups. There were no significant differences in offspring weight between the exercised and control group at either time point. Voluntary exercise in the pregnant rat can improve some post-lactation bone parameters and does not adversely affect early postnatal outcomes of the offspring.

Distribution and biomarker of carbon-14 labeled fullerene C60 ([(14) C(U)]C60 ) in pregnant and lactating rats and their offspring after maternal intravenous exposure.

PubMed

Snyder, Rodney W; Fennell, Timothy R; Wingard, Christopher J; Mortensen, Ninell P; Holland, Nathan A; Shannahan, Jonathan H; Pathmasiri, Wimal; Lewin, Anita H; Sumner, Susan C J

2015-12-01

A comprehensive distribution study was conducted in pregnant and lactating rats exposed to a suspension of uniformly carbon-14 labeled C60 ([(14) C(U)]C60 ). Rats were administered [(14) C(U)]C60 (~0.2 mg [(14) C(U)]C60 kg(-1) body weight) or 5% polyvinylpyrrolidone (PVP)-saline vehicle via a single tail vein injection. Pregnant rats were injected on gestation day (GD) 11 (terminated with fetuses after either 24 h or 8 days), GD15 (terminated after 24 h or 4 days), or GD18 (terminated after 24 h). Lactating rats were injected on postnatal day 8 and terminated after 24 h, 3 or 11 days. The distribution of radioactivity in pregnant dams was influenced by both the state of pregnancy and time of termination after exposure. The percentage of recovered radioactivity in pregnant and lactating rats was highest in the liver and lungs. Radioactivity was quantitated in over 20 tissues. Radioactivity was found in the placenta and in fetuses of pregnant dams, and in the milk of lactating rats and in pups. Elimination of radioactivity was < 2% in urine and feces at each time point. Radioactivity remained in blood circulation up to 11 days after [(14) C(U)]C60 exposure. Biomarkers of inflammation, cardiovascular injury and oxidative stress were measured to study the biological impacts of [(14) C(U)]C60 exposure. Oxidative stress was elevated in female pups of exposed dams. Metabolomics analysis of urine showed that [(14) C(U)]C60 exposure to pregnant rats impacted the pathways of vitamin B, regulation of lipid and sugar metabolism and aminoacyl-tRNA biosynthesis. This study demonstrated that [(14) C(U)]C60 crosses the placenta at all stages of pregnancy examined, and is transferred to pups via milk. Copyright © 2015 John Wiley & Sons, Ltd.

Exposure to a glyphosate-based herbicide during pregnancy and lactation induces neurobehavioral alterations in rat offspring.

PubMed

Gallegos, Cristina E; Bartos, Mariana; Bras, Cristina; Gumilar, Fernanda; Antonelli, Marta C; Minetti, Alejandra

2016-03-01

The impact of sub-lethal doses of herbicides on human health and the environment is a matter of controversy. Due to the fact that evidence particularly of the effects of glyphosate on the central nervous system of rat offspring by in utero exposure is scarce, the purpose of the present study was to assess the neurobehavioral effects of chronic exposure to a glyphosate-containing herbicide during pregnancy and lactation. To this end, pregnant Wistar rats were exposed through drinking water to 0.2% or 0.4% of a commercial formulation of glyphosate (corresponding to a concentration of 0.65 or 1.30g/L of glyphosate, respectively) during pregnancy and lactation and neurobehavioral alterations in offspring were analyzed. The postnatal day on which each pup acquired neonatal reflexes (righting, cliff aversion and negative geotaxis) and that on which eyes and auditory canals were fully opened were recorded for the assessment of sensorimotor development. Locomotor activity and anxiety levels were monitored via open field test and plus maze test, respectively, in 45- and 90-day-old offspring. Pups exposed to a glyphosate-based herbicide showed early onset of cliff aversion reflex and early auditory canal opening. A decrease in locomotor activity and in anxiety levels was also observed in the groups exposed to a glyphosate-containing herbicide. Findings from the present study reveal that early exposure to a glyphosate-based herbicide affects the central nervous system in rat offspring probably by altering mechanisms or neurotransmitter systems that regulate locomotor activity and anxiety. Copyright © 2015 Elsevier Inc. All rights reserved.

Feeding 5-hydroxy-l-tryptophan during the transition from pregnancy to lactation increases calcium mobilization from bone in rats.

PubMed

Laporta, J; Peters, T L; Weaver, S R; Merriman, K E; Hernandez, L L

2013-05-01

An increasing demand for calcium during pregnancy and lactation can result in both clinical and subclinical hypocalcemia during the early lactation period in several mammalian species, in particular the dairy cow. Serotonin (5-HT) was recently identified as a regulator of lactation and bone turnover. The purpose of this study was to determine whether supplementation of the maternal diet with a 5-HT precursor would increase maternal bone turnover and calcium mobilization to maintain appropriate circulating maternal concentrations of ionized calcium during lactation. Female Sprague-Dawley rats (n = 30) were fed either a control diet (n = 15) or a diet supplemented with the 5-HT precursor 5-hydroxytryptophan (5-HTP, 0.2%; n = 15) from day 13 of pregnancy through day 9 of lactation. Maternal serum and plasma (day 1 and day 9 of lactation), milk and pup weight (daily), mammary gland and bone tissue (day 9 of lactation) were collected for analysis. The 5-HTP diet elevated circulating maternal concentrations of 5-HT on day 1 and day 9 of lactation and parathyroid hormone related-protein (PTHrP) on day 9 of lactation (P < 0.033). In addition, 5-HTP supplementation increased total serum calcium concentrations on day 1 of lactation and total milk calcium concentration on day 9 of lactation (P < 0.032). Supplemental 5-HTP did not alter milk yield, maternal body weight, mammary gland structure, or pup litter weights (P > 0.05). Supplemental 5-HTP also resulted in increased concentrations of mammary 5-HT and PTHrP, as well as increased mRNA expression of rate-limiting enzyme in 5-HT synthesis, tryptophan hydroxylase 1, and Pthrp mRNA on day 9 of lactation (P < 0.028). In addition, supplementation of 5-HTP resulted in increased mRNA expression of maternal mammary calcium transporters and resorption of bone in the femur, indicated by increase osteoclast number and diameter as well as mRNA expression of classical markers of bone resorption on day 9 of lactation (P < 0

A maternal 'junk food' diet in pregnancy and lactation promotes an exacerbated taste for 'junk food' and a greater propensity for obesity in rat offspring.

PubMed

Bayol, Stéphanie A; Farrington, Samantha J; Stickland, Neil C

2007-10-01

Obesity is generally associated with high intake of junk foods rich in energy, fat, sugar and salt combined with a dysfunctional control of appetite and lack of exercise. There is some evidence to suggest that appetite and body mass can be influenced by maternal food intake during the fetal and suckling life of an individual. However, the influence of a maternal junk food diet during pregnancy and lactation on the feeding behaviour and weight gain of the offspring remains largely uncharacterised. In this study, six groups of rats were fed either rodent chow alone or with a junk food diet during gestation, lactation and/or post-weaning. The daily food intakes and body mass were measured in forty-two pregnant and lactating mothers as well as in 216 offspring from weaning up to 10 weeks of age. Results showed that 10 week-old rats born to mothers fed the junk food diet during gestation and lactation developed an exacerbated preference for fatty, sugary and salty foods at the expense of protein-rich foods when compared with offspring fed a balanced chow diet prior to weaning or during lactation alone. Male and female offspring exposed to the junk food diet throughout the study also exhibited increased body weight and BMI compared with all other offspring. This study shows that a maternal junk food diet during pregnancy and lactation may be an important contributing factor in the development of obesity.

Early postweaning exercise improves central leptin sensitivity in offspring of rat dams fed high-fat diet during pregnancy and lactation.

PubMed

Sun, Bo; Liang, Nu-Chu; Ewald, Erin R; Purcell, Ryan H; Boersma, Gretha J; Yan, Jianqun; Moran, Timothy H; Tamashiro, Kellie L K

2013-11-01

Maternal high-fat (HF) diet has long-term consequences on the metabolic phenotype of the offspring. Here, we determined the effects of postweaning exercise in offspring of rat dams fed HF diet during gestation and lactation. Pregnant Sprague-Dawley rats were maintained on chow or HF diet throughout gestation and lactation. All pups were weaned onto chow diet on postnatal day (PND) 21. At 4 wk of age, male pups were given free access to running wheels (RW) or remained sedentary (SED) for 3 wk, after which all rats remained sedentary, resulting in four groups: CHOW-SED, CHOW-RW, HF-SED, and HF-RW. Male HF offspring gained more body weight by PND7 compared with CHOW pups and maintained this weight difference through the entire experiment. Three weeks of postweaning exercise did not affect body weight gain in either CHOW or HF offspring, but reduced adiposity in HF offspring. Plasma leptin was decreased at the end of the 3-wk running period in HF-RW rats but was not different from HF-SED 9 wk after the exercise period ended. At 14 wk of age, intracerebroventricular injection of leptin suppressed food intake in CHOW-SED, CHOW-RW, and HF-RW, while it did not affect food intake in HF-SED group. At death, HF-RW rats also had higher leptin-induced phospho-STAT3 level in the arcuate nucleus than HF-SED rats. Both maternal HF diet and postweaning exercise had effects on hypothalamic neuropeptide and receptor mRNA expression in adult offspring. Our data suggest that postweaning exercise improves central leptin sensitivity and signaling in this model.

A maternal low protein diet during pregnancy and lactation in the rat impairs male reproductive development

PubMed Central

Zambrano, E; Rodríguez-González, GL; Guzmán, C; García-Becerra, R; Boeck, L; Díaz, L; Menjivar, M; Larrea, F; Nathanielsz, PW

2005-01-01

Nutrient restriction during pregnancy and lactation impairs growth and development. Recent studies demonstrate long-term programming of function of specific organ systems resulting from suboptimal environments during fetal life and development up to weaning. We determined effects of maternal protein restriction (50% control protein intake) during fetal development and/or lactation in rats on the reproductive system of male progeny. Rats were fed either a control 20% casein diet (C) or a restricted diet (R) of 10% casein during pregnancy. After delivery mothers received either C or R diet until weaning to provide four groups: CC, RR, CR and RC. We report findings in male offspring only. Maternal protein restriction increased maternal serum corticosterone, oestradiol and testosterone (T) concentrations at 19 days gestation. Pup birth weight was unchanged but ano-genital distance was increased by maternal protein restriction (P < 0.05). Testicular descent was delayed 4.4 days in RR, 2.1 days in CR and 2.2 days in RC and was not related to body weight. Body weight and testis weight were reduced in RR and CR groups at all ages with the exception of CR testis weight at 270 days postnatal age (PN). At 70 days PN luteinizing hormone and T concentrations were reduced in RR, CR and RC. mRNA for P450 side chain cleavage (P450scc) was reduced in RR and CR at 21 days PN but was unchanged at 70 days PN. Fertility rate was reduced at 270 days PN in RC and sperm count in RR and RC. We conclude that maternal protein delays sexual maturation in male rats and that some effects only emerge in later life. PMID:15611025

Maternal Dietary Supplementation with Oligofructose-Enriched Inulin in Gestating/Lactating Rats Preserves Maternal Bone and Improves Bone Microarchitecture in Their Offspring

PubMed Central

Diaz-Castro, Javier; López-Aliaga, Inmaculada; Rueda, Ricardo

2016-01-01

Nutrition during pregnancy and lactation could exert a key role not only on maternal bone, but also could influence the skeletal development of the offspring. This study was performed in rats to assess the relationship between maternal dietary intake of prebiotic oligofructose-enriched inulin and its role in bone turnover during gestation and lactation, as well as its effect on offspring peak bone mass/architecture during early adulthood. Rat dams were fed either with standard rodent diet (CC group), calcium-fortified diet (Ca group), or prebiotic oligofructose-enriched inulin supplemented diet (Pre group), during the second half of gestation and lactation. Bone mineral density (BMD) and content (BMC), as well as micro-structure of dams and offspring at different stages were analysed. Dams in the Pre group had significantly higher trabecular thickness (Tb.Th), trabecular bone volume fraction (BV/TV) and smaller specific bone surface (BS/BV) of the tibia in comparison with CC dams. The Pre group offspring during early adulthood had an increase of the lumbar vertebra BMD when compared with offspring of CC and Ca groups. The Pre group offspring also showed significant increase versus CC in cancellous and cortical structural parameters of the lumbar vertebra 4 such as Tb.Th, cortical BMD and decreased BS/BV. The results indicate that oligofructose-enriched inulin supplementation can be considered as a plausible nutritional option for protecting against maternal bone loss during gestation and lactation preventing bone fragility and for optimizing peak bone mass and architecture of the offspring in order to increase bone strength. PMID:27115490

Flaxseed flour (Linum usitatissinum) consumption improves bone quality and decreases the adipocyte area of lactating rats in the post-weaning period.

PubMed

Ribeiro, Danielle Cavalcante; Pereira, Aline D'Avila; da Silva, Paula Cristina Alves; dos Santos, Aline de Sousa; de Santana, Fernanda Carvalho; Boueri, Bianca Ferolla da Camara; Pessanha, Carolina Ribeiro; de Abreu, Maíra Duque Coutinho; Mancini-Filho, Jorge; da Silva, Eduardo Moreira; do Nascimento-Saba, Celly Cristina Alves; da Costa, Carlos Alberto Soares; Boaventura, Gilson Teles

2016-01-01

The aim of this work was to evaluate the effects of flaxseed flour in the intake on adiposity and femur structure of the lactating rats during the post-weaning period. After weaning, the lactating rats were divided into control (C, n = 6) and experimental (F, n = 6) groups treated with a diet containing flaxseed flour. Serum hormone and fatty acids composition, morphology of intra-abdominal adipocytes, computed tomography and biomechanical analyses of femur were determined. Food intake, body mass and hormone analysis have shown similar results. The F group showed the following (p < 0.05): lower arachidonic acid (-60%), total polyunsaturated fatty acids (-30%) and retroperitoneal adipocytes (-36%) area. Higher radiodensity of femoral head region (+29%) and higher maximum force (+18%), breaking strength (+18%) and rigidity (+31%). Fatty acid composition of flaxseed flour decreased the area of adipocytes and improved the bone quality, which may be associated with lower serum levels of arachidonic acid levels, during the post-weaning period.

Nutritional Recovery with a Soybean Diet after Weaning Reduces Lipogenesis but Induces Inflammation in the Liver in Adult Rats Exposed to Protein Restriction during Intrauterine Life and Lactation

PubMed Central

Reis, Sílvia Regina de Lima; Feres, Naoel Hassan; Ignacio-Souza, Leticia Martins; Veloso, Roberto Vilela; Arantes, Vanessa Cristina; Kawashita, Nair Honda; Colodel, Edson Moleta; Botosso, Bárbara Laet; Reis, Marise Auxiliadora de Barros; Latorraca, Márcia Queiroz

2015-01-01

We evaluated the effects of postweaning nutritional recovery with a soybean flour diet on de novo hepatic lipogenesis and inflammation in adult rats exposed to protein restriction during intrauterine life and lactation. Rats from mothers fed with protein (casein) in a percentage of 17% (control, C) or 6% (low, L) during pregnancy and lactation were fed with diet that contained 17% casein (CC and LC groups, resp.) or soybean (CS and LS groups, resp.) after weaning until 90 days of age. LS and CS rats had low body weight, normal basal serum triglyceride levels, increased ALT concentrations, and high HOMA-IR indices compared with LC and CC rats. The soybean diet reduced PPARγ as well as malic enzyme and citrate lyase contents and activities. The lipogenesis rate and liver fat content were lower in LS and CS rats relative to LC and CC rats. TNFα mRNA and protein levels were higher in LS and CS rats than in LC and CC rats. NF-κB mRNA levels were lower in the LC and LS groups compared with the CC and LC groups. Thus, the soybean diet prevented hepatic steatosis at least in part through reduced lipogenesis but resulted in TNFα-mediated inflammation. PMID:25892856

Mechanisms involved in the adaptations of the adipocyte adrenergic signal-transduction system and their modulation by growth hormone during the lactation cycle in the rat.

PubMed Central

Vernon, R G; Piperova, L; Watt, P W; Finley, E; Lindsay-Watt, S

1993-01-01

The mechanisms responsible for the diminished lipolytic response of adipocytes to catecholamines after litter removal from lactating rats and their modulation by growth hormone have been investigated. Lactation, litter removal and growth-hormone treatment did not alter the ability of noradrenaline to activate protein kinase A (A-kinase), showing that the defect in signal transduction in rats after litter removal is after A-kinase. Litter removal had no effect on hormone-sensitive lipase activity itself, but the proportion of the lipase associated with the fat droplet was decreased; growth-hormone treatment increased hormone-sensitive lipase activity and the proportion associated with the fat droplet. In addition, a number of other adaptations in the beta-adrenergic signal-transduction system occur during the lactation cycle and in response to growth hormone treatment, including changes in receptor number, adenylate cyclase activity and cyclic AMP phosphodiesterase activity, but a defect in the ability of hormone-sensitive lipase to associate with the lipid droplet appears to be the major reason for the diminished response to catecholamines on litter removal. PMID:8382054

[NUCLEAR STRUCTURE IN THE SECRETORY CELLS OF MAMMARY GLANDS IN LACTATING AND NON-LACTATING RATS].

PubMed

Tyutina, K V; Skopichev, V G; Bogolyubov, D S; Bogolyubova, I O

2016-01-01

The features of structural and functional organization of the main nuclear compartments and distribution of their key molecular components (chromatin-remodeling protein ATRX, RNA polymerase I and II, and the splicing factor SC35) has been studied in the nuclei of mammary gland cells at different functional states. No significant differences between the nuclei of the cells in the lactating and non-lactating mammary glands have been revealed at the ultrastructural level. At the same time, photometric analysis has revealed higher intensity of nucleoplasmic immunofluorescent staining of mammary glands in the lactating animals when antibodies against the proteins ATRX and SC35 were used. Apparently, this observation reflects the changes of the structural and functional status of chromatin as well as the redistribution of splicing factors between the sites of their deposition and transcription.

Bromocriptine treatment at the end of lactation prevents hyperphagia, higher visceral fat and liver triglycerides in early-weaned rats at adulthood.

PubMed

Peixoto-Silva, Nayara; Moura, Egberto G; Carvalho, Janaine C; Nobre, Jéssica L; Quitete, Fernanda T; Pinheiro, Cintia R; Santos-Silva, Ana Paula; de Oliveira, Elaine; Lisboa, Patricia C

2017-04-01

Non-pharmacological early weaning (NPEW) leads offspring to obesity, higher liver oxidative stress and microsteatosis in adulthood. Pharmacological EW (PEW) by maternal treatment with bromocriptine (BRO) causes obesity in the adult progeny but precludes hepatic injury. To test the hypothesis that BRO prevents the deleterious changes of NPEW, we injected BRO into the pups from the NPEW model in late lactation. Lactating rats were divided into two groups: dams with an adhesive bandage around the body to prevent breastfeeding on the last 3 days of lactation and dams whose pups had free suckling (C). Offspring from both groups were subdivided into two groups: pups treated with BRO (intraperitoneal (i.p.) 4 mg/kg per day) on the last 3 days of lactation (NPEW/BRO and C/BRO) or pups treated with the vehicle (NPEW and C). At PN120, offspring were challenged with a high fat diet (HFD), and food intake was recorded after 30 minutes and 12 hours. Rats were killed at PN120 and PN200. At PN120, adipocyte size was greater in the NPEW group but was normal in the NPEW/BRO group. At PN200, the NPEW group presented hyperphagia, higher adiposity, adipocyte hypertrophy, hyperleptinaemia, glucose intolerance and increased hepatic triglycerides. These parameters were normalized in the NPEW/BRO group. In the feeding test, BRO groups showed lower HFD intake at 30 minutes than did their controls; however, at 12 hours, the NPEW group ate more HFD. The treatment with BRO can preclude some deleterious effects of the NPEW model, which prevented the development of overweight and its comorbidities. © 2017 John Wiley & Sons Australia, Ltd.

Impact of cafeteria feeding during lactation in the rat on novel object discrimination in the offspring.

PubMed

Wright, Thomas M; King, Madeleine V; Davey, William G; Langley-Evans, Simon C; Voigt, Jörg-Peter W

2014-12-28

There is increasing evidence that hyperenergetic diets have an impact on memory in rodents. However, it is largely unknown how diets, such as a cafeteria diet (CD), that mimic a Western-type diet act on learning and memory, in particular when fed during early stages of development. Here, we fed lactating dams a CD and exposed both male and female offspring to a novel object discrimination (NOD) task, a two-trial test of recognition memory in which rats exposed to two identical objects during a training/familiarisation trial can discriminate a novel from a familiar object during the subsequent choice trial. The choice trial was performed following inter-trial interval (ITI) delays of up to 4 h. Maternal diet did not have an impact on exploration of the objects by either sex during the familiarisation trial. Control males discriminated the novel from the familiar object, indicating intact memory with an ITI of 1 h, but not 2 or 4 h. The CD delayed this natural forgetting in male rats such that discrimination was also evident after a 2 h ITI. In contrast, control females exhibited discrimination following both 1 and 2 h ITI, but the CD impaired performance. In summary, the present study shows that maternal exposure to the CD programmes NOD in the adult. In better-performing females, dietary programming interferes with NOD, whereas NOD was improved in males after lactational CD feeding.

Swimming training prevents metabolic imprinting induced by hypernutrition during lactation.

PubMed

Fischer, Stefani Valeria; Capriglioni Cancian, Cláudia Regina; Montes, Elisangela Gueiber; de Carvalho Leite, Nayara; Grassiolli, Sabrina

2015-02-01

Reduction in litter size during lactation induces hypernutrition of the offspring culminating with altered metabolic programming during adult life. Overnourished rats present alterations in the endocrine pancreas and major predisposition to the development of type 2 diabetes. Our study evaluated the impact of swimming training on insulin secretion control in overnourished rats. At postnatal day 3 male rat pup litters were redistributed randomly into Small Litters (SL, 3 pups) or Normal Litters (NL, 9 pups) to induce early overfeeding during lactation. Both groups were subjected to swimming training (3 times/week/30 min) post-weaning (21 days) for 72 days. At 92 days of life pancreatic islets were isolated using collagenase technique and incubated with glucose in the presence or absence of acetylcholine (Ach, 0.1-1000 μM) or glucagon-like peptide 1 (GLP1, 10 nM). Adipose tissue depots (white and brown) and endocrine pancreas samples were examined by histological analysis. Food intake and body weight were measured. Blood biochemical parameters were also evaluated. Swimming training prevented metabolic program alteration by hypernutrition during lactation. Exercise reduced obesity and hyperglycemia in overnourished rats. Pancreatic islets isolated from overnourished rats showed a reduction in glucose-induced insulin secretion and cholinergic responses while the insulinotropic action of GLP1 was increased. Physical training effectively restored glucose-induced insulin secretion and GLP1-stimulated action in pancreatic islets from overnourished rats. However, swimming training did not correct the weak cholinergic response in pancreatic islets isolated from overnourished rats. Swimming training avoids obesity development, corrects glucose-induced insulin secretion, as well as, GLP1 insulinotropic response in overnourished rats. Copyright © 2014 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

Maternal Flaxseed Oil During Lactation Enhances Bone Development in Male Rat Pups.

PubMed

Pereira, Aline D'Avila; Ribeiro, Danielle Cavalcante; de Santana, Fernanda Carvalho; de Sousa Dos Santos, Aline; Mancini-Filho, Jorge; do Nascimento-Saba, Celly Cristina Alves; Velarde, Luis Guillermo Coca; da Costa, Carlos Alberto Soares; Boaventura, Gilson Teles

2016-08-01

Flaxseed oil is an alpha linolenic acid source important in the growth and body development stage; furthermore, this acid acts on adipose tissue and bone health. The aim of this study was to evaluate body composition, fatty acid composition, hormone profile, retroperitoneal adipocyte area and femur structure of pups at weaning, whose mothers were fed a diet containing flaxseed oil during lactation. After birth, pups were randomly assigned: control (C, n = 12) and flaxseed oil (FO, n = 12), rats whose mothers were treated with diet containing soybean or flaxseed oil. At 21 days, the pups were weaned and body mass, length, body composition, biochemical parameter, leptin, osteoprotegerin, osteocalcin, fatty acids composition, intra-abdominal fat mass and femur structure were analyzed. FO showed (p < 0.05): higher body mass (+12 %) and length (+9 %); body fat mass (g, +45 %); bone mineral density (+8 %), bone mineral content (+55 %) and bone area (+35 %), osteocalcin (+173 %) and osteoprotegerin (+183 %). Arachidonic acid was lower (p < 0.0001), alpha-linolenic and eicosapentaenoic were higher (p < 0.0001). Intra-abdominal fat mass was higher (+25 %), however, the retroperitoneal adipocytes area was lower (-44 %). Femur mass (+10 %), distance between epiphyses (+4 %) and bone mineral density (+13 %) were higher. The study demonstrates that adequate flaxseed oil content during a lactation diet plays an important role in the development of pups.

A temporary local energy pool coupled to neuronal activity: fluctuations of extracellular lactate levels in rat brain monitored with rapid-response enzyme-based sensor.

PubMed

Hu, Y; Wilson, G S

1997-10-01

A successfully developed enzyme-based lactate microsensor with rapid response time allows the direct and continuous in vivo measurement of lactic acid concentration with high temporal resolution in brain extracellular fluid. The fluctuations coupled to neuronal activity in extracellular lactate concentration were explored in the dentate gyrus of the hippocampus of the rat brain after electrical stimulation of the perforant pathway. Extracellular glucose and oxygen levels were also detected simultaneously by coimplantation of a fast-response glucose sensor and an oxygen electrode, to provide novel information of trafficking of energy substances in real time related to local neuronal activity. The results first give a comprehensive picture of complementary energy supply and use of lactate and glucose in the intact brain tissue. In response to acute neuronal activation, the brain tissue shifts immediately to significant energy supply by lactate. A local temporary fuel "reservoir" is established behind the blood-brain barrier, evidenced by increased extracellular lactate concentration. The pool can be depleted rapidly, up to 28% in 10-12 s, by massive, acute neuronal use after stimulation and can be replenished in approximately 20 s. Glutamate-stimulated astrocytic glycolysis and the increase of regional blood flow may regulate the lactate concentration of the pool in different time scales to maintain local energy homeostasis.

Lactate metabolism and cytosolic NADH reducing equivalents in ovine adipocytes.

PubMed

Yang, Y T; White, L S; Muir, L A

1982-01-01

1. Isolated ovine adipocytes, unlike rat adipose tissue, could utilize lactate at a high rate. 2. When the rate of fatty acid synthesis was attenuated with 5-(tetradecyloxy)-2-furoic acid, a fatty acid synthesis inhibitor, there was a good positive correlation between the rates of lactate oxidation to CO2 and lactate incorporation into fatty acids. 3. Addition of 2,4-dinitrophenol enhanced lactate oxidation to CO2 independent of fatty acid synthesis. Under this condition, estimated cytosolic NADH formation from lactate dehydrogenation exceeded the need of NADH for cytosolic oxaloacetate reduction and for glyceride glycerol formation. 4. Mitochondria isolated from ovine adipocytes oxidized added NADH rapidly in a reconstituted alpha-glycerophosphate shuttle system. 5. It is possible that the ability of ovine adipocytes to utilize lactate may be related to the active alpha-glycerophosphate shuttle for cytosolic NADH reoxidation.

Hypothyroxinemia induced by maternal mild iodine deficiency impairs hippocampal myelinated growth in lactational rats.

PubMed

Wei, Wei; Wang, Yi; Dong, Jing; Wang, Yuan; Min, Hui; Song, Binbin; Shan, Zhongyan; Teng, Weiping; Xi, Qi; Chen, Jie

2015-11-01

Hypothyroxinemia induced by maternal mild iodine deficiency causes neurological deficits and impairments of brain function in offspring. Hypothyroxinemia is prevalent in developing and developed countries alike. However, the mechanism underlying these deficits remains less well known. Given that the myelin plays an important role in learning and memory function, we hypothesize that hippocampal myelinated growth may be impaired in rat offspring exposed to hypothyroxinemia induced by maternal mild iodine deficiency. To test this hypothesis, the female Wistar rats were used and four experimental groups were prepared: (1) control; (2) maternal mild iodine deficiency diet inducing hypothyroxinemia; (3) hypothyroidism induced by maternal severe iodine deficiency diet; (4) hypothyroidism induced by maternal methimazole water. The rats were fed the diet from 3 months before pregnancy to the end of lactation. Our results showed that the physiological changes occuring in the hippocampal myelin were altered in the mild iodine deficiency group as indicated by the results of immunofluorescence of myelin basic proteins on postnatal day 14 and postnatal day 21. Moreover, hypothyroxinemia reduced the expressions of oligodendrocyte lineage transcription factor 2 and myelin-related proteins in the treatments on postnatal day 14 and postnatal day 21. Our data suggested that hypothyroxinemia induced by maternal mild iodine deficiency may impair myelinated growth of the offspring. © 2014 Wiley Periodicals, Inc.

The Effect of Maternal Thyroid Disorders (Hypothyroidism and Hyperthyroidism) During Pregnancy and Lactation on Skin Development in Wistar Rat Newborns

PubMed Central

Amerion, Maryam; Tahajjodi, Somayye; Hushmand, Zahra; Mahdavi Shahri, Nasser; Nikravesh, Mohammad Reza; Jalali, Mahdi

2013-01-01

Objective(s): Previous studies have shown that thyroid hormones are necessary for normal development of many organs and because of the importance of skin as the largest and the most important organ in human body protection in spite of external environment, the study of thyroid hormones effects on skin development is considerable. In this survey we have tried to study the effects of maternal hypothyroidism on skin development in fetus during pregnancy and lactation by immunohistochemistry technique. Materials and Methods: Rats were divided into 4 groups, hypothyroids, hyperthyroids, hypothyroids are treated with levothyroxin and a control group. The rat mothers were exposed to PTU with 50 mg/lit dosage and levothyroxin with 1 mg/lit dosage and PTU and levothyroxin simultaneously and with the same dosage respectively in hypothyroid, hyperthyroid and treated hypothyroids with levothyroxin groups. After 14 days, blood sample was taken from mothers, and if thyroid hormones level had change well, mating was allowed. After pregnancy and delivery, 1th day dorsal skin (as the sample for pregnancy assay) and 10th day skin (as for lactation assay) was used for immunohystochemical and morphometric studies. Results: In this study it was observed that maternal hypothyroidism during pregnancy and lactation causes significant increase in laminin expression, in most areas of skin, and maternal hyperthyroidism during pregnancy and lactation causes significant decrease in laminin expression. Also significant decrease was observed in hair follicles number and epidermis thickness in hypothyroidism groups. Conclusion: This study showed maternal hypothyroidism causes significant decrease in epidermis thickness and hair follicles number and it causes less hair in fetus. Also maternal hypothyroidism causes large changes in laminin expression in different parts of skin. At the same time,maternal hyperthyroidism causes opposite results. In fact, thyroid hormones regulate laminin expression

Effects of in utero and lactational exposure to SbV on rat neurobehavioral development and fertility.

PubMed

Coelho, Deise R; De-Carvalho, Rosangela R; Rocha, Rafael C C; Saint'Pierre, Tatiana D; Paumgartten, Francisco J R

2014-12-01

Meglumine antimoniate (MA) is a pentavalent antimony drug used to treat leishmaniases. We investigated the neurobehavioral development, sexual maturation and fertility of the offspring of MA-treated rats. Dams were administered MA (0, 75, 150, 300 mg Sb(V)/kg body wt/d, sc) from gestation day 0, throughout parturition and lactation, until weaning. At the highest dose, MA reduced the birth weight and the number of viable newborns. In the male offspring, MA did not impair development (somatic, reflex maturation, weight gain, puberty onset, open field test), sperm count, or reproductive performance. Except for a minor effect on body weight gain and vertical exploration in the open field, MA also did not affect the development of female offspring. Measurements of the Sb levels (ICP-MS) in the blood of MA-treated female rats and their offspring demonstrated that Sb is transferred to the fetuses via the placenta and to the suckling pups via milk. Copyright © 2014 Elsevier Inc. All rights reserved.

Partial reconstruction of in vitro gluconeogenesis arising from mitochondrial l-lactate uptake/metabolism and oxaloacetate export via novel L-lactate translocators.

PubMed

De Bari, Lidia; Atlante, Anna; Valenti, Daniela; Passarella, Salvatore

2004-05-15

In the light of the occurrence of L-lactate dehydrogenase inside the mitochondrial matrix, we looked at whether isolated rat liver mitochondria can take up and metabolize L-lactate, and provide oxaloacetate outside mitochondria, thus contributing to a partial reconstruction of gluconeogenesis in vitro. We found that: (1) L-lactate (10 mM), added to mitochondria in the presence of a cocktail of glycolysis/gluconeogenesis enzymes and cofactors, can lead to synthesis of glyceraldehyde-3-phosphate at a rate of about 7 nmol/min per mg mitochondrial protein. (2) Three novel translocators exist to mediate L-lactate traffic across the inner mitochondrial membrane. An L-lactate/H+ symporter was identified by measuring fluorimetrically the rate of endogenous pyridine nucleotide reduction. Consistently, L-lactate oxidation was found to occur with P/O ratio=3 (where P/O ratio is the ratio of mol of ATP synthesized to mol of oxygen atoms reduced to water during oxidative phosphorylation) and with generation of membrane potential. Proton uptake, which occurred as a result of addition of L-lactate to RLM together with electron flow inhibitors, and mitochondrial swelling in ammonium L-lactate solutions were also monitored. L-Lactate/oxaloacetate and L-lactate/pyruvate anti-porters were identified by monitoring photometrically the appearance of L-lactate counter-anions outside mitochondria. These L-lactate translocators, which are distinct from the monocarboxylate carrier, were found to differ from each other in V(max) values and in inhibition and pH profiles, and proved to regulate mitochondrial L-lactate metabolism in vitro. The role of lactate/mitochondria interactions in gluconeogenesis is discussed.

Exercise prevents the increased anxiety-like behavior in lactational di-(2-ethylhexyl) phthalate-exposed female rats in late adolescence by improving the regulation of hypothalamus-pituitary-adrenal axis.

PubMed

Wang, Dean-Chuan; Chen, Tsan-Ju; Lin, Ming-Lu; Jhong, Yue-Cih; Chen, Shih-Chieh

2014-09-01

Both the detrimental effects of early life adversity and the beneficial effects of exercise on the hypothalamic-pituitary-adrenal (HPA) axis have been reported. Early life exposure to di-(2-ethylhexyl)-phthalate (DEHP) may impair the development of endocrine system. In this study, we investigated the effects of lactational DEHP exposure on stress responses in late adolescent female rats and examined the protective role of treadmill running. Sprague-Dawley dams were fed with DEHP (10mg/kg per day) or vehicle during lactation. After weaning, the female offspring rats were trained to exercise on a treadmill for 5 weeks and then stressed by exploring on an elevated plus maze. The activities of HPA axis were evaluated by measuring the plasma levels of ACTH and corticosterone, the expressions of adrenal enzymes cholesterol side-chain cleavage enzyme (CYP11A1) and cytochrome P-450 11β-hydroxylase (CYP11B1), and the expression of hypothalamic glucocorticoid receptors (GR). The results demonstrate that DEHP-exposed rats exhibited enhanced anxiety-like behaviors. Increased hypothalamic GR and plasma ACTH levels, but decreased adrenal CYP11A1 and corticosterone levels, were observed in DEHP-exposed animals under stressed condition. Importantly, in DEHP-exposed animals, exercise during childhood-adolescence reduced anxiety-like behaviors by normalizing stress-induced alterations in ACTH level and adrenal CYP11A1 expression. The findings of this study suggest that treadmill running may provide beneficial effects on ameliorating the dysregulation of HPA axis in lactational DEHP-exposed adolescent female rats. Copyright © 2014 Elsevier Inc. All rights reserved.

Lactation exposure to BDE-153 damages learning and memory, disrupts spontaneous behavior and induces hippocampus neuron death in adult rats.

PubMed

Zhang, Hongmei; Li, Xin; Nie, Jisheng; Niu, Qiao

2013-06-23

To study the effects of 2,2',4,4',5,5'-hexa-brominated diphenyl ether (BDE-153) exposure during lactation on the learning and memory abilities, spontaneous behavior and brain cells of adult rats and to elicit basic information on PBDE's developmental neurotoxicity. Newborn male rat pups were randomly categorized into the following groups (15 pups per group), according to their weights and litters: a control group, and 1mg/kg, 5mg/kg and 10mg/kg BDE-153 groups. At postnatal day 10 (PND10), the pups in the BDE-153 groups were intraperitoneally injected once with BDE-153 plant oil solutions at 0.1ml/10g body weight, and the controls were injected with plant oil. Throughout the entire experiment, physiological measures were recorded, such as food and water consumption, body weight and clinical symptoms. At 1 month and 2 months after treatment, the learning and memory abilities of the rats were tested by the Morris water maze test, the step-down test, and the step-through test; spontaneous behavior was tested by the open-field test. After all tests were accomplished, rats were weighed and sacrificed, and the brain tissue was immediately isolated and divided into two parts. Sections were fabricated from one part, and changes in the morphology and ultrastructure in CA3 region of hippocampus were observed under an optical microscope and transmission electron microscope, along with the detection of apoptotic cells with the terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) method. The tissue of the second part was digested into single-cell suspension liquid, and the cell apoptosis was assayed with flow cytometry and the lactate dehydrogenase (LDH) leakage was detected with spectrophotometry. There was no obvious change in food and water consumption, body weight and the ratio of brain to body weight, or any overt clinical symptoms in the BDE-153-treated rats. Compared to the control group, rats' latency time in the test session (LT2) in the step

Training-induced elevations in extracellular lactate in hippocampus and striatum: Dissociations by cognitive strategy and type of reward.

PubMed

Newman, Lori A; Scavuzzo, Claire J; Gold, Paul E; Korol, Donna L

2017-01-01

Recent evidence suggests that astrocytes convert glucose to lactate, which is released from the astrocytes and supports learning and memory. This report takes a multiple memory perspective to test the role of astrocytes in cognition using real-time lactate measurements during learning and memory. Extracellular lactate levels in the hippocampus or striatum were determined with lactate biosensors while rats were learning place (hippocampus-sensitive) or response (striatum-sensitive) versions of T-mazes. In the first experiment, rats were trained on the place and response tasks to locate a food reward. Extracellular lactate levels in the hippocampus increased beyond those of feeding controls during place training but not during response training. However, striatal lactate levels did not increase beyond those of controls when rats were trained on either the place or the response version of the maze. Because food ingestion itself increased blood glucose and brain lactate levels, the contribution of feeding may have confounded the brain lactate measures. Therefore, we conducted a second similar experiment using water as the reward. A very different pattern of lactate responses to training emerged when water was used as the task reward. First, provision of water itself did not result in large increases in either brain or blood lactate levels. Moreover, extracellular lactate levels increased in the striatum during response but not place learning, whereas extracellular lactate levels in the hippocampus did not differ across tasks. The findings from the two experiments suggest that the relative engagement of the hippocampus and striatum dissociates not only by task but also by reward type. The divergent lactate responses of the hippocampus and striatum in place and response tasks under different reward conditions may reflect ethological constraints tied to foraging for food and water. Copyright © 2016 Elsevier Inc. All rights reserved.

Lactate is oxidized outside of the mitochondrial matrix in rodent brain.

PubMed

Herbst, Eric A F; George, Mitchell A J; Brebner, Karen; Holloway, Graham P; Kane, Daniel A

2018-05-01

The nature and existence of mitochondrial lactate oxidation is debated in the literature. Obscuring the issue are disparate findings in isolated mitochondria, as well as relatively low rates of lactate oxidation observed in permeabilized muscle fibres. However, respiration with lactate has yet to be directly assessed in brain tissue with the mitochondrial reticulum intact. To determine if lactate is oxidized in the matrix of brain mitochondria, oxygen consumption was measured in saponin-permeabilized mouse brain cortex samples, and rat prefrontal cortex and hippocampus (dorsal) subregions. While respiration in the presence of ADP and malate increased with the addition of lactate, respiration was maximized following the addition of exogenous NAD + , suggesting maximal lactate metabolism involves extra-matrix lactate dehydrogenase. This was further supported when NAD + -dependent lactate oxidation was significantly decreased with the addition of either low-concentration α-cyano-4-hydroxycinnamate or UK-5099, inhibitors of mitochondrial pyruvate transport. Mitochondrial respiration was comparable between glutamate, pyruvate, and NAD + -dependent lactate oxidation. Results from the current study demonstrate that permeabilized brain is a feasible model for assessing lactate oxidation, and support the interpretation that lactate oxidation occurs outside the mitochondrial matrix in rodent brain.

Astrocyte-neuron lactate transport is required for long-term memory formation.

PubMed

Suzuki, Akinobu; Stern, Sarah A; Bozdagi, Ozlem; Huntley, George W; Walker, Ruth H; Magistretti, Pierre J; Alberini, Cristina M

2011-03-04

We report that, in the rat hippocampus, learning leads to a significant increase in extracellular lactate levels that derive from glycogen, an energy reserve selectively localized in astrocytes. Astrocytic glycogen breakdown and lactate release are essential for long-term but not short-term memory formation, and for the maintenance of long-term potentiation (LTP) of synaptic strength elicited in vivo. Disrupting the expression of the astrocytic lactate transporters monocarboxylate transporter 4 (MCT4) or MCT1 causes amnesia, which, like LTP impairment, is rescued by L-lactate but not equicaloric glucose. Disrupting the expression of the neuronal lactate transporter MCT2 also leads to amnesia that is unaffected by either L-lactate or glucose, suggesting that lactate import into neurons is necessary for long-term memory. Glycogenolysis and astrocytic lactate transporters are also critical for the induction of molecular changes required for memory formation, including the induction of phospho-CREB, Arc, and phospho-cofilin. We conclude that astrocyte-neuron lactate transport is required for long-term memory formation. Copyright © 2011 Elsevier Inc. All rights reserved.

Astrocyte-neuron lactate transport is required for long-term memory formation

PubMed Central

Suzuki, Akinobu; Stern, Sarah A.; Bozdagi, Ozlem; Huntley, George W.; Walker, Ruth H.; Magistretti, Pierre J.; Alberini, Cristina M.

2011-01-01

SUMMARY We report that in the rat hippocampus learning leads to a significant increase in extracellular lactate levels, which derive from glycogen, an energy reserve selectively localized in astrocytes. Astrocytic glycogen breakdown and lactate release are essential for long-term but not short-term memory formation, and for the maintenance of long-term potentiation (LTP) of synaptic strength elicited in-vivo. Disrupting the expression of the astrocytic lactate transporters monocarboxylate transporter 4 (MCT4) or MCT1 causes amnesia, which, like LTP impairment, is rescued by lactate but not equicaloric glucose. Disrupting the expression of the neuronal lactate transporter MCT2 also leads to amnesia that is unaffected by either L-lactate or glucose, suggesting that lactate import into neurons is necessary for long-term memory. Glycogenolysis and astrocytic lactate transporters are also critical for the induction of molecular changes required for memory formation, including the induction of phospho-CREB, Arc and phospho-cofilin. We conclude that astrocyte-neuron lactate transport is required for long-term memory formation. PMID:21376239

[Degradation of prolactin 125-I in the mammary gland of lactating rats].

PubMed

Marinchenko, G V; Taranenko, A G

1977-01-01

Prolactin-125I metabolism in the mammary gland of lactating rats was studied; the hormone was injected intraperitoneally. Radioactive products accumulated by the mammary gland tissue were extracted with isotonic medium. Tissue extracts, blood serum and milk were analyzed by gel filtration on Sephadex G-200. The Blood displayed a gradual reduction of prolactin-125I content as a result of its splitting in the organs and binding with blood proteins; as to the mammary gland--there occurred accumulation of the products of prolactin-125I degradation. Some hormone was inactivated losing immunological properties without any significant changes in the molecular weight. Besides, the mammary gland displayed an intensive accumulation of the products of prolactin-125I splitting in the other organs and in the gland proper. Radioactivity accumulated in the milk was mainly referred to the products of prolactin-125I degradation. There was also shown the presence of immunologically active prolactin-125I in the milk.

Oxidative damage and antioxidant defense in thymus of malnourished lactating rats.

PubMed

Gavia-García, Graciela; González-Martínez, Haydeé; Miliar-García, Ángel; Bonilla-González, Edmundo; Rosas-Trejo, María de Los Ángeles; Königsberg, Mina; Nájera-Medina, Oralia; Luna-López, Armando; González-Torres, María Cristina

2015-01-01

Malnutrition has been associated with oxidative damage by altered antioxidant protection mechanisms. Specifically, the aim of this study was to evaluate oxidative damage (DNA and lipid) and antioxidant status (superoxide dismutase [SOD], glutathione peroxidase [GPx], and catalase [CAT] mRNA, and protein expression) in thymus from malnourished rat pups. Malnutrition was induced during the lactation period by the food competition method. Oxidative DNA damage was determined quantifying 8-oxo-7, 8-dihydro-2'-deoxyguanosine adduct by high-performance liquid chromatography. Lipid peroxidation was assessed by the formation of thiobarbituric acid-reactive substances. Levels of gene and protein expression of SOD, GPx, and CAT were evaluated by real-time polymerase chain reaction and Western blot, respectively. Antioxidant enzyme activities were measured spectrophotometrically. Oxidative DNA damage and lipid peroxidation significantly increased in second-degree (MN-2) and third-degree malnourished (MN-3) rats compared with well-nourished rats. Higher amounts of oxidative damage, lower mRNA expression, and lower relative concentrations of protein, as well as decreased antioxidant activity of SOD, GPx, and CAT were associated with the MN-2 and MN-3 groups. The results of this study demonstrated that higher body-weight deficits were related to alterations in antioxidant protection, which contribute to increased levels of damage in the thymus. To our knowledge, this study demonstrated for the first time that early in life, malnutrition leads to increased DNA and lipid oxidative damage, attributable to damaged antioxidant mechanisms including transcriptional and enzymatic activity alterations. These findings may contribute to the elucidation of the causes of previously reported thymus dysfunction, and might explain partially why children and adults who have overcome child undernourishment experience immunologic deficiencies. Copyright © 2015 Elsevier Inc. All rights reserved.

Long-term effects of in utero and lactational exposure to butyl paraben in female rats.

PubMed

Guerra, Marina Trevizan; Sanabria, Marciana; Cagliarani, Stephannie Vieira; Leite, Gabriel Adan Araújo; Borges, Cibele Dos Santos; De Grava Kempinas, Wilma

2017-03-01

Parabens are used as preservatives in cosmetic, pharmaceutical, and food industries, and are frequently detected as contaminants in human fluids and tissues. The endocrine disrupting effects of parabens in female rodents include uterotrophic response, steroidogenesis impairment, and ovarian disturbances. The objective of this study was to determine the effects of maternal butyl paraben (BP) exposure on female sexual development. Pregnant Wistar rats were treated subcutaneously with either corn oil or BP at doses of 10, 100, or 200 mg/kg, from gestational day (GD) 12 until GD 20 for female foetal gonad evaluation, and from GD 12 until the end of lactation to evaluate sexual parameters on the female offspring. Immature female rats were also used in the uterotrophic assay to evaluate the possible estrogenic action of parabens. Our results revealed that, in this experimental protocol, BP did not show estrogenic activity at the doses used and did not impair sexual development and fertility capacity in the female rats, but impaired sexual behavior. We conclude that brain sexual development may be more sensitive to BP effects and we speculate that doses higher than 100 mg/kg (the male lowest observed adverse effect level (LOAEL) for rodent reproductive parameters) would be necessary to promote damages in the female reproduction, regarding the same protocol of exposure. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 776-788, 2017. © 2016 Wiley Periodicals, Inc.

A wire-based dual-analyte sensor for glucose and lactate: in vitro and in vivo evaluation.

PubMed

Ward, W Kenneth; House, Jody L; Birck, Jonathan; Anderson, Ellen M; Jansen, Lawrence B

2004-06-01

Continuous measurement of lactate is potentially useful for detecting physical exhaustion and for monitoring critical care conditions characterized by hypoperfusion, such as heart failure. In some conditions, it may be desirable to monitor more than one metabolic parameter concurrently. For this reason, we designed and fabricated twisted wire-based microelectrodes that can measure both lactate and glucose. These dual-analyte sensors were characterized in vitro by measuring their response to the analyte of interest and to assess whether they were susceptible to interference from the other analyte. When measured in stirred aqueous buffer, lactate sensors detected a very small amount of crosstalk from glucose in vitro, although this signal was less than 3% of the response to lactate. Glucose sensors did not detect crosstalk from lactate. Sensors were implanted subcutaneously in rats and tested during infusions of lactate and glucose. Each sensing electrode responded rapidly to changes in its analyte concentration, and there was no evidence of in vivo crosstalk. This study constitutes proof of the concept that oxidase-based, amperometric wire microsensors can detect changes in glucose and lactate during subcutaneous implantation in rats.

MCT Expression and Lactate Influx/Efflux in Tanycytes Involved in Glia-Neuron Metabolic Interaction

PubMed Central

Cortés-Campos, Christian; Elizondo, Roberto; Llanos, Paula; Uranga, Romina María; Nualart, Francisco; García, María Angeles

2011-01-01

Metabolic interaction via lactate between glial cells and neurons has been proposed as one of the mechanisms involved in hypothalamic glucosensing. We have postulated that hypothalamic glial cells, also known as tanycytes, produce lactate by glycolytic metabolism of glucose. Transfer of lactate to neighboring neurons stimulates ATP synthesis and thus contributes to their activation. Because destruction of third ventricle (III-V) tanycytes is sufficient to alter blood glucose levels and food intake in rats, it is hypothesized that tanycytes are involved in the hypothalamic glucose sensing mechanism. Here, we demonstrate the presence and function of monocarboxylate transporters (MCTs) in tanycytes. Specifically, MCT1 and MCT4 expression as well as their distribution were analyzed in Sprague Dawley rat brain, and we demonstrate that both transporters are expressed in tanycytes. Using primary tanycyte cultures, kinetic analyses and sensitivity to inhibitors were undertaken to confirm that MCT1 and MCT4 were functional for lactate influx. Additionally, physiological concentrations of glucose induced lactate efflux in cultured tanycytes, which was inhibited by classical MCT inhibitors. Because the expression of both MCT1 and MCT4 has been linked to lactate efflux, we propose that tanycytes participate in glucose sensing based on a metabolic interaction with neurons of the arcuate nucleus, which are stimulated by lactate released from MCT1 and MCT4-expressing tanycytes. PMID:21297988

Methylglyoxal treatment in lactating mothers leads to type 2 diabetes phenotype in male rat offspring at adulthood.

PubMed

Francisco, Flávio Andrade; Barella, Luiz Felipe; Silveira, Sandra da Silva; Saavedra, Lucas Paulo Jacinto; Prates, Kelly Valério; Alves, Vander Silva; Franco, Claudinéia Conationi da Silva; Miranda, Rosiane Aparecida; Ribeiro, Tatiane Aparecida; Tófolo, Laize Peron; Malta, Ananda; Vieira, Elaine; Palma-Rigo, Kesia; Pavanello, Audrei; Martins, Isabela Peixoto; Moreira, Veridiana Mota; de Oliveira, Júlio Cezar; Mathias, Paulo Cezar de Freitas; Gomes, Rodrigo Mello

2018-03-01

Environmental and nutritional disorders during perinatal period cause metabolic dysfunction in the progeny and impair human health. Advanced glycation end products (AGEs) are primarily produced during metabolism of excess blood glucose, which is observed in diabetes. Methylglyoxal (MG) is a precursor for the generation of endogenous AGEs, which disturbs the metabolism. This work aimed to investigate whether the maternal MG treatment during lactation programs the progeny to metabolic dysfunction later in life. Female Wistar rats were divided into two groups: control group (C) treated with saline and MG group treated with MG (60 mg/kg/day) by gavage throughout the lactation period. Both mothers and offspring were fed a standard chow. At weaning, breast milk composition was analyzed and mothers euthanized for blood and tissue sample collections. At 90 days of age, offspring were submitted to glucose tolerance test (ivGTT) and euthanized for blood and tissue samples collection. MG mothers showed increase in glucose and fructosamine levels; however, they showed low insulin levels and failure in β-cell function (p < 0.05). MG mothers also showed dyslipidemia (p < 0.05). Moreover, breast milk had elevated levels of glucose, triglycerides, cholesterol and fructosamine and low insulin (p < 0.05). Interestingly, MG offspring had increased body weight and adipose tissue at adulthood, and they also showed glucose intolerance and failure in β-cell function (p < 0.05). Besides, MG offspring showed dyslipidemia (p < 0.05) increasing cardiovascular diseases risk. Maternal MG treatment negatively affects the male rat offspring, leading to type 2 diabetes and dyslipidemia in later life, possibly by changes in breast milk composition.

Effect of hyperthyroidism on circulating prolactin and hypothalamic expression of tyrosine hydroxylase, prolactin signaling cascade members and estrogen and progesterone receptors during late pregnancy and lactation in the rat.

PubMed

Pennacchio, Gisela E; Neira, Flavia J; Soaje, Marta; Jahn, Graciela A; Valdez, Susana R

2017-02-15

Hyperthyroidism (HyperT) compromises pregnancy and lactation, hindering suckling-induced PRL release. We studied the effect of HyperT on hypothalamic mRNA (RT-qPCR) and protein (Western blot) expression of tyrosine hydroxylase (TH), PRL receptor (PRLR) and signaling pathway members, estrogen-α (ERα) and progesterone (PR) receptors on late pregnancy (days G19, 20 and 21) and early lactation (L2) in rats. HyperT advanced pre-partum PRL release, reduced circulating PRL on L2 and increased TH mRNA (G21 and L2), p-TH, PRLR mRNA, STAT5 protein (G19 and L2), PRLR protein (G21) and CIS protein (G19). PRs mRNAs and protein decreased on G19 but afterwards PRA mRNA (G20), PRB mRNA (G21) and PRA mRNA and protein (L2) increased. ERα protein increased on G19 and decreased on G20. Thus, the altered hypothalamic PRLR, STAT5, PR and ERα expression in hyperthyroid rats may induce elevated TH expression and activation, that consequently, elevate dopaminergic tone during lactation, blunting suckling-induced PRL release and litter growth. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Carbohydrate metabolism of the perfused rat liver

PubMed Central

Ross, B. D.; Hems, R.; Freedland, R. A.; Krebs, H. A.

1967-01-01

1. The rates of gluconeogenesis from most substrates tested in the perfused livers of well-fed rats were about half of those obtained in the livers of starved rats. There was no difference for glycerol. 2. A diet low in carbohydrate increased the rates of gluconeogenesis from some substrates but not from all. In general the effects of a low-carbohydrate diet on rat liver are less marked than those on rat kidney cortex. 3. Glycogen was deposited in the livers of starved rats when the perfusion medium contained about 10mm-glucose. The shedding of glucose from the glycogen stores by the well-fed liver was greatly diminished by 10mm-glucose and stopped by 13·3mm-glucose. Livers of well-fed rats that were depleted of their glycogen stores by treatment with phlorrhizin and glucagon synthesized glycogen from glucose. 4. When two gluconeogenic substrates were added to the perfusion medium additive effects occurred only when glycerol was one of the substrates. Lactate and glycerol gave more than additive effects owing to an increased rate of glucose formation from glycerol. 5. Pyruvate also accelerated the conversion of glycerol into glucose, and the accelerating effect of lactate can be attributed to a rapid formation of pyruvate from lactate. 6. Butyrate and oleate at 2mm, which alone are not gluconeogenic, increased the rate of gluconeogenesis from lactate. 7. The acceleration of gluconeogenesis from lactate by glucagon was also found when gluconeogenesis from lactate was stimulated by butyrate and oleate. This finding is not compatible with the view that the primary action of glucagon in promoting gluconeogenesis is an acceleration of lipolysis. 8. The rate of gluconeogenesis from pyruvate at 10mm was only 70% of that at 5mm. This `inhibition' was abolished by oleate or glucagon. PMID:5584023

Influence of cafeteria diet and fish oil in pregnancy and lactation on pups' body weight and fatty acid profiles in rats.

PubMed

Sánchez-Blanco, Clara; Amusquivar, Encarnación; Bispo, Kenia; Herrera, Emilio

2016-06-01

The aim was to determine the effects of cafeteria diet (CD) and fish oil supplements given to pregnant and lactating rats on the birth weight and fatty acid profiles of their offspring. Female rats were given standard diet (STD) or CD for 22 days before pregnancy. After mating, some animals remained on STD or CD; for some CD rats, the diet was supplemented with 8.78 % fish oil (CD-FO). After 12 days, half the CD-FO group returned to CD (CD-FO12) and the others remained on CD-FO. At birth, body weights of pups of the three CD groups were lower than STD, maintained until 21 days in the CD-FO group only. At the end of lactation, dams of the CD groups had increased plasma triacylglycerols (TAG), non-esterified fatty acids, and glycerol concentrations, whereas most n-6 long-chain polyunsaturated fatty acids (LCPUFA) were decreased, the effect being greatest in the CD-FO group, where most n-3 LCPUFA were increased and indices of Δ(5) and Δ(6) desaturase activities decreased. The 21-day-old pups of the CD group had increased plasma TAG, not present in the CD-FO group, which had increased 3-hydroxybutyrate concentrations. In both 2- and 21-day-old CD pups, plasma concentrations of ARA were lower than STD, and even lower in the two CD-FO groups. The effect of CD and CD-FO decreasing pups body weight could be related to decreased concentrations of ARA, caused by the inhibition of the Δ(5) and Δ(6) desaturases in the pathway of n-6 LCPUFA biosynthesis.

Influence of oxygen therapy on glucose-lactate metabolism after diffuse brain injury.

PubMed

Reinert, Michael; Schaller, Benoit; Widmer, Hans Rudolf; Seiler, Rolf; Bullock, Ross

2004-08-01

Severe traumatic brain injury (TBI) imposes a huge metabolic load on brain tissue, which can be summarized initially as a state of hypermetabolism and hyperglycolysis. In experiments O2 consumption has been shown to increase early after trauma, especially in the presence of high lactate levels and forced O2 availability. In recent clinical studies the effect of increasing O2 availability on brain metabolism has been analyzed. By their nature, however, clinical trauma models suffer from a heterogeneous injury distribution. The aim of this study was to analyze, in a standardized diffuse brain injury model, the effect of increasing the fraction of inspired O2 on brain glucose and lactate levels, and to compare this effect with the metabolism of the noninjured sham-operated brain. A diffuse severe TBI model developed by Foda and Maramarou, et al., in which a 420-g weight is dropped from a height of 2 m was used in this study. Forty-one male Wistar rats each weighing approximately 300 g were included. Anesthesized rats were monitored by placing a femoral arterial line for blood pressure and blood was drawn for a blood gas analysis. Two time periods were defined: Period A was defined as preinjury and Period B as postinjury. During Period B two levels of fraction of inspired oxygen (FiO2) were studied: air (FiO2 0.21) and oxygen (FiO2 1). Four groups were studied including sham-operated animals: air-air-sham (AAS); air-O2-sham (AOS); air-air-trauma (AAT); and air-O2-trauma (AOT). In six rats the effect of increasing the FiO2 on serum glucose and lactate was analyzed. During Period B lactate values in the brain determined using microdialysis were significantly lower (p < 0.05) in the AOT group than in the AAT group and glucose values in the brain determined using microdialysis were significantly higher (p < 0.04). No differences were demonstrated in the other groups. Increasing the FiO2 had no significant effect on the serum levels of glucose and lactate. Increasing the Fi

Abnormal peripubertal development of the rat mammary gland following exposure in utero and during lactation to a mixture of genistein and the food contaminant vinclozolin.

PubMed

El Sheikh Saad, H; Meduri, G; Phrakonkham, P; Bergès, R; Vacher, S; Djallali, M; Auger, J; Canivenc-Lavier, M C; Perrot-Applanat, M

2011-07-01

The impact of early exposure to endocrine disruptor mixtures on mammary gland development is poorly known. Here, we identify the effects of a conception to weaning exposure of rats to the phytoestrogen genistein (G) and/or the antiandrogen vinclozolin (V) at 1mg/kg-d, alone or in association. Using several approaches, we found that G- and GV-exposed rats displayed significantly greater epithelial branching and proliferation, wider terminal end buds than controls at PND35, as well as ductal hyperplasia and periductal fibrosis. Focal branching defects were present in V-exposed rats. An increased ER and AR expression was observed in G- and GV- as compared to V-exposed rats at PND35. Surprisingly, a significant number of GV- and to a lesser extent, V-exposed animals displayed abnormal hyperplasic alveolar structures at PND50. Thus, gestational and lactational exposure to low doses of genistein plus vinclozolin may seriously affect peripubertal development of the rat mammary gland. Copyright © 2011 Elsevier Inc. All rights reserved.

Effect of zinc supplementation on lipid peroxidation and lactate levels in rats with diabetes induced by streptozotocin and subjected to acute swimming exercise.

PubMed

Bicer, M; Gunay, M; Baltaci, A K; Uney, K; Mogulkoc, R; Akil, M

2012-01-01

The present study aims to explore the effect of zinc supplementation on lipid peroxidation and lactate levels in rats having diabetes induced by streptozotocin and subjected to acute swimming exercise. A total of 80 adult male rats of Sprague-Dawley type were equally allocated to 8 groups: Group 1, general control. Group 2, zinc-supplemented group. Group 3, zinc-supplemented, diabetic group. Group 4, swimming control group. Group 5, zinc-supplemented swimming group. Group 6, zinc-supplemented diabetic swimming group. Group 7, diabetic swimming group. Group 8, diabetic group. At the end of the 4-week study, blood samples were collected to determine MDA, GSH, GPx, SOD, lactate and zinc levels. The highest MDA values were found in group 7 and 8 (p<0.001). GSH values in groups 5 and 6 were higher (p<0.001). The highest GPx values were established in groups 2, 5 and 6 (p<0.001). SOD values were the highest in groups 5 and 6 (p<0.001) and lowest in groups 2, 3 and 8 (p<0.001). The highest plasma lactate levels were found in group 7 (p<0.001). The highest zinc levels were obtained in groups 1, 2 and 5 (p<0.001), and the lowest zinc levels were found in groups 7 and 8 (p<0.001). Results of the study reveal that zinc supplementation prevents the increase of free radical formation, suppression of antioxidant activity and muscle exhaustion, all of which result from diabetes and acute exercise. Zinc supplementation may contribute to health performance in diabetes and acute exercise (Tab. 2, Fig. 1 Ref. 47). Full Text in PDF www.elis.sk.

Caudal hindbrain lactate infusion alters glucokinase, SUR1, and neuronal substrate fuel transporter gene expression in the dorsal vagal complex, lateral hypothalamic area, and ventromedial nucleus hypothalamus of hypoglycemic male rats.

PubMed

Vavaiya, Kamlesh V; Briski, Karen P

2007-10-24

While in vitro studies show that the oxidizable energy substrate, lactate, is a preferred fuel for CNS neurons during states of energy crisis, and that lactate may regulate neuronal glucose uptake under those conditions, its role in neuronal function in vivo remains controversial. Glucose-excited neurons in hindbrain dorsal vagal complex (DVC) monitor both glucose and lactate, and express both the glucose sensor, glucokinase (GK), and the SUR1 subunit of the plasma membrane energy transducer, K(ATP). Fourth ventricular lactate infusion exacerbates insulin-induced hypoglycemia (IIH) and IIH-associated patterns of DVC neuronal activation. We investigated the hypothesis that during glucoprivation, lactate regulates neuronal monocarboxylate and glucose transporter gene transcription in the DVC, and adjustments in these gene profiles are correlated with altered GK and SUR1 mRNA expression. We also examined whether caudal hindbrain lactate repletion alters the impact of hypoglycemia on substrate fuel uptake and metabolic sensing functions in other characterized metabolic monitoring sites, e.g., the ventromedial hypothalamic nucleus (VMH) and lateral hypothalamic area (LHA). qPCR was used to measure MCT2, GLUT3, GLUT4, GK, and SUR1 transcripts in the microdissected DVC, VMH, and LHA from groups of male rats treated by continuous infusion of aCSF or lactate into the caudal fourth ventricle (CV4), initiated prior to injection of Humulin R or saline. Blood glucose was decreased in response to insulin, a response that was significantly augmented by CV4 lactate infusion. IIH alone did not alter mean DVC MCT2, GLUT3, GLUT4, GK, or SUR1 mRNA levels, but these transcripts were increased in the lactate plus insulin group, relative to both euglycemic and aCSF-infused hypoglycemic rats. IIH decreased MCT2, GLUT3, and SUR1 gene profiles in the VMH; CV4 lactate infusion during IIH further diminished these transcripts, and suppressed GLUT4 and GK mRNA levels in this site. In LHA, IIH

Feeding of soy protein isolate to rats during pregnancy and lactation suppresses formation of aberrant crypt foci in their progeny's colons: interaction of diet with fetal alcohol exposure

PubMed Central

Linz, Amanda L; Xiao, Rijin; Parker, James G; Simpson, Pippa M; Badger, Thomas M; Simmen, Frank A

2004-01-01

Soy protein isolate (SPI) in the diet may inhibit colon tumorigenesis. We examined azoxymethane (AOM)-induced aberrant crypt foci (ACF) in male rats in relation to lifetime, pre-weaning, or post-weaning dietary exposure to SPI and also within the context of fetal alcohol exposure. Pregnant Sprague Dawley rats were fed AIN-93G diets containing casein (20%, the control diet) or SPI (20%) as the sole protein source starting on gestation day 4 (GD 4). Progeny were weaned on postnatal day (PND) 21 to the same diet as their dams and were fed this diet until termination of the experiment at PND 138. Rats received AOM on PND 89 and 96. Lifetime (GD 4 to PND 138) feeding of SPI led to reduced frequency of ACF with 4 or more crypts in the distal colon. Progeny of dams fed SPI only during pregnancy and lactation or progeny fed SPI only after weaning exhibited similarly reduced frequency of large ACF in distal colon. Number of epithelial cells, in the distal colon, undergoing apoptosis was unaffected by diet. SPI reduced weight gain and adiposity, but these were not correlated with fewer numbers of large ACF. Lifetime SPI exposure similarly inhibited development of large ACF in Sprague Dawley rats whose dams were exposed to ethanol during pregnancy. In summary, feeding of SPI to rat dams during pregnancy and lactation suppresses numbers of large ACF in their progeny, implying a long-term or permanent change elicited by the maternal diet. Moreover, results support the use of ACF as an intermediate endpoint for elucidating effects of SPI and its biochemical constituents in colon cancer prevention in rats. PMID:15488141

Cariogenicity of a lactate dehydrogenase-deficient mutant of Streptococcus mutans serotype c in gnotobiotic rats.

PubMed

Fitzgerald, R J; Adams, B O; Sandham, H J; Abhyankar, S

1989-03-01

A lactate dehydrogenase-deficient (Ldh-) mutant of a human isolate of Streptococcus mutans serotype c was tested in a gnotobiotic rat caries model. Compared with the wild-type Ldh-positive (Ldh+) strains, it was significantly (alpha less than or equal to 0.005) less cariogenic in experiments with two different sublines of Sprague-Dawley rats. The Ldh- mutant strain 044 colonized the oral cavity of the test animals to the same extent as its parent strain 041, although its initial implantation was slightly but not significantly (P greater than or equal to 0.2) less. Multiple oral or fecal samples plated on 2,3,5-triphenyltetrazolium indicator medium revealed no evidence of back mutation from Ldh- to Ldh+ in vivo. Both Ldh+ strain 041 and Ldh- strain 044 demonstrated bacteriocinlike activity in vitro against a number of human strains of mutans streptococci representing serotype a (S. cricetus) and serotypes c and e (S. mutans). Serotypes b (S. rattus) and f (S. mutans) and strains of S. mitior, S. sanguis, and S. salivarius were not inhibited. Thus, Ldh mutant strain 044 possesses a number of desirable traits that suggest it should be investigated further as a possible effector strain for replacement therapy of dental caries. These traits include its stability and low cariogenicity in the sensitive gnotobiotic rat caries model, its bacteriocinlike activity against certain other cariogenic S. mutans (but not against more inocuous indigenous oral streptococci), and the fact that it is a member of the most prevalent human serotype of cariogenic streptococci.

Extracellular levels of lactate, but not oxygen, reflect sleep homeostasis in the rat cerebral cortex.

PubMed

Dash, Michael B; Tononi, Giulio; Cirelli, Chiara

2012-07-01

It is well established that brain metabolism is higher during wake and rapid eye movement (REM) sleep than in nonrapid eye movement (NREM) sleep. Most of the brain's energy is used to maintain neuronal firing and glutamatergic transmission. Recent evidence shows that cortical firing rates, extracellular glutamate levels, and markers of excitatory synaptic strength increase with time spent awake and decline throughout NREM sleep. These data imply that the metabolic cost of each behavioral state is not fixed but may reflect sleep-wake history, a possibility that is investigated in the current report. Chronic (4d) electroencephalographic (EEG) recordings in the rat cerebral cortex were coupled with fixed-potential amperometry to monitor the extracellular concentration of oxygen ([oxy]) and lactate ([lac]) on a second-by-second basis across the spontaneous sleep-wake cycle and in response to sleep deprivation. Basic sleep research laboratory. Wistar Kyoto (WKY) adult male rats. N/A. Within 30-60 sec [lac] and [oxy] progressively increased during wake and REM sleep and declined during NREM sleep (n = 10 rats/metabolite), but with several differences. [Oxy], but not [lac], increased more during wake with high motor activity and/or elevated EEG high-frequency power. Meanwhile, only the NREM decline of [lac] reflected sleep pressure as measured by slow-wave activity, mirroring previous results for cortical glutamate. The observed state-dependent changes in cortical [lac] and [oxy] are consistent with higher brain metabolism during waking and REM sleep in comparison with NREM sleep. Moreover, these data suggest that glycolytic activity, most likely through its link with glutamatergic transmission, reflects sleep homeostasis.

Lactational Vitamin E Protects Against the Histotoxic Effects of Systemically Administered Vanadium in Neonatal Rats.

PubMed

Olaolorun, F A; Obasa, A A; Balogun, H A; Aina, O O; Olopade, J O

2014-12-29

The work investigated the protective role of lactational vitamin E administration on vanadium-induced histotoxicity. Three groups of Wistar rats, with each group comprising of two dams and their pups, were used in this study. Group I pups were administered intraperitoneal injection of sterile water at volumes corresponding to the dose rate of the vanadium (sodium metavanadate) treated group from postnatal day (PND) 1-14 while those in Group II were administered intraperitoneal injection of 3mg/kg vanadium from PND 1-14. Group III pups were administered intraperitoneal injection of 3mg/kg vanadium while the dam received oral vitamin E (500 mg) concurrently every 72 hours. The results showed that group II pups exhibited histopathological changes which included seminiferous tubule disruption of the testes characterised by vacuolar degeneration and coagulative necrosis of spermatogonia and Sertoli cells with reduction in mitosis, and areas of interstitial thickening with fibroblast proliferation. In addition, the lungs showed disruption of the bronchiolar wall and denudation of the bronchiolar respiratory epithelium while the liver showed hydropic degeneration and coagulative necrosis of the centrilobular hepatocytes. These histotoxic changes were ameliorated in the vanadium + vitamin E group. We conclude that lactational vitamin E protects against the histotoxic effects of vanadium and could be a consideration for supplementation in the occupationally and environmentally exposed neonates. However, caution should be taken in vitamin E supplementation because there is still equivocal evidence surrounding its benefits as a supplement at the moment.

Consumption of sucrose, but not high fructose corn syrup, leads to increased adiposity and dyslipidaemia in the pregnant and lactating rat.

PubMed

Toop, C R; Muhlhausler, B S; O'Dea, K; Gentili, S

2015-02-01

Excess consumption of added sugars, including sucrose and high fructose corn syrup (HFCS-55), have been implicated in the global epidemics of obesity and type 2 diabetes. This study aimed to investigate and compare the impact of maternal consumption of sucrose or HFCS-55 during pregnancy and lactation on the metabolic health of the dam and her offspring at birth. Female Albino Wistar rats were given access to chow and water, in addition to a sucrose or HFCS-55 beverage (10% w/v) before, and during pregnancy and lactation. Maternal glucose tolerance was determined throughout the study, and a postmortem was conducted on dams following lactation, and on offspring within 24 h of birth. Sucrose and HFCS-55 consumption resulted in increased total energy intake compared with controls, however the increase from sucrose consumption was accompanied by a compensatory decrease in chow consumption. There was no effect of sucrose or HFCS-55 consumption on body weight, however sucrose consumption resulted in increased adiposity and elevated total plasma cholesterol in the dam, while HFCS-55 consumption resulted in increased plasma insulin and decreased plasma non-esterified fatty acids (NEFA). Maternal HFCS-55 consumption was associated with decreased relative liver weight and plasma NEFA in the offspring at birth. There was no effect of either treatment on pup weight at birth. These findings suggest that both sucrose and HFCS-55 consumption during pregnancy and lactation have the potential to impact negatively on maternal metabolic health, which may have adverse consequences for the long-term health of the offspring.

Lactate dehydrogenase activity is inhibited by methylmalonate in vitro.

PubMed

Saad, Laura O; Mirandola, Sandra R; Maciel, Evelise N; Castilho, Roger F

2006-04-01

Methylmalonic acidemia (MMAemia) is an inherited metabolic disorder of branched amino acid and odd-chain fatty acid metabolism, involving a defect in the conversion of methylmalonyl-coenzyme A to succinyl-coenzyme A. Systemic and neurological manifestations in this disease are thought to be associated with the accumulation of methylmalonate (MMA) in tissues and biological fluids with consequent impairment of energy metabolism and oxidative stress. In the present work we studied the effect of MMA and two other inhibitors of mitochondrial respiratory chain complex II (malonate and 3-nitropropionate) on the activity of lactate dehydrogenase (LDH) in tissue homogenates from adult rats. MMA potently inhibited LDH-catalyzed conversion of lactate to pyruvate in liver and brain homogenates as well as in a purified bovine heart LDH preparation. LDH was about one order of magnitude less sensitive to inhibition by MMA when catalyzing the conversion of pyruvate to lactate. Kinetic studies on the inhibition of brain LDH indicated that MMA inhibits this enzyme competitively with lactate as a substrate (K (i)=3.02+/-0.59 mM). Malonate and 3-nitropropionate also strongly inhibited LDH-catalyzed conversion of lactate to pyruvate in brain homogenates, while no inhibition was observed by succinate or propionate, when present in concentrations of up to 25 mM. We propose that inhibition of the lactate/pyruvate conversion by MMA contributes to lactate accumulation in blood, metabolic acidemia and inhibition of gluconeogenesis observed in patients with MMAemia. Moreover, the inhibition of LDH in the central nervous system may also impair the lactate shuttle between astrocytes and neurons, compromising neuronal energy metabolism.

Antagonism of V1b receptors promotes maternal motivation to retrieve pups in the MPOA and impairs pup-directed behavior during maternal defense in the mpBNST of lactating rats.

PubMed

Bayerl, Doris S; Kaczmarek, Veronika; Jurek, Benjamin; van den Burg, Erwin H; Neumann, Inga D; Gaßner, Barbara M; Klampfl, Stefanie M; Bosch, Oliver J

2016-03-01

Recent studies using V1b receptor (V1bR) knockout mice or central pharmacological manipulations in lactating rats highlighted the influence of this receptor for maternal behavior. However, its role in specific brain sites known to be important for maternal behavior has not been investigated to date. In the present study, we reveal that V1bR mRNA (qPCR) and protein levels (Western blot) within either the medial preoptic area (MPOA) or the medial-posterior part of the bed nucleus of the stria terminalis (mpBNST) did not differ between virgin and lactating rats. Furthermore, we characterized the effects of V1bR blockade via bilateral injections of the receptor subtype-specific antagonist SSR149415 within the MPOA or the mpBNST on maternal behavior (maternal care under non-stress and stress conditions, maternal motivation to retrieve pups in a novel environment, maternal aggression) and anxiety-related behavior in lactating rats. Blocking V1bR within the MPOA increased pup retrieval, whereas within the mpBNST it decreased pup-directed behavior, specifically licking/grooming the pups, during the maternal defense test. In addition, immediately after termination of the maternal defense test, V1bR antagonism in both brain regions reduced nursing, particularly arched back nursing. Anxiety-related behavior was not affected by V1bR antagonism in either brain region. In conclusion our data indicate that V1bR antagonism significantly modulates different aspects of maternal behavior in a brain region-dependent manner. Copyright © 2015 Elsevier Inc. All rights reserved.

MCT2 Expression and Lactate Influx in Anorexigenic and Orexigenic Neurons of the Arcuate Nucleus

PubMed Central

Cortes-Campos, Christian; Elizondo, Roberto; Carril, Claudio; Martínez, Fernando; Boric, Katica; Nualart, Francisco; Garcia-Robles, Maria Angeles

2013-01-01

Hypothalamic neurons of the arcuate nucleus control food intake, releasing orexigenic and anorexigenic neuropeptides in response to changes in glucose concentration. Several studies have suggested that the glucosensing mechanism is governed by a metabolic interaction between neurons and glial cells via lactate flux through monocarboxylate transporters (MCTs). Hypothalamic glial cells (tanycytes) release lactate through MCT1 and MCT4; however, similar analyses in neuroendocrine neurons have yet to be undertaken. Using primary rat hypothalamic cell cultures and fluorimetric assays, lactate incorporation was detected. Furthermore, the expression and function of MCT2 was demonstrated in the hypothalamic neuronal cell line, GT1-7, using kinetic and inhibition assays. Moreover, MCT2 expression and localization in the Sprague Dawley rat hypothalamus was analyzed using RT-PCR, in situ hybridization and Western blot analyses. Confocal immunohistochemistry analyses revealed MCT2 localization in neuronal but not glial cells. Moreover, MCT2 was localized to ∼90% of orexigenic and ∼60% of anorexigenic neurons as determined by immunolocalization analysis of AgRP and POMC with MCT2-positives neurons. Thus, MCT2 distribution coupled with lactate uptake by hypothalamic neurons suggests that hypothalamic neurons control food intake using lactate to reflect changes in glucose levels. PMID:23638108

Lack of appropriate stoichiometry: Strong evidence against an energetically important astrocyte-neuron lactate shuttle in brain.

PubMed

Dienel, Gerald A

2017-11-01

Glutamate-stimulated aerobic glycolysis in astrocytes coupled with lactate shuttling to neurons where it can be oxidized was proposed as a mechanism to couple excitatory neuronal activity with glucose utilization (CMR glc ) during brain activation. From the outset, this model was not viable because it did not fulfill critical stoichiometric requirements: (i) Calculated glycolytic rates and measured lactate release rates were discordant in cultured astrocytes. (ii) Lactate oxidation requires oxygen consumption, but the oxygen-glucose index (OGI, calculated as CMR O2 /CMR glc ) fell during activation in human brain, and the small rise in CMR O2 could not fully support oxidation of lactate produced by disproportionate increases in CMR glc . (iii) Labeled products of glucose metabolism are not retained in activated rat brain, indicating rapid release of a highly labeled, diffusible metabolite identified as lactate, thereby explaining the CMR glc -CMR O2 mismatch. Additional independent lines of evidence against lactate shuttling include the following: astrocytic oxidation of glutamate after its uptake can help "pay" for its uptake without stimulating glycolysis; blockade of glutamate receptors during activation in vivo prevents upregulation of metabolism and lactate release without impairing glutamate uptake; blockade of β-adrenergic receptors prevents the fall in OGI in activated human and rat brain while allowing glutamate uptake; and neurons upregulate glucose utilization in vivo and in vitro under many stimulatory conditions. Studies in immature cultured cells are not appropriate models for lactate shuttling in adult brain because of their incomplete development of metabolic capability and astrocyte-neuron interactions. Astrocyte-neuron lactate shuttling does not make large, metabolically significant contributions to energetics of brain activation. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Oleuropein and hydroxytyrosol protect from bisphenol A effects in livers and kidneys of lactating mother rats and their pups'.

PubMed

Mahmoudi, Asma; Ghorbel, Héla; Bouallegui, Zouhair; Marrekchi, Rim; Isoda, Hiroko; Sayadi, Sami

2015-01-01

Bisphenol A (BPA) is a chemical found in hard plastics and the coatings of food and drinks cans which can behave in a similar way to estrogen and other hormones in the human body. This study aimed to evaluate the significance of the treatment with oleuropein and hydroxytyrosol olive leaves rich extracts in reducing functional perturbations and oxidative stress arising from BPA treatment in livers and kidneys of lactating mother rats and their pups'. For this, four groups of lactating mothers were used: controls (group A), treated with bisphenol A (group B), treated with bisphenol A and oleuropein (group C) and with bisphenol A and hydroxytyrosol (group D). As results, we had found, in BPA treated group, either in mothers or in their pups', a significant decrease in morphological parameters, in catalase activity and in total antioxidant capacity associated to an increase in malondialdehyde levels in livers and kidneys. For these rats, the histological aspect showed, also, deep changes. Indeed, we had observed, in livers, hepatocellular necrosis associated to leucocytes infiltration and in kidneys tubular and glomerular necrosis. The co-treatments with BPA and oleuropein (group C) or with BPA and hydroxytyrosol (group D) ameliorate all morphological, biochemical and histological parameters as compared to BPA treated group B. The analysis of BPA and its derivatives with LC-MS/MS showed changes in their localizations between serum, livers or kidneys in all studied groups. In conclusion, the present study demonstrates the hepato-protective and reno-protective effects of oleuropein and hydroxytyrosol olive leaves extracts from BPA and its derivates toxicity. Copyright © 2015 Elsevier GmbH. All rights reserved.

Effect of ornithine and lactate on urea synthesis in isolated hepatocytes.

PubMed Central

Briggs, S; Freedland, R A

1976-01-01

1. In hepatocytes isolated from 24 h-starved rats, urea production from ammonia was stimulated by addition of lactate, in both the presence and the absence of ornithine. The relationship of lactate concentration to the rate of urea synthesis was hyperbolic. 2. Other glucose precursors also stimulated urea production to varying degrees, but none more than lactate. Added oleate and butyrate did not stimulate urea synthesis. 3. Citrulline accumulation was largely dependent on ornithine concentration. As ornithine was increased from 0 to 40 mM, the rate of citrulline accumulation increased hyperbolically, and was half-maximal when ornithine was 8-12 mM. 4. The rate of citrulline accumulation was independent of the presence of lactate, but with pyruvate the rate increased. 5. The rate of urea production continued to increase as ornithine was varied from 0 to 40 mM. 6. It was concluded that intermediates provided by both ornithine and lactate are limiting for urea production from ammonia in isolated liver cells. It was suggested that the stimulatory effect of lactate lies in increased availability of cytosolic aspartate for condensation with citrulline. PMID:1008850

Comparative effect of lidocaine and bupivacaine on glucose uptake and lactate production in the perfused working rat heart

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cronau, L.H. Jr.; Merin, R.G.; Aboulish, E.

1986-03-01

It has been suggested that at equivalent therapeutic concentrations, lidocaine and bupivacaine may have different cardiotoxic potency. In the isolated working rat heart preparation, the effect of a range of lidocaine and bupivacaine concentrations on glucose uptake and lactate production (LP) were observed. Insulin was added, 10 ..mu../L, to Ringer's solution containing /sup 3/H-labeled glucose to measure the glycolytic flux (GF). The effect of the local anesthetics on LP at the indicated concentrations were similar. Lidocaine appears to depress the glycolytic flux from exogenous glucose to a lesser degree. Bupivacaine, 10 mg/L, depresses VO/sub 2/ to a greater degree thanmore » does lidocaine, 40 mg/L.« less

High-Protein Exposure during Gestation or Lactation or after Weaning Has a Period-Specific Signature on Rat Pup Weight, Adiposity, Food Intake, and Glucose Homeostasis up to 6 Weeks of Age.

PubMed

Desclée de Maredsous, Caroline; Oozeer, Raish; Barbillon, Pierre; Mary-Huard, Tristan; Delteil, Corine; Blachier, François; Tomé, Daniel; van der Beek, Eline M; Davila, Anne-Marie

2016-01-01

Early-life nutrition has a programming effect on later metabolic health; however, the impact of exposure to a high-protein (HP) diet is still being investigated. This study evaluated the consequences on pup phenotype of an HP diet during gestation and lactation and after weaning. Wistar rat dams were separated into 2 groups fed an HP (55% protein) or normal protein (NP) (control; 20% protein) isocaloric diet during gestation, and each group subsequently was separated into 2 subgroups that were fed an HP or NP diet during lactation. After weaning, male and female pups from each mother subgroup were separated into 2 groups that were fed either an NP or HP diet until they were 6 wk old. Measurements included weight, food intake, body composition, blood glucose, insulin, glucagon, leptin, insulin-like growth factor I, and lipids. Feeding mothers the HP diet during gestation or lactation induced lower postweaning pup weight (gestation diet × time, P < 0.0001; lactation diet × time, P < 0.0001). Regardless of dams' diets, pups receiving HP compared with NP diet after weaning had 7% lower weight (NP, 135.0 ± 2.6 g; HP, 124.4 ± 2.5 g; P < 0.0001), 16% lower total energy intake (NP, 777 ± 14 kcal; HP, 649 ± 13 kcal; P < 0.0001) and 31% lower adiposity (P < 0.0001). Pups receiving HP compared with NP diet after weaning had increased blood glucose, insulin, and glucagon when food deprived (P < 0.0001 for all). The HP compared with the NP diet during gestation induced higher blood glucose in food-deprived rats (NP, 83.2 ± 2.1 mg/dL; HP, 91.2 ± 2.1 mg/dL; P = 0.046) and increased plasma insulin in fed pups receiving the postweaning NP diet (gestation diet × postweaning diet, P = 0.02). Increasing the protein concentration of the rat dams' diet during gestation, and to a lesser extent during lactation, and of the pups' diet after weaning influenced pup phenotype, including body weight, fat accumulation, food intake, and glucose tolerance at 6 wk of age. © 2016 American

Increased male offspring's risk of metabolic-neuroendocrine dysfunction and overweight after fructose-rich diet intake by the lactating mother.

PubMed

Alzamendi, Ana; Castrogiovanni, Daniel; Gaillard, Rolf C; Spinedi, Eduardo; Giovambattista, Andrés

2010-09-01

An adverse endogenous environment during early life predisposes the organism to develop metabolic disorders. We evaluated the impact of intake of an iso-caloric fructose rich diet (FRD) by lactating mothers (LM) on several metabolic functions of their male offspring. On postnatal d 1, ad libitum eating, lactating Sprague-Dawley rats received either 10% F (wt/vol; FRD-LM) or tap water (controls, CTR-LM) to drink throughout lactation. Weaned male offspring were fed ad libitum a normal diet, and body weight (BW) and food intake were registered until experimentation (60 d of age). Basal circulating levels of metabolic markers were evaluated. Both iv glucose tolerance and hypothalamic leptin sensitivity tests were performed. The hypothalamus was dissected for isolation of total RNA and Western blot analysis. Retroperitoneal (RP) adipose tissue was dissected and either kept frozen for gene analysis or digested to isolate adipocytes or for histological studies. FRD rats showed increased BW and decreased hypothalamic sensitivity to exogenous leptin, enhanced food intake (between 49-60 d), and decreased hypothalamic expression of several anorexigenic signals. FRD rats developed increased insulin and leptin peripheral levels and decreased adiponectinemia; although FRD rats normally tolerated glucose excess, it was associated with enhanced insulin secretion. FRD RP adipocytes were enlarged and spontaneously released high leptin, although they were less sensitive to insulin-induced leptin release. Accordingly, RP fat leptin gene expression was high in FRD rats. Excessive fructose consumption by lactating mothers resulted in deep neuroendocrine-metabolic disorders of their male offspring, probably enhancing the susceptibility to develop overweight/obesity during adult life.

Hypertonic sodium lactate reverses brain oxygenation and metabolism dysfunction after traumatic brain injury.

PubMed

Millet, A; Cuisinier, A; Bouzat, P; Batandier, C; Lemasson, B; Stupar, V; Pernet-Gallay, K; Crespy, T; Barbier, E L; Payen, J F

2018-06-01

The mechanisms by which hypertonic sodium lactate (HSL) solution act in injured brain are unclear. We investigated the effects of HSL on brain metabolism, oxygenation, and perfusion in a rodent model of diffuse traumatic brain injury (TBI). Thirty minutes after trauma, anaesthetised adult rats were randomly assigned to receive a 3 h infusion of either a saline solution (TBI-saline group) or HSL (TBI-HSL group). The sham-saline and sham-HSL groups received no insult. Three series of experiments were conducted up to 4 h after TBI (or equivalent) to investigate: 1) brain oedema using diffusion-weighted magnetic resonance imaging and brain metabolism using localized 1 H-magnetic resonance spectroscopy (n = 10 rats per group). The respiratory control ratio was then determined using oxygraphic analysis of extracted mitochondria, 2) brain oxygenation and perfusion using quantitative blood-oxygenation-level-dependent magnetic resonance approach (n = 10 rats per group), and 3) mitochondrial ultrastructural changes (n = 1 rat per group). Compared with the TBI-saline group, the TBI-HSL and the sham-operated groups had reduced brain oedema. Concomitantly, the TBI-HSL group had lower intracellular lactate/creatine ratio [0.049 (0.047-0.098) vs 0.097 (0.079-0.157); P < 0.05], higher mitochondrial respiratory control ratio, higher tissue oxygen saturation [77% (71-79) vs 66% (55-73); P < 0.05], and reduced mitochondrial cristae thickness in astrocytes [27.5 (22.5-38.4) nm vs 38.4 (31.0-47.5) nm; P < 0.01] compared with the TBI-saline group. Serum sodium and lactate concentrations and serum osmolality were higher in the TBI-HSL than in the TBI-saline group. These findings indicate that the hypertonic sodium lactate solution can reverse brain oxygenation and metabolism dysfunction after traumatic brain injury through vasodilatory, mitochondrial, and anti-oedema effects. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Disrupting astrocyte-neuron lactate transfer persistently reduces conditioned responses to cocaine.

PubMed

Boury-Jamot, B; Carrard, A; Martin, J L; Halfon, O; Magistretti, P J; Boutrel, B

2016-08-01

A central problem in the treatment of drug addiction is the high risk of relapse often precipitated by drug-associated cues. The transfer of glycogen-derived lactate from astrocytes to neurons is required for long-term memory. Whereas blockade of drug memory reconsolidation represents a potential therapeutic strategy, the role of astrocyte-neuron lactate transport in long-term conditioning has received little attention. By infusing an inhibitor of glycogen phosphorylase into the basolateral amygdala of rats, we report that disruption of astrocyte-derived lactate not only transiently impaired the acquisition of a cocaine-induced conditioned place preference but also persistently disrupted an established conditioning. The drug memory was rescued by L-Lactate co-administration through a mechanism requiring the synaptic plasticity-related transcription factor Zif268 and extracellular signal-regulated kinase (ERK) signalling pathway but not the brain-derived neurotrophic factor (Bdnf). The long-term amnesia induced by glycogenolysis inhibition and the concomitant decreased expression of phospho-ERK were both restored with L-Lactate co-administration. These findings reveal a critical role for astrocyte-derived lactate in positive memory formation and highlight a novel amygdala-dependent reconsolidation process, whose disruption may offer a novel therapeutic target to reduce the long-lasting conditioned responses to cocaine.

Radiation-induced enzyme efflux from rat heart: sedentary animals. [Gamma radiation, lactate dehydrogenase, creative kinase, glutamate oxaloacetate transaminase

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacWilliam, L.D.; Bhakthan, N.M.G.

1976-01-01

Serum levels of lactate dehydrogenase, creatine kinase, and glutamate oxaloacetate transaminase show initial elevations within 12 hr of exposure to 2,000 rads of ..gamma..-radiation to the thoracic region of rats. Significant decreases in heart muscle homogenate levels of these enzymes parallel initial elevations in the serum and may suggest that enhanced leakage of enzymes is a consequence of radiation injury to heart muscle. Insignificant alterations in mitochondrial glutamate oxaloacetate transaminase levels after exposure indicate that in vivo injury to the mitochondria from therapeutic levels of ..gamma..-radiation is questionable. The results support the contention that ionizing radiation instigates alterations in themore » dynamic permeability of membranes, allowing leakage of biologically active material out of the injured cell.« less

A Comparison of Vasopressin, Terlipressin, and Lactated Ringers for Resuscitation of Uncontrolled Hemorrhagic Shock in an Animal Model

PubMed Central

Lee, Chien-Chang; Lee, Meng-Tse Gabriel; Chang, Shy-Shin; Lee, Si-Huei; Huang, Yu-Chi; Yo, Chia-Hung; Lee, Shih-Hao; Chen, Shyr-Chyr

2014-01-01

Aim The aim of this study is to compare the effect of lactated ringer (LR), vasopressin (Vaso) or terlipressin (Terli) on uncontrolled hemorrhagic shock (UHS) in rats. Methods 48 rats were divided into four treatment groups for UHS study. Vaso group was given bolus vasopressin (0.8 U/kg); the Terli group was given bolus terlipressin (15 mcg/kg); LR group was given LR and the sham group was not given anything. Mean arterial pressure (MAP), serum lactate level, plasma cytokine levels, lung injury and mortality are investigated for these different treatment groups. Results Compared with LR group, vasopressin and terlipressin-treated groups were associated with higher MAP, lowered mortality rates, less lung injury, lowered serum lactate level, less proinflammatory and more anti-inflammatory cytokine production at certain time points. Comparing between vasopressin and terlipressin treated groups, there is no statistical difference in mortality rates, lung injury, serum lactate level and cytokine level. However, there is a difference in the length of time in maintaining a restored level of MAP (80 to 110 mmHg). The terlipressin treated rats can maintain this restored level of MAP for 45 minutes, but the vasopressin treated rats can only maintain this restored level of MAP for 5 minutes before decreasing gradually to the MAP observed in LR group (40 mmHg). Conclusion Early optimization of hemodynamics with terlipressin or vasopressin in an animal model of UHS was associated with improved hemodynamics and inflammatory cytokine profile than the LR control. Compared with vasopressin, terlipressin has the advantage of ease of use and sustained effects. PMID:24759799

Transplacental passage of 26Al from pregnant rats to fetuses and 26Al transfer through maternal milk to suckling rats

NASA Astrophysics Data System (ADS)

Yumoto, S.; Nagai, H.; Matsuzaki, H.; Kobayashi, T.; Tada, W.; Ohki, Y.; Kakimi, S.; Kobayashi, K.

2000-10-01

Aluminium (Al) is toxic to the growth of fetuses and sucklings. However, the incorporation of Al into fetuses and sucklings in the periods of gestation and lactation has not been well clarified because Al lacks a suitable isotope for a tracer experiment. In this study, we used 26Al (a radioisotope of Al with half-life of 716,000 yr) as a tracer, and measured 26Al incorporation into fetuses and sucklings by accelerator mass spectrometry (AMS). To investigate Al incorporation into fetuses through transplacental passage, 26Al ( 26AlCl 3) was subcutaneously injected into pregnant rats on day 15 of gestation. 26Al was also subcutaneoulsy injected into lactating rats from day 1 to day 20 postpartum. By day 20 of gestation, 0.2% of the 26Al injected into a pregnant rat had been transferred to the fetuses, and 26Al was detected in the brain and liver of the fetuses. On day 9 postpartum, high levels of 26Al were demonstrated in the brain, liver, kidneys and blood of suckling rats. It is concluded that 26Al subcutaneously injected into pregnant rats and/or lactating rats is incorporated into their offspring through transplacental passage and/or maternal milk.

Effects of Hypergravity Exposure on Plasma Oxytocin (OT) Concentrations in Pregnant and Lactating Rat Dams

NASA Technical Reports Server (NTRS)

Baer, Lisa A.; Wade, Charles E.; Plaut, Karen; Ronca, April E.; Dalton, Bonnie (Technical Monitor)

2002-01-01

From pregnancy to weaning there is a progressive elevation of plasma oxytocin (OT) levels associated with nursing activity, irrespective of litter size. In the present study, we analyzed the effects of continuous 1.5G, 1.75G and 2.0G hypergravity exposure on OT plasma concentration in prepartum (Gestation Day 20) (G20) and lactating (Postnatal day) (P10) rat dams. For this study, litter size was controlled with a yoking procedure established in our lab where individual control litters were yoked-matched to individual hypergravity litters. We reviewed all data at hypergravity irrespective of gravitational level and compared the values with the controls in both G20 (HG, n=15;SC, n=9) and P10 (HG, n=21;SC, n=16). Results showed that over time, we did observe the expected OT increase in both groups. In G20 dams, measurement of OT concentrations showed no significance. However, at P10, measurements of OT concentrations suggest a reduction of about 20% compared to established controls in our laboratory, 0.9+/-0.09 ng/ml for the controls and 0.7+/-0.06 ng/ml for centrifuged animals (p<0.02). These data suggest that exposure to centrifugation may reduce OT levels during lactation. When these plasma samples were obtained, the dams were removed from the litters, and values were not adjusted for the size of the litters. The reduction in OT with centrifugation may reflect a decrease in nursing activity or a decreased responsiveness of the mammary hypothalamic axis. In addition, we have analyzed data on plasma prolactin concentrations and mammary gland development, which may give additional insight to the results of our OT measurements.

Evidence for the absence of the terminal adenine nucleotide at the amino acid-acceptor end of transfer ribonucleic acid in non-lactating bovine mammary gland and its inhibitory effect on the aminoacylation of rat liver transfer ribonucleic acid

PubMed Central

Herrington, M. D.; Hawtrey, A. O.

1970-01-01

1. tRNA isolated from non-lactating bovine mammary gland competitively inhibits the formation of aminoacyl-tRNA in the rat liver system. 2. Non-lactating bovine mammary gland tRNA and twice-pyrophosphorolysed rat liver tRNA are unable to accept amino acids in a reaction catalysed by aminoacyl-tRNA synthetases from either rat liver or bovine mammary gland. Deacylated rat liver tRNA can however be aminoacylated in the presence of either enzyme. 3. Bovine mammary gland tRNA lacks the terminal adenine nucleotide at the 3′-terminus amino acid acceptor end, which can be replaced by incubation in the presence of rat liver nucleotide-incorporating enzyme, ATP and CTP. 4. The enzymically modified bovine tRNA (tRNApCpCpA) can bind labelled amino acids to form aminoacyl-tRNA, which can then transfer its labelled amino acids to growing polypeptide chains on ribosomes. 5. Molecules of rat liver tRNA or bovine mammary gland tRNA that lack the terminal adenine nucleotide or the terminal cytosine and adenine nucleotides inhibit the aminoacylation of normal rat liver tRNA to varying degrees. tRNA molecules lacking the terminal −pCpCpA nucleotide sequence exhibit the major inhibitory effect. 6. The enzyme fraction from bovine mammary gland corresponding to that containing the nucleotide-incorporating enzyme in rat liver is unable to catalyse the incorporation of cytosine and adenine nucleotides in pyrophosphorolysed rat liver tRNA and deacylated bovine tRNA. This fraction also markedly inhibits the action of the rat liver nucleotide-incorporating enzyme. PMID:5435687

Hindbrain lactate regulates preoptic gonadotropin-releasing hormone (GnRH) neuron GnRH-I protein but not AMPK responses to hypoglycemia in the steroid-primed ovariectomized female rat.

PubMed

Shrestha, P K; Briski, K P

2015-07-09

Steroid positive-feedback activation of the gonadotropin-releasing hormone (GnRH)-pituitary luteinizing hormone (LH) neuroendocrine axis propagates the pre ovulatory LH surge, a crucial component of female reproduction. Our work shows that this key event is restrained by inhibitory metabolic input from hindbrain A2 noradrenergic neurons. GnRH neurons express the ultra-sensitive energy sensor adenosine 5'-monophosphate-activated protein kinase (AMPK); here, we investigated the hypothesis that GnRH nerve cell AMPK and peptide neurotransmitter responses to insulin-induced hypoglycemia are controlled by hindbrain lack of the oxidizable glycolytic end-product L-lactate. Data show that hypoglycemic inhibition of LH release in steroid-primed ovariectomized female rats was reversed by coincident caudal hindbrain lactate infusion. Western blot analyses of laser-microdissected A2 neurons demonstrate hypoglycemic augmentation [Fos, estrogen receptor-beta (ER-β), phosphoAMPK (pAMPK)] and inhibition (dopamine-beta-hydroxylase, GLUT3, MCT2) of protein expression in these cells, responses that were normalized by insulin plus lactate treatment. Hypoglycemia diminished rostral preoptic GnRH nerve cell GnRH-I protein and pAMPK content; the former, but not the latter response was reversed by lactate. Results implicate caudal hindbrain lactoprivic signaling in hypoglycemia-induced suppression of the LH surge, demonstrating that lactate repletion of that site reverses decrements in A2 catecholamine biosynthetic enzyme and GnRH neuropeptide precursor protein expression. Lack of effect of lactate on hypoglycemic patterns of GnRH AMPK activity suggests that this sensor is uninvolved in metabolic-inhibition of positive-feedback-stimulated hypophysiotropic signaling to pituitary gonadotropes. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Plasma first resuscitation reduces lactate acidosis, enhances redox homeostasis, amino acid and purine catabolism in a rat model of profound hemorrhagic shock

PubMed Central

D’Alessandro, Angelo; Moore, Hunter B; Moore, Ernest E; Wither, Matthew J.; Nemkov, Travis; Morton, Alexander P; Gonzalez, Eduardo; Chapman, Michael P; Fragoso, Miguel; Slaughter, Anne; Sauaia, Angela; Silliman, Christopher C; Hansen, Kirk C; Banerjee, Anirban

2016-01-01

The use of aggressive crystalloid resuscitation to treat hypoxemia, hypovolemia and nutrient deprivation promoted by massive blood loss may lead to the development of the blood vicious cycle of acidosis, hypothermia, and coagulopathy and, utterly, death. Metabolic acidosis is one of the many metabolic derangements triggered by severe trauma/hemorrhagic shock, also including enhanced proteolysis, lipid mobilization, as well as traumatic diabetes. Appreciation of the metabolic benefit of plasma first resuscitation is an important concept. Plasma resuscitation has been shown to correct hyperfibrinolysis secondary to severe hemorrhage better than normal saline. Here we hypothesize that plasma first resuscitation corrects metabolic derangements promoted by severe hemorrhage better than resuscitation with normal saline. Ultra-high-performance liquid chromatography-mass spectrometry-based metabolomics analyses were performed to screen plasma metabolic profiles upon shock and resuscitation with either platelet-free plasma or normal saline in a rat model of severe hemorrhage. Of the 251 metabolites that were monitored, 101 were significantly different in plasma vs normal saline resuscitated rats. Plasma resuscitation corrected lactate acidosis by promoting glutamine/amino acid catabolism and purine salvage reactions. Plasma first resuscitation may benefit critically injured trauma patients by relieving the lactate burden and promoting other non-clinically measured metabolic changes. In the light of our results, we propose that plasma resuscitation may promote fueling of mitochondrial metabolism, through the enhancement of glutaminolysis/amino acid catabolism and purine salvage reactions. The treatment of trauma patients in hemorrhagic shock with plasma first resuscitation is likely not only to improve coagulation, but also to promote substrate-specific metabolic corrections. PMID:26863033

Single oral dose toxicity test of polycalcium, a mixed composition of polycan and calcium lactate-gluconate 1:9 (G/G) in SD rat.

PubMed

Kim, Joo-Wan; Choi, Jae-Suk; Ha, Yu-Mi; Choi, In Soon; Kim, Ki-Young; Cho, Hyung-rae; Rha, Chae-hun; Ku, Sae-Kwang

2013-11-01

The object of this study was to obtain acute oral toxicity information of Polycalcium, a mixed composition of Polycan and Calcium lactate-gluconate 1:9 (g/g), in Sprague-Dawely (SD) rats. In order to investigate the toxicity and identify target organs, Polycalcium were once orally administered to female and male SD rats at dose levels of 2000, 1000, 500 and 0 (control) mg/kg body weights. The mortality, changes on body weight and clinical signs were monitored during 14 days after treatment with gross observation, changes on the organ weights and histopathology of principle organs and treatment sites based on the recommendation of KFDA Guidelines [2009-116, 2009]. As the results of single oral treatment of Polycalcium, no treatment related mortalities were observed within 14 days after end of treatment up to 2000 mg/kg, the limited dosage of rodents in the both genders. In addition, no Polycalcium treatment related changes on the body and organ weights, clinical signs, necropsy and histopathological findings were detected. The results obtained in this study suggest that the Polycalcium is non-toxic in rats. The LD50 and approximate LD in rats after single oral dose of Polycalcium were considered over 2000 mg/kg in both female and male, respectively.

Short- and long-term effects of maternal nicotine exposure during lactation on body adiposity, lipid profile, and thyroid function of rat offspring.

PubMed

Oliveira, E; Moura, E G; Santos-Silva, A P; Fagundes, A T S; Rios, A S; Abreu-Villaça, Y; Nogueira Neto, J F; Passos, M C F; Lisboa, P C

2009-09-01

Epidemiological studies show a higher prevalence of obesity in children from smoking mothers and smoking may affect human thyroid function. To evaluate the mechanism of smoking as an imprinting factor for these dysfunctions, we evaluated the programming effects of maternal nicotine (NIC) exposure during lactation. Two days after birth, osmotic minipumps were implanted in lactating rats, divided into: NIC (6 mg/kg per day s.c.) for 14 days; Control - saline. All the significant data were P<0.05 or less. Body weight was increased from 165 days old onwards in NIC offspring. Both during exposure (at 15 days old) and in adulthood (180 days old), NIC group showed higher total fat (27 and 33%). In addition, NIC offspring presented increased visceral fat and total body protein. Lipid profile was not changed in adulthood. Leptinemia was higher at 15 and 180 days old (36 and 113%), with no changes in food intake. Concerning the thyroid status, the 15-days-old NIC offspring showed lower serum-free tri-iodothyronine (FT(3)) and thyroxine (FT(4)) with higher TSH. The 180-days-old NIC offspring exhibited lower TSH, FT(3), and FT(4)). In both periods, liver type 1 deiodinase was lower (26 and 55%). We evidenced that NIC imprints a neonatal thyroid dysfunction and programs for a higher adiposity, hyperleptinemia, and secondary hypothyroidism in adulthood. Our study identifies lactation as a critical period to NIC programming for obesity, with hypothyroidism being a possible contributing factor.

Post-natal growth in the rat pineal gland: a stereological study.

PubMed

Erbagci, H; Kizilkan, N; Ozbag, D; Erkilic, S; Kervancioglu, P; Canan, S; Gumusburun, E

2012-10-01

The purpose was to observe the changes in a rat pineal gland using stereological techniques during lactation and post-weaning periods. Thirty Wistar albino rats were studied during different post-natal periods using light microscopy. Pineal gland volume was estimated using the Cavalieri Method. Additionally, the total number of pinealocytes was estimated using the optical fractionator technique. Pineal gland volume displayed statistically significant changes between lactation and after weaning periods. A significant increase in pineal gland volume was observed from post-natal day 10 to post-natal day 90. The numerical density of pinealocytes became stabilized during lactation and decreased rapidly after weaning. However, the total number of pinealocytes continuously increased during post-natal life of all rats in the study. However, this increment was not statistically significant when comparing the lactation and after weaning periods. The increase in post-natal pineal gland volume may depend on increment of immunoreactive fibres, capsule thickness or new synaptic bodies. © 2012 Blackwell Verlag GmbH.

Exogenous lactate supply affects lactate kinetics of rainbow trout, not swimming performance

PubMed Central

Omlin, Teye; Langevin, Karolanne

2014-01-01

Intense swimming causes circulatory lactate accumulation in rainbow trout because lactate disposal (Rd) is not stimulated as strongly as lactate appearance (Ra). This mismatch suggests that maximal Rd is limited by tissue capacity to metabolize lactate. This study uses exogenous lactate to investigate what constrains maximal Rd and minimal Ra. Our goals were to determine how exogenous lactate affects: 1) Ra and Rd of lactate under baseline conditions or during graded swimming, and 2) exercise performance (critical swimming speed, Ucrit) and energetics (cost of transport, COT). Results show that exogenous lactate allows swimming trout to boost maximal Rd lactate by 40% and reach impressive rates of 56 μmol·kg−1·min−1. This shows that the metabolic capacity of tissues for lactate disposal is not responsible for setting the highest Rd normally observed after intense swimming. Baseline endogenous Ra (resting in normoxic water) is not significantly reduced by exogenous lactate supply. Therefore, trout have an obligatory need to produce lactate, either as a fuel for oxidative tissues and/or from organs relying on glycolysis. Exogenous lactate does not affect Ucrit or COT, probably because it acts as a substitute for glucose and lipids rather than extra fuel. We conclude that the observed 40% increase in Rd lactate is made possible by accelerating lactate entry into oxidative tissues via monocarboxylate transporters (MCTs). This observation together with the weak expression of MCTs and the phenomenon of white muscle lactate retention show that lactate metabolism of rainbow trout is significantly constrained by transmembrane transport. PMID:25121611

Lactation and reproduction*

PubMed Central

Thomson, A. M.; Hytten, F. E.; Black, A. E.

1975-01-01

The authors review the literature on the effect of lactation on fertility in the absence of contraception and on the effects of contraceptive measures on lactation. They examine data from several countries on the intervals between births and on the return of menstruation and ovulation after childbirth, comparing lactating with nonlactating women. They conclude that lactation is an inefficient contraceptive for the individual, but that in populations sustained lactation is associated with reduced fertility. Possible physiological mechanisms causing lactation amenorrhoea are discussed. Though much of the literature on the effect of contraceptives on lactation is inadequate, there is general agreement that the estrogen component of hormonal preparations has an adverse effect on lactation, but that progestins alone do not. Many questions remain. Is this effect seen in established lactation, or only in the puerperal period? Is it a direct pharmacological effect, or are pill-users the mothers least motivated to maintain breast-feeding? Does a close relationship exist between hormones given and lactation performance? The authors comment on some of the technical deficiencies of previous studies in this field and discuss practical possibilities of, and limitations to, obtaining adequate scientific information in the future. PMID:1084804

Lactate shuttles in nature.

PubMed

Brooks, G A

2002-04-01

Once thought to be the consequence of oxygen lack in contracting skeletal muscle, the glycolytic product lactate is formed and utilized continuously under fully aerobic conditions. "Cell-cell" and "intracellular lactate shuttle" concepts describe the roles of lactate in the delivery of oxidative and gluconeogenic substrates, as well as in cell signalling. Examples of cell-cell shuttles include lactate exchanges between white-glycolytic and red-oxidative fibres within a working muscle bed, between working skeletal muscle and heart, and between tissues of net lactate release and gluconeogenesis. Lactate exchange between astrocytes and neurons that is linked to glutamatergic signalling in the brain is an example of a lactate shuttle supporting cell-cell signalling. Lactate uptake by mitochondria and pyruvate-lactate exchange in peroxisomes are examples of intracellular lactate shuttles. Lactate exchange between sites of production and removal is facilitated by monocarboxylate transport proteins, of which there are several isoforms, and, probably, also by scaffolding proteins. The mitochondrial lactate-pyruvate transporter appears to work in conjunction with mitochondrial lactate dehydrogenase, which permits lactate to be oxidized within actively respiring cells. Hence mitochondria function to establish the concentration and proton gradients necessary for cells with high mitochondrial densities (e.g. cardiocytes) to take up and oxidize lactate. Arteriovenous difference measurements on working cardiac and skeletal muscle beds as well as NMR spectral analyses of these tissues show that lactate is formed and oxidized within the cells of formation in vivo. Glycolysis and lactate oxidation within cells permits high flux rates and the maintenance of redox balance in the cytosol and mitochondria. Other examples of intracellular lactate shuttles include lactate uptake and oxidation in sperm mitochondria and the facilitation of beta-oxidation in peroxisomes by pyruvate-lactate

Group II metabotropic glutamate receptor type 2 allosteric potentiators prevent sodium lactate-induced panic-like response in panic-vulnerable rats

PubMed Central

Johnson, Philip L; Fitz, Stephanie D; Engleman, Eric A; Svensson, Kjell A; Schkeryantz, Jeffrey M; Shekhar, Anantha

2015-01-01

Rats with chronic inhibition of GABA synthesis by infusion of l-allyglycine, a glutamic acid decarboxylase inhibitor, into their dorsomedial/perifornical hypothalamus are anxious and exhibit panic-like cardio-respiratory responses to treatment with intravenous (i.v.) sodium lactate (NaLac) infusions, in a manner similar to what occurs in patients with panic disorder. We previously showed that either NMDA receptor antagonists or metabotropic glutamate receptor type 2/3 receptor agonists can block such a NaLac response, suggesting that a glutamate mechanism is contributing to this panic-like state. Using this animal model of panic, we tested the efficacy of CBiPES and THIIC, which are selective group II metabotropic glutamate type 2 receptor allosteric potentiators (at 10–30mg/kg i.p.), in preventing NaLac-induced panic-like behavioral and cardiovascular responses. The positive control was alprazolam (3mg/kg i.p.), a clinically effective anti-panic benzodiazepine. As predicted, panic-prone rats given a NaLac challenge displayed NaLac-induced panic-like cardiovascular (i.e. tachycardia and hypertensive) responses and “anxiety” (i.e. decreased social interaction time) and “flight” (i.e. increased locomotion) -associated behaviors; however, systemic injection of the panic-prone rats with CBiPES, THIIC or alprazolam prior to the NaLac dose blocked all NaLac-induced panic-like behaviors and cardiovascular responses. These data suggested that in a rat animal model, selective group II metabotropic glutamate type 2 receptor allosteric potentiators show an anti-panic efficacy similar to alprazolam. PMID:22914798

Prognostic significance of blood lactate and lactate clearance in trauma patients.

PubMed

Régnier, Marie-Alix; Raux, Mathieu; Le Manach, Yannick; Asencio, Yves; Gaillard, Johann; Devilliers, Catherine; Langeron, Olivier; Riou, Bruno

2012-12-01

Lactate has been shown to be a prognostic biomarker in trauma. Although lactate clearance has already been proposed as an intermediate endpoint in randomized trials, its precise role in trauma patients remains to be determined. Blood lactate levels and lactate clearance (LC) were calculated at admission and 2 and 4 h later in trauma patients. The association of initial blood lactate level and lactate clearance with mortality was tested using receiver-operating characteristics curve, logistic regression using triage scores, Trauma Related Injury Severity Score as a reference standard, and reclassification method. The authors evaluated 586 trauma patients (mean age 38±16 yr, 84% blunt and 16% penetrating, mortality 13%). Blood lactate levels at admission were elevated in 327 (56%) patients. The lactate clearance should be calculated within the first 2 h after admission as LC0-2 h was correlated with LC0-4 h (R=0.55, P<0.001) but not with LC2-4 h (R=0.04, not significant). The lactate clearance provides additional predictive information to initial blood lactate levels and triage scores and the reference score. This additional information may be summarized using a categorical approach (i.e., less than or equal to -20 %/h) in contrast to initial blood lactate. The results were comparable in patients with high (5 mM/l or more) initial blood lactate. Early (0-2 h) lactate clearance is an important and independent prognostic variable that should probably be incorporated in future decision schemes for the resuscitation of trauma patients.

Maternal diet during gestation and lactation modifies the severity of salt-induced hypertension and renal injury in Dahl salt-sensitive rats.

PubMed

Geurts, Aron M; Mattson, David L; Liu, Pengyuan; Cabacungan, Erwin; Skelton, Meredith M; Kurth, Theresa M; Yang, Chun; Endres, Bradley T; Klotz, Jason; Liang, Mingyu; Cowley, Allen W

2015-02-01

Environmental exposure of parents or early in life may affect disease development in adults. We found that hypertension and renal injury induced by a high-salt diet were substantially attenuated in Dahl SS/JrHsdMcwiCrl (SS/Crl) rats that had been maintained for many generations on the grain-based 5L2F diet compared with SS/JrHsdMcwi rats (SS/Mcw) maintained on the casein-based AIN-76A diet (mean arterial pressure, 116±9 versus 154±25 mm Hg; urinary albumin excretion, 23±12 versus 170±80 mg/d). RNAseq analysis of the renal outer medulla identified 129 and 82 genes responding to a high-salt diet uniquely in SS/Mcw and SS/Crl rats, respectively, along with minor genetic differences between the SS substrains. The 129 genes responding to salt in the SS/Mcw strain included numerous genes with homologs associated with hypertension, cardiovascular disease, or renal disease in human. To narrow the critical window of exposure, we performed embryo-transfer experiments in which single-cell embryos from 1 colony (SS/Mcw or SS/Crl) were transferred to surrogate mothers from the other colony, with parents and surrogate mothers maintained on their respective original diet. All offspring were fed the AIN-76A diet after weaning. Salt-induced hypertension and renal injury were substantially exacerbated in rats developed from SS/Crl embryos transferred to SS/Mcw surrogate mothers. Conversely, salt-induced hypertension and renal injury were significantly attenuated in rats developed from SS/Mcw embryos transferred to SS/Crl surrogate mothers. Together, the data suggest that maternal diet during the gestational-lactational period has substantial effects on the development of salt-induced hypertension and renal injury in adult SS rats. © 2014 American Heart Association, Inc.

Inhibition of lactation.

PubMed

Llewellyn-Jones, D

1975-01-01

The mechanism and hormonal regulation of lactation is explained and illustrated with a schematic representation. Circulating estrogen above a critical amount seems to be the inhibitory factor controlling lactation during pregnancy. Once delivery occurs, the level of estrogen falls, that of prolactin rises, and lactation begins. Nonsuckling can be used to inhibit lactation. Estrogens can also be used to inhibit lactation more quickly and with less pain. The reported association between estrogens and puerperal thromboembolism cannot be considered conclusive due to defects in the reporting studies. There is no reason not to use estrogens in lactation inhibition except for women over 35 who experienced a surgical delivery. Alternative therapy is available for these women. The recently-developed drug, brom-ergocryptine, may replace other methods of lactation inhibition.

Tandospirone, a 5-HT1A partial agonist, ameliorates aberrant lactate production in the prefrontal cortex of rats exposed to blockade of N-methy-D-aspartate receptors; Toward the therapeutics of cognitive impairment of schizophrenia.

PubMed

Uehara, Takashi; Matsuoka, Tadasu; Sumiyoshi, Tomiki

2014-01-01

Augmentation therapy with serotonin-1A (5-HT1A) receptor partial agonists has been suggested to improve cognitive impairment in patients with schizophrenia. Decreased activity of prefrontal cortex may provide a basis for cognitive deficits of the disease. Lactate plays a significant role in the supply of energy to the brain, and glutamatergic neurotransmission contributes to lactate production. The purposes of this study were to examine the effect of repeated administration (once a daily for 4 days) of tandospirone (0.05 or 5 mg/kg) on brain energy metabolism, as represented by extracellular lactate concentration (eLAC) in the medial prefrontal cortex (mPFC) of a rat model of schizophrenia. Four-day treatment with MK-801, an NMDA-R antagonist, prolonged eLAC elevation induced by foot-shock stress (FS). Co-administration with the high-dose tandospirone suppressed prolonged FS-induced eLAC elevation in rats receiving MK-801, whereas tandospirone by itself did not affected eLAC increment. These results suggest that stimulation of 5-HT1A receptors ameliorates abnormalities of energy metabolism in the mPFC due to blockade of NMDA receptors. These findings provide a possible mechanism, based on brain energy metabolism, by which 5-HT1A agonism improve cognitive impairment of schizophrenia and related disorders.

A maternal "junk food" diet in pregnancy and lactation promotes nonalcoholic Fatty liver disease in rat offspring.

PubMed

Bayol, Stéphanie A; Simbi, Bigboy H; Fowkes, Robert C; Stickland, Neil C

2010-04-01

With rising obesity rates, nonalcoholic fatty liver disease is predicted to become the main cause of chronic liver disease in the next decades. Rising obesity prevalence is attributed to changes in dietary habits with increased consumption of palatable junk foods, but maternal malnutrition also contributes to obesity in progeny. This study examines whether a maternal junk food diet predisposes offspring to nonalcoholic fatty liver disease. The 144 rat offspring were fed either a balanced chow diet alone or with palatable junk foods rich in energy, fat, sugar, and/or salt during gestation, lactation, and/or after weaning up to the end of adolescence. Offspring fed junk food throughout the study exhibited exacerbated hepatic steatosis, hepatocyte ballooning, and oxidative stress response compared with offspring given free access to junk food after weaning only. These offspring also displayed sex differences in their hepatic molecular metabolic adaptation to diet-induced obesity with increased expression of genes associated with insulin sensitivity, de novo lipogenesis, lipid oxidation, and antiinflammatory properties in males, whereas the gene expression profile in females was indicative of hepatic insulin resistance. Hepatic inflammation and fibrosis were not detected indicating that offspring had not developed severe steatohepatitis by the end of adolescence. Hepatic steatosis and increased oxidative stress response also occurred in offspring born to junk food-fed mothers switched to a balanced chow diet from weaning, highlighting a degree of irreversibility. This study shows that a maternal junk food diet in pregnancy and lactation contributes to the development of nonalcoholic fatty liver disease in offspring.

Brain lactate kinetics: Modeling evidence for neuronal lactate uptake upon activation.

PubMed

Aubert, Agnès; Costalat, Robert; Magistretti, Pierre J; Pellerin, Luc

2005-11-08

A critical issue in brain energy metabolism is whether lactate produced within the brain by astrocytes is taken up and metabolized by neurons upon activation. Although there is ample evidence that neurons can efficiently use lactate as an energy substrate, at least in vitro, few experimental data exist to indicate that it is indeed the case in vivo. To address this question, we used a modeling approach to determine which mechanisms are necessary to explain typical brain lactate kinetics observed upon activation. On the basis of a previously validated model that takes into account the compartmentalization of energy metabolism, we developed a mathematical model of brain lactate kinetics, which was applied to published data describing the changes in extracellular lactate levels upon activation. Results show that the initial dip in the extracellular lactate concentration observed at the onset of stimulation can only be satisfactorily explained by a rapid uptake within an intraparenchymal cellular compartment. In contrast, neither blood flow increase, nor extracellular pH variation can be major causes of the lactate initial dip, whereas tissue lactate diffusion only tends to reduce its amplitude. The kinetic properties of monocarboxylate transporter isoforms strongly suggest that neurons represent the most likely compartment for activation-induced lactate uptake and that neuronal lactate utilization occurring early after activation onset is responsible for the initial dip in brain lactate levels observed in both animals and humans.

Brain lactate kinetics: Modeling evidence for neuronal lactate uptake upon activation

PubMed Central

Aubert, Agnès; Costalat, Robert; Magistretti, Pierre J.; Pellerin, Luc

2005-01-01

A critical issue in brain energy metabolism is whether lactate produced within the brain by astrocytes is taken up and metabolized by neurons upon activation. Although there is ample evidence that neurons can efficiently use lactate as an energy substrate, at least in vitro, few experimental data exist to indicate that it is indeed the case in vivo. To address this question, we used a modeling approach to determine which mechanisms are necessary to explain typical brain lactate kinetics observed upon activation. On the basis of a previously validated model that takes into account the compartmentalization of energy metabolism, we developed a mathematical model of brain lactate kinetics, which was applied to published data describing the changes in extracellular lactate levels upon activation. Results show that the initial dip in the extracellular lactate concentration observed at the onset of stimulation can only be satisfactorily explained by a rapid uptake within an intraparenchymal cellular compartment. In contrast, neither blood flow increase, nor extracellular pH variation can be major causes of the lactate initial dip, whereas tissue lactate diffusion only tends to reduce its amplitude. The kinetic properties of monocarboxylate transporter isoforms strongly suggest that neurons represent the most likely compartment for activation-induced lactate uptake and that neuronal lactate utilization occurring early after activation onset is responsible for the initial dip in brain lactate levels observed in both animals and humans. PMID:16260743

Calcium deprivation increases the palatability of calcium solutions in rats.

PubMed

McCaughey, Stuart A; Forestell, Catherine A; Tordoff, Michael G

2005-02-15

Calcium-deprived rats have elevated intakes of CaCl2, other calcium salts, and some non-calcium compounds. We used taste reactivity to examine the effects of calcium deprivation on the palatability of CaCl2 and other solutions. Nine male Sprague-Dawley rats were calcium-deprived by maintenance on a low-calcium diet, and eight replete rats were used as controls. All rats were videotaped during intraoral infusion of the following solutions: 30 and 300 mM CaCl2, 30 mM calcium lactate, 100 and 600 mM NaCl, 30 mM MgCl2, 1 mM quinine.HCl, 2.5 mM sodium saccharin, and deionized water. We counted individual orofacial and somatic movements elicited by the infusions and used them to calculate total ingestive and aversive scores. Relative to controls, calcium-deprived rats gave a significantly larger number of tongue protrusions and had higher total ingestive scores for CaCl2, calcium lactate, NaCl, and MgCl2. Our results suggest that CaCl2, calcium lactate, NaCl, and MgCl2 taste more palatable to rats when they are calcium-deprived than replete, and this may be responsible for the increased intake of these solutions following calcium deprivation.

Influence of acute and chronic treadmill exercise on rat plasma lactate and brain NPY, L-ENK, DYN A1-13.

PubMed

Chen, Jia-Xu; Zhao, Xin; Yue, Guang-Xin; Wang, Zhu-Feng

2007-02-01

This study was designed to investigate the effect of acute and chronic high-intensity treadmill exercise on changes in plasma lactate and brain neuropeptide (NPY), leucine-enkephalin (L-ENK), and dynorphin A(1-13) (DYN A(1-13)). Avidin-biotin complex (ABC) immunohistochemistry and image pattern analysis were used to observe the effect of chronic (total 7 weeks) and acute treadmill exercise (an initial speed of 15 m min(-1) gradually increased to 35 m min(-1) with 0 degrees, 20-25 min per day duration) on the changes of NPY, L-ENK, and DYN A(1-13) in different areas of rat brain. Plasma lactate was also measured in response to such exercise. Compared with preexercise control (P < 0.01), plasma lactate concentration significantly increased in the immediate postexercise; but it returned to the normal level soon after the 30 min postexercise. The content of NPY in paraventricular (PVN), dorsomedial (DMN), and ventromedial (VMN) hypothalamic nuclei continued to increase in 0, 30, and 180 min postexercise compared with preexercise control (P < 0.01). The content of L-ENK in caudate-putamen (CPu) significantly increased in the immediate postexercise compared with preexercise control (P < 0.01), but it gradually returned to the normal level after the 180 min postexercise. However, the content of DYN A(1-13) in PVN rose substantially only in 30 min postexercise in comparison with the preexercise control (P < 0.01). Thus, different changes of NPY, L-ENK, and DYN A(1-13) in response to such high-intensity exercise depend on the brain region and the time examined, especially, the contents of NPY in different brain regions continuously remain at a high level after such high-intensity exercise. And this high level might reduce energy expenditure and thus contribute to the stimulation of brain NPY neurons.

Ambient but not local lactate underlies neuronal tolerance to prolonged glucose deprivation

PubMed Central

Sobieski, Courtney; Shu, Hong-Jin

2018-01-01

Neurons require a nearly constant supply of ATP. Glucose is the predominant source of brain ATP, but the direct effects of prolonged glucose deprivation on neuronal viability and function remain unclear. In sparse rat hippocampal microcultures, neurons were surprisingly resilient to 16 h glucose removal in the absence of secondary excitotoxicity. Neuronal survival and synaptic transmission were unaffected by prolonged removal of exogenous glucose. Inhibition of lactate transport decreased microculture neuronal survival during concurrent glucose deprivation, suggesting that endogenously released lactate is important for tolerance to glucose deprivation. Tandem depolarization and glucose deprivation also reduced neuronal survival, and trace glucose concentrations afforded neuroprotection. Mass cultures, in contrast to microcultures, were insensitive to depolarizing glucose deprivation, a difference attributable to increased extracellular lactate levels. Removal of local astrocyte support did not reduce survival in response to glucose deprivation or alter evoked excitatory transmission, suggesting that on-demand, local lactate shuttling is not necessary for neuronal tolerance to prolonged glucose removal. Taken together, these data suggest that endogenously produced lactate available globally in the extracellular milieu sustains neurons in the absence of glucose. A better understanding of resilience mechanisms in reduced preparations could lead to therapeutic strategies aimed to bolster these mechanisms in vulnerable neuronal populations. PMID:29617444

Electro-acupuncture up-regulates astrocytic MCT1 expression to improve neurological deficit in middle cerebral artery occlusion rats.

PubMed

Lu, Yan; Zhao, Haijun; Wang, Yuan; Han, Bingbing; Wang, Tong; Zhao, Hong; Cui, Kemi; Wang, Shijun

2015-08-01

Cerebral ischemia is one of the common diseases treated by electro-acupuncture (EA). Although the clinical efficacy has been widely affirmed, the mechanisms of action leading to the health benefits are not understood. In this study, the role of EA in modulating the lactate energy metabolism and lactate transportation was explored on the middle cerebral artery occlusion (MCAO) ischemic rat model. Repeated EA treatments once daily for 7 days were applied to the MCAO rats and neurological function evaluation was performed. Brain tissues were harvested for lactate concentration examination, immunohistochemical staining, Western blot and qRT-PCR analyses for the expressions of lactate transporter (monocarboxylate transporter 1, MCT1) and glial fibrillary acidic protein (GFAP). The animal behavioral tests showed that the 7-day EA treatments significantly promoted the recovery of neurological deficits in the MCAO rats, which correlated with the enhanced lactate energy metabolism in the ischemic brain. In the cortical ischemic area of the MCAO rats, EA treatments led to the activation of astrocytes, and induced a further increase of lactate transporter (monocarboxylate transporter 1, MCT1) expression in astrocytes at both protein and mRNA levels. Our results suggest that the EA treatments activated lactate metabolism in the resident astrocytes around the ischemic area and up-regulated the expression of MCT1 in these astrocytes which facilitated the transfer of intracellular lactate to extracellular domain to be utilized by injured neurons to improve the neurological deficit. Copyright © 2015 Elsevier Inc. All rights reserved.

Histological study on hippocampus, amygdala and cerebellum following low lead exposure during prenatal and postnatal brain development in rats.

PubMed

Barkur, Rajashekar Rao; Bairy, Laxminarayana K

2016-06-01

Neuropsychological studies in children who are exposed to lead during their early brain development have shown to develop behavioural and cognitive deficit. The aim of the present study was to assess the cellular damage in hippocampus, amygdala and cerebellum of rat pups exposed to lead during different periods of early brain development. Five groups of rat pups were investigated. (a) Control group (n = 8) (mothers of these rats were given normal drinking water throughout gestation and lactation), (b) pregestation lead-exposed group (n = 8) (mothers of these rats were exposed to 0.2% lead acetate in the drinking water for one month before conception), (c) gestation lead-exposed group (n = 8) (exposed to 0.2% lead acetate in the drinking water through the mother throughout gestation [gestation day 01 to day 21]), (d) lactation lead-exposed group (n = 8) (exposed to 0.2% lead acetate in the drinking water through the mother throughout lactation [postnatal day 01 to day 21]) and (e) gestation and lactation lead-exposed group (n = 8) (exposed to 0.2% lead acetate throughout gestation and lactation). On postnatal day 30, rat pups of all the groups were killed. Numbers of surviving neurons in the hippocampus, amygdala and cerebellum regions were counted using cresyl violet staining technique. Histological data indicate that lead exposure caused significant damage to neurons of hippocampus, amygdala and cerebellum regions in all lead-exposed groups except lactation lead-exposed group. The extent of damage to neurons of hippocampus, amygdala and cerebellum regions in lactation lead-exposed group was comparable to gestation and lactation groups even though the duration of lead exposure was much less in lactation lead-exposed group. To conclude, the postnatal period of brain development seems to be more vulnerable to lead neurotoxicity compared to prenatal period of brain development. © The Author(s) 2014.

Effects of high and low blood lactate concentrations on sweat lactate response.

PubMed

Green, J M; Bishop, P A; Muir, I H; McLester, J R; Heath, H E

2000-11-01

Sweat lactate results from eccrine gland metabolism, however, the possible clearance of blood lactate through sweat has not been resolved. On separate days in an environmental chamber (32 +/- 1 C) 12 subjects completed a constant load (CON) (30 min at 40% VO2 max) and an interval cycling trial (INT) (15 one-min intervals at 80% VO2 max, each separated by one min rest) each designed to elicit different blood lactate responses. Each 30 min cycling trial was preceded by 15 min warm-up (30 watts) and followed by 15 min passive rest. Sweat and blood were analyzed for lactate concentration at 15, 25, 35, 45, and 60 min during CON and INT. Total body water loss was used to calculate sweat rate (ml/hr). Blood lactate was significantly greater (p < or = 0.05) at 25, 35, 45, and 60 min during INT compared to CON (approximately 5 mmol/L vs 1.5 mmol/L). Sweat lactate was not significantly different (p>0.05) between trials at any time (approximately 10 mmol/L). Sweat rates (approximately 600ml/hr) and estimated total lactate secretion were not significantly different (CON vs. INT) (p > 0.05). Elevated blood lactate was not associated with changes in sweat lactate concentration. Sweat lactate seems to originate in eccrine glands independent of blood lactate.

Disposition of styrene-acrylonitrile (SAN) trimer in female rats: single dose intravenous and gavage studies.

PubMed

Gargas, Michael L; Collins, Brad; Fennell, Timothy R; Gaudette, Norman F; Sweeney, Lisa M

2008-04-21

Styrene-acrylonitrile trimer (SAN Trimer), a mixture of six isomers (four isomers of 4-cyano-1,2,3,4-tetrahydro-alpha-methyl-1-naphthaleneacetonitrile [THAN] and two isomers of 4-cyano-1,2,3,4-tetrahydro-1-naphthaleneproprionitrile [THNP]), is a by-product of a specific production process of styrene-acrylonitrile polymer. Disposition studies in female rats were conducted to evaluate the pharmacokinetic behavior of [3H]SAN Trimer following a single intravenous administration (26 mg/kg) to nonpregnant rats; a single gavage administration (nominal doses of 25 mg/kg, 75 mg/kg, or 200 mg/kg in corn oil) to nonpregnant rats; and a single gavage administration (nominal dose of 200 mg/kg in corn oil) to pregnant and lactating rats. SAN Trimer was rapidly eliminated from blood (T1/2 approximately 1h) following a single intravenous dose and following single oral doses (T1/2 approximately 3-4h). SAN Trimer was also rapidly excreted in the urine and feces following single oral doses, while total radioactivity was cleared more slowly. In pregnant rats, the concentrations of both radioactivity and SAN Trimer 2h after dosing were highest in the blood, followed by the placenta, with the lowest levels in the fetus. In lactating rats, the concentrations of both radioactivity and SAN Trimer were higher in milk than in maternal blood. Total radioactivity and SAN Trimer blood concentrations in nonpregnant, pregnant, and lactating rats were both higher in lactating rats compared to nonpregnant and pregnant rats.

Peroxisome proliferator-activated receptor γ agonism attenuates endotoxaemia-induced muscle protein loss and lactate accumulation in rats.

PubMed

Crossland, Hannah; Constantin-Teodosiu, Dumitru; Gardiner, Sheila M; Greenhaff, Paul L

2017-07-01

The peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone (Rosi) appears to provide protection against organ dysfunction during endotoxaemia. We examined the potential benefits of Rosi on skeletal muscle protein maintenance and carbohydrate metabolism during lipopolysaccharide (LPS)-induced endotoxaemia. Sprague-Dawley rats were fed either standard chow (control) or standard chow containing Rosi (8.5 ± 0.1 mg·kg -1 ·day -1 ) for 2 weeks before and during 24 h continuous intravenous infusion of LPS (15 μg·kg -1 ·h -1 ) or saline. Rosi blunted LPS-induced increases in muscle tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) mRNA by 70% ( P <0.05) and 64% ( P <0.01) respectively. Furthermore, Rosi suppressed the LPS-induced reduction in phosphorylated AKT and phosphorylated Forkhead box O (FOXO) 1 protein, as well as the up-regulation of muscle RING finger 1 (MuRF1; P <0.01) mRNA and the LPS-induced increase in 20S proteasome activity ( P <0.05). Accordingly, LPS reduced the muscle protein:DNA ratio (∼30%, P <0.001), which Rosi offset. Increased muscle pyruvate dehydrogenase kinase 4 (PDK4) mRNA ( P <0.001) and muscle lactate accumulation ( P <0.001) during endotoxaemia were suppressed by Rosi. Thus, pre-treatment with Rosi reduced muscle cytokine accumulation and blunted muscle protein loss and lactate accumulation during endotoxaemia, and at least in part by reducing activation of molecular events known to increase muscle protein breakdown and mitochondrial pyruvate use. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Evaluation of passive avoidance learning and spatial memory in rats exposed to low levels of lead during specific periods of early brain development.

PubMed

Rao Barkur, Rajashekar; Bairy, Laxminarayana K

2015-01-01

Widespread use of heavy metal lead (Pb) for various commercial purposes has resulted in the environmental contamination caused by this metal. The studies have shown a definite relationship between low level lead exposure during early brain development and deficit in children's cognitive functions. This study investigated the passive avoidance learning and spatial learning in male rat pups exposed to lead through their mothers during specific periods of early brain development. Experimental male rats were divided into 5 groups: i) the normal control group (NC) (N = 12) consisted of rat offspring born to mothers who were given normal drinking water throughout gestation and lactation, ii) the pre-gestation lead exposed group (PG) (N = 12) consisted of rat offspring, mothers of these rats had been exposed to 0.2% lead acetate in the drinking water for 1 month before conception, iii) the gestation lead exposed group (G) (N = 12) contained rat offspring born to mothers who had been exposed to 0.2% lead acetate in the drinking water throughout gestation, iv) the lactation lead exposed group (L) (N = 12) had rat offspring, mothers of these rats exposed to 0.2% lead acetate in the drinking water throughout lactation and v) the gestation and lactation lead exposed group (GL) (N = 12) contained rat offspring, mothers of these rats were exposed to 0.2% lead acetate throughout gestation and lactation. The study found deficit in passive avoidance learning in the G, L and GL groups of rats. Impairment in spatial learning was found in the PG, G, L and GL groups of rats. Interestingly, the study found that gestation period only and lactation period only lead exposure was sufficient to cause deficit in learning and memory in rats. The extent of memory impairment in the L group of rats was comparable with the GL group of rats. So it can be said that postnatal period of brain development is more sensitive to neurotoxicity compared to prenatal exposure. This work is available in Open

Exposure to sorbitol during lactation causes metabolic alterations and genotoxic effects in rat offspring.

PubMed

Cardoso, Felipe S; Araujo-Lima, Carlos F; Aiub, Claudia A F; Felzenszwalb, Israel

2016-10-17

Sorbitol is a polyol used by the food industry as a sweetener. Women are consuming diet and light products containing sorbitol during pregnancy and in the postnatal period to prevent themselves from excessive weight gain and maintain a slim body. Although there is no evidence for the genotoxicity of sorbitol in the perinatal period, this study focused on evaluating the effects of the maternal intake of sorbitol on the biochemical and toxicological parameters of lactating Wistar rat offspring after 14days of mother-to-offspring exposure. A dose-dependent reduction of offspring length was observed. An increase in sorbitol levels determined in the milk was also observed. However, we detected an inverse relationship between the exposition dose in milk fructose and triacylglycerols concentrations. There was an increase in the plasmatic levels of ALT, AST and LDLc and a decrease in proteins, cholesterol and glucose levels in the offspring. Sorbitol exposure caused hepatocyte genotoxicity, including micronuclei induction. Maternal sorbitol intake induced myelotoxicity and myelosuppression in their offspring. The Comet assay of the blood cells detected a dose-dependent genotoxic response within the sorbitol-exposed offspring. According to our results, sorbitol is able to induce important metabolic alterations and genotoxic responses in the exposed offspring. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A Maternal “Junk Food” Diet in Pregnancy and Lactation Promotes Nonalcoholic Fatty Liver Disease in Rat Offspring

PubMed Central

Bayol, Stéphanie A.; Simbi, Bigboy H.; Fowkes, Robert C.; Stickland, Neil C.

2010-01-01

With rising obesity rates, nonalcoholic fatty liver disease is predicted to become the main cause of chronic liver disease in the next decades. Rising obesity prevalence is attributed to changes in dietary habits with increased consumption of palatable junk foods, but maternal malnutrition also contributes to obesity in progeny. This study examines whether a maternal junk food diet predisposes offspring to nonalcoholic fatty liver disease. The 144 rat offspring were fed either a balanced chow diet alone or with palatable junk foods rich in energy, fat, sugar, and/or salt during gestation, lactation, and/or after weaning up to the end of adolescence. Offspring fed junk food throughout the study exhibited exacerbated hepatic steatosis, hepatocyte ballooning, and oxidative stress response compared with offspring given free access to junk food after weaning only. These offspring also displayed sex differences in their hepatic molecular metabolic adaptation to diet-induced obesity with increased expression of genes associated with insulin sensitivity, de novo lipogenesis, lipid oxidation, and antiinflammatory properties in males, whereas the gene expression profile in females was indicative of hepatic insulin resistance. Hepatic inflammation and fibrosis were not detected indicating that offspring had not developed severe steatohepatitis by the end of adolescence. Hepatic steatosis and increased oxidative stress response also occurred in offspring born to junk food-fed mothers switched to a balanced chow diet from weaning, highlighting a degree of irreversibility. This study shows that a maternal junk food diet in pregnancy and lactation contributes to the development of nonalcoholic fatty liver disease in offspring. PMID:20207831

In utero and lactational exposure of male rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin. 3. Effects on spermatogenesis and reproductive capability.

PubMed

Mably, T A; Bjerke, D L; Moore, R W; Gendron-Fitzpatrick, A; Peterson, R E

1992-05-01

When administered in overtly toxic doses to postweanling male rats, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces adverse effects on the reproductive system including a decrease in spermatogenesis. Because the male reproductive system may be particularly susceptible to toxic insult during the perinatal period, the effects of in utero and lactational TCDD exposure on its development were examined. Male rats born to dams given TCDD (0.064, 0.16, 0.40, or 1.0 micrograms/kg, po) or vehicle on Day 15 of gestation were evaluated at various stages of development; effects on spermatogenesis and male reproductive capability are reported herein. Testis, epididymis, and cauda epididymis weights were decreased in a dose-related fashion at 32, 49, 63, and 120 days of age, that is, when males were at the juvenile, pubertal, postpubertal, and mature stages of sexual development, respectively. When measured on Days 49, 63, and 120, daily sperm production by the testis was reduced at the highest maternal TCDD dose to 57-74% of the control rate. Cauda epididymal sperm reserves in 63- and 120-day-old males were decreased to as low as 25 and 44%, respectively, of control values, although the motility and morphology of these sperm appeared to be unaffected. The magnitude of the effects described above tended to lessen with time; nevertheless, the decreases in epididymis and cauda epididymis weights, daily sperm production, and cauda epididymal sperm number were statistically significant at the lowest maternal dose tested (0.064 micrograms TCDD/kg) on Day 120 and at most earlier times. To determine if in utero and lactational TCDD exposure also affects male reproductive capability, rats were mated at approximately 70 and 120 days of age with control females. Little if any effect on fertility was seen, and the survival and growth of offspring was unaffected. These results are not inconsistent with the pronounced reductions in daily sperm production and cauda epididymal sperm

Effect of Swimming on the Production of Aldosterone in Rats

PubMed Central

Wang, Paulus S.; Jian, Cai-Yun; Yeh, Yung-Hsing; Chen, Yi-An; Wang, Kai-Lee; Lin, Yi-Chun; Chang, Ling-Ling; Wang, Guei-Jane; Wang, Shyi-Wu

2014-01-01

It has been demonstrated that exercise is one of the stresses known to increase the aldosterone secretion. Both potassium and angiotensin II (Ang II) levels are shown to be correlated with aldosterone production during exercise, but the mechanism is still unclear. In an in vivo study, male rats were catheterized via right jugular vein (RJV), and divided into four groups namely water immersion, swimming, lactate infusion (13 mg/kg/min) and pyruvate infusion (13 mg/kg/min) groups. Each group was treated for 10 min. Blood samples were collected at 0, 10, 15, 30, 60 and 120 min from RJV after administration. In an in vitro study, rat zona glomerulosa (ZG) cells were challenged by lactate (1–10 mM) in the presence or absence of Ang II (10−8 M) for 60 min. The levels of aldosterone in plasma and medium were measured by radioimmunoassay. Cell lysates were analyzed by immunoblotting assay. After exercise and lactate infusion, plasma levels of aldosterone and lactate were significantly higher than those in the control group. Swimming for 10 min significantly increased the plasma Ang II levels in male rats. Administration of lactate plus Ang II significantly increased aldosterone production and enhanced protein expression of steroidogenic acute regulatory protein (StAR) in ZG cells. These results demonstrated that acute exercise led to the increase of both aldosterone and Ang II secretion, which is associated with lactate action on ZG cells and might be dependent on the activity of renin-angiotensin system. PMID:25289701

Insulin secretion and GLUT-2 expression in undernourished neonate rats.

PubMed

Lopes Da Costa, Célia; Sampaio De Freitas, Marta; Sanchez Moura, Anibal

2004-04-01

In previous studies, we verified increased insulin sensitivity in adult male offspring of lactating rats readjusting to lack of insulin secretion reduction brought about by protein restriction during lactation. The present study aims to evaluate the effects of maternal protein undernutrition during lactation on glucose-induced insulin secretion and GLUT-2 expression in beta-cells of neonate male and female rats. Lactating Wistar rats were given a protein-free diet during the first 10 days and a normal diet (22% of protein) until weaning. The neonates were separated at birth by sex and diet and studied at 4, 8 and 21 days of lactation. Glucose-induced insulin secretion by pancreatic islets was analyzed by radioimmunoassay and GLUT-2 expression in beta-cells by Western blot. Glucose-induced insulin secretion of the undernourished groups was higher than in the control groups except among females. When comparing the male and female groups and the control and undernourished groups, female neonates showed significantly greater insulin secretion than the male group. Also it was noted that undernutrition induced greater GLUT-2 expression. For instance, comparing the undernourished male and female neonates there was an increase in female GLUT-2 expression on day 4. On the other hand, in undernourished male neonates a GLUT-2 expression increased later in lactation. In conclusion, during a short term, maternal undernutrition induces an increase of the glucose-induced insulin secretion only in male neonates and is associated with an increase in GLUT-2 expression in the beta-cell.

Moderate caloric restriction in lactating rats programs their offspring for a better response to HF diet feeding in a sex-dependent manner.

PubMed

Palou, Mariona; Torrens, Juana María; Priego, Teresa; Sánchez, Juana; Palou, Andreu; Picó, Catalina

2011-06-01

We aimed to assess the lasting effects of moderate caloric restriction in lactating rats on the expression of key genes involved in energy balance of their adult offspring (CR) and their adaptations under high-fat (HF) diet. Dams were fed with either ad libitum normal-fat (NF) diet or a 30% caloric restricted diet throughout lactation. After weaning, the offspring were fed with NF diet until the age of 15 weeks and then with an NF or a HF diet until the age of 28 weeks, when they were sacrificed. Body weight and food intake were followed. Blood parameters and the expression of selected genes in hypothalamus and white adipose tissue (WAT) were analysed. CR ate fewer calories and showed lower body weight gain under HF diet than their controls. CR males were also resistant to the increase of insulin and leptin occurring in their controls under HF diet, and HF diet exposed CR females showed lower circulating fasting triglyceride levels than controls. In the hypothalamus, CR males had higher ObRb mRNA levels than controls, and CR females displayed greater InsR mRNA levels than controls and decreased neuropeptide Y mRNA levels when exposed to HF diet. CR males maintained WAT capacity of fat uptake and storage and of fatty-acid oxidation under HF diet, whereas these capacities were impaired in controls; female CR showed higher WAT ObRb mRNA levels than controls. These results suggest that 30% caloric restriction in lactating dams ameliorates diet-induced obesity in their offspring by enhancing their sensitivity to insulin and leptin signaling, but in a gender-dependent manner. Copyright © 2011 Elsevier Inc. All rights reserved.

Effect of chlorocamphene on the isoenzyme spectrum of lactate dehydrogenase in rat serum and liver.

PubMed Central

Kuz'minskaya, U A; Alekhina, S M

1976-01-01

Rats were used to study the general activity and the isoenzyme spectrum of lactate dehydrogenase (LDH) during single-instance and long-term introduction of polychlorocamphene. Total lactate dehydrogenase activity decreases in the liver during the single-instance introduction of half the LD50 (120 mg/kg). The isoenzyme spectrum of LDH is characterized by an increase in the quantity of LDH1, LDH2, and LDH3 and by a decrease in the amount of LDH4. The overall LDH activity does not change in blood serum. The isoform ratio changes insignificantly and LDH1 falls, but normalized 15 days after the introduction of the compound. Long-term introduction of polychlorocamphene at levels 1/100 the LD50 dose over 1.3 and 6 months causes a reduction in the overall LDH activity, both in the liver and in the serum. A decrease in the activity of the basic LDH isoenzyme of the liver (LDH5) and a sharp increase in LDH3 are characteristic for the isoenzyme spectrum of the liver. LDH1 and LDH4 decrease and LDH2 and LDH3 increase in blood serum. Beginning with the third month of polychlorocamphene introduction, LDH1 tends to return to normal levels. LDH2, LDH3, and LDH4 do return to normal levels, while LDH5 increases regularly. This results in a reduction of the number of H subunits and an increase of M subunits. This is characteristic of hypoxic states. On comparing the changes in the LDH enzymes of the liver and blood serum, it can be considered that the introduction of polychlorocamphene does not result in an increase in the permeability of the cellular membranes of the liver for LDH isoenzymes, while the observed isoenzyme spectrum shifts in blood serum are either the result of the biosynthesis of the isoforms of this enzyme changed by the compound or the result of the permeability for them of cells of other tissues. PMID:1269500

The distribution of atrazine (ATR) and ATR metabolites in the Wistar rat following gestational/lactational exposures

EPA Science Inventory

Gestational/lactational exposure to ATR is reported to alter reproductive/developmental function, yet our understanding of the transfer of ATR and/or its metabolites from the dam to the fetus/offspring is limited. Previously we examined the lactational transfer of CI4-ATR, but sp...

Inhibition of Lactate Transport Erases Drug Memory and Prevents Drug Relapse.

PubMed

Zhang, Yan; Xue, Yanxue; Meng, Shiqiu; Luo, Yixiao; Liang, Jie; Li, Jiali; Ai, Sizhi; Sun, Chengyu; Shen, Haowei; Zhu, Weili; Wu, Ping; Lu, Lin; Shi, Jie

2016-06-01

Drug memories that associate drug-paired stimuli with the effects of abused drugs contribute to relapse. Exposure to drug-associated contexts causes consolidated drug memories to be in a labile state, during which manipulations can be given to impair drug memories. Although substantial evidence demonstrates the crucial role of neuronal signaling in addiction, little is known about the contribution of astrocyte-neuron communication. Rats were trained for cocaine-induced conditioned place preference (CPP) or self-administration and microinjected with the glycogen phosphorylation inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol into the basolateral amygdala (BLA) immediately after retrieval. The concentration of lactate was measured immediately after retrieval via microdialysis, and the CPP score and number of nosepokes were recorded 24 hours later. Furthermore, we used antisense oligodeoxynucleotides to disrupt the expression of astrocytic lactate transporters (monocarboxylate transporters 1 and 2) in the BLA after retrieval, tested the expression of CPP 1 day later, and injected L-lactate into the BLA 15 minutes before retrieval to rescue the effects of the oligodeoxynucleotides. Injection of 1,4-dideoxy-1,4-imino-D-arabinitol into the BLA immediately after retrieval prevented the subsequent expression of cocaine-induced CPP, decreased the concentration of lactate in the BLA, and reduced the number of nosepokes for cocaine self-administration. Disrupting the expression of monocarboxylate transporters 1 and 2 in the BLA also caused subsequent deficits in the expression of cocaine-induced CPP, which was rescued by pretreatment with L-lactate. Our results suggest that astrocyte-neuron lactate transport in the BLA is critical for the reconsolidation of cocaine memory. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Growth advantage of Streptococcus thermophilus over Lactobacillus bulgaricus in vitro and in the gastrointestinal tract of gnotobiotic rats.

PubMed

Ben-Yahia, L; Mayeur, C; Rul, F; Thomas, M

2012-09-01

The yoghurt bacteria, Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus, are alleged to have beneficial effects on human health. The objective of this study was to characterise growth, biochemical activity and competitive behaviour of these two bacteria in vitro and in vivo. S. thermophilus LMD-9 and L. bulgaricus ATCC 11842 growth and lactate production were monitored in different media and in the gastrointestinal tract (GIT) of germ-free rats. In vitro, particularly in milk, S. thermophilus had a selective growth advantage over L. bulgaricus. The GIT of germ-free rats not supplemented with lactose was colonised by S. thermophilus but not by L. bulgaricus. Both bacteria were able to colonise the GIT of germ-free rats supplemented with 45 g/l lactose in their drinking water. However, if germ-free rats were inoculated with a mixture of the two bacteria and were supplemented with lactose, S. thermophilus rapidly and extensively colonised the GIT (1010 cfu/g faeces) at the expense of L. bulgaricus, which remained in most cases at levels <102 cfu/g faeces. S. thermophilus specifically produced L-lactate, while L. bulgaricus produced only D-lactate, both in vitro and in vivo. S. thermophilus showed competitive and growth advantage over L. bulgaricus in vitro as well as in vivo in the GIT of germ-free rats and, accordingly, L-lactate was the main lactate isomer produced.

Reproductive experience modified dendritic spines on cortical pyramidal neurons to enhance sensory perception and spatial learning in rats.

PubMed

Chen, Jeng-Rung; Lim, Seh Hong; Chung, Sin-Cun; Lee, Yee-Fun; Wang, Yueh-Jan; Tseng, Guo-Fang; Wang, Tsyr-Jiuan

2017-01-27

Behavioral adaptations during motherhood are aimed at increasing reproductive success. Alterations of hormones during motherhood could trigger brain morphological changes to underlie behavioral alterations. Here we investigated whether motherhood changes a rat's sensory perception and spatial memory in conjunction with cortical neuronal structural changes. Female rats of different statuses, including virgin, pregnant, lactating, and primiparous rats were studied. Behavioral test showed that the lactating rats were most sensitive to heat, while rats with motherhood and reproduction experience outperformed virgin rats in a water maze task. By intracellular dye injection and computer-assisted 3-dimensional reconstruction, the dendritic arbors and spines of the layer III and V pyramidal neurons of the somatosensory cortex and CA1 hippocampal pyramidal neurons were revealed for closer analysis. The results showed that motherhood and reproductive experience increased dendritic spines but not arbors or the lengths of the layer III and V pyramidal neurons of the somatosensory cortex and CA1 hippocampal pyramidal neurons. In addition, lactating rats had a higher incidence of spines than pregnant or primiparous rats. The increase of dendritic spines was coupled with increased expression of the glutamatergic postsynaptic marker protein (PSD-95), especially in lactating rats. On the basis of the present results, it is concluded that motherhood enhanced rat sensory perception and spatial memory and was accompanied by increases in dendritic spines on output neurons of the somatosensory cortex and CA1 hippocampus. The effect was sustained for at least 6 weeks after the weaning of the pups.

Changing patterns of daily rhythmicity across reproductive states in diurnal female Nile grass rats (Arvicanthis niloticus)

PubMed Central

Schradera, Jessica A.; Walaszczykb, Erin J.; Smalea, Laura

2009-01-01

SCHRADER, J.A., E. J. WALASZCZYK, AND L. SMALE. Changing patterns of daily rhythmicity across reproductive states in diurnal female Nile grass rats (Arvicanthis niloticus). PHYSIOL BEHAV XX(X) XXX-XXX, XXXX. -- A suite of changes in circadian rhythms have been described in nocturnal rodents as females go through pregnancy and lactation, but there is no information on such patterns in diurnal species. As the challenges faced by these two groups of animals are somewhat different, we characterized changes in activity and core body temperature (Tb) in female diurnal Nile grass rats (Arvicanthis niloticus) as they went through a series of reproductive states: virgin, pregnant, pregnant and lactating, lactating only, and post-weaning. The phase of neither rhythm varied, but the amplitude did. Females increased their overall levels of daily activity from early to late pregnancy, regardless of whether they were also lactating. The pattern of activity was less rhythmic during early than mid-lactation, in both non-pregnant and pregnant females, as a consequence of a decrease in daytime relative to nighttime activity. The Tb rhythm amplitude dropped from mid-pregnancy through mid-lactation, and there were rises in Tb troughs during the mid-light and mid-dark phases of the day, though pregnancy and lactation affected Tb at these times in somewhat different ways. This study demonstrates that rhythms in diurnal grass rats change during pregnancy and lactation in different ways than those of nocturnal species that have been studied to date and that the effects of pregnancy and lactation are not additive in any simple way. PMID:19744504

Improved biocompatibility of bicarbonate/lactate-buffered PDF is not related to pH.

PubMed

Zareie, Mohammad; Keuning, Eelco D; ter Wee, Piet M; Schalkwijk, Casper G; Beelen, Robert H J; van den Born, Jacob

2006-01-01

Chronic exposure to conventional peritoneal dialysis fluid (PDF) is associated with functional and structural alterations of the peritoneal membrane. The bioincompatibility of conventional PDF can be due to hypertonicity, high glucose concentration, lactate buffering system, presence of glucose degradation products (GDPs) and/or acidic pH. Although various investigators have studied the sole effects of hyperosmolarity, high glucose, GDPs and lactate buffer in experimental PD, less attention has been paid to the chronic impact of low pH in vivo. Rats received daily 10 ml of either conventional lactate-buffered PDF (pH 5.2; n=7), a standard bicarbonate/lactate-buffered PDF with physiological pH (n=8), bicarbonate/lactate-buffered PDF with acidic pH (adjusted to pH 5.2 with 1 N hydrochloride, n=5), or bicarbonate/lactate buffer, without glucose, pH 7.4 (n=7). Fluids were instilled via peritoneal catheters connected to implanted subcutaneous mini vascular access ports for 8 weeks. Control animals with or without peritoneal catheters served as control groups (n=8/group). Various functional (2 h PET) and morphological/cellular parameters were analyzed. Compared with control groups and the buffer group, conventional lactate-buffered PDF induced a number of morphological/cellular changes, including angiogenesis and fibrosis in various peritoneal tissues (all parameters P<0.05), accompanied by increased glucose absorption and reduced ultrafiltration capacity. Daily exposure to standard or acidified bicarbonate/lactate-buffered PDF improved the performance of the peritoneal membrane, evidenced by reduced new vessel formation in omentum (P<0.02) and parietal peritoneum (P<0.008), reduced fibrosis (P<0.02) and improved ultrafiltration capacity. No significant differences were found between standard and acidified bicarbonate/lactate-buffered PDF. During PET, acidic PDF was neutralized within 15 to 20 min. The bicarbonate/lactate-buffered PDF, acidity per se did not contribute

Lactate shuttling and lactate use as fuel after traumatic brain injury: metabolic considerations

PubMed Central

Dienel, Gerald A

2014-01-01

Lactate is proposed to be generated by astrocytes during glutamatergic neurotransmission and shuttled to neurons as ‘preferred' oxidative fuel. However, a large body of evidence demonstrates that metabolic changes during activation of living brain disprove essential components of the astrocyte–neuron lactate shuttle model. For example, some glutamate is oxidized to generate ATP after its uptake into astrocytes and neuronal glucose phosphorylation rises during activation and provides pyruvate for oxidation. Extension of the notion that lactate is a preferential fuel into the traumatic brain injury (TBI) field has important clinical implications, and the concept must, therefore, be carefully evaluated before implementation into patient care. Microdialysis studies in TBI patients demonstrate that lactate and pyruvate levels and lactate/pyruvate ratios, along with other data, have important diagnostic value to distinguish between ischemia and mitochondrial dysfunction. Results show that lactate release from human brain to blood predominates over its uptake after TBI, and strong evidence for lactate metabolism is lacking; mitochondrial dysfunction may inhibit lactate oxidation. Claims that exogenous lactate infusion is energetically beneficial for TBI patients are not based on metabolic assays and data are incorrectly interpreted. PMID:25204393

Maternal Exposure to Ethanol During Pregnancy and Lactation Affects Glutamatergic System and Induces Oxidative Stress in Offspring Hippocampus.

PubMed

Cesconetto, Patricia A; Andrade, Camila M; Cattani, Daiane; Domingues, Juliana T; Parisotto, Eduardo B; Filho, Danilo W; Zamoner, Ariane

2016-01-01

Alcohol abuse during pregnancy leads to intellectual disability and morphological defects in the offspring. The aim of this study was to determine the effect of chronic maternal ethanol (EtOH) consumption during pregnancy and lactation on glutamatergic transmission regulation, energy deficit, and oxidative stress in the hippocampus of the offspring. EtOH was administered to dams in drinking water at increasing doses (2 to 20%) from the gestation day 5 to lactation day 21. EtOH and tap water intake by treated and control groups, respectively, were measured daily. Results showed that EtOH exposure does not affect fluid intake over the course of pregnancy and lactation. The toxicity of maternal exposure to EtOH was demonstrated by decreased offspring body weight at experimental age, on postnatal day 21. Moreover, maternal EtOH exposure decreased (45) Ca(2+) influx in the offspring's hippocampus. Corroborating this finding, EtOH increased both Na(+) -dependent and Na(+) -independent glial [(14) C]-glutamate uptake in hippocampus of immature rats. Also, maternal EtOH exposure decreased glutamine synthetase activity and induced aspartate aminotransferase enzymatic activity, suggesting that in EtOH-exposed offspring hippocampus, glutamate is preferentially used as a fuel in tricarboxylic acid cycle instead of being converted into glutamine. In addition, EtOH exposure decreased [U-14C]-2-deoxy-D-glucose uptake in offspring hippocampus. The decline in glucose transport coincided with increased lactate dehydrogenase activity, suggesting an adaptative response in EtOH-exposed offspring hippocampus, using lactate as an alternative fuel. These events were associated with oxidative damage, as demonstrated by changes in the enzymatic antioxidant defense system and lipid peroxidation. Taken together, the results demonstrate that maternal exposure to EtOH during pregnancy and lactation impairs glutamatergic transmission, as well as inducing oxidative stress and energy deficit in

Cultured 3T3L1 adipocytes dispose of excess medium glucose as lactate under abundant oxygen availability

NASA Astrophysics Data System (ADS)

Sabater, David; Arriarán, Sofía; Romero, María Del Mar; Agnelli, Silvia; Remesar, Xavier; Fernández-López, José Antonio; Alemany, Marià

2014-01-01

White adipose tissue (WAT) produces lactate in significant amount from circulating glucose, especially in obesity;Under normoxia, 3T3L1 cells secrete large quantities of lactate to the medium, again at the expense of glucose and proportionally to its levels. Most of the glucose was converted to lactate with only part of it being used to synthesize fat. Cultured adipocytes were largely anaerobic, but this was not a Warburg-like process. It is speculated that the massive production of lactate, is a process of defense of the adipocyte, used to dispose of excess glucose. This way, the adipocyte exports glucose carbon (and reduces the problem of excess substrate availability) to the liver, but the process may be also a mechanism of short-term control of hyperglycemia. The in vivo data obtained from adipose tissue of male rats agree with this interpretation.

Maternal protein restriction during lactation induces early and lasting plasma metabolomic and hepatic lipidomic signatures of the offspring in a rodent programming model.

PubMed

Martin Agnoux, Aurore; El Ghaziri, Angélina; Moyon, Thomas; Pagniez, Anthony; David, Agnès; Simard, Gilles; Parnet, Patricia; Qannari, El Mostafa; Darmaun, Dominique; Antignac, Jean-Philippe; Alexandre-Gouabau, Marie-Cécile

2018-05-01

Perinatal undernutrition affects not only fetal and neonatal growth but also adult health outcome, as suggested by the metabolic imprinting concept. However, the exact mechanisms underlying offspring metabolic adaptations are not yet fully understood. Specifically, it remains unclear whether the gestation or the lactation is the more vulnerable period to modify offspring metabolic flexibility. We investigated in a rodent model of intrauterine growth restriction (IUGR) induced by maternal protein restriction (R) during gestation which time window of maternal undernutrition (gestation, lactation or gestation-lactation) has more impact on the male offspring metabolomics phenotype. Plasma metabolome and hepatic lipidome of offspring were characterized through suckling period and at adulthood using liquid chromatography-high-resolution mass spectrometry. Multivariate analysis of these fingerprints highlighted a persistent metabolomics signature in rats suckled by R dams, with a clear-cut discrimination from offspring fed by control (C) dams. Pups submitted to a nutritional switch at birth presented a metabolomics signature clearly distinct from that of pups nursed by dams maintained on a consistent perinatal diet. Control rats suckled by R dams presented transiently higher branched-chain amino acid (BCAA) oxidation during lactation besides increased fatty acid (FA) β-oxidation, associated with preserved insulin sensitivity and lesser fat accretion that persisted throughout their life. In contrast, IUGR rats displayed permanently impaired β-oxidation, associated to increased glucose or BCAA oxidation at adulthood, depending on the fact that pups experienced slow postnatal or catch-up growth, as suckled by R or C dams, respectively. Taken together, these findings provide evidence for a significant contribution of the lactation period in metabolic programming. Copyright © 2018 Elsevier Inc. All rights reserved.

Sodium selenite supplementation during pregnancy and lactation promotes anxiolysis and improves mnemonic performance in wistar rats' offspring.

PubMed

Laureano-Melo, Roberto; Império, Güínever Eustáquio do; da Silva-Almeida, Claudio; Kluck, George Eduardo Gabriel; Cruz Seara, Fernando de Azevedo; da Rocha, Fábio Fagundes; da Silveira, Anderson Luiz Bezerra; Reis, Luís Carlos; Ortiga-Carvalho, Tania Maria; da Silva Côrtes, Wellington

2015-11-01

Selenium is a micronutrient which is part of selenoprotein molecules and participates in a vast number of physiological roles and, among them,we have fetal and neonatal development. Therefore, the aimof this studywas to evaluate possible behavioral changes in offspring of female rats supplemented during pregnancy and lactation with sodium selenite. To address that, we treated two groups of female rats by saline or sodium selenite at a dose of 1mg/kg through oral route and performed neurochemical and behavioral tests. In the offspring, the thyroid profile and hippocampal neurochemistrywere evaluated. Behavioral testswere performed in pups both during childhood and adulthood. We found out that selenium (Se) supplementation increased serum levels of triiodothyronine (25%, p b 0.001) and thyroxine (18%, p b 0.05) and promoted a tryptophan hydroxylase 2 (TPH 2) expression decrease (17%, p b 0.01) and tyrosine hydroxylase (TH) expression increase (202%, p b 0.01) in the hippocampus. The cholinesterase activity was decreased (28%, p b 0.01) in Se supplemented rats, suggesting a neurochemical modulation in the hippocampal activity. During childhood, the Sesupplemented offspring had a reduction in anxiety-like behavior both in elevated plus maze test and in light–dark box test. In adulthood, Se-treated pups had an increase in the locomotor activity (36%, p b 0.05) and in rearing episodes (77%, p b 0.001) in the open field test, while in the elevated plus maze test they also exhibited an increase in the time spent in the open arms (243%, p b 0.01). For the object recognition test, Se-treated offspring showed increase in the absolute (230.16%, p b 0.05) and relative index discrimination (234%, p b 0.05). These results demonstrate that maternal supplementation by sodium selenite promoted psychobiological changes both during childhood and adulthood. Therefore, the behavioral profile observed possibly can be explained by neurochemical changes induced by thyroid hormones during

Astrocytic glycogen-derived lactate fuels the brain during exhaustive exercise to maintain endurance capacity

PubMed Central

Matsui, Takashi; Omuro, Hideki; Liu, Yu-Fan; Soya, Mariko; Shima, Takeru; McEwen, Bruce S.; Soya, Hideaki

2017-01-01

Brain glycogen stored in astrocytes provides lactate as an energy source to neurons through monocarboxylate transporters (MCTs) to maintain neuronal functions such as hippocampus-regulated memory formation. Although prolonged exhaustive exercise decreases brain glycogen, the role of this decrease and lactate transport in the exercising brain remains less clear. Because muscle glycogen fuels exercising muscles, we hypothesized that astrocytic glycogen plays an energetic role in the prolonged-exercising brain to maintain endurance capacity through lactate transport. To test this hypothesis, we used a rat model of exhaustive exercise and capillary electrophoresis-mass spectrometry–based metabolomics to observe comprehensive energetics of the brain (cortex and hippocampus) and muscle (plantaris). At exhaustion, muscle glycogen was depleted but brain glycogen was only decreased. The levels of MCT2, which takes up lactate in neurons, increased in the brain, as did muscle MCTs. Metabolomics revealed that brain, but not muscle, ATP was maintained with lactate and other glycogenolytic/glycolytic sources. Intracerebroventricular injection of the glycogen phosphorylase inhibitor 1,4-dideoxy-1,4-imino-d-arabinitol did not affect peripheral glycemic conditions but suppressed brain lactate production and decreased hippocampal ATP levels at exhaustion. An MCT2 inhibitor, α-cyano-4-hydroxy-cinnamate, triggered a similar response that resulted in lower endurance capacity. These findings provide direct evidence for the energetic role of astrocytic glycogen-derived lactate in the exhaustive-exercising brain, implicating the significance of brain glycogen level in endurance capacity. Glycogen-maintained ATP in the brain is a possible defense mechanism for neurons in the exhausted brain. PMID:28515312

Astrocytic glycogen-derived lactate fuels the brain during exhaustive exercise to maintain endurance capacity.

PubMed

Matsui, Takashi; Omuro, Hideki; Liu, Yu-Fan; Soya, Mariko; Shima, Takeru; McEwen, Bruce S; Soya, Hideaki

2017-06-13

Brain glycogen stored in astrocytes provides lactate as an energy source to neurons through monocarboxylate transporters (MCTs) to maintain neuronal functions such as hippocampus-regulated memory formation. Although prolonged exhaustive exercise decreases brain glycogen, the role of this decrease and lactate transport in the exercising brain remains less clear. Because muscle glycogen fuels exercising muscles, we hypothesized that astrocytic glycogen plays an energetic role in the prolonged-exercising brain to maintain endurance capacity through lactate transport. To test this hypothesis, we used a rat model of exhaustive exercise and capillary electrophoresis-mass spectrometry-based metabolomics to observe comprehensive energetics of the brain (cortex and hippocampus) and muscle (plantaris). At exhaustion, muscle glycogen was depleted but brain glycogen was only decreased. The levels of MCT2, which takes up lactate in neurons, increased in the brain, as did muscle MCTs. Metabolomics revealed that brain, but not muscle, ATP was maintained with lactate and other glycogenolytic/glycolytic sources. Intracerebroventricular injection of the glycogen phosphorylase inhibitor 1,4-dideoxy-1,4-imino-d-arabinitol did not affect peripheral glycemic conditions but suppressed brain lactate production and decreased hippocampal ATP levels at exhaustion. An MCT2 inhibitor, α-cyano-4-hydroxy-cinnamate, triggered a similar response that resulted in lower endurance capacity. These findings provide direct evidence for the energetic role of astrocytic glycogen-derived lactate in the exhaustive-exercising brain, implicating the significance of brain glycogen level in endurance capacity. Glycogen-maintained ATP in the brain is a possible defense mechanism for neurons in the exhausted brain.

Localisation of Lactate Transporters in Rat and Rabbit Placentae

PubMed Central

Picut, Catherine A.; Charlap, Jeffrey H.

2016-01-01

The distribution of monocarboxylate transporter (MCT) isoforms 1 and 4, which mediate the plasmalemmal transport of l-lactic and pyruvic acids, has been identified in the placentae of rats and rabbits at different ages of gestation. Groups of three pregnant Sprague-Dawley rats and New Zealand White rabbits were sacrificed on gestation days (GD) 11, 14, 18, or 20 and on GD 13, 18, or 28, respectively. Placentae were removed and processed for immunohistochemical detection of MCT1 and MCT4. In the rat, staining for MCT1 was associated with lakes and blood vessels containing enucleated red blood cells (maternal vessels) while staining for MCT4 was associated with vessels containing nucleated red blood cells (embryofoetal vessels). In the rabbit, staining for MCT1 was associated with blood vessels containing nucleated red blood cells while staining for MCT4 was associated with vessels containing enucleated red blood cells. Strength of staining for MCT1 decreased during gestation in both species, but that for MCT4 was stronger than that for MCT1 and was consistent between gestation days. The results imply an opposite polarity of MCT1 and MCT4 across the trophoblast between rat and rabbit. PMID:27843454

Hypoglycemia Prevents Increase in Lactic Acidosis During Reperfusion After Temporary Cerebral Ischemia in Rats

PubMed Central

Sappey-Marinier, Dominique; Chileuitt, Laureano; Weiner, Michael W.; Faden, Alan I.; Weinstein, Philip R.

2009-01-01

Sequential 31P and 1H MRS was used to measure cerebral phosphate metabolites, intracellular pH, and lactate in normoglycemic and hypoglycemic rats during 30 min of complete cerebral ischemia and 5.5 h of reperfusion. These results were correlated with brain levels of free fatty acids (FFAs), excitatory amino acids, cations, and water content at death. The lactate/N-acetyl aspartate ratio was not significantly different between groups before or during occlusion. During reperfusion, the ratio was higher in normoglycemic rats from 3 to 85 min (p≤ 0.05), and recovery time was faster in hypoglycemic rats (29 vs 45 min; p = 0.04), suggesting reduced lactate production and faster recovery of aerobic metabolism. During occlusion, significant but comparable decrease of intracellular pH occurred in each group. Intracellular pH was higher in hypoglycemic rats at 140 min and 260 min of reperfusion. Water content, Na and K+ concentrations, and FFA and excitatory amino acid levels were not significantly different between groups, but hypoglycemic rats had less depletion of levels of Mg2+ (p=0.011). These results show that hypoglycemia has a limited but potentially beneficial effect on postischemic lactic acidosis. PMID:8771092

BIOCHEMICAL EFFECTS IN NORMAL AND STONE FORMING RATS TREATED WITH THE RIPE KERNEL JUICE OF PLANTAIN (MUSA PARADISIACA)

PubMed Central

Devi, V. Kalpana; Baskar, R.; Varalakshmi, P.

1993-01-01

The effect of Musa paradisiaca stem kernel juice was investigated in experimental urolithiatic rats. Stone forming rats exhibited a significant elevation in the activities of two oxalate synthesizing enzymes - Glycollic acid oxidase and Lactate dehydrogenase. Deposition and excretion of stone forming constituents in kidney and urine were also increased in these rats. The enzyme activities and the level of crystalline components were lowered with the extract treatment. The extract also reduced the activities of urinary alkaline phosphatase, lactate dehydrogenase, r-glutamyl transferase, inorganic pyrophosphatase and β-glucuronidase in calculogenic rats. No appreciable changes were noticed with leucine amino peptidase activity in treated rats. PMID:22556626

Effects of ethanol and folic acid consumption during pregnancy and lactation on basal enzymatic secretion in the duodenal juice of offspring rats.

PubMed

Cano, Ma José; Murillo, Ma Luisa; Delgado, Ma José; Carreras, Olimpia

2003-09-01

Studies on duodenal juice enzyme activities were carried out on suckling Wistar rats born to dams given ethanol during gestation and suckling. The results were compared with offspring of dams given diets containing no ethanol. Comparisons were also made with offspring of dams given ethanol and folic acid supplementation to observe whether a folate supplement could sufficiently reverse the negative effect of ethanol consumption. The dams were fed increased amounts of ethanol (5% to 20%, vol/vol) in tap water for 4 wk. The maximum quantity, 20% ethanol, was given to the dams during pregnancy and lactation. Offspring animals were randomized into three groups: control (CG), ethanol treated (EG), and ethanol plus folic acid (EFG). Body weight at birth and at 21 d after birth and pancreatic weight were lower in offspring after ethanol treatment. Folic acid supplement increased these parameters in the EFG. Under basal conditions, decreases in amylase, lipase, and chymotrypsin activities in the duodenal juice after ethanol treatment were detected. Serum and urine amylase activities also decreased in the EG and EFG. These changes were different in the ethanol-treated progenitors. In these progenitors, ethanol treatment increased serum amylase levels. In the offspring, amylase activities in the EFG decreased with respect to the CG; however, an increase in the EG was observed. In dams the folic acid supplement did not significantly alter the serum amylase activities. Lipase and chymotrypsin activities in the EFG were similar to those in the EG. An increase of serum and urine amylase in the EFG with respect to the EG was found. Our findings indicated that, under basal conditions, ethanol treatment during gestation and lactation negatively affects the digestive function in offspring. The effects of ethanol were slightly attenuated in rats supplemented with folic acid for amylase activities. Although extrapolation from animal studies can be tenuous, the present findings may

Methylphenidate increases glucose uptake in the brain of young and adult rats.

PubMed

Réus, Gislaine Z; Scaini, Giselli; Titus, Stephanie E; Furlanetto, Camila B; Wessler, Leticia B; Ferreira, Gabriela K; Gonçalves, Cinara L; Jeremias, Gabriela C; Quevedo, João; Streck, Emilio L

2015-10-01

Methylphenidate (MPH) is the drug of choice for pharmacological treatment of attention deficit hyperactivity disorder. Studies have pointed to the role of glucose and lactate as well as in the action mechanisms of drugs used to treat these neuropsychiatric diseases. Thus, this study aims to evaluate the effects of MPH administration on lactate release and glucose uptake in the brains of young and adult rats. MPH (1.0, 2.0 and 10.0mg/kg) or saline was injected in young and adult Wistar male rats either acutely (once) or chronically (once daily for 28 days). Then, the levels of lactate release and glucose uptake were assessed in the prefrontal cortex, hippocampus, striatum, cerebellum and cerebral cortex. Chronic MPH treatment increased glucose uptake at the dose of 10.0mg/kg in the prefrontal cortex and striatum, and at the dose of 2.0mg/kg in the cerebral cortex of young rats. In adult rats, an increase in glucose uptake was observed after acute administration of MPH at the dose of 10.0mg/kg in the prefrontal cortex. After chronic treatment, there was an increase in glucose uptake with MPH doses of 2.0 and 10.0mg/kg in the prefrontal cortex, and at an MPH dose of 2.0mg/kg in the striatum of adult rats. The lactate release did not change with either acute or chronic treatments in young or adult rats. These findings indicate that MPH increases glucose consumption in the brain, and that these changes are dependent on age and posology. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Lactate and glutamate dynamics during prolonged stimulation of the rat barrel cortex suggest adaptation of cerebral glucose and oxygen metabolism.

PubMed

Sonnay, Sarah; Duarte, João M N; Just, Nathalie

2017-03-27

A better understanding of BOLD responses stems from a better characterization of the brain's ability to metabolize glucose and oxygen. Non-invasive techniques such as functional magnetic resonance spectroscopy (fMRS) have thus been developed allowing for the reproducible assessment of metabolic changes during barrel cortex (S1BF) activations in rats. The present study aimed at further exploring the role of neurotransmitters on local and temporal changes in vascular and metabolic function in S1BF. fMRS and fMRI data were acquired sequentially in α-chloralose anesthetized rats during 32-min rest and trigeminal nerve stimulation periods. During stimulation, concentrations of lactate (Lac) and glutamate (Glu) increased in S1BF by 0.23±0.05 and 0.34±0.05μmol/g respectively in S1BF. Dynamic analysis of metabolite concentrations allowed estimating changes in cerebral metabolic rates of glucose (ΔCMR Glc ) and oxygen (ΔCMR O2 ). Findings confirmed a prevalence of oxidative metabolism during prolonged S1BF activation. Habituation led to a significant BOLD magnitude decline as a function of time while both total ΔCMR Glc and ΔCMR O2 remained constant revealing adaptation of glucose and oxygen metabolisms to support ongoing trigeminal nerve stimulation. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Effects of PEG-PLA-nano Artificial Cells Containing Hemoglobin on Kidney Function and Renal Histology in Rats

PubMed Central

Liu, Zun Chang; Chang, Thomas M.S.

2012-01-01

This study is to investigate the long-term effects of PEG-PLA nano artificial cells containing hemoglobin (NanoRBC) on renal function and renal histology after 1/3 blood volume top loading in rats. The experimental rats received one of the following infusions: NanoRBC in Ringer lactate, Ringer lactate, stroma-free hemoglobin (SFHB), polyhemoglobin (PolyHb), autologous rat whole blood (rat RBC). Blood samples were taken before infusions and on days 1, 7 and 21 after infusions for biochemistry analysis. Rats were sacrificed on day 21 after infusions and kidneys were excised for histology examination. Infusion of SFHB induced significant decrease in renal function damage evidenced by elevated serum urea, creatinine and uric acid throughout the 21 days. Kidney histology in SFHb infusion group revealed focal tubular necrosis and intraluminal cellular debris in the proximal tubules, whereas the glomeruli were not observed damaged. In all the other groups, NanoRBC, PolyHb, Ringer lactate and rat RBC, there were no abnormalities in renal biochemistry or histology. In conclusion, injection of NanoRBC did not have adverse effects on renal function nor renal histology. PMID:18979292

Dinosaur lactation?

PubMed

Else, Paul L

2013-02-01

Lactation is a process associated with mammals, yet a number of birds feed their newly hatched young on secretions analogous to the milk of mammals. These secretions are produced from various sections (crop organ, oesophageal lining and proventriculus) of the upper digestive tract and possess similar levels of fat and protein, as well as added carotenoids, antibodies and, in the case of pigeons and doves, epidermal growth factor. Parental care in avian species has been proposed to originate from dinosaurs. This study examines the possibility that some dinosaurs used secretory feeding to increase the rate of growth of their young, estimated to be similar to that of present day birds and mammals. Dinosaur 'lactation' could also have facilitated immune responses as well as extending parental protection as a result of feeding newly hatched young in nest environments. While the arguments for dinosaur lactation are somewhat generic, a case study for lactation in herbivorous site-nesting dinosaurs is presented. It is proposes that secretory feeding could have been used to bridge the gap between hatching and establishment of the normal diet in some dinosaurs.

Effects of genistein in the maternal diet on reproductive development and spatial learning in male rats.

PubMed

Ball, Evan R; Caniglia, Mary Kay; Wilcox, Jenna L; Overton, Karla A; Burr, Marra J; Wolfe, Brady D; Sanders, Brian J; Wisniewski, Amy B; Wrenn, Craige C

2010-03-01

Endocrine disruptors, chemicals that disturb the actions of endogenous hormones, have been implicated in birth defects associated with hormone-dependent development. Phytoestrogens are a class of endocrine disruptors found in plants. In the current study we examined the effects of exposure at various perinatal time periods to genistein, a soy phytoestrogen, on reproductive development and learning in male rats. Dams were fed genistein-containing (5 mg/kg feed) food during both gestation and lactation, during gestation only, during lactation only, or during neither period. Measures of reproductive development and body mass were taken in the male offspring during postnatal development, and learning and memory performance was assessed in adulthood. Genistein exposure via the maternal diet decreased body mass in the male offspring of dams fed genistein during both gestation and lactation, during lactation only, but not during gestation only. Genistein decreased anogenital distance when exposure was during both gestation and lactation, but there was no effect when exposure was limited to one of these time periods. Similarly, spatial learning in the Morris water maze was impaired in male rats exposed to genistein during both gestation and lactation, but not in rats exposed during only one of these time periods. There was no effect of genistein on cued or contextual fear conditioning. In summary, the data indicate that exposure to genistein through the maternal diet significantly impacts growth in male offspring if exposure is during lactation. The effects of genistein on reproductive development and spatial learning required exposure throughout the pre- and postnatal periods. Copyright 2009 Elsevier Inc. All rights reserved.

Low arsenic concentrations impair memory in rat offpring exposed during pregnancy and lactation: Role of α7 nicotinic receptor, glutamate and oxidative stress.

PubMed

Mónaco, Nina María; Bartos, Mariana; Dominguez, Sergio; Gallegos, Cristina; Bras, Cristina; Esandi, María Del Carmen; Bouzat, Cecilia; Giannuzzi, Leda; Minetti, Alejandra; Gumilar, Fernanda

2018-04-17

Inorganic arsenic (iAs) is an important natural pollutant. Millions of individuals worldwide drink water with high levels of iAs. Arsenic exposure has been associated to cognitive deficits. However, the underlying mechanisms remain unknown. In the present work we investigated in female adult offspring the effect of the exposure to low arsenite sodium levels through drinking water during pregnancy and lactation on short- and long-term memory. We also considered a possible underlying neurotoxic mechanism. Pregnant rats were exposed during pregnancy and lactation to environmentally relevant iAs concentrations (0.05 and 0.10 mg/L). In 90-day-old female offspring, short-term memory (STM) and long-term memory (LTM) were evaluated using a step-down inhibitory avoidance task. In addition, we evaluated the α7 nicotinic receptor (α7-nAChR) expression, the transaminases and the oxidative stress levels in hippocampus. The results showed that the exposure to 0.10 mg/L iAs in this critical period produced a significant impairment in the LTM retention. This behavioral alteration might be associated with several events that occur in the hippocampus: decrease in α7-nAChR expression, an increase of glutamate levels that may produce excitotoxicity, and a decrease in the antioxidant enzyme catalase (CAT) activity. Copyright © 2018 Elsevier B.V. All rights reserved.

Early lactation production, health, and welfare characteristics of cows selected for extended lactation.

PubMed

Lehmann, J O; Mogensen, L; Kristensen, T

2017-02-01

Some cows are able to achieve relatively high milk yields during extended lactations beyond 305 d in milk, and farmers may be able to use this potential by selecting the most suitable cows for an extended lactation. However, the decision to postpone insemination has to rely on information available in early lactation. The main objectives of this study were, therefore, to assess the association between the information available in early lactation and the relative milk production of cows on extended lactation, and to investigate if this information can be used to differentiate time of first insemination between cows. Data came from 4 Danish private herds practicing extended lactation in which some cows are selected to have a delayed time of planned first insemination. Average herd size varied from 93 to 157 cows, and milk yield varied from 7,842 to 12,315 kg of energy-corrected milk (ECM) per cow per year across herds. The analysis was based on 422 completed extended lactations (427 ± 87 d), and each lactation was assigned to 1 of 3 (low, medium, and high) milk performance groups (MPG) within parity group within herd based on a standardized lactation yield. For cows in the high MPG, peak ECM yield, and ECM yield at dry off were significantly greater, the relative reduction in milk yield between 60 and 305 d in milk was significantly smaller, and a smaller proportion had a body condition score (scale: 1-5) at dry off of 3.5 or greater compared with cows in low MPG. Previous lactation days in milk at peak ECM yield and ECM yield at dry off were higher, the relative reduction in milk yield between 60 and 305 d in milk was smaller, and the number of inseminations per conception was higher for multiparous cows in high MPG compared with low. Current lactation ECM yield at second and third milk recording were greater for cows in high MPG compared with low. A principal component analysis indicated that variables related to fertility, diseases, and milk yield explained most

Direct evidence for activity-dependent glucose phosphorylation in neurons with implications for the astrocyte-to-neuron lactate shuttle

PubMed Central

Patel, Anant B.; Lai, James C. K.; Chowdhury, Golam M. I.; Hyder, Fahmeed; Rothman, Douglas L.; Shulman, Robert G.; Behar, Kevin L.

2014-01-01

Previous 13C magnetic resonance spectroscopy experiments have shown that over a wide range of neuronal activity, approximately one molecule of glucose is oxidized for every molecule of glutamate released by neurons and recycled through astrocytic glutamine. The measured kinetics were shown to agree with the stoichiometry of a hypothetical astrocyte-to-neuron lactate shuttle model, which predicted negligible functional neuronal uptake of glucose. To test this model, we measured the uptake and phosphorylation of glucose in nerve terminals isolated from rats infused with the glucose analog, 2-fluoro-2-deoxy-d-glucose (FDG) in vivo. The concentrations of phosphorylated FDG (FDG6P), normalized with respect to known neuronal metabolites, were compared in nerve terminals, homogenate, and cortex of anesthetized rats with and without bicuculline-induced seizures. The increase in FDG6P in nerve terminals agreed well with the increase in cortical neuronal glucose oxidation measured previously under the same conditions in vivo, indicating that direct uptake and oxidation of glucose in nerve terminals is substantial under resting and activated conditions. These results suggest that neuronal glucose-derived pyruvate is the major oxidative fuel for activated neurons, not lactate-derived from astrocytes, contradicting predictions of the original astrocyte-to-neuron lactate shuttle model under the range of study conditions. PMID:24706914

Direct evidence for activity-dependent glucose phosphorylation in neurons with implications for the astrocyte-to-neuron lactate shuttle.

PubMed

Patel, Anant B; Lai, James C K; Chowdhury, Golam M I; Hyder, Fahmeed; Rothman, Douglas L; Shulman, Robert G; Behar, Kevin L

2014-04-08

Previous (13)C magnetic resonance spectroscopy experiments have shown that over a wide range of neuronal activity, approximately one molecule of glucose is oxidized for every molecule of glutamate released by neurons and recycled through astrocytic glutamine. The measured kinetics were shown to agree with the stoichiometry of a hypothetical astrocyte-to-neuron lactate shuttle model, which predicted negligible functional neuronal uptake of glucose. To test this model, we measured the uptake and phosphorylation of glucose in nerve terminals isolated from rats infused with the glucose analog, 2-fluoro-2-deoxy-D-glucose (FDG) in vivo. The concentrations of phosphorylated FDG (FDG6P), normalized with respect to known neuronal metabolites, were compared in nerve terminals, homogenate, and cortex of anesthetized rats with and without bicuculline-induced seizures. The increase in FDG6P in nerve terminals agreed well with the increase in cortical neuronal glucose oxidation measured previously under the same conditions in vivo, indicating that direct uptake and oxidation of glucose in nerve terminals is substantial under resting and activated conditions. These results suggest that neuronal glucose-derived pyruvate is the major oxidative fuel for activated neurons, not lactate-derived from astrocytes, contradicting predictions of the original astrocyte-to-neuron lactate shuttle model under the range of study conditions.

High postnatal susceptibility of hippocampal cytoskeleton in response to ethanol exposure during pregnancy and lactation.

PubMed

Reis, Karina Pires; Heimfarth, Luana; Pierozan, Paula; Ferreira, Fernanda; Loureiro, Samanta Oliveira; Fernandes, Carolina Gonçalves; Carvalho, Rônan Vivian; Pessoa-Pureur, Regina

2015-11-01

Ethanol exposure to offspring during pregnancy and lactation leads to developmental disorders, including central nervous system dysfunction. In the present work, we have studied the effect of chronic ethanol exposure during pregnancy and lactation on the phosphorylating system associated with the astrocytic and neuronal intermediate filament (IF) proteins: glial fibrillary acidic protein (GFAP), and neurofilament (NF) subunits of low, medium, and high molecular weight (NFL, NFM, and NFH, respectively) in 9- and 21-day-old pups. Female rats were fed with 20% ethanol in their drinking water during pregnancy and lactation. The homeostasis of the IF phosphorylation was not altered in the cerebral cortex, cerebellum, or hippocampus of 9-day-old pups. However, GFAP, NFL, and NFM were hyperphosphorylated in the hippocampus of 21-day-old pups. PKA had been activated in the hippocampus, and Ser55 in the N-terminal region of NFL was hyperphosphorylated. In addition, JNK/MAPK was activated and KSP repeats in the C-terminal region of NFM were hyperphosphorylated in the hippocampus of 21-day-old pups. Decreased NFH immunocontent but an unaltered total NFH/phosphoNFH ratio suggested altered stoichiometry of NFs in the hippocampus of ethanol-exposed 21-day-old pups. In contrast to the high susceptibility of hippocampal cytoskeleton in developing rats, the homeostasis of the cytoskeleton of ethanol-fed adult females was not altered. Disruption of the cytoskeletal homeostasis in neural cells supports the view that regions of the brain are differentially vulnerable to alcohol insult during pregnancy and lactation, suggesting that modulation of JNK/MAPK and PKA signaling cascades target the hippocampal cytoskeleton in a window of vulnerability in 21-day-old pups. Our findings are relevant, since disruption of the cytoskeleton in immature hippocampus could contribute to later hippocampal damage associated with ethanol toxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of maternal and lactational exposure to 2-hydroxy-4-methoxybenzone on development and reproductive organs in male and female rat offspring

PubMed Central

Nakamura, Noriko; Inselman, Amy L.; White, Gene A.; Chang, Ching-Wei; Trbojevich, Raul A.; Sepehr, Estatira; Voris, Kristie L.; Patton, Ralph E.; Bryant, Matthew S.; Harrouk, Wafa; McIntyre, Barry; Foster, Paul M.; Hansen, Deborah K.

2015-01-01

BACKGROUND 2-hydroxy-4-methoxybenzophenone (HMB) is an ultraviolet (UV)-absorbing compound used in many cosmetic products as a UV-protecting agent and in plastics for preventing UV-induced photodecomposition. HMB has been detected in over 95% of randomly collected human urine samples from adults and from premature infants, and it may have estrogenic potential. METHODS To determine the effects of maternal and lactational exposure to HMB on development and reproductive organs of offspring, time-mated female Harlan Sprague-Dawley rats were dosed with 0, 1,000, 3,000, 10,000, 25,000, or 50,000 ppm HMB (7-8 per group) added to chow from gestation day 6 until weaning on postnatal day (PND) 23. RESULTS AND CONCLUSION Exposure to HMB was associated with reduced body and organ weights in female and male offspring. No significant differences were observed in the number of implantation sites/litter, mean resorptions/litter, % litters with resorptions, number and weights of live fetuses, or sex ratios between the control and HMB dose groups. Normalized anogenital distance in male pups at PND 23 was decreased in the highest dose group. Spermatocyte development was impaired in testes of male offspring in the highest dose group. In females, follicular development was delayed in the highest dose group. However, by evaluating levels of the compound in rat serum, the doses at which adverse events occurred are much higher than usual human exposure levels. Thus, exposure to less than 10,000 ppm HMB does not appear to be associated with adverse effects on the reproductive system in rats. PMID:25707689

Metabolic syndrome and selenium during gestation and lactation.

PubMed

Nogales, Fátima; Ojeda, M Luisa; Del Valle, Paulina Muñoz; Serrano, Alejandra; Murillo, M Luisa; Carreras Sánchez, Olimpia

2017-03-01

Selenium (Se) has a dual role in metabolic syndrome (MS) development as it has an antioxidant action against both "good" and "bad" reactive oxygen species. This study evaluates Se body profile in dams which present MS during gestation and lactation, in order to elucidate a normal dietary Se's implication in this pathology. Rats were randomized into control (C) and fructose (F) groups. The rich fructose diet (65 %) during gestation and lactation periods induced MS in dams. Se body distribution was determined by atomic absorption spectrophotometry, and the hepatic activity of the four antioxidant enzymes and the bimolecular oxidation were determined by spectrophotometry. The cardiac activity was monitored using the indirect tail occlusion method. Lipid and glucidic profile was also analyzed. Despite the fact that the diet supplied has 0.1 ppm of Se, the minimal dietary requirement for rats, F dams ate less amount of food, and therefore, they had lower Se retention. However, they had normal levels of Se in serum and milk. Dams with MS had Se depletion in heart and muscle joint to hypertension and a lower heart rate, and Se repletion in liver and kidney. Despite the increase in hepatic glutathione peroxidase (GPx) and catalase activity found, lipid oxidation occurred-probably because superoxide dismutase activity was diminished. In heart, the activity and expression of the selenoprotein GPx1 were decreased. With these results, it is not possible to elucidate whether a dietary Se supplementation or a Se-restricted diet are good for MS; because despite the fact that GPx activity is increased in liver, it is also found, for the first time, that heart Se deposits are significantly decreased during MS.

Acidosis mediates recurrent hypoglycemia-induced increase in ischemic brain injury in treated diabetic rats.

PubMed

Rehni, Ashish K; Shukla, Vibha; Perez-Pinzon, Miguel A; Dave, Kunjan R

2018-03-15

Cerebral ischemia is a serious possible manifestation of diabetic vascular disease. Recurrent hypoglycemia (RH) enhances ischemic brain injury in insulin-treated diabetic (ITD) rats. In the present study, we determined the role of ischemic acidosis in enhanced ischemic brain damage in RH-exposed ITD rats. Diabetic rats were treated with insulin and mild/moderate RH was induced for 5 days. Three sets of experiments were performed. The first set evaluated the effects of RH exposure on global cerebral ischemia-induced acidosis in ITD rats. The second set evaluated the effect of an alkalizing agent (Tris-(hydroxymethyl)-aminomethane: THAM) on ischemic acidosis-induced brain injury in RH-exposed ITD rats. The third experiment evaluated the effect of the glucose transporter (GLUT) inhibitor on ischemic acidosis-induced brain injury in RH-exposed ITD rats. Hippocampal pH and lactate were measured during ischemia and early reperfusion for all three experiments. Neuronal survival in Cornu Ammonis 1 (CA1) hippocampus served as a measure of ischemic brain injury. Prior RH exposure increases lactate concentration and decreases pH during ischemia and early reperfusion when compared to controls. THAM and GLUT inhibitor treatments attenuated RH-induced increase in ischemic acidosis. GLUT inhibitor treatment reduced the RH-induced increase in lactate levels. Both THAM and GLUT inhibitor treatments significantly decreased ischemic damage in RH-exposed ITD rats. Ischemia causes increased acidosis in RH-exposed ITD rats via a GLUT-sensitive mechanism. Exploring downstream pathways may help understand mechanisms by which prior exposure to RH increases cerebral ischemic damage. Copyright © 2018 Elsevier Ltd. All rights reserved.

Comparative studies on fatty acid synthesis, glycogen metabolism, and gluconeogenesis by hepatocytes isolated from lean and obese Zucker rats.

PubMed

McCune, S A; Durant, P J; Jenkins, P A; Harris, R A

1981-12-01

Hepatocytes isolated from genetically obese female Zucker rats and lean female Zucker rats were compared. Hepatocytes from fed obese rats exhibited greater rates of fatty acid synthesis, more extensive accumulation of lactate and pyruvate from their glycogen stores, increased rates of net glucose utilization but produced less ketone bodies from exogenous fatty acids and had lower citrate levels than hepatocytes from lean rats. Lipogenesis was not as sensitive to dibutyryl cyclic AMP (DBcAMP) inhibition in hepatocytes from obese rats but glycogenolysis was stimulated to the same extent by this nucleotide in both preparations. Ketogenesis was less sensitive to stimulation by DBcAMP in hepatocytes from obese rats. A difference in sensitivity of lipogenesis to DBcAMP was not found when lactate plus pyruvate was added to the incubation medium, suggesting that a greater rate of glycolysis by hepatocytes from obese rats accounts for their relative insensitivity to DBcAMP. Citrate levels were elevated by DBcAMP to a greater extent in hepatocytes from obese rats. Hepatocytes prepared from lean rats starved for 48 hr were glycogen depleted and lacked significant capacity for lipogenesis and glycogen synthesis. In contrast, hepatocytes isolated from starved obese rats retained considerable amounts of liver glycogen and exhibited detectable rates of lipogenesis and glycogen synthesis. Hepatocytes prepared from starved lean rats gave faster apparent rates of lactate gluconeogenesis than hepatocytes prepared from starved obese rats. Thus, hepatocytes prepared from obese Zucker rats are more glycogenic, glycolytic, and lipogenic but less ketogenic and glucogenic than hepatocytes prepared from lean rats.

Maternal protein-free diet during lactation programs male Wistar rat offspring for increased novelty-seeking, locomotor activity, and visuospatial performance.

PubMed

Lotufo, Bruna M; Tenório, Frank; Barradas, Penha C; Guedes, Paulo L; Lima, Sebastião S; Rocha, Michael L M; Duarte-Pinheiro, Vitor Hugo; Rodrigues, Vanessa S T; Lisboa, Patrícia C; Filgueiras, Cláudio C; Abreu-Villaça, Yael; Manhães, Alex C

2018-04-01

It is well established that chronic undernutrition has detrimental impacts on brain development and maturation. However, protein malnutrition during the period specifically encompassing the brain growth spurt has not been widely studied, particularly regarding its effects on adolescent and adult offspring behavior. Here, we assessed the effects of a protein-free diet during the 1st 10 postnatal days on the macronutrient content of the milk produced by lactating Wistar rats, on their maternal behavior, and on the offspring's behavior. Lactating dams were fed either a protein-free or a normoprotein diet from litter parturition to Postnatal Day 10 (P10). All dams received the normoprotein diet after P10. Offspring were tested in the elevated plus-maze (anxiety-like behavior), hole board arena (novelty-seeking and locomotor activity), and radial arm water maze (memory-learning) at either P40 (adolescents) or P90 (adults). The protein-free diet reduced milk protein content at P10 but not at P20. Carbohydrate and lipid contents were unaffected. Serum corticosterone levels in the offspring (at P10, P40, or P90) and dams (at P21) were not affected by the protein-free diet. Maternal behavior was also unchanged. In the offspring, no differences were observed between groups regarding anxiety-like behaviors at both ages. The protein-free diet increased adolescent locomotor activity as well as adult novelty-seeking behavior and memory performance. Our results indicate that the brain growth spurt period is particularly sensitive to protein malnutrition, showing that even a brief nutritional insult during this period can cause specific age-dependent behavioral effects on the offspring. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

A Review of Worksite Lactation Accommodations.

PubMed

Hilliard, Elizabeth Dianne

2017-01-01

The purpose of this review was to examine workplace lactation accommodations, and their association with breastfeeding duration, and identify strategies occupational health professionals can use to promote lactation improvements. This study included literature published from 1985 through 2015 and listed in PubMed and CINAHL. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), 11 articles were identified for review. Presence of a corporate lactation program, on-site child care, and return to work/telephone lactation consultation were consistently associated with breastfeeding at 6 months. Other breastfeeding accommodations (i.e., lactation spaces, lactation breaks, worksite lactation policies, and supervisor/coworker support) were not consistently associated with breastfeeding duration. Occupational health professionals can play key roles in improving the effectiveness of lactation accommodations. Assuring adequate implementation of accommodations, increasing communication and marketing of accommodations, and promoting supervisor and coworker support are areas that occupational health professionals should explore for improving lactation duration.

Characterization of sustained BOLD activation in the rat barrel cortex and neurochemical consequences.

PubMed

Just, Nathalie; Xin, Lijing; Frenkel, Hanne; Gruetter, Rolf

2013-07-01

To date, only a couple of functional MR spectroscopy (fMRS) studies were conducted in rats. Due to the low temporal resolution of (1)H MRS techniques, prolonged stimulation paradigms are necessary for investigating the metabolic outcome in the rat brain during functional challenge. However, sustained activation of cortical areas is usually difficult to obtain due to neural adaptation. Anesthesia, habituation, high variability of the basal state metabolite concentrations as well as low concentrations of the metabolites of interest such as lactate (Lac), glucose (Glc) or γ-aminobutyric acid (GABA) and small expected changes of metabolite concentrations need to be addressed. In the present study, the rat barrel cortex was reliably and reproducibly activated through sustained trigeminal nerve (TGN) stimulation. In addition, TGN stimulation induced significant positive changes in lactate (+1.01 μmol/g, p<0.008) and glutamate (+0.92 μmol/g, p<0.02) and significant negative aspartate changes (-0.63 μmol/g, p<0.004) using functional (1)H MRS at 9.4 T in agreement with previous changes observed in human fMRS studies. Finally, for the first time, the dynamics of lactate, glucose, aspartate and glutamate concentrations during sustained somatosensory activation in rats using fMRS were assessed. These results allow demonstrating the feasibility of fMRS measurements during prolonged barrel cortex activation in rats. Copyright © 2013 Elsevier Inc. All rights reserved.

Effective Treatment of Traumatic Brain Injury in Rowett Nude Rats with Stromal Vascular Fraction Transplantation.

PubMed

Berman, Sean; Uhlendorf, Toni L; Berman, Mark; Lander, Elliot B

2018-06-18

Traumatic brain injury (TBI) affects 1.9 million Americans, including blast TBI that is the signature injury of the Iraq and Afghanistan wars. Our project investigated whether stromal vascular fraction (SVF) can assist in post-TBI recovery. We utilized strong acoustic waves (5.0 bar) to induce TBI in the cortex of adult Rowett Nude (RNU) rats. One hour post-TBI, harvested human SVF (500,000 cells suspended in 0.5 mL lactated Ringers) was incubated with Q-Tracker cell label and administered into tail veins of RNU rats. For comparison, we utilized rats that received SVF 72 h post-TBI, and a control group that received lactated Ringers solution. Rotarod and water maze assays were used to monitor motor coordination and spatial memories. Rats treated immediately after TBI showed no signs of motor skills and memory regression. SVF treatment 72 h post-TBI enabled the rats maintain their motor skills, while controls treated with lactated Ringers were 25% worse statistically in both assays. Histological analysis showed the presence of Q-dot labeled human cells near the infarct in both SVF treatment groups; however, labeled cells were twice as numerous in the one hour group. Our study suggests that immediate treatment with SVF would serve as potential therapeutic agents in TBI.

Therapeutic mild hypothermia improves early outcomes in rats subjected to severe sepsis.

PubMed

Ding, Wu; Shen, Yuehong; Li, Qiang; Jiang, Shouyin; Shen, Huahao

2018-04-15

Therapeutic hypothermia has shown beneficial effects in sepsis. This study focused on its mechanism. Sixteen male Sprague-Dawley rats underwent cecal ligation and perforation and subsequently were treated with either hypothermia (HT; body temperature cooled and maintained at 34 °C by ice pad for 10 h; n = 8) or normothermia (NT; n = 8). Three additional rats underwent sham surgery. The body temperatures of the sham-operated and NT groups were maintained at 38 °C with a thermal pad. After the hypothermia treatment, the HT rats were rewarmed for 2 h. The groups were compared for circulating cytokines (IL-6, IL-10), lactate, high mobility group box-1 protein (HMGB1), and lung and intestinal lesions. Animals were observed for 24 h. Compared with the sham-operated group, the 2 sepsis group rats had significantly higher circulating IL-6, HMGB1, and lactate levels, and tissue injury. In the HT rats, the levels of IL-6, HMGB1, and lactate, the lung wet-to-dry ratio, and lung and intestinal damage were significantly lower than that of the NT group. Circulating IL-10 levels increased significantly after 12 h in the sepsis groups compared with sham animals, while that of the NT and HT groups were comparable. The survival rates of the NT and HT rats were also comparable. Therapeutic hypothermia in a rat model of sepsis was associated with lower levels of circulating IL-6 and HMGB1, and less capillary leakage and tissue edema. These results suggest that mild hypothermia has potential as a therapy in sepsis. Copyright © 2018 Elsevier Inc. All rights reserved.

Continuous Aerobic Training in Individualized Intensity Avoids Spontaneous Physical Activity Decline and Improves MCT1 Expression in Oxidative Muscle of Swimming Rats.

PubMed

Scariot, Pedro P M; Manchado-Gobatto, Fúlvia de Barros; Torsoni, Adriana S; Dos Reis, Ivan G M; Beck, Wladimir R; Gobatto, Claudio A

2016-01-01

Although aerobic training has been shown to affect the lactate transport of skeletal muscle, there is no information concerning the effect of continuous aerobic training on spontaneous physical activity (SPA). Because every movement in daily life (i.e., SPA) is generated by skeletal muscle, we think that it is possible that an improvement of SPA could affect the physiological properties of muscle with regard to lactate transport. The aim of this study was to evaluate the effect of 12 weeks of continuous aerobic training in individualized intensity on SPA of rats and their gene expressions of monocarboxylate transporters (MCT) 1 and 4 in soleus (oxidative) and white gastrocnemius (glycolytic) muscles. We also analyzed the effect of continuous aerobic training on aerobic and anaerobic parameters using the lactate minimum test (LMT). Sixty-day-old rats were randomly divided into three groups: a baseline group in which rats were evaluated prior to initiation of the study; a control group (Co) in which rats were kept without any treatment during 12 weeks; and a chronic exercise group (Tr) in which rats swam for 40 min/day, 5 days/week at 80% of anaerobic threshold during 12 weeks. After the experimental period, SPA of rats was measured using a gravimetric method. Rats had their expression of MCTs determined by RT-PCR analysis. In essence, aerobic training is effective in maintaining SPA, but did not prevent the decline of aerobic capacity and anaerobic performance, leading us to propose that the decline of SPA is not fully attributed to a deterioration of physical properties. Changes in SPA were concomitant with changes in MCT1 expression in the soleus muscle of trained rats, suggestive of an additional adaptive response toward increased lactate clearance. This result is in line with our observation showing a better equilibrium on lactate production-remotion during the continuous exercise (LMT). We propose an approach to combat the decline of SPA of rats in their home

n-Octyl gallate as inhibitor of pyruvate carboxylation and lactate gluconeogenesis.

PubMed

Eler, Gabrielle Jacklin; Santos, Israel Souza; de Moraes, Amarilis Giaretta; Comar, Jurandir Fernando; Peralta, Rosane Marina; Bracht, Adelar

2015-04-01

The alkyl gallates are found in several natural and industrial products. In the latter products, these compounds are added mainly for preventing oxidation. In the present work, the potencies of methyl gallate, n-propyl gallate, n-pentyl gallate, and n-octyl gallate as inhibitors of pyruvate carboxylation and lactate gluconeogenesis were evaluated. Experiments were done with isolated mitochondria and the isolated perfused rat liver. The potency of the gallic acid esters as inhibitors of pyruvate carboxylation in isolated mitochondria obeyed the following decreasing sequence: n-octyl gallate > n-pentyl gallate > n-propyl gallate > methyl gallate. A similar sequence of decreasing potency for lactate gluconeogenesis inhibition in the perfused liver was found in terms of the portal venous concentration. Both actions correlate with the lipophilicity of the compounds. The effects are harmful at high concentrations. At appropriate concentrations, however, octyl gallate should act therapeutically because its inhibitory action on gluconeogenesis will contribute further to its proposed antihyperglycemic effects. © 2014 Wiley Periodicals, Inc.

Inhibition of monocarboxylate transporter 2 in the retrotrapezoid nucleus in rats – a test of the astrocyte-neuron lactate-shuttle hypothesis

PubMed Central

Erlichman, J.S.; Hewitt, Amy; Damon, Tracey L.; Hart, Michael; Kurascz, Jennifer; Li, A.; Leiter, J.C.

2009-01-01

The astrocyte-neuronal lactate shuttle hypothesis (ANLSH) posits that lactate released from astrocytes into the extracellular space is metabolized by neurons. The lactate released should alter extracellular pH (pHe), and changes in pH in central chemosensory regions of the brainstem stimulate ventilation. Therefore, we assessed the impact of disrupting the lactate shuttle by administering 100 microM α-cyano-4-hydroxy-cinnamate (4-CIN), a dose that blocks the neuronal monocarboxylate transporter (MCT2), but not the astrocytic MCTs (MCT1 and MCT4). Administration of 4-CIN focally in the retrotrapezoid nucleus (RTN), a medullary central chemosensory nucleus, increased ventilation and decreased pHe in intact animals. In medullary brain slices, 4-CIN reduced astrocytic intracellular pH (pHi) slightly, but alkalinized neuronal pHi. Nonetheless, pHi fell significantly in both cell types when they were treated with exogenous lactate, although 100 microM 4-CIN significantly reduced the magnitude of the acidosis in neurons, but not astrocytes. Finally, 4-CIN treatment increased the uptake of a fluorescent 2-deoxy-d-glucose analogue in neurons, but did not alter the uptake rate of this 2-deoxy-d-glucose analogue in astrocytes. These data confirm the existence of an astrocyte to neuron lactate shuttle in intact animals in the RTN, and lactate derived from astrocytes forms part of the central chemosensory stimulus for ventilation in this nucleus. When the lactate shuttle was disrupted by treatment with 4-CIN, neurons increased the uptake of glucose. Thus, neurons seem to metabolize a combination of glucose and lactate (and other substances such as pyruvate) depending, in part, on the availability of each of these particular substrates. PMID:18463242

A Lactate Kinetics Method for Assessing the Maximal Lactate Steady State Workload

PubMed Central

Hering, Gernot O.; Hennig, Ewald M.; Riehle, Hartmut J.; Stepan, Jens

2018-01-01

During a continuously increasing exercise workload (WL) a point will be reached at which arterial lactate accumulates rapidly. This so-called lactate threshold (LT) is associated with the maximal lactate steady state workload (MLSSW), the highest WL, at which arterial lactate concentration [LA] does not change. However, the physiological range in which the LT and the MLSSW occur has not been demonstrated directly. We used minor WL variations in the MLSSW range to assess arterial lactate kinetics in 278 treadmill and 148 bicycle ergometer exercise tests. At a certain workload, minimal further increment of running speed (0.1–0.15 m/s) or cycling power (7–10 W) caused a steep elevation of [LA] (0.9 ± 0.43 mM, maximum increase 2.4 mM), indicating LT achievement. This sharp [LA] increase was more pronounced when higher WL increments were used (0.1 vs. 0.30 m/s, P = 0.02; 0.15 vs. 0.30 m/s, P < 0.001; 7 vs. 15 W, P = 0.002; 10 vs. 15 W, P = 0.001). A subsequent workload reduction (0.1 m/s/7 W) stopped the [LA] increase indicating MLSSW realization. LT based determination of running speed (MLSSW) was highly reproducible on a day-to-day basis (r = 0.996, P < 0.001), valid in a 10 km constant velocity setting (r = 0.981, P < 0.001) and a half marathon race (r = 0.969, P < 0.001). These results demonstrate a fine-tuned regulation of exercise-related lactate metabolism, which can be reliably captured by assessing lactate kinetics at the MLSSW. PMID:29651253

Testosterone and muscle hypertrophy in female rats

NASA Technical Reports Server (NTRS)

Kuhn, F. E.; Max, S. R.

1985-01-01

The effects of chronic treatment with testosterone propionate (TP) on compensatory muscle hypertropy in female rats are examined. The 48 female rats were placed in one of four test groups: (1) no overload (synergist removal), no TP, (2) overload, no TP, (3) no overload + TP, and (4) overload + TP. The technique used to administer the TP is described. The preparation of the plantaris muscle, the analysis of pyruvate oxidation and the determination of malate and lactate dehydrogenases and the noncollogen protein are explained. The results which reveal the effect of overload and TP on body weight, noncollogen protein concentration, lactate and malate dehydrogenase activities, and pyruvate oxidation are presented and discussed. It is concluded that in terms of body weight, protein content, pyruvate, glycolysis, and oxidative metabolisms chronic TP treatments do not change compensatory muscle hypertropy.

Improvement of exercise capacity of rats with chronic heart failure by long-term treatment with trandolapril

PubMed Central

Yamaguchi, Fuminari; Kawana, Ken-ichiro; Tanonaka, Kouichi; Kamano, Isamu; Igarashi, Takahiro; Gen, Eigyoku; Fujimoto, Yoko; Maki, Toshiyuki; Sanbe, Atsushi; Nasa, Yoshihisa; Takeo, Satoshi

1999-01-01

The effects of long-term treatment with trandolapril, an angiotensin I-converting enzyme inhibitor, on exercise capacity of rats with chronic heart failure (CHF) following coronary artery ligation were examined. CHF was developed by 8 weeks after the coronary artery ligation. The running time of rats with CHF in the treadmill test was shortened to approximately 65% of that of sham-operated rats (16.3±1.2 vs 25.1±1.6 min, n=7; P<0.05). ATP, creatine phosphate (CP), and lactate contents of the gracilis muscle of rats with CHF were similar to those of sham-operated rats before running. After running, ATP and CP were decreased and lactate was increased in both rats with CHF and sham-operated rats. There were no significant differences in the levels of energy metabolites between rats with CHF and sham-operated rats. The rates of decrease in ATP and CP and rate of increase in lactate in the gracilis muscle of rats with CHF during exercise were greater than those of sham operated rats (2.5, 2.0 and 1.5 fold high, respectively), suggesting wastage of energy during exercise in the animals with CHF. Myofibrillar Ca2+-stimulated ATPase (Ca-ATPase) activity of skeletal muscle of rats with CHF was increased over that of the sham-operated control (62.03±1.88 vs 52.34±1.19 μmol Pi mg−1 protein h−1 n=7; P<0.05). The compositions of myosin heavy chain (MHC) isoforms of gracilis muscle were altered by CHF; decreases in MHC types I and IIb and an increase in MHC type IIa were found (P<0.05). Rats with CHF were treated with 1 mg kg−1 day−1 trandolapril from the 2nd to 8th week after surgery. Treatment with trandolapril prolonged the running time, reversed the rates of decrease in ATP and CP and the rate of increase in lactate, and restored the Ca-ATPase activity (51.11±0.56 μmol Pi mg−1 protein h−1, n=7; P<0.05) and composition ratio of MHC isoforms in the gracilis muscle. The results suggest that long-term trandolapril treatment of rats with CHF

Elevated lactate during psychogenic hyperventilation.

PubMed

ter Avest, E; Patist, F M; Ter Maaten, J C; Nijsten, M W N

2011-04-01

Elevated arterial lactate levels are closely related to morbidity and mortality in various patient categories. In the present retrospective study, the relation between arterial lactate, partial pressure of carbon dioxide (Pco(2)) and pH was systematically investigated in patients who visited the emergency department (ED) with psychogenic hyperventilation. Over a 5-month period, all the patients who visited the ED of a university hospital with presumed psychogenic hyperventilation were evaluated. Psychogenic hyperventilation was presumed to be present when an increased respiratory rate (>20 min) was documented at or before the ED visit and when somatic causes explaining the hyperventilation were absent. Arterial blood gas and lactate levels (reference values 0.5-1.5 mmol/l) were immediately measured by a point-of-care analyser that was managed and calibrated by the central laboratory. During the study period, 46 patients were diagnosed as having psychogenic hyperventilation. The median (range) Pco(2) for this group was 4.3 (2.0-5.5) kPa, the pH was 7.47 (7.40-7.68) and the lactate level was 1.2 (0.5-4.4) mmol/l. 14 participants (30%) had a lactate level above the reference value of 1.5 mmol/l. Pco(2) was the most important predictor of lactate in multivariate analysis. None of the participants underwent any medical treatment other than observation at the ED or had been hospitalised after their ED visit. In patients with psychogenic hyperventilation, lactate levels are frequently elevated. Whereas high lactates are usually associated with acidosis and an increased risk of poor outcome, in patients with psychogenic hyperventilation, high lactates are associated with hypocapnia and alkalosis. In this context, elevated arterial lactate levels should not be regarded as an adverse sign.

Evaluation of anaerobic threshold in non-pregnant and pregnant rats.

PubMed

Netto, Aline Oliveira; Macedo, Nathália C D; Gallego, Franciane Q; Sinzato, Yuri K; Volpato, Gustavo T; Damasceno, Débora C

2017-01-01

Several studies present different methodologies and results about intensity exercise, and many of them are performed in male rats. However, the impact of different type, intensity, frequency and duration of exercise on female rats needs more investigation. From the analysis of blood lactate concentration during lactate minimum test (LacMin) in the swimming exercise, the anaerobic threshold (AT) was identified, which parameter is defined as the transition point between aerobic and anaerobic metabolism. LacMin test is considered a good indicator of aerobic conditioning and has been used in prescription of training in different exercise modalities. However, there is no evidence of LacMin test in female rats. The objective was to determine AT in non-pregnant and pregnant Wistar rats. The LacMin test was performed and AT defined for mild exercise intensity was from a load equivalent to 1% of body weight (bw), moderate exercise as carrying 4% bw and severe intensity as carrying 7% bw. In pregnant rats, the AT was reached at a lower loading from 5.0% to 5.5% bw, while in non-pregnant the load was from 5.5% to 6.0% bw. Thus, this study was effective to identify exercise intensities in pregnant and non-pregnant rats using anaerobic threshold by LacMin test.

In utero and lactational β-carotene supplementation attenuates D-galactose-induced hearing loss in newborn rats.

PubMed

Yu, Fei; Hao, Shuai; Zhao, Yue; Yang, Hui; Fan, Xiao-Lan; Yang, Jun

2011-08-01

D-Galactose could give rise to free radical damage by disturbing the some maternal antioxidants. The oxidative stress induced by D-galactose is a potent inducer of apoptosis, which is accompanied by the activation of protein-splitting enzymes called caspases. Apoptosis is a crucial physiological determinant of embryonic and neonatal development, and play an essential role in the development of the inner ear structures. Recently the increasing of D-galactose exposure is due to high consumption of dairy foods or reduced galactose metabolism. An overwhelming presence of D-galactose is known to become highly ototoxicity to humans. The purpose of this study was to investigate whether supplementation of pregnant and lactational mothers with β-carotene could attenuate cochlear function damage and hair cells apoptosis induced by d-galactose in newborn rats. Pregnant rats were supplemented with D-galactose, or D-galactose and β-carotene from gestational day (GD) 7 until postnatal day (PND) 21. On PND 22, offspring were examined in the distortion product otoacoustic emission (DPOAE) task, cochleae were then harvested for assessment of apoptosis by immunohistochemical stain for cysteine-aspartic acid proteases 3 (caspase-3) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. Maternal and offspring blood samples were then collected by direct cardiac puncture in heparin tubes, blood levels of D-galactose and β-carotene were measured, plasma was separated for malondialdehyde (MDA) analysis, erythrocytes were left for superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione (GSH). D-Galactose could significantly disturb the balance between maternal antioxidants and free radicals, and induce hearing loss in the offspring and cochlear hair cell apoptosis. In contrast, β-carotene supplementation, coincidentally with D-galactose exposure, ameliorated these changes. Our data offer a conceptual framework for designing

Foetal and lactational exposure to alcohol increases oxidative capacity of brown adipose tissue in the rat. A possible relationship to cot death.

PubMed Central

Huttunen, P.; Kortelainen, M. L.; Hirvonen, J.

1989-01-01

The effect was studied of chronic alcohol intake in the rat during pregnancy and lactation on the brown adipose tissue (BAT) in pups. The idea was to find a possible relationship to cot death since in some cot death victims increased amounts of BAT have been observed. Exposure to ethanol increased the relative weight of the brown adipose tissue in pups and enhanced both its total protein content and the activities of the oxidative enzymes, succinate dehydrogenase and cytochrome oxidase. In the BAT of pups sympathetic activity, as demonstrated by noradrenaline, was also increased by long-term exposure to alcohol. In theory, an increased thermogenic capacity of the BAT in the newborn together with other factors such as emotional stress and infections could lead to death from hyperthermia, in which case only non-specific morphological signs would be found in the cadaver. PMID:2605116

Lactate: link between glycolytic and oxidative metabolism.

PubMed

Brooks, George A

2007-01-01

Once thought to be the consequence of oxygen lack in contracting skeletal muscle, the glycolytic product lactate is formed and utilised continuously under fully aerobic conditions. 'Cell-cell' and 'intracellular lactate shuttle' concepts describe the roles of lactate in delivery of oxidative and gluconeogenic substrates as well as in cell signalling. Examples of cell-cell shuttles include lactate exchanges (i) between white-glycolytic and red-oxidative fibres within a working muscle bed; (ii) between working skeletal muscle and heart; and (iii) between tissues of net lactate release and gluconeogenesis. Lactate shuttles exist in diverse tissues including in the brain, where a shuttle between astrocytes and neurons is linked to glutamatergic signalling. Because lactate, the product of glycogenolysis and glycolysis, is disposed of by oxidative metabolism, lactate shuttling unites the two major processes of cellular energy transduction. Lactate disposal is mainly through oxidation, especially during exercise when oxidation accounts for 70-75% of removal and gluconeogenesis the remainder. Lactate flux occurs down proton and concentration gradients that are established by the mitochondrial lactate oxidation complex. Marathon running is a power activity requiring high glycolytic and oxidative fluxes; such activities require lactate shuttling. Knowledge of the lactate shuttle is yet to be imparted to the sport.

Effect of dietary protein quality and feeding level on milk secretion and mammary protein synthesis in the rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sampson, D.A.; Jansen, G.R.

1985-04-01

Protein synthesis was studied in mammary tissue of rats fed diets deficient in protein quality and/or restricted in food intake throughout gestation and lactation. Diets containing 25% wheat gluten (WG), wheat gluten plus lysine and threonine (WGLT), or casein (C) were pair-fed from conception until day 15 of lactation at 100% or 85% of WG ad libitum consumption (PF100 and PF85, respectively). A seventh group was fed C ad libitum. Rates of protein synthesis were measured in vivo at day 15 of lactation from incorporation of (3-/sup 3/H)phenylalanine. At both PF100 and PF85, fractional and absolute rates of mammary glandmore » protein synthesis were two- to three-fold higher in rats fed C than in those fed WG. Pup weights showed similar treatment effects. Both mammary protein synthesis rates and pup weights were significantly higher in rats fed C at PF85 than rats fed WG ad libitum. Food restriction from PF100 to PF85 depressed pup weights and mammary protein synthesis rates in rats fed WGLT, but had no effect in rats fed WG. These results demonstrate that when food intake is restricted, improvement of protein quality of the maternal diet increases milk output in the rat in association with increased rates of mammary protein synthesis.« less

Effect of nutritional status on oxidative stress in an ex vivo perfused rat liver.

PubMed

Stadler, Michaela; Nuyens, Vincent; Seidel, Laurence; Albert, Adelin; Boogaerts, Jean G

2005-11-01

Normothermic ischemia-reperfusion is a determinant in liver injury occurring during surgical procedures, ischemic state, and multiple organ failure. The preexisting nutritional status of the liver might contribute to the extent of tissue injury and primary nonfunction. The aim of this study was to determine the role of starvation on hepatic ischemia-reperfusion injury in normal rat livers. Rats were randomly divided into two groups: one had free access to food, the other was fasted for 16 h. The portal vein was cannulated, and the liver was removed and perfused in a closed ex vivo system. Two modes of perfusion were applied in each series of rats, fed and fasting. In the ischemia-reperfusion mode, the experiment consisted of perfusion for 15 min, warm ischemia for 60 min, and reperfusion during 60 min. In the nonischemia mode, perfusion was maintained during the 135-min study period. Five rats were included in each experimental condition, yielding a total of 20 rats. Liver enzymes, potassium, glucose, lactate, free radicals, i.e., dienes and trienes, and cytochrome c were analyzed in perfusate samples. The proportion of glycogen in hepatocytes was determined in tissue biopsies. Transaminases, lactate dehydrogenase, potassium, and free radical concentrations were systematically higher in fasting rats in both conditions, with and without ischemia. Cytochrome c was higher after reperfusion in the fasting rats. Glucose and lactate concentrations were greater in the fed group. The glycogen content decreased in both groups during the experiment but was markedly lower in the fasting rats. In fed rats, liver injury was moderate, whereas hepatocytes integrity was notably impaired both after continuous perfusion and warm ischemia in fasting animals. Reduced glycogen store in hepatocytes may explain reduced tolerance.

INVESTIGATIONS ON THE BIOLOGICAL BEHAVIOR OF RADIOACTIVE FISSION PRODUCTS IN PREGNANT ANIMALS. III. ENRICHMENT OF RADIOCESIUM IN NURSING RATS AND THE MODIFICATION OF THE Cs RETENTION IN ORGANS OF THE MOTHER DURING THE LACTATION PERIOD (in German)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kriegel, H.; Weber, E.

In a continuation of the investigation on the placental turnover of radiocesium in the rat, the changes of the postpartum cesium content in the young nursing animals caused by the amounts of cesium, which are excreted with the mother-milk, are described. The cesium content in the organs of the mother at the end of the lactation period is decreased by 50% in contrast to the un- pregnant controls. (auth)

Diminution in energy expenditure during lactation.

PubMed Central

Illingworth, P J; Jung, R T; Howie, P W; Leslie, P; Isles, T E

1986-01-01

Energy expenditure at rest and in response to a meal and to an infusion of noradrenaline was measured in 12 lactating women and compared with that in seven bottle feeding women and seven non-pregnant, non-lactating controls. The energy response of the lactating women was remeasured after lactation stopped. During lactation the resting metabolic rate was unaltered but there was a reduced response to infusion of noradrenaline and to a meal, which increased to normal control values after lactation stopped. Such reductions in expenditure were not found in women who had been bottle feeding and were tested at a similar six to eight weeks post partum. These findings suggest that metabolic efficiency is enhanced in lactating women, who may not need to increase energy intake to the extent suggested by current recommended dietary allowances. PMID:3081114

Zoledronate prevents lactation induced bone loss and results in additional post-lactation bone mass in mice.

PubMed

Wendelboe, Mette Høegh; Thomsen, Jesper Skovhus; Henriksen, Kim; Vegger, Jens Bay; Brüel, Annemarie

2016-06-01

In rodents, lactation is associated with a considerable and very rapid bone loss, which almost completely recovers after weaning. The aim of the present study was to investigate whether the bisphosphonate Zoledronate (Zln) can inhibit lactation induced bone loss, and if Zln interferes with recovery of bone mass after lactation has ceased. Seventy-six 10-weeks-old NMRI mice were divided into the following groups: Baseline, Pregnant, Lactation, Lactation+Zln, Recovery, Recovery+Zln, and Virgin Control (age-matched). The lactation period was 12days, then the pups were removed, and thereafter recovery took place for 28days. Zln, 100μg/kg, was given s.c. on the day of delivery, and again 4 and 8days later. Mechanical testing, μCT, and dynamic histomorphometry were performed. At L4, lactation resulted in a substantial loss of bone strength (-55% vs. Pregnant, p<0.01), BV/TV (-40% vs. Pregnant, p<0.01), and trabecular thickness (Tb.Th) (-29% vs. Pregnant, p<0.001). Treatment with Zln completely prevented lactation induced loss of bone strength, BV/TV, and Tb.Th at L4. Full recovery of micro-architectural and mechanical properties was found 28days after weaning in vehicle-treated mice. Interestingly, the recovery group treated with Zln during the lactation period had higher BV/TV (+45%, p<0.01) and Tb.Th (+16%, p<0.05) compared with virgin controls. Similar results were found at the proximal tibia and femur. This indicates that Zln did not interfere with the bone formation taking place after weaning. On this background, we conclude that post-lactation bone formation is not dependent on a preceding lactation induced bone loss. Copyright © 2016 Elsevier Inc. All rights reserved.

Hüftgelenks-Endoprothesen

NASA Astrophysics Data System (ADS)

Widmer, Markus; von Felten-Rösler, Ursula; Wintermantel, Erich

Die Hüftgelenk-Endoprothese wird im vorliegenden Buch als herausragendes Beispiel eines lasttragenden orthopädischen Implantates aufgeführt. Lasttragende Implantate werden in dieser Monographie den metabolisch induktiven Implantaten gegenübergestellt, bei denen Kräfte eine untergeordnete Rolle sowohl in der Werkstoffentwicklung als auch beim späteren Einsatz im Empfängerorganismus darstellen. Zu den metabolisch induktiven Implantaten werden beispielsweise Zellträger und “drug-release”-Systeme gerechnet.

Dichloroacetate effects on glucose and lactate oxidation by neurons and astroglia in vitro and on glucose utilization by brain in vivo.

PubMed

Itoh, Yoshiaki; Esaki, Takanori; Shimoji, Kazuaki; Cook, Michelle; Law, Mona J; Kaufman, Elaine; Sokoloff, Louis

2003-04-15

Neuronal cultures in vitro readily oxidized both D-[(14)C]glucose and l-[(14)C]lactate to (14)CO(2), whereas astroglial cultures oxidized both substrates sparingly and metabolized glucose predominantly to lactate and released it into the medium. [(14)C]Glucose oxidation to (14)CO(2) varied inversely with unlabeled lactate concentration in the medium, particularly in neurons, and increased progressively with decreasing lactate concentration. Adding unlabeled glucose to the medium inhibited [(14)C]lactate oxidation to (14)CO(2) only in astroglia but not in neurons, indicating a kinetic preference in neurons for oxidation of extracellular lactate over intracellular pyruvatelactate produced by glycolysis. Protein kinase-catalyzed phosphorylation inactivates pyruvate dehydrogenase (PDH), which regulates pyruvate entry into the tricarboxylic acid cycle. Dichloroacetate inhibits this kinase, thus enhancing PDH activity. In vitro dichloroacetate stimulated glucose and lactate oxidation to CO(2) and reduced lactate release mainly in astroglia, indicating that limitations in glucose and lactate oxidation by astroglia may be due to a greater balance of PDH toward the inactive form. To assess the significance of astroglial export of lactate to neurons in vivo, we attempted to diminish this traffic in rats by administering dichloroacetate (50 mgkg) intravenously to stimulate astroglial lactate oxidation and then examined the effects on baseline and functionally activated local cerebral glucose utilization (lCMR(glc)). Dichloroacetate raised baseline lCMR(glc) throughout the brain and decreased the percent increases in lCMR(glc) evoked by functional activation. These studies provide evidence in support of the compartmentalization of glucose metabolism between astroglia and neurons but indicate that the compartmentalization may be neither complete nor entirely obligatory.

[The effect of bemithyl in rats with experimental pneumonia].

PubMed

Solov'ev, M V; Krivoruchko, B I; Zarubina, I V; Mironova, O P

2002-01-01

The tests on rats with experimental pneumonia showed that bemithyl (50 mg/kg, i.p.) reduces lethal outcome frequency, decreases the accumulation of lactate in lung tissues, and impedes activation of lipid peroxidation.

21 CFR 184.1311 - Ferrous lactate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... prepared by reacting calcium lactate or sodium lactate with ferrous sulfate, direct reaction of lactic acid with iron filings, reaction of ferrous chloride with sodium lactate, or reaction of ferrous sulfate...

21 CFR 184.1311 - Ferrous lactate.

Code of Federal Regulations, 2011 CFR

2011-04-01

.... It is prepared by reacting calcium lactate or sodium lactate with ferrous sulfate, direct reaction of lactic acid with iron filings, reaction of ferrous chloride with sodium lactate, or reaction of ferrous...

Lactating Mother and Psychotropic Drugs

PubMed Central

Tripathi, B. M.; Majumder, Pradipta

2010-01-01

Usage of psychotropics during pregnancy and lactation has always been a topic of debate and controversy. The debate stems from the potential adverse effects on the growing fetus or infants due to the transfer of psychotropic drugs through placenta or breast milk of mothers receiving them; and the problem of discontinuing psychotropics in lactating mother considering chances of relapse. However, most of the psychotropics are found to be relatively safe when used cautiously during the lactation phase. This article describes available data on the use of psychotropics in lactating mothers, in particular, in relation to the safety profile of infants. PMID:21327172

Effects of an overload of animal protein on the rat: brain DNA alterations and tissue morphological modifications during fetal and post-natal stage.

PubMed

Greco, A M; Sticchi, R; Boschi, G; Vetrani, A; Salvatore, G

1985-01-01

On account of many literature reports about the definite correlation between high animal protein intake and cardiovascular diseases, we have studied the effect of a hyperproteic purified diet (casein 40%, lactalbumin 20%) on fetal and post-natal (not further than 40th day) stage of the rat, when cell subdivision process is faster and therefore damage by nutritional imbalance is certainly more serious. Litters of rats were grouped according to mother's (either hyperproteic or common basic) and rat's (after lactation) diet. Brain DNA and histology of various organs were studied. Hyperproteic diet during fetal stage and lactation would inhibit brain cell subdivision since overall content of brain DNA would be decreased on autoptic finding. Structural changes were also shown in liver, heart, kidney and adrenal cortex, especially when hyperproteic diet was continued even after lactation.

Basal levels of metabolic activity are elevated in Genetic Absence Epilepsy Rats from Strasbourg (GAERS): measurement of regional activity of cytochrome oxidase and lactate dehydrogenase by histochemistry.

PubMed

Dufour, Franck; Koning, Estelle; Nehlig, Astrid

2003-08-01

The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are considered an isomorphic, predictive, and homologous model of human generalized absence epilepsy. It is characterized by the expression of spike-and-wave discharges in the thalamus and cortex. In this strain, basal regional rates of cerebral glucose utilization measured by the quantitative autoradiographic [(14)C]2-deoxyglucose technique display a widespread consistent increase compared to a selected strain of genetically nonepileptic rats (NE). In order to verify whether these high rates of glucose metabolism are paralleled by elevated activities of the enzymes of the glycolytic and tricarboxylic acid cycle pathways, we measured by histochemistry the regional activity of the two key enzymes of glucose metabolism, lactate dehydrogenase (LDH) for the anaerobic pathway and cytochrome oxidase (CO) for the aerobic pathway coupled to oxidative phosphorylation. CO and LDH activities were significantly higher in GAERS than in NE rats in 24 and 28 of the 30 brain regions studied, respectively. The differences in CO and LDH activity between both strains were widespread, affected all brain systems studied, and ranged from 12 to 63%. The data of the present study confirm the generalized increase in cerebral glucose metabolism in GAERS, occurring both at the glycolytic and at the oxidative step. However, they still do not allow us to understand why the ubiquitous mutation(s) generates spike-and-wave discharges only in the thalamocortical circuit.

Iodothyronine 5'-deiodinase activity and thyroid hormone content in brown adipose tissue during the breeding cycle of the rat.

PubMed Central

Viñas, O; Giralt, M; Obregón, M J; Iglesias, R; Villarroya, F; Mampel, T

1988-01-01

Brown adipose tissue iodothyronine 5'-deiodinase activity is significantly lower in 17-day pregnant rats compared with virgin controls and remains low during late pregnancy and lactation. It fully recovers with abrupt weaning, but only partially with spontaneous weaning. Even though this profile of changes is remarkably in step with the known pattern of modifications in brown fat thermogenesis during the breeding cycle, the lowered iodothyronine 5'-deiodinase activity appearing between days 15 and 17 of pregnancy occurs earlier than the reduction in brown adipose tissue thermogenesis. Brown fat 3,3',5-tri-iodothyronine content is also reduced in late pregnant, early and mid-lactating rats, most probably as a consequence of the lowered 5'-deiodination of thyroxine in situ. Acute insulin treatment increases brown fat iodothyronine 5'-deiodinase activity in virgin animals as well as in late-pregnant and lactating rats, despite the lowered basal enzyme activity levels in the latter groups. Thus an impaired response to insulin in brown fat does not appear to be a factor leading to the lowered iodothyronine 5'-deiodinase activity during late pregnancy and lactation. PMID:3060112

Cumulative lactate and hospital mortality in ICU patients

PubMed Central

2013-01-01

Background Both hyperlactatemia and persistence of hyperlactatemia have been associated with bad outcome. We compared lactate and lactate-derived variables in outcome prediction. Methods Retrospective observational study. Case records from 2,251 consecutive intensive care unit (ICU) patients admitted between 2001 and 2007 were analyzed. Baseline characteristics, all lactate measurements, and in-hospital mortality were recorded. The time integral of arterial blood lactate levels above the upper normal threshold of 2.2 mmol/L (lactate-time-integral), maximum lactate (max-lactate), and time-to-first-normalization were calculated. Survivors and nonsurvivors were compared and receiver operating characteristic (ROC) analysis were applied. Results A total of 20,755 lactate measurements were analyzed. Data are srpehown as median [interquartile range]. In nonsurvivors (n = 405) lactate-time-integral (192 [0–1881] min·mmol/L) and time-to-first normalization (44.0 [0–427] min) were higher than in hospital survivors (n = 1846; 0 [0–134] min·mmol/L and 0 [0–75] min, respectively; all p < 0.001). Normalization of lactate <6 hours after ICU admission revealed better survival compared with normalization of lactate >6 hours (mortality 16.6% vs. 24.4%; p < 0.001). AUC of ROC curves to predict in-hospital mortality was the largest for max-lactate, whereas it was not different among all other lactate derived variables (all p > 0.05). The area under the ROC curves for admission lactate and lactate-time-integral was not different (p = 0.36). Conclusions Hyperlactatemia is associated with in-hospital mortality in a heterogeneous ICU population. In our patients, lactate peak values predicted in-hospital mortality equally well as lactate-time-integral of arterial blood lactate levels above the upper normal threshold. PMID:23446002

Reliability of the Lactate Scout point-of-care instrument for the determination of blood L-lactate concentration in sheep.

PubMed

Kaynar, Ozgur; Karapinar, Tolga; Hayirli, Armagan; Baydar, Ersoy

2015-12-01

Data on accuracy and precision of the Lactate Scout point-of-care (POC) analyzer in ovine medicine are lacking. The purpose of the study was to assess the reliability of the Lactate Scout in sheep. Fifty-seven sheep at varying ages with various diseases were included. Blood lactate concentration in samples collected from the jugular vein was measured immediately on the Lactate Scout. Plasma L-lactate concentration was measured by the Cobas autoanalyzer as the reference method. Data were subjected to Student's t-test, Passing-Bablok regression, and Bland-Altman plot analyses for comparison and assessment of accuracy, precision, and reliability. Plasma l-lactate concentration was consistently lower than blood L-lactate concentration (3.06 ± 0.24 vs 3.3 ± 0.3 mmol/L, P < .0001). There was a positive correlation between plasma and blood L-lactate concentrations (r = .98, P < .0001). The Lactate Scout had 99% accuracy and 98% precision with the reference method. Blood (Y) and plasma (X) L-lactate concentrations were fitted to Y = 0.28 + 1.00 · X, with a residual standard deviation of 0.31 and a negligible deviation from the identity line (P = .93). The bias was fitted to Y = 0.10 + 0.05 · X, with Sy.x of 0.44 (P < .07). The Lactate Scout has high accuracy and precision, with a negligible bias. It is a reliable POC analyzer to assess L-lactate concentration in ovine medicine. © 2015 American Society for Veterinary Clinical Pathology.

Metabolism and disposition of bisphenol A in female rats.

PubMed

Snyder, R W; Maness, S C; Gaido, K W; Welsch, F; Sumner, S C; Fennell, T R

2000-11-01

Bisphenol A (BPA), which is used in the manufacture of polycarbonates, elicits weak estrogenic activity in in vitro and in vivo test systems. The objectives of this study were to compare the patterns of disposition of radioactivity in adult female F-344 and CD rats after oral administration of (14)C BPA (100 mg/kg), to isolate the glucuronide of BPA and to assess its estrogenic activity in vitro, and to evaluate the transfer of radioactivity to pups from lactating dams administered (14)C BPA. Over 6 days, F-344 rats excreted more radioactivity in urine than CD rats. The major metabolite in urine was identified as bisphenol A glucuronide (BPA gluc) by incubation with beta-glucuronidase and (1)H and (13)C NMR spectroscopy. In lactating CD rats administered (14)C BPA (100 mg/kg) by gavage, only a small fraction of the label was found in milk, with 0.95 +/- 0.66, 0.63 +/- 0.13, and 0.26 +/- 0.10 microg equiv/ml (mean +/- SD) from dams collected 1, 8, and 26 h after dosing, respectively. Radioactivity in pup carcasses indicated exposure in the range of microgram equivalents per kilogram; those values ranged from 44.3 +/- 24.4 for pups separated from their lactating dams at 2 h to 78.4 +/- 10.9 at 24 h. BPA gluc was the prominent metabolite in milk and plasma. In test systems for activation of in vitro estrogen receptors alpha and beta, BPA gluc did not show appreciable efficacy at concentrations up to 0.03 mM, indicating that metabolism via glucuronidation is a detoxication reaction. Copyright 2000 Academic Press.

Hindbrain medulla catecholamine cell group involvement in lactate-sensitive hypoglycemia-associated patterns of hypothalamic norepinephrine and epinephrine activity.

PubMed

Shrestha, P K; Tamrakar, P; Ibrahim, B A; Briski, K P

2014-10-10

Cell-type compartmentation of glucose metabolism in the brain involves trafficking of the oxidizable glycolytic end product, l-lactate, by astrocytes to fuel neuronal mitochondrial aerobic respiration. Lactate availability within the hindbrain medulla is a monitored function that regulates systemic glucostasis as insulin-induced hypoglycemia (IIH) is exacerbated by lactate repletion of that brain region. A2 noradrenergic neurons are a plausible source of lactoprivic input to the neural gluco-regulatory circuit as caudal fourth ventricular (CV4) lactate infusion normalizes IIH-associated activation, e.g. phosphorylation of the high-sensitivity energy sensor, adenosine 5'-monophosphate-activated protein kinase (AMPK), in these cells. Here, we investigated the hypothesis that A2 neurons are unique among medullary catecholamine cells in directly screening lactate-derived energy. Adult male rats were injected with insulin or vehicle following initiation of continuous l-lactate infusion into the CV4. Two hours after injections, A1, C1, A2, and C2 neurons were collected by laser-microdissection for Western blot analysis of AMPKα1/2 and phosphoAMPKα1/2 proteins. Results show that AMPK is expressed in each cell group, but only a subset, e.g. A1, C1, and A2 neurons, exhibit increased sensor activity in response to IIH. Moreover, hindbrain lactate repletion reversed hypoglycemic augmentation of pAMPKα1/2 content in A2 and C1 but not A1 cells, and normalized hypothalamic norepinephrine and epinephrine content in a site-specific manner. The present evidence for discriminative reactivity of AMPK-expressing medullary catecholamine neurons to the screened energy substrate lactate implies that that lactoprivation is selectively signaled to the hypothalamus by A2 noradrenergic and C1 adrenergic cells. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Reproductive experience alters prolactin receptor expression in mammary and hepatic tissues in female rats.

PubMed

Bridges, Robert S; Scanlan, Victoria F; Lee, Jong-O; Byrnes, Elizabeth M

2011-08-01

Recent studies have reported that reproductive experience in female rats alters prolactin (PRL) receptor gene expression in the brain as well as neural sensitivity to PRL. Given PRL's actions in nonneural tissues, that is, mammary tissue and liver, it was asked whether reproductive experience may also alter prolactin receptor (Prlr) gene expression in these tissues. Groups of age-matched female rats were generated with varying reproductive histories. Separate groups of primiparous (first lactation) and multiparous (second lactation) had mammary tissue and liver samples collected on Day 3 or 10 of lactation. A fifth group raised one litter to weaning and then resumed estrous cyclicity. This group and a final group of age-matched, virgin controls were killed on diestrus. Tissue was processed by quantitative PCR for expression rates of the long and short forms of Prlr mRNA as well as casein beta mRNA (mammary tissue only). Western blots were performed to quantify receptor protein content. Multiple lactations as well as lactation itself resulted in alterations in Prlr expression. Prlr gene expression in mammary tissue was increased in primiparous mothers compared with that in multiparous dams, whereas in the liver, Prlr expression was reduced during an initial lactation. In contrast, PRLR protein levels declined during lactation in mammary, but not hepatic, tissues. Overall, the results demonstrate that the prolactin receptor system is altered in nonneural tissues as a result of the female's reproductive history. The findings are discussed in the context of milk and bile production and PRL's possible role in breast cancer.

The Effects of Direct Oxygen Supply During Static Cold Preservation of Rat Livers: An Experimental Study.

PubMed

Zumrutdal, Emin; Karateke, Faruk; Eser, Pınar Eylem; Turan, Umit; Ozyazici, Sefa; Sozutek, Alper; Gulkaya, Mustafa; Kunt, Mevlut

2016-12-01

We aimed to determine the biochemical and histopathologic effects of direct oxygen supply to the preservation fluid of static cold storage system with a simple method on rat livers. Sixteen rats were randomly divided into 2 groups: the control group, which contained Ringer's lactate as preservation fluid; and the oxygen group, which contained oxygen and Ringer's lactate for preservation. Each liver was placed in a bag containing 50 mL Ringer's lactate and placed in ice-filled storage containers. One hundred percent oxygen supplies were given via a simple, inexpensive system created in our laboratory, to the livers in oxygen group. We obtained samples for histopathologic evaluation in the 12th hour. In addition, 3 mL of preservation fluid was subjected to biochemical analysis at 0, sixth, and twelfth hours. Aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and pH levels were measured from the preservation fluid. In oxygen-supplemented group, the acceleration speed of increase in alanine aminotransferase and lactate dehydrogenase levels at sixth hour and lactate dehydrogenase, alanine aminotransferase, and lactate dehydrogenase levels at 12th hour were statistically significantly reduced. In histopathologic examination, all parameters except ballooning were statistically significantly better in the oxygen-supplemented group. This simple system for oxygenation of liver tissues during static cold storage was shown to be effective with good results in biochemical and histopathologic assessments. Because this is a simple, inexpensive, and easily available method, larger studies are warranted to evaluate its effects (especially in humans).

Long-term Effects on the Histology and Function of Livers and Spleens in Rats after 33% Toploading of PEG-PLA-nano Artificial Red Blood Cells

PubMed Central

Liu, Zun Chang; Chang, Thomas M.S.

2012-01-01

This study is to investigate the long-term effects of nanodimension PEG-PLA artificial red blood cells containing hemoglobin and red blood cell enzymes on the liver and spleen after 1/3 blood volume top loading in rats. The experimental rats received one of the following infusions: Nano artificial red blood cells in Ringer lactate, Ringer lactate, stroma-free hemoglobin, polyhemoglobin, and autologous rat whole blood. Blood samples were taken before infusions and on days 1, 7, and 21 after infusions for analysis. Nano artificial red blood cells, polyhemoglobin, Ringer lactate and rat red blood cells did not have any significant adverse effects on alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatine kinase, amylase and creatine kinase. On the other hand, stroma-free hemoglobin induced significant adverse effects on liver as shown by elevation in alanine aminotransferase and aspartate aminotransferase throughout the 21 days. On day 21 after infusions rats were sacrificed and livers and spleens were excised for histological examination. Nano artificial red blood cells, polyhemoglobin, Ringer lactate and rat red blood cells did not cause any abnormalities in the microscopic histology of the livers and spleens. In the stroma-free hemoglobin group the livers showed accumulation of hemoglobin in central veins and sinusoids, and hepatic steatosis. In conclusion, injected nano artificial red blood cells can be efficiently metabolized and removed by the reticuloendothelial system, and do not have any biochemical or histological adverse effects on the livers or the spleens. PMID:19043818

ATRAZINE DISPOSITION IN PREGNANT AND LACTATING LONG-EVANS RATS

EPA Science Inventory

Atrazine (ATR) is a widely used herbicide shown to delay early mammary development in female offspring of gestationally exposed rats. The effects of ATR can be induced by in utero exposure and/or suckling from a dam exposed during late pregnancy, but ATR is reported to have a hal...

Are arterial, muscle and working limb lactate exchange data obtained on men at altitude consistent with the hypothesis of an intracellular lactate shuttle?

PubMed

Brooks, G A

1999-01-01

The "Lactate Shuttle" Hypothesis posits that lactate removal requires exchange among producing and consuming cells. The "Intra-cellular Lactate Shuttle" hypothesis posits that lactate exchange occurs among compartments within cells, and that mitochondria are the major sites of cellular lactate disposal. Thus, cells with high mitochondrial densities (cardiocytes, myocytes, hepatocytes) are those which participate in lactate clearance. The model of an Intracellular Lactate Shuttle recognizes that the Keq for LDH is 3.6 x 10(4) M-1; thus, glycolysis results in cytosolic lactate production regardless of the intracellular PO2. The model also requires presence of a mitochondrial monocarboxylate transporter (MCT) that allows uptake of lactate as well as pyruvate, and intra-mitochondrial LDH whose function is linked to the ETC, and which permits lactate-->pyruvate conversion and oxidation. Recently, we have shown that liver, heart and muscle mitochondria readily oxidize lactate and contain LDH and MCT1. Accordingly, we have concluded that lactate is the predominant monocarboxylate oxidized by mitochondria in vivo. The model of an "Intra-cellular Lactate Shuttle" is consistent with many of the observations on men at sea level and altitude. The observations include: oxidation is the primary fate of lactate disposal during rest and exercise; lactate production and oxidation occur simultaneously within resting and working muscle; increasing [lactate]a increases muscle lactate extraction, and that by increasing SaO2 acclimatization reduces blood [lactate].

Nutritional recovery with a soybean diet impaired the glucagon response but did not alter liver gluconeogenesis in the adult offspring of rats deprived of protein during pregnancy and lactation.

PubMed

Pacheco, Nelma Cristina Silva; de Almeida, Ana Paula Carli; de Siqueira, Kariny Cássia; de Lima, Faena Moura; Reis, Silvia Regina de Lima; Latorraca, Marcia Queiroz; Stoppiglia, Luiz Fabrizio

2018-06-22

Nutritional recovery of early malnutrition with soybean diet reduces liver glycogen stores in the fed state and produces liver insulin resistance. We investigated whether nutritional recovery on a soybean flour diet alters hepatic gluconeogenesis in the adult offspring of rats deprived of protein during pregnancy and lactation. Male rats from mothers that were fed either 17% (C) or 6% (L) protein during pregnancy and lactation were maintained on a 17% casein (CC, n=16 and LC, n=17), 17% soybean flour (CS, n=10 and LS, n=10) or 6% casein (LL, n=10) diet after weaning. The soybean diet reduced basal serum glucose (soybean diet=5.6±0.6 mmol/L vs casein diet= 6.2±0.6 mmol/L; p<0.05), but increased alanine aminotransferase mRNA/GAPDH (soybean diet =0.062 ±0.038 vs casein diet= 0.024 ±0.011; p<0.01) and phosphoenolpyruvate carboxykinase mRNA/GAPDH (soybean diet =1.53 ±0.52 vs casein diet= 0.95 ±0.43; p<0.05), and the glycerokinase protein content (soybean diet =0.86 ±0.08 vs casein diet= 0.75 ±0.11; p<0.05). The serum glucose concentration (recovered groups=5.6±0.5mmol/L vs control groups=6.2±0.7mmol/L, p<0.05) and pophosphoenolpyruvate carboxykinase activity (recovered groups=2.8±0.6μU/mg vs control groups=3.6±0.6μU/mg; p<0.05) were decreased in rats subjected to protein restriction in early life. The glucose area under the curve during the pyruvate tolerance test did not differ among the groups, whereas glucose area under the curve after glucagon infusion was reduced by early malnutrition (recovered groups=4210±572mg/dL.40min vs control groups=4493±688mg/dL.40min; p<0.001), and by the soybean diet (soybean diet= 3995±500mg/dL.40min vs casein diet=4686±576 mg/dL.40min, p<0.05). Thus, soybean diet impaired the response to glucagon, but did not alter gluconeogenesis.

Reproductive Experience Alters Prolactin Receptor Expression in Mammary and Hepatic Tissues in Female Rats1

PubMed Central

Bridges, Robert S.; Scanlan, Victoria F.; Lee, Jong-O; Byrnes, Elizabeth M.

2011-01-01

Recent studies have reported that reproductive experience in female rats alters prolactin (PRL) receptor gene expression in the brain as well as neural sensitivity to PRL. Given PRL's actions in nonneural tissues, that is, mammary tissue and liver, it was asked whether reproductive experience may also alter prolactin receptor (Prlr) gene expression in these tissues. Groups of age-matched female rats were generated with varying reproductive histories. Separate groups of primiparous (first lactation) and multiparous (second lactation) had mammary tissue and liver samples collected on Day 3 or 10 of lactation. A fifth group raised one litter to weaning and then resumed estrous cyclicity. This group and a final group of age-matched, virgin controls were killed on diestrus. Tissue was processed by quantitative PCR for expression rates of the long and short forms of Prlr mRNA as well as casein beta mRNA (mammary tissue only). Western blots were performed to quantify receptor protein content. Multiple lactations as well as lactation itself resulted in alterations in Prlr expression. Prlr gene expression in mammary tissue was increased in primiparous mothers compared with that in multiparous dams, whereas in the liver, Prlr expression was reduced during an initial lactation. In contrast, PRLR protein levels declined during lactation in mammary, but not hepatic, tissues. Overall, the results demonstrate that the prolactin receptor system is altered in nonneural tissues as a result of the female's reproductive history. The findings are discussed in the context of milk and bile production and PRL's possible role in breast cancer. PMID:21508351

Early metabolic responses to lithium/pilocarpine-induced status epilepticus in rat brain.

PubMed

Imran, Imran; Hillert, Markus H; Klein, Jochen

2015-12-01

The lithium-pilocarpine model of status epilepticus is a well-known animal model of temporal lobe epilepsy. We combined this model with in vivo microdialysis to investigate energy metabolites and acute cellular membrane damage during seizure development. Rats were implanted with dialysis probes and pretreated with lithium chloride (127 mg/kg i.p.). Twenty-four hours later, they received pilocarpine (30 mg/kg s.c.) which initiated seizures within 30 min. In the dialysate from rat hippocampus, we observed a transient increase in glucose and a prominent, five-fold increase in lactate during seizures. Lactate release was because of neuronal activation as it was strongly reduced by infusion of tetrodotoxin, administration of atropine or when seizures were terminated by diazepam or ketamine. In ex vivo assays, mitochondrial function as measured by respirometry was not affected by 90 min of seizures. Extracellular levels of choline, however, increased two-fold and glycerol levels 10-fold, which indicate cellular phospholipid breakdown during seizures. Within 60 min of pilocarpine administration, hydroxylation of salicylate increased two-fold and formation of isoprostanes 20-fold, revealing significant oxidative stress in hippocampal tissue. Increases in lactate, glycerol and isoprostanes were abrogated, and increases in choline were completely prevented, when hippocampal probes were perfused with calcium-free solution. Similarly, administration of pregabalin (100 mg/kg i.p.), a calcium channel ligand, 15 min prior to pilocarpine strongly attenuated parameters of membrane damage and oxidative stress. We conclude that seizure development in a rat model of status epilepticus is accompanied by increases in extracellular lactate, choline and glycerol, and by oxidative stress, while mitochondrial function remains intact for at least 90 min. Membrane damage depends on calcium influx and can be prevented by treatment with pregabalin. Status epilepticus (SE) was induced in rats by

21 CFR 582.1207 - Calcium lactate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Calcium lactate. 582.1207 Section 582.1207 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1207 Calcium lactate. (a) Product. Calcium lactate. (b) Conditions of use. This substance is...

21 CFR 582.1207 - Calcium lactate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium lactate. 582.1207 Section 582.1207 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1207 Calcium lactate. (a) Product. Calcium lactate. (b) Conditions of use. This substance is...

DISTRIBUTION OF 14C-ATRAZINE FOLLOWING AN ACUTE LACTATIONAL EXPOSURE IN THE WISTAR RAT.

EPA Science Inventory

The purpose of the present study was to examine the distribution of atrazine in the lactating dam and suckling neonate following an acute exposure to either 2 or 4 mg/kg 14C-atrazine (14C-ATR) by gavage. 14C-ATR was administered to the nursing dam on postnatal day 3 by oral gavag...

Ambient temperature shapes reproductive output during pregnancy and lactation in the common vole (Microtus arvalis): a test of the heat dissipation limit theory.

PubMed

Simons, Mirre J P; Reimert, Inonge; van der Vinne, Vincent; Hambly, Catherine; Vaanholt, Lobke M; Speakman, John R; Gerkema, Menno P

2011-01-01

The heat dissipation limit theory suggests that heat generated during metabolism limits energy intake and, thus, reproductive output. Experiments in laboratory strains of mice and rats, and also domestic livestock generally support this theory. Selection for many generations in the laboratory and in livestock has increased litter size or productivity in these animals. To test the wider validity of the heat dissipation limit theory, we studied common voles (Microtus arvalis), which have small litter sizes by comparison with mice and rats, and regular addition of wild-caught individuals of this species to our laboratory colony ensures a natural genetic background. A crossover design of ambient temperatures (21 and 30°C) during pregnancy and lactation was used. High ambient temperature during lactation decreased milk production, slowing pup growth. The effect on pup growth was amplified when ambient temperature was also high during pregnancy. Shaving fur off dams at 30°C resulted in faster growth of pups; however, no significant increase in food intake and or milk production was detected. With increasing litter size (natural and enlarged), asymptotic food intake during lactation levelled off in the largest litters at both 21 and 30°C. Interestingly, the effects of lactation temperature on pup growth where also observed at smaller litter sizes. This suggests that vole dams trade-off costs associated with hyperthermia during lactation with the yield from investment in pup growth. Moreover, pup survival was higher at 30°C, despite lower growth, probably owing to thermoregulatory benefits. It remains to be seen how the balance is established between the negative effect of high ambient temperature on maternal milk production and pup growth (and/or future reproduction of the dam) and the positive effect of high temperatures on pup survival. This balance ultimately determines the effect of different ambient temperatures on reproductive success.

Bisphenol S Alters the Lactating Mammary Gland and Nursing Behaviors in Mice Exposed During Pregnancy and Lactation.

PubMed

LaPlante, Charlotte D; Catanese, Mary C; Bansal, Ruby; Vandenberg, Laura N

2017-10-01

High doses of estrogenic pharmaceuticals were once prescribed to women to halt lactation. Yet, the effects of low-level xenoestrogens on lactation remain poorly studied. We investigated the effects of bisphenol S (BPS), an estrogen receptor (ER) agonist, on the lactating mammary gland; the arcuate nucleus, a region of the hypothalamus important for neuroendocrine control of lactational behaviors; and nursing behavior in CD-1 mice. Female mice were exposed to vehicle, 2 or 200 µg BPS/kg/d from pregnancy day 9 until lactational day (LD) 20, and tissues were collected on LD21. Tissues were also collected from a second group at LD2. BPS exposure significantly reduced the fraction of the mammary gland comprised of lobules, the milk-producing units, on LD21, but not LD2. BPS also altered expression of Esr1 and ERα in the mammary gland at LD21, consistent with early involution. In the arcuate nucleus, no changes were observed in expression of signal transducer and activator of transcription 5, a marker of prolactin signaling, or ERα, suggesting that BPS may act directly on the mammary gland. However, observations of nursing behavior collected during the lactational period revealed stage-specific effects on both pup and maternal nursing behaviors; BPS-treated dams spent significantly more time nursing later in the lactational period, and BPS-treated pups were less likely to initiate nursing. Pup growth and development were also stunted. These data indicate that low doses of BPS can alter lactational behaviors and the maternal mammary gland. Together, they support the hypothesis that pregnancy and lactation are sensitive to low-dose xenoestrogen exposures. Copyright © 2017 Endocrine Society.

Protein-restriction diet during the suckling phase programs rat metabolism against obesity and insulin resistance exacerbation induced by a high-fat diet in adulthood.

PubMed

Martins, Isabela Peixoto; de Oliveira, Júlio Cezar; Pavanello, Audrei; Matiusso, Camila Cristina Ianoni; Previate, Carina; Tófolo, Laize Peron; Ribeiro, Tatiane Aparecida; da Silva Franco, Claudinéia Conationi; Miranda, Rosiane Aparecida; Prates, Kelly Valério; Alves, Vander Silva; Francisco, Flávio Andrade; de Moraes, Ana Maria Praxedes; de Freitas Mathias, Paulo Cezar; Malta, Ananda

2018-04-03

Protein restriction during the suckling phase can malprogram rat offspring to a lean phenotype associated with metabolic dysfunctions later in life. We tested whether protein-caloric restriction during lactation can exacerbate the effect of a high-fat (HF) diet at adulthood. To test this hypothesis, we fed lactating Wistar dams with a low-protein (LP; 4% protein) diet during the first 2 weeks of lactation or a normal-protein (NP; 23% protein) diet throughout lactation. Rat offspring from NP and LP mothers received a normal-protein diet until 60 days old. At this time, a batch of animals from both groups was fed an HF (35% fat) diet, while another received an NF (7% fat) diet. Maternal protein-caloric restriction provoked lower body weight and fat pad stores, hypoinsulinemia, glucose intolerance, higher insulin sensitivity, reduced insulin secretion and altered autonomic nervous system (ANS) function in adult rat offspring. At 90 days old, NP rats fed an HF diet in adulthood displayed obesity, impaired glucose homeostasis and altered insulin secretion and ANS activity. Interestingly, the LP/HF group also presented fat pad and body weight gain, altered glucose homeostasis, hyperleptinemia and impaired insulin secretion but at a smaller magnitude than the NP-HF group. In addition, LP/HF rats displayed elevated insulin sensitivity. We concluded that protein-caloric restriction during the first 14 days of life programs the rat metabolism against obesity and insulin resistance exacerbation induced by an obesogenic HF diet. Copyright © 2017 Elsevier Inc. All rights reserved.

Lactation and changes in maternal metabolic risk factors.

PubMed

Gunderson, Erica P; Lewis, Cora E; Wei, Gina S; Whitmer, Rachel A; Quesenberry, Charles P; Sidney, Steve

2007-03-01

To examine the relationship between duration of lactation and changes in maternal metabolic risk factors. This 3-year prospective study examined changes in metabolic risk factors among lactating women from preconception to postweaning and among nonlactating women from preconception to postdelivery, in comparison with nongravid women. Of 1,051 (490 black, 561 white) women who attended two consecutive study visits in years 7 (1992-1993) and 10 (1995-1996), 942 were nongravid and 109 had one interim birth. Of parous women, 48 (45%) did not lactate, and 61 (55%) lactated and weaned before year 10. The lactated and weaned women were subdivided by duration of lactation into less than 3 months and 3 months or more. Multiple linear regression models estimated mean 3-year changes in metabolic risk factors adjusted for age, race, parity, education, and behavioral covariates. Both parous women who did not lactate and parous women who lactated and weaned gained more weight (+5.6, +4.4 kg) and waist girth (+5.3, +4.9 cm) than nongravid women over the 3-year interval; P<.001. Low-density lipoprotein cholesterol (+6.7 mg/dL, P<.05) and fasting insulin (+2.6 microunits, P=.06) increased more for parous women who did not lactate than for nongravid and parous women who lactated and weaned. High-density lipoprotein cholesterol decrements for both parous women who did not lactate and parous women who lactated and weaned were 4.0 mg/dL greater than for nongravid women (P<.001). Among parous, lactated and weaned women, lactation for 3 months or longer was associated with a smaller decrement in high-density lipoprotein cholesterol (-1.3 mg/dL versus -7.3 mg/dL for less than 3 months; P<.01). Lactation may attenuate unfavorable metabolic risk factor changes that occur with pregnancy, with effects apparent after weaning. As a modifiable behavior, lactation may affect women's future risk of cardiovascular and metabolic diseases. II.

Relationship between season, lactation number and incidence of clinical mastitis in different stages of lactation in a Holstein dairy farm.

PubMed

Moosavi, Maede; Mirzaei, Abdolah; Ghavami, Mohsen; Tamadon, Amin

2014-01-01

The aim of the present study was to compare the occurrence and duration of clinical mastitis in different seasons, stages of lactation period and parities in a Holstein dairy farm in Iran. A retrospective epidemiological survey from April 2005 to March 2008 was conducted on 884 clinical mastitis cases of 7437 lactations. Data of each case including calendar-date of mastitis onset, days in milk (DIM) of mastitis onset (early: 0-74 DIM; middle: 75-150 DIM, and late ≥ 150 DIM), duration of mastitis, and parity (1, 2, and ≥ 3) were recorded. Based on date of mastitis onset, cases were classified into stages of lactation. Moreover, beginning of mastitis was seasonally categorized. Duration of clinical mastitis after treatment in early lactation was less than late lactation in the first-parity cows (p = 0.005). In early lactation period, the first-parity cows suffered clinical mastitis in days earlier than two other parity groups (p < 0.001). Moreover, in late lactation period, the first-parity cows had clinical mastitis in days later than cows in the third and more parities (p = 0.002). Occurrence of clinical mastitis in summer increased in late lactation period but in winter increased in early lactation period (p = 0.001). In addition, occurrence time of clinical mastitis in summer were in days later than in spring (p = 0.02) and winter (p = 0.03) in early lactation period. In conclusion, occurrence of mastitis in winter and spring during early lactation and in summer during late lactation period were more prevalent especially in lower parities.

Relationship between season, lactation number and incidence of clinical mastitis in different stages of lactation in a Holstein dairy farm

PubMed Central

Moosavi, Maede; Mirzaei, Abdolah; Ghavami, Mohsen; Tamadon, Amin

2014-01-01

The aim of the present study was to compare the occurrence and duration of clinical mastitis in different seasons, stages of lactation period and parities in a Holstein dairy farm in Iran. A retrospective epidemiological survey from April 2005 to March 2008 was conducted on 884 clinical mastitis cases of 7437 lactations. Data of each case including calendar-date of mastitis onset, days in milk (DIM) of mastitis onset (early: 0-74 DIM; middle: 75-150 DIM, and late ≥ 150 DIM), duration of mastitis, and parity (1, 2, and ≥ 3) were recorded. Based on date of mastitis onset, cases were classified into stages of lactation. Moreover, beginning of mastitis was seasonally categorized. Duration of clinical mastitis after treatment in early lactation was less than late lactation in the first-parity cows (p = 0.005). In early lactation period, the first-parity cows suffered clinical mastitis in days earlier than two other parity groups (p < 0.001). Moreover, in late lactation period, the first-parity cows had clinical mastitis in days later than cows in the third and more parities (p = 0.002). Occurrence of clinical mastitis in summer increased in late lactation period but in winter increased in early lactation period (p = 0.001). In addition, occurrence time of clinical mastitis in summer were in days later than in spring (p = 0.02) and winter (p = 0.03) in early lactation period. In conclusion, occurrence of mastitis in winter and spring during early lactation and in summer during late lactation period were more prevalent especially in lower parities. PMID:25568687

Higher Accuracy of the Lactate Minimum Test Compared to Established Threshold Concepts to Determine Maximal Lactate Steady State in Running.

PubMed

Wahl, Patrick; Zwingmann, Lukas; Manunzio, Christian; Wolf, Jacob; Bloch, Wilhelm

2018-05-18

This study evaluated the accuracy of the lactate minimum test, in comparison to a graded-exercise test and established threshold concepts (OBLA and mDmax) to determine running speed at maximal lactate steady state. Eighteen subjects performed a lactate minimum test, a graded-exercise test (2.4 m·s -1 start,+0.4 m·s -1 every 5 min) and 2 or more constant-speed tests of 30 min to determine running speed at maximal lactate steady state. The lactate minimum test consisted of an initial lactate priming segment, followed by a short recovery phase. Afterwards, the initial load of the subsequent incremental segment was individually determined and was increased by 0.1 m·s -1 every 120 s. Lactate minimum was determined by the lowest measured value (LM abs ) and by a third-order polynomial (LM pol ). The mean difference to maximal lactate steady state was+0.01±0.14 m·s -1 (LM abs ), 0.04±0.15 m·s -1 (LM pol ), -0.06±0.31 m·s 1 (OBLA) and -0.08±0.21 m·s 1 (mDmax). The intraclass correlation coefficient (ICC) between running velocity at maximal lactate steady state and LM abs was highest (ICC=0.964), followed by LM pol (ICC=0.956), mDmax (ICC=0.916) and OBLA (ICC=0.885). Due to the higher accuracy of the lactate minimum test to determine maximal lactate steady state compared to OBLA and mDmax, we suggest the lactate minimum test as a valid and meaningful concept to estimate running velocity at maximal lactate steady state in a single session for moderately up to well-trained athletes. © Georg Thieme Verlag KG Stuttgart · New York.

Effects of Hypergravity Rearing on Growth Hormone (GH) Secretion In Preweanling Rats

NASA Technical Reports Server (NTRS)

Baer, L. A.; Chowdhury, J. H.; Wade, C. E.; Ronca, A. E.; Dalton, Bonnie (Technical Monitor)

2002-01-01

We previously reported that rat pups reared at 1.5-g, 1.75 or 2.0-g hypergravity weigh 6-15% less than 1.0-g controls. To account for these findings. we measured the lactational hormones, prolaction (Prl) and oxytocin (OT), in the pups' mothers. Gravity related differences in Prl were not observed whereas OT of lactating dams was significantly reduced relative to controls. Milk transfer from dam to pup was not impaired in hypergravity-reared litters tested at 1-g. Together, these findings suggest that impaired lactation and milk transfer do not account for reduced body masses of postnatal rats reared in hypergravity. In the present study, we analyzed growth hormone (GH) secretion and maternal licking in pups reared in hypergravity and in 1.0-g controls. Recent reports using dwarfing phenotypes in mouse mutants have provided evidence for postnatal dependence on GH and insulin-like growth factors (IGFs). Beginning on Gestational day (G)11 of the rats' 22 day pregnancy, rat dams and their litters were exposed to either 1.5-g, 1.75-g or 2.0-g. On Postnatal day (P)10, we measured plasma GH using enzyme immunoassay (EIA). Contrary to our hypothesis, GH was significantly elevated in pups reared at 2.0-g relative to 1.0-g controls. Pup-oriented behaviors of the hypergravity dams were also changed, possibly accounting for the increase in pup GH. GH alone does not appear to play a role in reduced body weights of hypergravity-reared pups.

Lipidomic fatty acid profile and global gene expression pattern in mammary gland of rats that were exposed to lard-based high fat diet during fetal and lactation periods associated to breast cancer risk in adulthood.

PubMed

Andrade, Fábia de Oliveira; de Assis, Sonia; Jin, Lu; Fontelles, Camile Castilho; Barbisan, Luís Fernando; Purgatto, Eduardo; Hilakivi-Clarke, Leena; Ong, Thomas Prates

2015-09-05

The persistent effects of animal fat consumption during pregnancy and nursing on the programming of breast cancer risk among female offspring were studied here. We have previously found that female offspring of rat dams that consumed a lard-based high-fat (HF) diet (60% fat-derived energy) during pregnancy, or during pregnancy and lactation, were at a reduced risk of developing mammary cancer. To better understand the unexpected protective effects of early life lard exposure, we have applied lipidomics and nutrigenomics approaches to investigate the fatty acid profile and global gene expression patterns in the mammary tissue of the female offspring. Consumption of this HF diet during gestation had few effects on the mammary tissue fatty acids profile of young adult offspring, while exposure from gestation throughout nursing promoted significant alterations in the fatty acids profile. Major differences were related to decreases in saturated fatty acids (SFA) and increases in omega-6 polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids (MUFAs) and conjugated linolenic acid (CLA) concentrations. In addition several differences in gene expression patterns by microarray analysis between the control and in utero or in utero and during lactation HF exposed offspring were identified. Differential dependency network (DDN) analysis indicated that many of the genes exhibited unique connections to other genes only in the HF offspring. These unique connections included Hrh1-Ythdf1 and Repin1-Elavl2 in the in utero HF offspring, and Rnf213-Htr3b and Klf5-Chrna4 in the in utero and lactation HF offspring, compared with the control offspring. We conclude that an exposure to a lard-based HF diet during early life changes the fatty acid profile and transcriptional network in mammary gland in young adult rats, and these changes appear to be consistent with reduced mammary cancer risk observed in our previous study. Copyright © 2015 Elsevier Ireland Ltd. All rights

Creatine supplementation and oxidative stress in rat liver

PubMed Central

2013-01-01

Background The objective of this study was to determine the effects of creatine supplementation on liver biomarkers of oxidative stress in exercise-trained rats. Methods Forty 90-day-old adult male Wistar rats were assigned to four groups for the eight-week experiment. Control group (C) rats received a balanced control diet; creatine control group (CCr) rats received a balanced diet supplemented with 2% creatine; trained group (T) rats received a balanced diet and intense exercise training equivalent to the maximal lactate steady state phase; and supplemented-trained (TCr) rats were given a balanced diet supplemented with 2% creatine and subjected to intense exercise training equivalent to the maximal lactate steady state phase. At the end of the experimental period, concentrations of creatine, hydrogen peroxide (H2O2) and thiobarbituric acid reactive substances (TBARS) were measured as well as the enzyme activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-GPx) and catalase (CAT). Liver tissue levels of reduced glutathione (GSH), oxidized glutathione (GSSG) and the GSH/GSSG ratio were also determined. Results Hepatic creatine levels were highest in the CCr and TCr groups with increased concentration of H2O2 observed in the T and TCr animal groups. SOD activity was decreased in the TCr group. GSH-GPx activity was increased in the T and TCr groups while CAT was elevated in the CCr and TCr groups. GSH, GGS and the GSH/GSSG ratio did not differ between all animal subsets. Conclusions Our results demonstrate that creatine supplementation acts in an additive manner to physical training to raise antioxidant enzymes in rat liver. However, because markers of liver oxidative stress were unchanged, this finding may also indicate that training-induced oxidative stress cannot be ameliorated by creatine supplementation. PMID:24325803

Comparative transcriptome analysis reveals different molecular mechanisms of Bacillus coagulans 2-6 response to sodium lactate and calcium lactate during lactic acid production.

PubMed

Qin, Jiayang; Wang, Xiuwen; Wang, Landong; Zhu, Beibei; Zhang, Xiaohua; Yao, Qingshou; Xu, Ping

2015-01-01

Lactate production is enhanced by adding calcium carbonate or sodium hydroxide during fermentation. However, Bacillus coagulans 2-6 can produce more than 180 g/L L-lactic acid when calcium lactate is accumulated, but less than 120 g/L L-lactic acid when sodium lactate is formed. The molecular mechanisms by which B. coagulans responds to calcium lactate and sodium lactate remain unclear. In this study, comparative transcriptomic methods based on high-throughput RNA sequencing were applied to study gene expression changes in B. coagulans 2-6 cultured in non-stress, sodium lactate stress and calcium lactate stress conditions. Gene expression profiling identified 712 and 1213 significantly regulated genes in response to calcium lactate stress and sodium lactate stress, respectively. Gene ontology assignments of the differentially expressed genes were performed. KEGG pathway enrichment analysis revealed that 'ATP-binding cassette transporters' were significantly affected by calcium lactate stress, and 'amino sugar and nucleotide sugar metabolism' was significantly affected by sodium lactate stress. It was also found that lactate fermentation was less affected by calcium lactate stress than by sodium lactate stress. Sodium lactate stress had negative effect on the expression of 'glycolysis/gluconeogenesis' genes but positive effect on the expression of 'citrate cycle (TCA cycle)' genes. However, calcium lactate stress had positive influence on the expression of 'glycolysis/gluconeogenesis' genes and had minor influence on 'citrate cycle (TCA cycle)' genes. Thus, our findings offer new insights into the responses of B. coagulans to different lactate stresses. Notably, our RNA-seq dataset constitute a robust database for investigating the functions of genes induced by lactate stress in the future and identify potential targets for genetic engineering to further improve L-lactic acid production by B. coagulans.

Comparative Transcriptome Analysis Reveals Different Molecular Mechanisms of Bacillus coagulans 2-6 Response to Sodium Lactate and Calcium Lactate during Lactic Acid Production

PubMed Central

Qin, Jiayang; Wang, Xiuwen; Wang, Landong; Zhu, Beibei; Zhang, Xiaohua; Yao, Qingshou; Xu, Ping

2015-01-01

Lactate production is enhanced by adding calcium carbonate or sodium hydroxide during fermentation. However, Bacillus coagulans 2-6 can produce more than 180 g/L L-lactic acid when calcium lactate is accumulated, but less than 120 g/L L-lactic acid when sodium lactate is formed. The molecular mechanisms by which B. coagulans responds to calcium lactate and sodium lactate remain unclear. In this study, comparative transcriptomic methods based on high-throughput RNA sequencing were applied to study gene expression changes in B. coagulans 2-6 cultured in non-stress, sodium lactate stress and calcium lactate stress conditions. Gene expression profiling identified 712 and 1213 significantly regulated genes in response to calcium lactate stress and sodium lactate stress, respectively. Gene ontology assignments of the differentially expressed genes were performed. KEGG pathway enrichment analysis revealed that ‘ATP-binding cassette transporters’ were significantly affected by calcium lactate stress, and ‘amino sugar and nucleotide sugar metabolism’ was significantly affected by sodium lactate stress. It was also found that lactate fermentation was less affected by calcium lactate stress than by sodium lactate stress. Sodium lactate stress had negative effect on the expression of ‘glycolysis/gluconeogenesis’ genes but positive effect on the expression of ‘citrate cycle (TCA cycle)’ genes. However, calcium lactate stress had positive influence on the expression of ‘glycolysis/gluconeogenesis’ genes and had minor influence on ‘citrate cycle (TCA cycle)’ genes. Thus, our findings offer new insights into the responses of B. coagulans to different lactate stresses. Notably, our RNA-seq dataset constitute a robust database for investigating the functions of genes induced by lactate stress in the future and identify potential targets for genetic engineering to further improve L-lactic acid production by B. coagulans. PMID:25875592

High brain lactate is a hallmark of aging and caused by a shift in the lactate dehydrogenase A/B ratio

PubMed Central

Ross, Jaime M.; Öberg, Johanna; Brené, Stefan; Coppotelli, Giuseppe; Terzioglu, Mügen; Pernold, Karin; Goiny, Michel; Sitnikov, Rouslan; Kehr, Jan; Trifunovic, Aleksandra; Larsson, Nils-Göran; Hoffer, Barry J.; Olson, Lars

2010-01-01

At present, there are few means to track symptomatic stages of CNS aging. Thus, although metabolic changes are implicated in mtDNA mutation-driven aging, the manifestations remain unclear. Here, we used normally aging and prematurely aging mtDNA mutator mice to establish a molecular link between mitochondrial dysfunction and abnormal metabolism in the aging process. Using proton magnetic resonance spectroscopy and HPLC, we found that brain lactate levels were increased twofold in both normally and prematurely aging mice during aging. To correlate the striking increase in lactate with tissue pathology, we investigated the respiratory chain enzymes and detected mitochondrial failure in key brain areas from both normally and prematurely aging mice. We used in situ hybridization to show that increased brain lactate levels were caused by a shift in transcriptional activities of the lactate dehydrogenases to promote pyruvate to lactate conversion. Separation of the five tetrameric lactate dehydrogenase (LDH) isoenzymes revealed an increase of those dominated by the Ldh-A product and a decrease of those rich in the Ldh-B product, which, in turn, increases pyruvate to lactate conversion. Spectrophotometric assays measuring LDH activity from the pyruvate and lactate sides of the reaction showed a higher pyruvate → lactate activity in the brain. We argue for the use of lactate proton magnetic resonance spectroscopy as a noninvasive strategy for monitoring this hallmark of the aging process. The mtDNA mutator mouse allows us to conclude that the increased LDH-A/LDH-B ratio causes high brain lactate levels, which, in turn, are predictive of aging phenotypes. PMID:21041631

High brain lactate is a hallmark of aging and caused by a shift in the lactate dehydrogenase A/B ratio.

PubMed

Ross, Jaime M; Öberg, Johanna; Brené, Stefan; Coppotelli, Giuseppe; Terzioglu, Mügen; Pernold, Karin; Goiny, Michel; Sitnikov, Rouslan; Kehr, Jan; Trifunovic, Aleksandra; Larsson, Nils-Göran; Hoffer, Barry J; Olson, Lars

2010-11-16

At present, there are few means to track symptomatic stages of CNS aging. Thus, although metabolic changes are implicated in mtDNA mutation-driven aging, the manifestations remain unclear. Here, we used normally aging and prematurely aging mtDNA mutator mice to establish a molecular link between mitochondrial dysfunction and abnormal metabolism in the aging process. Using proton magnetic resonance spectroscopy and HPLC, we found that brain lactate levels were increased twofold in both normally and prematurely aging mice during aging. To correlate the striking increase in lactate with tissue pathology, we investigated the respiratory chain enzymes and detected mitochondrial failure in key brain areas from both normally and prematurely aging mice. We used in situ hybridization to show that increased brain lactate levels were caused by a shift in transcriptional activities of the lactate dehydrogenases to promote pyruvate to lactate conversion. Separation of the five tetrameric lactate dehydrogenase (LDH) isoenzymes revealed an increase of those dominated by the Ldh-A product and a decrease of those rich in the Ldh-B product, which, in turn, increases pyruvate to lactate conversion. Spectrophotometric assays measuring LDH activity from the pyruvate and lactate sides of the reaction showed a higher pyruvate → lactate activity in the brain. We argue for the use of lactate proton magnetic resonance spectroscopy as a noninvasive strategy for monitoring this hallmark of the aging process. The mtDNA mutator mouse allows us to conclude that the increased LDH-A/LDH-B ratio causes high brain lactate levels, which, in turn, are predictive of aging phenotypes.

A maternal high-fat diet during pregnancy and lactation, in addition to a postnatal high-fat diet, leads to metabolic syndrome with spatial learning and memory deficits: beneficial effects of resveratrol

PubMed Central

Li, Shih-Wen; Yu, Hong-Ren; Sheen, Jiunn-Ming; Tiao, Mao-Meng; Tain, You-Lin; Lin, I-Chun; Lin, Yu-Ju; Chang, Kow-Aung; Tsai, Ching-Chou; Huang, Li-Tung

2017-01-01

We tested the hypothesis that high-fat diet consumption during pregnancy, lactation, and/or post weaning, altered the expression of molecular mediators involved in hippocampal synaptic efficacy and impaired spatial learning and memory in adulthood. The beneficial effect of resveratrol was assessed. Dams were fed a rat chow diet or a high-fat diet before mating, during pregnancy, and throughout lactation. Offspring were weaned onto either a rat chow or a high-fat diet. Four experimental groups were generated, namely CC, HC, CH, and HH (maternal chow diet or high-fat diet; postnatal chow diet or high-fat diet). A fifth group fed with HH plus resveratrol (HHR) was generated. Morris water maze test was used to evaluate spatial learning and memory. Blood pressure and IPGTT was measured to assess insulin resistance. Dorsal hippocampal expression of certain biochemical molecules, including sirtuin 1, ERK, PPARγ, adiponectin, and BDNF were measured. Rats in HH group showed impaired spatial memory, which was partly restored by the administration of resveratrol. Rats in HH group also showed impaired glucose tolerance and increased blood pressure, all of which was rescued by resveratrol administration. Additionally, SIRT1, phospho-ERK1/2, and phospho-PPARγ, adiponectin and BDNF were all dysregulated in rats placed in HH group; administration of resveratrol restored the expression and regulation of these molecules. Overall, our results suggest that maternal high-fat diet during pregnancy and/or lactation sensitizes the offspring to the adverse effects of a subsequent high-fat diet on hippocampal function; however, administration of resveratrol is demonstrated to be beneficial in rescuing these effects. PMID:29340106

21 CFR 862.1440 - Lactate dehydrogenase test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Systems § 862.1440 Lactate dehydrogenase test system. (a) Identification. A lactate dehydrogenase test system is a device intended to measure the activity of the enzyme lactate dehydrogenase in serum. Lactate... hepatitis, cirrhosis, and metastatic carcinoma of the liver, cardiac diseases such as myocardial infarction...

Transient gestational and neonatal hypothyroidism-induced specific changes in androgen receptor expression in skeletal and cardiac muscles of adult rat.

PubMed

Annapoorna, K; Anbalagan, J; Neelamohan, R; Vengatesh, G; Stanley, J; Amudha, G; Aruldhas, M M

2013-03-01

The present study aims to identify the association between androgen status and metabolic activity in skeletal and cardiac muscles of adult rats with transient gestational/neonatal-onset hypothyroidism. Pregnant and lactating rats were made hypothyroid by exposing to 0.05% methimazole in drinking water; gestational exposure was from embryonic day 9-14 (group II) or 21 (group III), lactational exposure was from postnatal day 1-14 (group IV) or 29 (group V). Serum was collected for hormone assay. Androgen receptor status, Glu-4 expression, and enzyme activities were assessed in the skeletal and cardiac muscles. Serum testosterone and estradiol levels decreased in adult rats of groups II and III, whereas testosterone remained normal but estradiol increased in group IV and V, when compared to coeval control. Androgen receptor ligand binding activity increased in both muscle phenotypes with a consistent increase in the expression level of its mRNA and protein expressions except in the forelimb of adult rats with transient hypothyroidism (group II-V). Glut-4 expression remained normal in skeletal and cardiac muscle of experimental rats. Specific activity of hexokinase and lactate dehydrogenase increased in both muscle phenotypes whereas, creatine kinase activity increased in skeletal muscles alone. It is concluded that transient gestational/lactational exposure to methimazole results in hypothyroidism during prepuberal life whereas it increases AR status and glycolytic activity in skeletal and cardiac muscles even at adulthood. Thus, the present study suggests that euthyroid status during prenatal and early postnatal life is essential to have optimal AR status and metabolic activity at adulthood. © Georg Thieme Verlag KG Stuttgart · New York.

Brain lactate metabolism: the discoveries and the controversies

PubMed Central

Dienel, Gerald A

2012-01-01

Potential roles for lactate in the energetics of brain activation have changed radically during the past three decades, shifting from waste product to supplemental fuel and signaling molecule. Current models for lactate transport and metabolism involving cellular responses to excitatory neurotransmission are highly debated, owing, in part, to discordant results obtained in different experimental systems and conditions. Major conclusions drawn from tabular data summarizing results obtained in many laboratories are as follows: Glutamate-stimulated glycolysis is not an inherent property of all astrocyte cultures. Synaptosomes from the adult brain and many preparations of cultured neurons have high capacities to increase glucose transport, glycolysis, and glucose-supported respiration, and pathway rates are stimulated by glutamate and compounds that enhance metabolic demand. Lactate accumulation in activated tissue is a minor fraction of glucose metabolized and does not reflect pathway fluxes. Brain activation in subjects with low plasma lactate causes outward, brain-to-blood lactate gradients, and lactate is quickly released in substantial amounts. Lactate utilization by the adult brain increases during lactate infusions and strenuous exercise that markedly increase blood lactate levels. Lactate can be an ‘opportunistic', glucose-sparing substrate when present in high amounts, but most evidence supports glucose as the major fuel for normal, activated brain. PMID:22186669

Regulation of glucose and ketone-body metabolism in brain of anaesthetized rats

PubMed Central

Ruderman, Neil B.; Ross, Peter S.; Berger, Michael; Goodman, Michael N.

1974-01-01

1. The effects of starvation and diabetes on brain fuel metabolism were examined by measuring arteriovenous differences for glucose, lactate, acetoacetate and 3-hydroxybutyrate across the brains of anaesthetized fed, starved and diabetic rats. 2. In fed animals glucose represented the sole oxidative fuel of the brain. 3. After 48h of starvation, ketone-body concentrations were about 2mm and ketone-body uptake accounted for 25% of the calculated O2 consumption: the arteriovenous difference for glucose was not diminished, but lactate release was increased, suggesting inhibition of pyruvate oxidation. 4. In severe diabetic ketosis, induced by either streptozotocin or phlorrhizin (total blood ketone bodies >7mm), the uptake of ketone bodies was further increased and accounted for 45% of the brain's oxidative metabolism, and the arteriovenous difference for glucose was decreased by one-third. The arteriovenous difference for lactate was increased significantly in the phlorrhizin-treated rats. 5. Infusion of 3-hydroxybutyrate into starved rats caused marked increases in the arteriovenous differences for lactate and both ketone bodies. 6. To study the mechanisms of these changes, steady-state concentrations of intermediates and co-factors of the glycolytic pathway were determined in freeze-blown brain. 7. Starved rats had increased concentrations of acetyl-CoA. 8. Rats with diabetic ketosis had increased concentrations of fructose 6-phosphate and decreased concentrations of fructose 1,6-diphosphate, indicating an inhibition of phosphofructokinase. 9. The concentrations of acetyl-CoA, glycogen and citrate, a potent inhibitor of phosphofructokinase, were increased in the streptozotocin-treated rats. 10. The data suggest that cerebral glucose uptake is decreased in diabetic ketoacidosis owing to inhibition of phosphofructokinase as a result of the increase in brain citrate. 11. The inhibition of brain pyruvate oxidation in starvation and diabetes can be related to the

Effect of HX108-CS supplementation on exercise capacity and lactate accumulation after high-intensity exercise.

PubMed

Oh, Seung-Lyul; Chang, Hyukki; Kim, Hee-Jae; Kim, Yong-An; Kim, Dong-Sik; Ho, Seong-Hyun; Kim, Seon-Hee; Song, Wook

2013-04-15

In the present study, we determined the effects of HX108-CS (mixed extract of Schisandra chinensis and Chaenomeles sinensis) supplementation on lactate accumulation and endurance capacity. Furthermore, we examined CK (creatine kinase), LDH (lactate dehydrogenase) activity to determine whether the HX108-CS affected markers of skeletal muscle injury in vivo and in vitro. Exercise capacity was measured by an exhaustive swimming test using ICR mice divided into four groups; one group received distilled water (DW) (Control group, n = 10), and the other groups received three different dosages of HX108-CS (10, 50 and 100 mg/kg, n = 10 per group) solution in water orally. Then, for the time-dependent measurements of blood lactate, CK, and LDH, Sprague-Dawley rats were divided into two groups; one received DW (Control group, n = 10), and the other group received HX108-CS (100 mg/kg, n = 10) solution in the same way as mice. Before the exercise test, the animals were given either DW or HX108-CS for 2 weeks. High-intensity treadmill exercise was performed for 30 minutes. Blood samples were collected and analyzed during and after exercise. For the in vitro experiment, C2C12 cells were treated with HX108-CS to examine its effect on lactate production, CK, and LDH activity. Blood lactate concentration was significantly lowered immediately after treadmill exercise in HX108-CS group; however, there were no significant differences in activities of CK and LDH between HX108-CS and control during treadmill exercise and recovery phase. Furthermore, treatment with 100 mg/kg of HX108-CS led to a significant increase in the time to exhaustion in swimming test, and concurrently blood lactate concentration was significantly decreased in 50 and 100 mg/kg treated group. Moreover, our results of in vitro experiment showed that HX108-CS suppressed lactate production, CK, and LDH activity in a dose-dependent manner. These results suggest that supplementation with HX

Effect of HX108-CS supplementation on exercise capacity and lactate accumulation after high-intensity exercise

PubMed Central

2013-01-01

Background In the present study, we determined the effects of HX108-CS (mixed extract of Schisandra chinensis and Chaenomeles sinensis) supplementation on lactate accumulation and endurance capacity. Furthermore, we examined CK (creatine kinase), LDH (lactate dehydrogenase) activity to determine whether the HX108-CS affected markers of skeletal muscle injury in vivo and in vitro. Methods Exercise capacity was measured by an exhaustive swimming test using ICR mice divided into four groups; one group received distilled water (DW) (Control group, n = 10), and the other groups received three different dosages of HX108-CS (10, 50 and 100 mg/kg, n = 10 per group) solution in water orally. Then, for the time-dependent measurements of blood lactate, CK, and LDH, Sprague–Dawley rats were divided into two groups; one received DW (Control group, n = 10), and the other group received HX108-CS (100 mg/kg, n = 10) solution in the same way as mice. Before the exercise test, the animals were given either DW or HX108-CS for 2 weeks. High-intensity treadmill exercise was performed for 30 minutes. Blood samples were collected and analyzed during and after exercise. For the in vitro experiment, C2C12 cells were treated with HX108-CS to examine its effect on lactate production, CK, and LDH activity. Results Blood lactate concentration was significantly lowered immediately after treadmill exercise in HX108-CS group; however, there were no significant differences in activities of CK and LDH between HX108-CS and control during treadmill exercise and recovery phase. Furthermore, treatment with 100 mg/kg of HX108-CS led to a significant increase in the time to exhaustion in swimming test, and concurrently blood lactate concentration was significantly decreased in 50 and 100 mg/kg treated group. Moreover, our results of in vitro experiment showed that HX108-CS suppressed lactate production, CK, and LDH activity in a dose-dependent manner. Conclusions These

A maternal high n-6 fat diet with fish oil supplementation during pregnancy and lactation in rats decreases breast cancer risk in the female offspring.

PubMed

Su, Hui-Min; Hsieh, Pei-Hsuan; Chen, Hui-Feng

2010-11-01

The timing of dietary fat intake may modify breast cancer risk. In addition, n-3 fatty acids reduce, and n-6 fatty acids increase, the risk of breast cancer and a maternal high n-6 fat diet results in a greater risk of breast cancer in the female offspring. We hypothesized that the timing of n-3 fatty acid-enriched fish oil supplementation would be important for reducing the risk of breast cancer. Female rats were fed to a high n-6 fat diet containing 20% of the sunflower oil by weight during pregnancy and lactation, and the female offspring were exposed to fish oil by oral gavage either during the perinatal period via maternal intake or during puberty or adulthood. Exposure during the perinatal period to a maternal high n-6 fat diet with fish oil supplementation significantly reduced the incidence of carcinogen-induced mammary tumors in the female offspring compared to a maternal high n-6 fat diet with no fish oil supplementation or fish oil supplementation later in life (P=.0228 by Cox proportional hazards model). We found that a maternal high n-6 fat diet during pregnancy is more important in increasing the risk of mammary tumors in the female offspring than a maternal high n-6 fat diet during lactation. This study suggests that fish oil supplementation during the perinatal period decreases the effect of a maternal high n-6 fat diet on subsequent carcinogen-induced mammary tumor risk, whereas fish oil supplementation during puberty or adulthood does not. Copyright © 2010 Elsevier Inc. All rights reserved.

Anxiety-like behaviour in adult rats perinatally exposed to maternal calorie restriction.

PubMed

Levay, Elizabeth A; Paolini, Antonio G; Govic, Antonina; Hazi, Agnes; Penman, Jim; Kent, Stephen

2008-08-22

Environmental stimuli such as caloric availability during the perinatal period exert a profound influence on the development of an organism. Studies in this domain have focused on the effects of under- and malnutrition while the effects of more mild levels of restriction have not been delineated. Rat dams and their offspring were subjected to one of five dietary regimens: control, CR50% for 3 days preconception, CR25% during gestation, CR25% during lactation, and CR25% during gestation, lactation, and post-weaning (lifelong). The pup retrieval test and maternal observations were conducted during lactation to quantify maternal care. In the pup retrieval test, dams that were concurrently experiencing CR (i.e., from the lactation and lifelong groups) displayed shorter latencies to retrieve all pups than the control and preconception groups and the lactation group constructed better nests than all groups. Adult offspring were tested in three tests of anxiety: the elevated plus maze, open field, and emergence test. No differences were observed in the elevated plus maze; however, in the open field preconception animals made fewer entries and spent more time in the central zone than controls. In addition, preconception offspring exhibited longer latencies to full body emergence, spent less time fully emerged, and spent more time engaged in risk assessment behaviours than all other groups. Offspring from the preconception group were also on average 11% heavier than control rats throughout life and displayed 37% higher serum leptin concentrations than controls. A potential role for leptin in the anxiogenic effect of preconception CR is discussed.

Striking differences in glucose and lactate levels between brain extracellular fluid and plasma in conscious human subjects: effects of hyperglycemia and hypoglycemia.

PubMed

Abi-Saab, Walid M; Maggs, David G; Jones, Tim; Jacob, Ralph; Srihari, Vinod; Thompson, James; Kerr, David; Leone, Paola; Krystal, John H; Spencer, Dennis D; During, Matthew J; Sherwin, Robert S

2002-03-01

Brain levels of glucose and lactate in the extracellular fluid (ECF), which reflects the environment to which neurons are exposed, have never been studied in humans under conditions of varying glycemia. The authors used intracerebral microdialysis in conscious human subjects undergoing electrophysiologic evaluation for medically intractable epilepsy and measured ECF levels of glucose and lactate under basal conditions and during a hyperglycemia-hypoglycemia clamp study. Only measurements from nonepileptogenic areas were included. Under basal conditions, the authors found the metabolic milieu in the brain to be strikingly different from that in the circulation. In contrast to plasma, lactate levels in brain ECF were threefold higher than glucose. Results from complementary studies in rats were consistent with the human data. During the hyperglycemia-hypoglycemia clamp study the relationship between plasma and brain ECF levels of glucose remained similar, but changes in brain ECF glucose lagged approximately 30 minutes behind changes in plasma. The data demonstrate that the brain is exposed to substantially lower levels of glucose and higher levels of lactate than those in plasma; moreover, the brain appears to be a site of significant anaerobic glycolysis, raising the possibility that glucose-derived lactate is an important fuel for the brain.

Estimation of placental and lactational transfer and tissue distribution of atrazine and its main metabolites in rodent dams, fetuses, and neonates with physiologically based pharmacokinetic modeling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Zhoumeng; Interdisciplinary Toxicology Program, University of Georgia, Athens, GA 30602; Fisher, Jeffrey W.

Atrazine (ATR) is a widely used chlorotriazine herbicide, a ubiquitous environmental contaminant, and a potential developmental toxicant. To quantitatively evaluate placental/lactational transfer and fetal/neonatal tissue dosimetry of ATR and its major metabolites, physiologically based pharmacokinetic models were developed for rat dams, fetuses and neonates. These models were calibrated using pharmacokinetic data from rat dams repeatedly exposed (oral gavage; 5 mg/kg) to ATR followed by model evaluation against other available rat data. Model simulations corresponded well to the majority of available experimental data and suggest that: (1) the fetus is exposed to both ATR and its major metabolite didealkylatrazine (DACT) atmore » levels similar to maternal plasma levels, (2) the neonate is exposed mostly to DACT at levels two-thirds lower than maternal plasma or fetal levels, while lactational exposure to ATR is minimal, and (3) gestational carryover of DACT greatly affects its neonatal dosimetry up until mid-lactation. To test the model's cross-species extrapolation capability, a pharmacokinetic study was conducted with pregnant C57BL/6 mice exposed (oral gavage; 5 mg/kg) to ATR from gestational day 12 to 18. By using mouse-specific parameters, the model predictions fitted well with the measured data, including placental ATR/DACT levels. However, fetal concentrations of DACT were overestimated by the model (10-fold). This overestimation suggests that only around 10% of the DACT that reaches the fetus is tissue-bound. These rodent models could be used in fetal/neonatal tissue dosimetry predictions to help design/interpret early life toxicity/pharmacokinetic studies with ATR and as a foundation for scaling to humans. - Highlights: • We developed PBPK models for atrazine in rat dams, fetuses, and neonates. • We conducted pharmacokinetic (PK) study with atrazine in pregnant mice. • Model predictions were in good agreement with experimental rat and mouse PK

Stimulus-dependent changes of extracellular glucose in the rat hippocampus determined by in vivo microdialysis.

PubMed

Rex, A; Bert, B; Fink, H; Voigt, J-P

2009-10-19

Neuronal activity is tightly coupled with brain energy metabolism; and glucose is an important energy substrate for neurons. The present in vivo microdialysis study was aimed at investigating changes in extracellular glucose concentrations in the rat ventral hippocampus due to exposure to the elevated plus maze. Determination of basal hippocampal glucose and lactate/pyruvate ratio in male Wistar rats was conducted in the home cage using in vivo microdialysis. Rats were exposed to the elevated plus maze, a rodent model of anxiety-related behaviour, or to unspecific stress induced by white noise (95dB) as a control condition. Basal hippocampal levels of glucose, as determined by zero-net-flux, and the basal lactate/pyruvate ratio were 1.49+/-0.05mmol/l and 13.8+/-1.1, respectively. In rats without manipulation, glucose levels remained constant throughout the experiment (120min). By contrast, exposure to the elevated plus maze led to a temporary decline in hippocampal glucose (-33.2+/-4.4%) which returned to baseline level in the home cage. White noise caused only a non-significant decrease in extracellular glucose level (-9.3+/-3.5%). In all groups, the lactate/pyruvate ratio remained unchanged by the experimental procedures. Our microdialysis study demonstrates that exposure to the elevated plus maze induces a transient decrease in extracellular hippocampal glucose concentration. In contrast, an unspecific stimulus did not change hippocampal glucose. The latter suggests that only specific behavioural stimuli increase hippocampal glucose utilization in the ventral hippocampus.

Effect of aged garlic extract against methotrexate-induced damage to the small intestine in rats.

PubMed

Yüncü, Mehmet; Eralp, Ayhan; Celik, Ahmet

2006-06-01

Methotrexate (MTX) chemotherapy is often accompanied by side effects such as gastrointestinal ulceration and diarrhea. The aim of this study was to examine histologically whether an aged garlic extract (AGE) had a protective effect on the small intestine of rats with MTX-induced damage. Forty male Wistar albino rats were randomized into experimental and control groups and divided into four groups of ten animals. To the first group, MTX was applied as a single dose (20 mg/kg) intraperitoneally. To the second group, in addition to MTX application, AGE (250 mg/kg) was administered orally every day at the same time by intragastric intubation until the rats were killed. To the third group, AGE only was given. The fourth group was the control. All animals were killed 4 days after the intraperitoneal injection of MTX for histopathologic analysis and tissue MDA levels. Before killing, intracardiac blood was obtained from each animal to perform biochemical analysis (plasma lactate level). MTX was found to lead to damage in the jejunal tissues and to increase the MDA and lactate levels in the plasma. Administration of the AGE decreased the severity of jejunal damage, but increased MDA and lactate levels caused by MTX treatment on the other hand. These results suggest that AGE may protect the small intestine of rats from MTX-induced damage. Thus this study substantiated the thought that the protective effect of AGE is derived from the manner in which it interacts with crypt cells.

Maternal protein restriction during pregnancy and lactation alters central leptin signalling, increases food intake, and decreases bone mass in 1 year old rat offspring.

PubMed

Qasem, Rani J; Li, Jing; Tang, Hee Man; Pontiggia, Laura; D'mello, Anil P

2016-04-01

The effects of perinatal nutrition on offspring physiology have mostly been examined in young adult animals. Aging constitutes a risk factor for the progressive loss of metabolic flexibility and development of disease. Few studies have examined whether the phenotype programmed by perinatal nutrition persists in aging offspring. Persistence of detrimental phenotypes and their accumulative metabolic effects are important for disease causality. This study determined the effects of maternal protein restriction during pregnancy and lactation on food consumption, central leptin sensitivity, bone health, and susceptibility to high fat diet-induced adiposity in 1-year-old male offspring. Sprague-Dawley rats received either a control or a protein restricted diet throughout pregnancy and lactation and pups were weaned onto laboratory chow. One-year-old low protein (LP) offspring exhibited hyperphagia. The inability of an intraperitoneal (i.p.) leptin injection to reduce food intake indicated that the hyperphagia was mediated by decreased central leptin sensitivity. Hyperphagia was accompanied by lower body weight suggesting increased energy expenditure in LP offspring. Bone density and bone mineral content that are negatively regulated by leptin acting via the sympathetic nervous system (SNS), were decreased in LP offspring. LP offspring did not exhibit increased susceptibility to high fat diet induced metabolic effects or adiposity. The results presented here indicate that the programming effects of perinatal protein restriction are mediated by specific decreases in central leptin signalling to pathways involved in the regulation of food intake along with possible enhancement of different CNS leptin signalling pathways acting via the SNS to regulate bone mass and energy expenditure. © 2016 John Wiley & Sons Australia, Ltd.

Effects of the neurotoxin MPTP and pargyline protection on extracellular energy metabolites and dopamine levels in the striatum of freely moving rats.

PubMed

Bazzu, Gianfranco; Rocchitta, Gaia; Migheli, Rossana; Alvau, Maria Domenica; Zinellu, Manuel; Puggioni, Giulia; Calia, Giammario; Mercanti, Giulia; Giusti, Pietro; Desole, Maria Speranza; Serra, Pier Andrea

2013-11-13

The neurotoxin MPTP is known to induce dopamine release and depletion of ATP in the striatum of rats. Therefore, we studied the changes induced by MPTP and pargyline protection both on striatal dopamine release and on extracellular energy metabolites in freely moving rats, using dual asymmetric-flow microdialysis. A dual microdialysis probe was inserted in the right striatum of rats. MPTP (25mg/kg, 15mg/kg, 10mg/kg) was intraperitoneally administered for three consecutive days. MAO-B inhibitor pargyline (15mg/kg) was systemically administered before neurotoxin administration. The first MPTP dose induced an increase in dialysate dopamine and a decrease of DOPAC levels in striatal dialysate. After the first neurotoxin administration, increases in striatal glucose, lactate, pyruvate, lactate/pyruvate (L/P) and lactate/glucose (L/G) ratios were observed. Subsequent MPTP administrations showed a progressive reduction of dopamine, glucose and pyruvate levels with a concomitant further increase in lactate levels and L/P and L/G ratios. At day 1, pargyline pre-treatment attenuated the MPTP-induced changes in all studied analytes. Starting from day 2, pargyline prevented the depletion of dopamine, glucose and pyruvate while reduced the increase of lactate, L/P ratio and L/G ratio. These in vivo results suggest a pargyline neuroprotection role against the MPTP-induced energetic impairment consequent to mitochondrial damage. This neuroprotective effect was confirmed by TH immunostaining of the substantia nigra. © 2013 Elsevier B.V. All rights reserved.

Alcohol consumption decreases lactate clearance in acutely injured patients☆

PubMed Central

Dezman, Zachary D.W.; Comer, Angela C.; Narayan, Mayur; Scalea, Thomas M.; Hirshon, Jon Mark; Smith, Gordon S.

2017-01-01

Introduction Alcohol, a common risk factor for injury, has direct toxic effects on the liver. The use of lactate clearance has been well described as an indicator of the adequacy of resuscitation in injured patients. We investigated whether acutely injured patients with positive blood alcohol content (+BAC) had less lactate clearance than sober patients. Methods We conducted a retrospective cohort study of acutely injured patients treated at an urban Level 1 trauma centre between January 2010 and December 2012. Blood alcohol and venous lactate levels were measured on all patients at the time of arrival. Study subjects were patients transported directly from the scene of injury, who had an elevated lactate concentration on arrival (≥3.0 mmol/L) and at least one subsequent lactate measurement within 24 h after admission. Lactate clearance ([Lactate1 − Lactate2]/Lactate1) was calculated for all patients. Chi-squared tests were used to compare values from sober and intoxicated subjects. Lactate clearance was plotted against alcohol levels and stratified by age and Injury Severity Score (ISS). Results Serial lactate concentration measurements were obtained in 3910 patients; 1674 of them had +BAC. Patients with +BAC were younger (mean age: 36.6 [SD 14.7] vs 41.0 [SD 19.9] years [p = 0.0001]), were more often male (83.4% vs 75.9% [p = 0.0001]), had more minor injuries (ISS < 9) (33.8% vs 27.1% [p = 0.0001]), had a lower in-hospital mortality rate (1.4% vs 3.9% [p = 0.0001]), but also had lower average lactate clearance (37.8% vs 47.6% [p = 0.0001]). The lactate clearance of the sober patients (47.6 [SD 33.5]) was twice that of those with +BAC >400 (23.5 [SD 6.5]). Lactate clearance decreased with increasing BAC irrespective of age and ISS. Conclusions In a large group of acutely injured patients, a dose-dependent decrease in lactate clearance was seen in those with elevated BAC. This relationship will cause a falsely elevated lactate reading or prolong lactate

21 CFR 582.5311 - Ferrous lactate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5311 Ferrous lactate. (a) Product. Ferrous lactate. (b) Conditions of use. This substance...

21 CFR 582.5311 - Ferrous lactate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5311 Ferrous lactate. (a) Product. Ferrous lactate. (b) Conditions of use. This substance...

21 CFR 582.5311 - Ferrous lactate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5311 Ferrous lactate. (a) Product. Ferrous lactate. (b) Conditions of use. This substance...

21 CFR 582.5311 - Ferrous lactate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5311 Ferrous lactate. (a) Product. Ferrous lactate. (b) Conditions of use. This substance...

21 CFR 582.5311 - Ferrous lactate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5311 Ferrous lactate. (a) Product. Ferrous lactate. (b) Conditions of use. This substance...

21 CFR 582.1207 - Calcium lactate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Additives § 582.1207 Calcium lactate. (a) Product. Calcium lactate. (b) Conditions of use. This substance is generally recognized as safe when used in accordance with good manufacturing or feeding practice. ...

21 CFR 582.1207 - Calcium lactate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Additives § 582.1207 Calcium lactate. (a) Product. Calcium lactate. (b) Conditions of use. This substance is generally recognized as safe when used in accordance with good manufacturing or feeding practice. ...

21 CFR 582.1207 - Calcium lactate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Additives § 582.1207 Calcium lactate. (a) Product. Calcium lactate. (b) Conditions of use. This substance is generally recognized as safe when used in accordance with good manufacturing or feeding practice. ...

Hypothyroxinemia induced by mild iodine deficiency deregulats thyroid proteins during gestation and lactation in dams.

PubMed

Wei, Wei; Wang, Yi; Dong, Jing; Wang, Yuan; Min, Hui; Song, Binbin; Shan, Zhongyan; Teng, Weiping; Xi, Qi; Chen, Jie

2013-08-02

The main object of the present study was to explore the effect on thyroidal proteins following mild iodine deficiency (ID)-induced maternal hypothyroxinemia during pregnancy and lactation. In the present study, we established a maternal hypothyroxinemia model in female Wistar rats by using a mild ID diet. Maternal thyroid iodine content and thyroid weight were measured. Expressions of thyroid-associated proteins were analyzed. The results showed that the mild ID diet increased thyroid weight, decreased thyroid iodine content and increased expressions of thyroid transcription factor 1, paired box gene 8 and Na+/I- symporter on gestational day (GD) 19 and postpartum days (PN) 21 in the maternal thyroid. Moreover, the up-regulated expressions of type 1 iodothyronine deiodinase (DIO1) and type 2 iodothyronine deiodinase (DIO2) were detected in the mild ID group on GD19 and PN21. Taken together, our data indicates that during pregnancy and lactation, a maternal mild ID could induce hypothyroxinemia and increase the thyroidal DIO1 and DIO2 levels.

The agreement between abnormal venous lactate and arterial lactate in the ED: a retrospective chart review.

PubMed

Bloom, B; Pott, J; Freund, Y; Grundlingh, J; Harris, T

2014-06-01

The evidence for prognostication using lactate is often based on arterial lactate (AL). Arterial sampling is painful and difficult, and carries risks. Studies comparing peripheral venous lactate (PVL) with AL showed little difference but predominantly included patients with normal lactate. The objective of this study was to measure agreement between PVL and AL in patients with elevated venous lactate. This is a retrospective cross-sectional study. ED patients age≥16, attending from October 2010 to June 2011 inclusive, with PVL≥2.0 mmol/L and AL taken within 1 hour. intravenous fluid prior to or between initial venous and arterial sampling. Primary endpoint: agreement between PVL and AL defined as mean difference±95% limits of agreement (LOA). The misclassification rate was assessed. N=232. VL median 3.50 mmol/L, range 2.00 to 15.00 mmol/L. AL median 2.45 mmol/L, range 1.0 to 13.2 mmol/L. The mean difference±SD between PVL and AL for all patients was 1.06±1.30 mmol/L (95%LOA -1.53 to 3.66 mmol/L). Using a cut-off of 2 mmol/L and 4 mmol/L, 36.2% and 17.9% of patients respectively were incorrectly classified as having elevated lactate. We report greater bias between VL and AL with broader LOA than previously documented. This may partly be due to the fact that we studied only patients with abnormal venous values, for whom close agreement would confer greatest clinical significance. The agreement between abnormal PVL and AL is poor and the high rate of misclassification may suggest that PVL is not a good substitute for AL if the venous lactate is abnormal. Copyright © 2014 Elsevier Inc. All rights reserved.

Trafficking of glucose, lactate, and amyloid-β from the inferior colliculus through perivascular routes

PubMed Central

Ball, Kelly K; Cruz, Nancy F; Mrak, Robert E; Dienel, Gerald A

2010-01-01

Metabolic brain imaging is widely used to evaluate brain function and disease, and quantitative assays require local retention of compounds used to register changes in cellular activity. As labeled metabolites of [1- and 6-14C]glucose are rapidly released in large quantities during brain activation, this study evaluated release of metabolites and proteins through perivascular fluid flow, a pathway that carries solutes from brain to peripheral lymphatic drainage sites. Assays with [3,4-14C]glucose ruled out local oxidation of glucose-derived lactate as a major contributor of label loss. Brief infusion of [1-14C]glucose and -[14C]lactate into the inferior colliculus of conscious rats during acoustic stimulation labeled the meninges, consistent with perivascular clearance of [14C]metabolites from interstitial fluid. Microinfusion of Evans blue albumin and amyloid-β1−40 (Aβ) caused perivascular labeling in the inferior colliculus, labeled the surrounding meninges, and Aβ-labeled-specific blood vessels in the caudate and olfactory bulb and was deposited in cervical lymph nodes. Efflux of extracellular glucose, lactate, and Aβ into perivascular fluid pathways is a normal route for clearance of material from the inferior colliculus that contributes to underestimates of brain energetics. Convergence of ‘watershed' drainage to common pathways may facilitate perivascular amyloid plaque formation and pathway obstruction in Alzheimer's disease. PMID:19794399

Protein quality and quantity and insulin control of mammary gland glucose utilization during lactation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Masor, M.L.

1987-01-01

Virgin Sprague-Dawley rats were bred, and fed laboratory stock (STOCK), 13% casein plus methionine, 13% wheat gluten, or 5% casein plus methionine through gestation and 4 days of lactation. Diets were switched at parturition to determine the effects of dietary protein quality and quantity fed during gestation and/or lactation on insulin stimulation of mammary glucose utilization. On day 20 of gestation (20G) and day 4 of lactation (4L) the right inguinal-abdominal mammary glands were removed, and acini and tissue slices were incubated in Krebs buffer with or without insulin containing (U-/sup 14/C)-glucose and 5mM glucose for 1 hour at 37/degrees/C.more » Glucose incorporation into CO/sub 2/, lipid and lactose was determined. Glucose incorporation into CO/sub 2/ and lipid, but not lactose was stimulated by insulin in mammary slices. Diet effects on glucose utilization in acini were confirmed in slices for basal and insulin stimulated levels. Treatment affected the absolute increase of insulin stimulation. Regression analysis significantly correlated pup weight gain with total glucose utilization. Poor dietary protein quality and quantity fed during gestation impaired both overall response of mammary glucose utilization to insulin stimulation, and mammary development during pregnancy. Improving protein value at parturition did not overcome those deficits by 4L.« less

Analysis of lactate concentrations in canine synovial fluid.

PubMed

Proot, J L J; de Vicente, F; Sheahan, D E

2015-01-01

To report synovial fluid lactate concentrations in normal and pathological canine joints. Controlled, prospective study. Lactate was measured in synovial fluid using a hand-held meter and the rest of the fluid was sent to a commercial laboratory for analysis. Samples were divided into four groups; group 1: control, group 2: osteoarthritis, group 3: immune-mediated inflammatory arthritis, and group 4: septic arthritis. Statistical analysis was performed to compare lactate concentrations between the four groups and to examine the predictive value of lactate in the diagnosis of septic arthritis. A correlation was sought between synovial fluid lactate and synovial fluid total nucleated cell count and total protein. Seventy-four samples were investigated from 55 dogs. Statistical analysis found that lactate concentrations were significantly higher in the septic arthritis group than in each of the other three groups. No significant correlation could be found between synovial fluid lactate concentrations and synovial fluid total nucleated cell count or synovial fluid total protein. Lactate concentration was found to be a useful predictor of septic arthritis, with a low concentration pointing towards exclusion rather than a high concentration to the diagnosis of septic arthritis. Synovial fluid lactate concentration is not a good marker for osteoarthritis or immune-mediated inflammatory arthritis, but it is significantly increased in septic arthritis and could help the clinician in ruling out this condition in a quick and cost-effective way.

A low maternal protein diet during pregnancy and lactation has sex- and window of exposure-specific effects on offspring growth and food intake, glucose metabolism and serum leptin in the rat

PubMed Central

Zambrano, E; Bautista, C J; Deás, M; Martínez-Samayoa, P M; González-Zamorano, M; Ledesma, H; Morales, J; Larrea, F; Nathanielsz, P W

2006-01-01

Extensive epidemiological and experimental evidence indicates that a sub-optimal environment during fetal and neonatal development in both humans and animals may programme offspring susceptibility to later development of chronic diseases including obesity and diabetes that are the result of altered carbohydrate metabolism. We determined the effects of protein restriction during pregnancy and/or lactation on growth, serum leptin, and glucose and insulin responses to a glucose tolerance test in male and female offspring at 110 days postnatal life. We fed Wistar rats a normal control 20% casein diet (C) or a restricted diet (R) of 10% casein during pregnancy. Female but not male R pups weighed less than C at birth. After delivery, mothers received the C or R diet during lactation to provide four offspring groups: CC (first letter maternal pregnancy diet and second maternal lactation diet), RR, CR and RC. All offspring were fed ad libitum with C diet after weaning. Relative food intake correlated inversely with weight. Offspring serum leptin correlated with body weight and relative, but not absolute, food intake in both male and female pups. Serum leptin was reduced in RR female pups compared with CC and increased in RC males compared with CC at 110 days of age. Offspring underwent a glucose tolerance test (GTT) at 110 days postnatal life. Female RR and CR offspring showed a lower insulin to glucose ratio than CC. At 110 days of age male RR and CR also showed some evidence of increased insulin sensitivity. Male but not female RC offspring showed evidence of insulin resistance compared with CC. Cholesterol was similar and triglycerides (TG) higher in male compared with female CC. Cholesterol and TG were higher in males than females in RR, CR and RC (P < 0.05). Cholesterol and TG did not differ between groups in females. Cholesterol and TG were elevated in RC compared with CC males. Nutrient restriction in lactation increased relative whole protein and decreased whole

Lactate Test

MedlinePlus

... by cells as the body turns food into energy (cell metabolism). Depending on pH , it is sometimes ... level or when the primary way of producing energy in the body's cells is disrupted. Excess lactate ...

High Fat Diet Alters Lactation Outcomes: Possible Involvement of Inflammatory and Serotonergic Pathways

PubMed Central

Hernandez, Laura L.; Grayson, Bernadette E.; Yadav, Ekta; Seeley, Randy J.; Horseman, Nelson D.

2012-01-01

Delay in the onset of lactogenesis has been shown to occur in women who are obese, however the mechanism altered within the mammary gland causing the delay remains unknown. Consumption of high fat diets (HFD) has been previously determined to result decreased litters and litter numbers in rodent models due to a decrease in fertility. We examined the effects of feeding a HFD (60% kcal from fat) diet versus a low-fat diet (LFD; 10% kcal from fat) to female Wistar rats on lactation outcomes. Feeding of HFD diet resulted in increased pup weights compared to pups from LFD fed animals for 4 d post-partum. Lactation was delayed in mothers on HFD but they began to produce copious milk volumes beginning 2 d post-partum, and milk yield was similar to LFD by day 3. Mammary glands collected from lactating animals on HFD diet, displayed a disrupted morphologies, with very few and small alveoli. Consistently, there was a significant decrease in the mRNA expression of milk protein genes, glucose transporter 1 (GLUT1) and keratin 5 (K5), a luminobasal cell marker in the mammary glands of HFD lactating animals. Expression of tryptophan hydroxylase 1 (TPH1), the rate-limiting enzyme in serotonin (5-HT) biosynthesis, and the 5-HT7 receptor (HTR7), which regulates mammary gland involution, were significantly increased in mammary glands of HFD animals. Additionally, we saw elevation of the inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor-α (TNF- α). These results indicate that consumption of HFD impairs mammary parenchymal tissue and impedes its ability to synthesize and secrete milk, possibly through an increase in 5-HT production within the mammary gland leading to an inflammatory process. PMID:22403677

Attenuated neuroendocrine responses to emotional and physical stressors in pregnant rats involve adenohypophysial changes

PubMed Central

Neumann, I D; Johnstone, H A; Hatzinger, M; Liebsch, G; Shipston, M; Russell, J A; Landgraf, R; Douglas, A J

1998-01-01

The responsiveness of the rat hypothalamo-pituitary-adrenal (HPA) axis and hypothalamo-neurohypophysial system (HNS) to emotional (elevated plus-maze) and physical (forced swimming) stressors and to administration of synthetic corticotrophin-releasing hormone (CRH) was investigated during pregnancy and lactation. In addition to pregnancy-related adaptations at the adenohypophysial level, behavioural responses accompanying the neuroendocrine changes were studied. Whereas basal (a.m.) plasma corticosterone, but not corticotrophin (adrenocorticotrophic hormone; ACTH), levels were increased on the last day (i.e. on day 22) of pregnancy, the stress-induced rise in both plasma hormone concentrations was increasingly attenuated with the progression of pregnancy beginning on day 15 and reaching a minimum on day 21 compared with virgin control rats. A similar attenuation of responses to both emotional and physical stressors was found in lactating rats. Although the basal plasma oxytocin concentration was elevated in late pregnancy, the stress-induced rise in oxytocin secretion was slightly lower in day 21 pregnant rats. In contrast to vasopressin, oxytocin secretion was increased by forced swimming in virgin and early pregnant rats indicating a differential stress response of these neurohypophysial hormones. The blunted HPA response to stressful stimuli is partly due to alterations at the level of corticotrophs in the adenohypophysis, as ACTH secretion in response to CRH in vivo (40 ng kg−1, i.v.) was reduced with the progression of pregnancy and during lactation. In vitro measurement of cAMP levels in pituitary segments demonstrated reduced basal levels of cAMP and a lower increase after CRH stimulation (10 nm, 10 min) in day 21 pregnant compared with virgin rats, further indicating reduced corticotroph responsiveness to CRH in pregnancy. The reduced pituitary response to CRH in late pregnancy is likely to be a consequence of a reduction in CRH receptor binding as

Suppression of male reproduction in rats after exposure to sodium fluoride during early stages of development

NASA Astrophysics Data System (ADS)

Reddy, P. Sreedhar; Pushpalatha, T.; Reddy, P. Sreenivasula

2007-07-01

Sodium fluoride (NaF), a widespread natural pollutant was given to sperm-positive female rats throughout gestation and lactation at a dose of 4.5 and 9.0 ppm via drinking water. The neonates were allowed to grow up to 90 days on tap water, and then sperm parameters, testicular steroidogenic marker enzyme activity levels, and circulatory hormone levels were studied. The sperm count, sperm motility, sperm coiling (hypoosmotic swelling test), and sperm viability were decreased in experimental rats when compared with controls. The activity levels of testicular steroidogenic marker enzymes (3β hydroxysteroid dehydrogenase and 17β hydroxysteroid dehydrogenase) were significantly decreased in experimental animals indicating decreased steroidogenesis. The serum testosterone, follicle stimulating hormone and luteinizing hormone levels were also significantly altered in experimental animals. Our data indicate that exposure to NaF during gestation and lactation affects male reproduction in adult rats by decreasing spermatogenesis and steroidogenesis.

Increased gluconeogenesis in rats exposed to hyper-G stress

NASA Technical Reports Server (NTRS)

Daligcon, B. C.; Oyama, J.; Hannak, K.

1985-01-01

The effect of glucogenesis on the plasma glucose and liver glycogen of rats exposed to hyper-G stress is investigated. Twelve male Sprague-Dawley rats are injected with C-14 lactate, alanine, of glycerol, and six of the rats are exposed to 3.1 G for 0.25, 0.50, and 1.0 hr. The plasma glucose and liver glycogen of the centrifuged and noncentrifuged rats are analyzed. A significant increase in the C-14 incorporation of the substrate into the plasma glucose and liver glycogen is observed in the centrifuged rats. The injection of 5-methoxyindole-2-carboxylic acid, a gluconeogenesis inhibitor, results in a blocked increase in plasma glucose and liver glycogen. The role of epinephrine on the hyperglycemic and liver glycogen responses of centrifuged rats is studied. It is concluded that the initial increase in plasma glucose and liver glycogen in rats exposed to hyper-G stress is the result of an increased rate of gluconeogenesis.

l-Lactate metabolism in HEP G2 cell mitochondria due to the l-lactate dehydrogenase determines the occurrence of the lactate/pyruvate shuttle and the appearance of oxaloacetate, malate and citrate outside mitochondria.

PubMed

Pizzuto, Roberto; Paventi, Gianluca; Porcile, Carola; Sarnataro, Daniela; Daniele, Aurora; Passarella, Salvatore

2012-09-01

As part of an ongoing study of l-lactate metabolism both in normal and in cancer cells, we investigated whether and how l-lactate metabolism occurs in mitochondria of human hepatocellular carcinoma (Hep G2) cells. We found that Hep G2 cell mitochondria (Hep G2-M) possess an l-lactate dehydrogenase (ml-LDH) restricted to the inner mitochondrial compartments as shown by immunological analysis, confocal microscopy and by assaying ml-LDH activity in solubilized mitochondria. Cytosolic and mitochondrial l-LDHs were found to differ from one another in their saturation kinetics. Having shown that l-lactate itself can enter Hep G2 cells, we found that Hep G2-M swell in ammonium l-lactate, but not in ammonium pyruvate solutions, in a manner inhibited by mersalyl, this showing the occurrence of a carrier-mediated l-lactate transport in these mitochondria. Occurrence of the l-lactate/pyruvate shuttle and the appearance outside mitochondria of oxaloacetate, malate and citrate arising from l-lactate uptake and metabolism together with the low oxygen consumption and membrane potential generation are in favor of an anaplerotic role for l-LAC in Hep G2-M. Copyright © 2012 Elsevier B.V. All rights reserved.

Chronic treatment with polychlorinated biphenyls (PCB) during pregnancy and lactation in the rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cocchi, Daniela; Tulipano, Giovanni; Colciago, Alessandra

Polychlorinated biphenyls (PCBs) are pollutants detected in animal tissues and breast milk. The experiments described in the present paper were aimed at evaluating whether the four PCB congeners most abundant in animal tissues (PCB-138, -153, -180 and -126), administered since fetal life till weaning, can induce long-term alterations of GH-axis activity and bone mass in the adult rat. We measured PCB accumulation in rat brain and liver, somatic growth, pituitary GH expression and plasma hormone concentrations at different ages. Finally, we studied hypothalamic somatostatin expression and bone structure in adulthood, following long-term PCB exposure. Dams were treated during pregnancy frommore » GD15 to GD19 and during breast-feeding. A constant reduction of the growth rate in both male and female offspring from weaning to adulthood was observed in exposed animals. Long-lasting alterations on hypothalamic-pituitary GH axis were indeed observed in PCB-exposed rats in adulthood: increased somatostatin expression in hypothalamic periventricular nucleus (both males and females) and lateral arcuate nucleus (males, only) and decreased GH mRNA levels in the pituitary of male rats. Plasma IGF-1 levels were higher in PCB-exposed male and female animals as compared with controls at weaning and tended to be higher at PN60. Plasma testosterone and thyroid hormone concentrations were not significantly affected by exposure to PCBs. In adulthood, PCBs caused a significant reduction of bone mineral content and cortical bone thickness of tibiae in male rat joint to increased width of the epiphyseal cartilage disk. In conclusion, the developmental exposure to the four selected PCB compounds used in the present study induced far-reaching effects in the adult offspring, the male rats appearing more sensitive than females.« less

Metabolic and histologic effects of sodium pyruvate treatment in the rat after cortical contusion injury.

PubMed

Fukushima, Masamichi; Lee, Stefan M; Moro, Nobuhiro; Hovda, David A; Sutton, Richard L

2009-07-01

This study determined the effects of intraperitoneal sodium pyruvate (SP) treatment on the levels of circulating fuels and on cerebral microdialysis levels of glucose (MD(glc)), lactate (MD(lac)), and pyruvate (MD(pyr)), and the effects of SP treatment on neuropathology after left cortical contusion injury (CCI) in rats. SP injection (1000 mg/kg) 5 min after sham injury (Sham-SP) or CCI (CCI-SP) significantly increased arterial pyruvate (p < 0.005) and lactate (p < 0.001) compared to that of saline-treated rats with CCI (CCI-Sal). Serum glucose also increased significantly in CCI-SP compared to that in CCI-Sal rats (p < 0.05), but not in Sham-SP rats. MD(pyr) was not altered after CCI-Sal, whereas MD(lac) levels within the cerebral cortex significantly increased bilaterally (p < 0.05) and those for MD(glc) decreased bilaterally (p < 0.05). MD(pyr) levels increased significantly in both Sham-SP and CCI-SP rats (p < 0.05 vs. CCI-Sal) and were higher in left/injured cortex of the CCI-SP group (p < 0.05 vs. sham-SP). In CCI-SP rats the contralateral MD(lac) decreased below CCI-Sal levels (p < 0.05) and the ipsilateral MD(glc) levels exceeded those of CCI-Sal rats (p < 0.05). Rats with a single low (500 mg/kg) or high dose (1000 mg/kg) SP treatment had fewer damaged cortical cells 6 h post-CCI than did saline-treated rats (p < 0.05), but three hourly injections of SP (1000 mg/kg) were needed to significantly reduce contusion volume 2 weeks after CCI. Thus, a single intraperitoneal SP treatment increases circulating levels of three potential brain fuels, attenuates a CCI-induced reduction in extracellular glucose while increasing extracellular levels of pyruvate, but not lactate, and can attenuate cortical cell damage occurring within 6 h of injury. Enduring (2 week) neuronal protection was achieved only with multiple SP treatments within the first 2 h post-CCI, perhaps reflecting the need for additional fuel throughout the acute period of increased metabolic demands

Metabolic and Histologic Effects of Sodium Pyruvate Treatment in the Rat after Cortical Contusion Injury

PubMed Central

Fukushima, Masamichi; Lee, Stefan M.; Moro, Nobuhiro; Hovda, David A.

2009-01-01

Abstract This study determined the effects of intraperitoneal sodium pyruvate (SP) treatment on the levels of circulating fuels and on cerebral microdialysis levels of glucose (MDglc), lactate (MDlac), and pyruvate (MDpyr), and the effects of SP treatment on neuropathology after left cortical contusion injury (CCI) in rats. SP injection (1000 mg/kg) 5 min after sham injury (Sham-SP) or CCI (CCI-SP) significantly increased arterial pyruvate (p < 0.005) and lactate (p < 0.001) compared to that of saline-treated rats with CCI (CCI-Sal). Serum glucose also increased significantly in CCI-SP compared to that in CCI-Sal rats (p < 0.05), but not in Sham-SP rats. MDpyr was not altered after CCI-Sal, whereas MDlac levels within the cerebral cortex significantly increased bilaterally (p < 0.05) and those for MDglc decreased bilaterally (p < 0.05). MDpyr levels increased significantly in both Sham-SP and CCI-SP rats (p < 0.05 vs. CCI-Sal) and were higher in left/injured cortex of the CCI-SP group (p < 0.05 vs. sham-SP). In CCI-SP rats the contralateral MDlac decreased below CCI-Sal levels (p < 0.05) and the ipsilateral MDglc levels exceeded those of CCI-Sal rats (p < 0.05). Rats with a single low (500 mg/kg) or high dose (1000 mg/kg) SP treatment had fewer damaged cortical cells 6 h post-CCI than did saline-treated rats (p < 0.05), but three hourly injections of SP (1000 mg/kg) were needed to significantly reduce contusion volume 2 weeks after CCI. Thus, a single intraperitoneal SP treatment increases circulating levels of three potential brain fuels, attenuates a CCI-induced reduction in extracellular glucose while increasing extracellular levels of pyruvate, but not lactate, and can attenuate cortical cell damage occurring within 6 h of injury. Enduring (2 week) neuronal protection was achieved only with multiple SP treatments within the first 2 h post-CCI, perhaps reflecting the need for additional fuel throughout the

Lactate Profile During Greco-Roman Wrestling Matchx

PubMed Central

Karnincic, Hrvoje; Tocilj, Zoran; Uljevic, Ognjen; Erceg, Marko

2009-01-01

The objective of this study was to determine and compare lactate profile of two groups of Greco-Roman wrestlers with different competences and training experience. Study was conducted on 10 wrestles that were members of Croatian national team and 10 wrestlers that were members of Wrestling club Split. Lactate samples were collected at four intervals during control fights that were held according to international wrestling rules of World wrestling federation FILA. Values of lactate increased as competition progressed, and they were highest at the end of the match for both groups of wrestlers. According to this study there were no significant differences in lactate between two groups at the end of the match, while significant differences were noted during the match. The information about lactate profile presented in this study can be used by coaches and wrestlers to develop condition programs. Key Points There were no significant differences in lactate concentrations at the end of the match between two proficiency levels of wrestlers. More proficient (elite) wrestlers raise lactates gradually through the wrestling match while less proficient (club) wrestlers raise it abruptly at the end of the first bout. Both groups of wrestlers are unable to sustain same level of activity through the match suggesting that they are utilizing too much energy from anaerobic glycolysis. PMID:24474881

[Enzyme activity in the subcellular fractions of the liver of rats following a flight on board the Kosmos-1129 biosatellite].

PubMed

Tigranian, R A; Vetrova, E G; Abraham, S; Lin, C; Klein, H

1983-01-01

The activities of malate, isocitrate, and lactate dehydrogenases were measured in the liver mitochondrial and cytoplasmatic fractions of rats flown for 18.5 days onboard Cosmos-1129. The activities of the oxidative enzymes, malate and isocitrate dehydrogenases, in the mitochondrial fraction and those of the glycolytic enzyme, lactate dehydrogenase, in the cytoplasmatic fraction were found to decrease.

Lactate storm marks cerebral metabolism following brain trauma.

PubMed

Lama, Sanju; Auer, Roland N; Tyson, Randy; Gallagher, Clare N; Tomanek, Boguslaw; Sutherland, Garnette R

2014-07-18

Brain metabolism is thought to be maintained by neuronal-glial metabolic coupling. Glia take up glutamate from the synaptic cleft for conversion into glutamine, triggering glial glycolysis and lactate production. This lactate is shuttled into neurons and further metabolized. The origin and role of lactate in severe traumatic brain injury (TBI) remains controversial. Using a modified weight drop model of severe TBI and magnetic resonance (MR) spectroscopy with infusion of (13)C-labeled glucose, lactate, and acetate, the present study investigated the possibility that neuronal-glial metabolism is uncoupled following severe TBI. Histopathology of the model showed severe brain injury with subarachnoid and hemorrhage together with glial cell activation and positive staining for Tau at 90 min post-trauma. High resolution MR spectroscopy of brain metabolites revealed significant labeling of lactate at C-3 and C-2 irrespective of the infused substrates. Increased (13)C-labeled lactate in all study groups in the absence of ischemia implied activated astrocytic glycolysis and production of lactate with failure of neuronal uptake (i.e. a loss of glial sensing for glutamate). The early increase in extracellular lactate in severe TBI with the injured neurons rendered unable to pick it up probably contributes to a rapid progression toward irreversible injury and pan-necrosis. Hence, a method to detect and scavenge the excess extracellular lactate on site or early following severe TBI may be a potential primary therapeutic measure. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Energy and glucose pathways in thiamine deficient primary rat brain microvascular endothelial cells.

PubMed

Ham, D; Karska-Wysocki, B

2005-12-01

Thiamine deficiency (TD) results in lactate acidosis, which is associated with neurodegeneration. The aim of this study was to investigate this alteration in primary rat brain endothelia. Spectrophotometric analysis of culture media revealed that only a higher concentration of pyrithiamine, which accelerates the intracellular blocking of thiamine, significantly elevated the lactate level and lactate dehydrogenase activity within 7 days. The medium without pyrithiamine and with a thiamine concentration comparable to pathophysiological plasma levels mildly reduced only the activity of transketolase. This suggests that significant metabolic changes may not occur at the early phase of TD in cerebral capillary cells, while anaerobic glycolysis in capillaries may be mediated during late stage/chronic TD.

Lactate transport and receptor actions in cerebral malaria

PubMed Central

Mariga, Shelton T.; Kolko, Miriam; Gjedde, Albert; Bergersen, Linda H.

2014-01-01

Cerebral malaria (CM), caused by Plasmodium falciparum infection, is a prevalent neurological disorder in the tropics. Most of the patients are children, typically with intractable seizures and high mortality. Current treatment is unsatisfactory. Understanding the pathogenesis of CM is required in order to identify therapeutic targets. Here, we argue that cerebral energy metabolic defects are probable etiological factors in CM pathogenesis, because malaria parasites consume large amounts of glucose metabolized mostly to lactate. Monocarboxylate transporters (MCTs) mediate facilitated transfer, which serves to equalize lactate concentrations across cell membranes in the direction of the concentration gradient. The equalizing action of MCTs is the basis for lactate’s role as a volume transmitter of metabolic signals in the brain. Lactate binds to the lactate receptor GPR81, recently discovered on brain cells and cerebral blood vessels, causing inhibition of adenylyl cyclase. High levels of lactate delivered by the parasite at the vascular endothelium may damage the blood–brain barrier, disrupt lactate homeostasis in the brain, and imply MCTs and the lactate receptor as novel therapeutic targets in CM. PMID:24904266

Channel-mediated lactate release by K⁺-stimulated astrocytes.

PubMed

Sotelo-Hitschfeld, Tamara; Niemeyer, María I; Mächler, Philipp; Ruminot, Iván; Lerchundi, Rodrigo; Wyss, Matthias T; Stobart, Jillian; Fernández-Moncada, Ignacio; Valdebenito, Rocío; Garrido-Gerter, Pamela; Contreras-Baeza, Yasna; Schneider, Bernard L; Aebischer, Patrick; Lengacher, Sylvain; San Martín, Alejandro; Le Douce, Juliette; Bonvento, Gilles; Magistretti, Pierre J; Sepúlveda, Francisco V; Weber, Bruno; Barros, L Felipe

2015-03-11

Excitatory synaptic transmission is accompanied by a local surge in interstitial lactate that occurs despite adequate oxygen availability, a puzzling phenomenon termed aerobic glycolysis. In addition to its role as an energy substrate, recent studies have shown that lactate modulates neuronal excitability acting through various targets, including NMDA receptors and G-protein-coupled receptors specific for lactate, but little is known about the cellular and molecular mechanisms responsible for the increase in interstitial lactate. Using a panel of genetically encoded fluorescence nanosensors for energy metabolites, we show here that mouse astrocytes in culture, in cortical slices, and in vivo maintain a steady-state reservoir of lactate. The reservoir was released to the extracellular space immediately after exposure of astrocytes to a physiological rise in extracellular K(+) or cell depolarization. Cell-attached patch-clamp analysis of cultured astrocytes revealed a 37 pS lactate-permeable ion channel activated by cell depolarization. The channel was modulated by lactate itself, resulting in a positive feedback loop for lactate release. A rapid fall in intracellular lactate levels was also observed in cortical astrocytes of anesthetized mice in response to local field stimulation. The existence of an astrocytic lactate reservoir and its quick mobilization via an ion channel in response to a neuronal cue provides fresh support to lactate roles in neuronal fueling and in gliotransmission. Copyright © 2015 the authors 0270-6474/15/354168-11$15.00/0.

Imperfect asymmetry of life: earth microbial communities prefer D-lactate but can use L-lactate also.

PubMed

Moazeni, Faegheh; Zhang, Gaosen; Sun, Henry J

2010-05-01

Asymmetrical utilization of chiral compounds has been sought on Mars as evidence for biological activity. This method was recently validated in glucose. Earth organisms utilize D-glucose, not L-glucose, a perfect asymmetry. In this study, we tested the method in lactate and found utilization of both enantiomers. Soil-, sediment-, and lake-borne microbial communities prefer D-lactate but can consume L-lactate if given extra time to acclimate. This situation is termed imperfect asymmetry. Future life-detection mission investigators need to be aware of imperfect asymmetry so as not to miss relatively subtle signs of life.

Electrochemical lactate biosensor based upon chitosan/carbon nanotubes modified screen-printed graphite electrodes for the determination of lactate in embryonic cell cultures.

PubMed

Hernández-Ibáñez, Naiara; García-Cruz, Leticia; Montiel, Vicente; Foster, Christopher W; Banks, Craig E; Iniesta, Jesús

2016-03-15

l-lactate is an essential metabolite present in embryonic cell culture. Changes of this important metabolite during the growth of human embryo reflect the quality and viability of the embryo. In this study, we report a sensitive, stable, and easily manufactured electrochemical biosensor for the detection of lactate within embryonic cell cultures media. Screen-printed disposable electrodes are used as electrochemical sensing platforms for the miniaturization of the lactate biosensor. Chitosan/multi walled carbon nanotubes composite have been employed for the enzymatic immobilization of the lactate oxidase enzyme. This novel electrochemical lactate biosensor analytical efficacy is explored towards the sensing of lactate in model (buffer) solutions and is found to exhibit a linear response towards lactate over the concentration range of 30.4 and 243.9 µM in phosphate buffer solution, with a corresponding limit of detection (based on 3-sigma) of 22.6 µM and exhibits a sensitivity of 3417 ± 131 µAM(-1) according to the reproducibility study. These novel electrochemical lactate biosensors exhibit a high reproducibility, with a relative standard deviation of less than 3.8% and an enzymatic response over 82% after 5 months stored at 4 °C. Furthermore, high performance liquid chromatography technique has been utilized to independently validate the electrochemical lactate biosensor for the determination of lactate in a commercial embryonic cell culture medium providing excellent agreement between the two analytical protocols. Copyright © 2015 Elsevier B.V. All rights reserved.

21 CFR 184.1311 - Ferrous lactate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... reacting calcium lactate or sodium lactate with ferrous sulfate, direct reaction of lactic acid with iron... section 412(a)(2) of the act (21 U.S.C. 350a(a)(2)). (d) Prior sanctions for this ingredient different...

Effects of Maternal Behavior Induction and Pup Exposure on Neurogenesis in Adult, Virgin Female Rats

PubMed Central

Furuta, Miyako; Bridges, Robert S.

2009-01-01

The states of pregnancy and lactation bring about a range of physiological and behavioral changes in the adult mammal that prepare the mother to care for her young. Cell proliferation increases in the subventricular zone (SVZ) of the female rodent brain during both pregnancy and lactation when compared to that in cycling, diestrous females. In the present study, the effects of maternal behavior induction and pup exposure on neurogenesis in nulliparous rats were examined in order to determine whether maternal behavior itself, independent of pregnancy and lactation, might affect neurogenesis. Adult, nulliparous, Sprague-Dawley, female rats were exposed daily to foster young in order to induce maternal behavior. Following the induction of maternal behavior each maternal subject plus females that were exposed to pups for a comparable number of test days, but did not display maternal behavior, and subjects that had received no pup exposure were injected with bromodeoxyuridine (BrdU, 90 mg/kg, i.v.). Brain sections were double-labeled for BrdU and the neural marker, NeuN, to examine the proliferating cell population. Increases in the number of double-labeled cells were found in the maternal virgin brain when compared with the number of double-labeled cells present in non-maternal, pup-exposed nulliparous rats and in females not exposed to young. No changes were evident in the dentate gyrus of the hippocampus as a function of maternal behavior. These data indicate that in nulliparous female rats maternal behavior itself is associated with the stimulation of neurogenesis in the SVZ. PMID:19712726

CD147 Required for Corneal Endothelial Lactate Transport

PubMed Central

Li, Shimin; Nguyen, Tracy T.; Bonanno, Joseph A.

2014-01-01

Purpose. CD147/basigin is a chaperone for lactate:H+ cotransporters (monocarboxylate transporters) MCT1 and MCT4. We tested the hypothesis that MCT1 and -4 in corneal endothelium contribute to lactate efflux from stroma to anterior chamber and that silencing CD147 expression would cause corneal edema. Methods. CD147 was silenced via small interfering ribonucleic acid (siRNA) transfection of rabbit corneas ex vivo and anterior chamber lenti-small hairpin RNA (shRNA) pseudovirus in vivo. CD147 and MCT expression was examined by Western blot, RT-PCR, and immunofluorescence. Functional effects were examined by measuring lactate-induced cell acidification, corneal lactate efflux, [lactate], central cornea thickness (CCT), and Azopt (a carbonic anhydrase inhibitor) sensitivity. Results. In ex vivo corneas, 100 nM CD147 siRNA reduced CD147, MCT1, and MCT4 expression by 85%, 79%, and 73%, respectively, while MCT2 expression was unaffected. CD147 siRNA decreased lactate efflux from 3.9 ± 0.81 to 1.5 ± 0.37 nmol/min, increased corneal [lactate] from 19.28 ± 7.15 to 56.73 ± 8.97 nmol/mg, acidified endothelial cells (pHi = 6.83 ± 0.07 vs. 7.19 ± 0.09 in control), and slowed basolateral lactate-induced acidification from 0.0034 ± 0.0005 to 0.0012 ± 0.0005 pH/s, whereas apical acidification was unchanged. In vivo, CD147 shRNA increased CCT by 28.1 ± 0.9 μm at 28 days; Azopt increased CCT to 24.4 ± 3.12 vs. 12.0 ± 0.48 μm in control, and corneal [lactate] was 47.63 ± 6.29 nmol/mg in shCD147 corneas and 17.82 ± 4.93 nmol/mg in paired controls. Conclusions. CD147 is required for the expression of MCT1 and MCT4 in the corneal endothelium. Silencing CD147 slows lactate efflux, resulting in stromal lactate accumulation and corneal edema, consistent with lactate efflux as a significant component of the corneal endothelial pump. PMID:24970254

CD147 required for corneal endothelial lactate transport.

PubMed

Li, Shimin; Nguyen, Tracy T; Bonanno, Joseph A

2014-06-26

CD147/basigin is a chaperone for lactate:H(+) cotransporters (monocarboxylate transporters) MCT1 and MCT4. We tested the hypothesis that MCT1 and -4 in corneal endothelium contribute to lactate efflux from stroma to anterior chamber and that silencing CD147 expression would cause corneal edema. CD147 was silenced via small interfering ribonucleic acid (siRNA) transfection of rabbit corneas ex vivo and anterior chamber lenti-small hairpin RNA (shRNA) pseudovirus in vivo. CD147 and MCT expression was examined by Western blot, RT-PCR, and immunofluorescence. Functional effects were examined by measuring lactate-induced cell acidification, corneal lactate efflux, [lactate], central cornea thickness (CCT), and Azopt (a carbonic anhydrase inhibitor) sensitivity. In ex vivo corneas, 100 nM CD147 siRNA reduced CD147, MCT1, and MCT4 expression by 85%, 79%, and 73%, respectively, while MCT2 expression was unaffected. CD147 siRNA decreased lactate efflux from 3.9 ± 0.81 to 1.5 ± 0.37 nmol/min, increased corneal [lactate] from 19.28 ± 7.15 to 56.73 ± 8.97 nmol/mg, acidified endothelial cells (pHi = 6.83 ± 0.07 vs. 7.19 ± 0.09 in control), and slowed basolateral lactate-induced acidification from 0.0034 ± 0.0005 to 0.0012 ± 0.0005 pH/s, whereas apical acidification was unchanged. In vivo, CD147 shRNA increased CCT by 28.1 ± 0.9 μm at 28 days; Azopt increased CCT to 24.4 ± 3.12 vs. 12.0 ± 0.48 μm in control, and corneal [lactate] was 47.63 ± 6.29 nmol/mg in shCD147 corneas and 17.82 ± 4.93 nmol/mg in paired controls. CD147 is required for the expression of MCT1 and MCT4 in the corneal endothelium. Silencing CD147 slows lactate efflux, resulting in stromal lactate accumulation and corneal edema, consistent with lactate efflux as a significant component of the corneal endothelial pump. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Importance of measuring lactate levels in children with sepsis.

PubMed

Anil, Nisha

2017-10-10

Sepsis is a major public health problem as well as one of the leading causes of preventable death in children because of failure to recognise the early signs and symptoms and to resuscitate rapidly. Blood lactate levels are used to assess the severity of sepsis and the effectiveness of resuscitation. Lactate levels are easily obtainable and should be checked in all patients admitted with suspected sepsis within six hours of presentation. The test should be repeated four and eight-hours post-diagnosis of sepsis. For the diagnosis of sepsis, patients' clinical symptoms, along with the combined analysis of partial pressure of oxygen, carbon dioxide and lactate levels, should be used. A multitude of factors can cause elevated lactate levels and so clinicians should use elevated levels cautiously by considering all other aetiologies. This article, which focuses on practice in Australia but makes reference to the UK, discusses the importance of measuring lactate levels in sepsis, the pathophysiology of lactate production, causes of elevated lactate levels, lactate measurement, nursing management of patients with elevated lactate levels, limitations of using lactate as a biomarker for diagnosing sepsis and implications for practice. ©2012 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.

Prior parity positively regulates learning and memory in young and middle-aged rats.

PubMed

Zimberknopf, Erica; Xavier, Gilberto F; Kinsley, Craig H; Felicio, Luciano F

2011-08-01

Reproductive experience in female rats modifies acquired behaviors, induces long-lasting functional neuroadaptations and can also modify spatial learning and memory. The present study supports and expands this knowledge base by employing the Morris water maze, which measures spatial memory. Age-matched young adult (YNG) nulliparous (NULL; nonmated) and primiparous (PRIM; one pregnancy and lactation) female rats were tested 15 d after the litter's weaning. In addition, corresponding middle-aged (AGD) PRIM (mated in young adulthood so that pregnancy, parturition, and lactation occurred at the same age as in YNG PRIM) and NULL female rats were tested at 18 mo of age. Behavioral evaluation included: 1) acquisition of reference memory (platform location was fixed for 14 to 19 d of testing); 2) retrieval of this information associated with extinction of the acquired response (probe test involving removal of the platform 24 h after the last training session); and 3) performance in a working memory version of the task (platform presented in a novel location every day for 13 d, and maintained in a fixed location within each day). YNG PRIM outperformed NULL rats and showed different behavioral strategies. These results may be related to changes in locomotor, mnemonic, and cognitive processes. In addition, YNG PRIM exhibited less anxiety-like behavior. Compared with YNG rats, AGD rats showed less behavioral flexibility but stronger memory consolidation. These data, which were obtained by using a well-documented spatial task, demonstrate long lasting modifications of behavioral strategies in both YNG and AGD rats associated with a single reproductive experience.

Tuning the brain for motherhood: prolactin-like central signalling in virgin, pregnant, and lactating female mice.

PubMed

Salais-López, Hugo; Lanuza, Enrique; Agustín-Pavón, Carmen; Martínez-García, Fernando

2017-03-01

Prolactin is fundamental for the expression of maternal behaviour. In virgin female rats, prolactin administered upon steroid hormone priming accelerates the onset of maternal care. By contrast, the role of prolactin in mice maternal behaviour remains unclear. This study aims at characterizing central prolactin activity patterns in female mice and their variation through pregnancy and lactation. This was revealed by immunoreactivity of phosphorylated (active) signal transducer and activator of transcription 5 (pSTAT5-ir), a key molecule in the signalling cascade of prolactin receptors. We also evaluated non-hypophyseal lactogenic activity during pregnancy by administering bromocriptine, which suppresses hypophyseal prolactin release. Late-pregnant and lactating females showed significantly increased pSTAT5-ir resulting in a widespread pattern of immunostaining with minor variations between pregnant and lactating animals, which comprises nuclei of the sociosexual and maternal brain, including telencephalic (septum, nucleus of the stria terminalis, and amygdala), hypothalamic (preoptic, paraventricular, supraoptic, and ventromedial), and midbrain (periaqueductal grey) regions. During late pregnancy, this pattern was not affected by the administration of bromocriptine, suggesting it to be elicited mostly by non-hypophyseal lactogenic agents, likely placental lactogens. Virgin females displayed, instead, a variable pattern of pSTAT5-ir restricted to a subset of the brain nuclei labelled in pregnant and lactating mice. A hormonal substitution experiment confirmed that estradiol and progesterone contribute to the variability found in virgin females. Our results reflect how the shaping of the maternal brain takes place prior to parturition and suggest that lactogenic agents are important candidates in the development of maternal behaviours already during pregnancy.

Metabolic changes in rat striatum following convulsive seizures.

PubMed

Darbin, Olivier; Risso, Jean Jacque; Carre, Emily; Lonjon, Michel; Naritoku, Dean K

2005-07-19

Generalized convulsive seizures increase glucose utilization within the brain but their impact on metabolism is not well known. The striatum receives excitatory input from widespread sources in the brain and could potentially reflect energy depletion in the brain resulting from generalized seizures. We utilized multiprobe microdialysis in freely moving rats subjected to maximal electroshock to simultaneously measure glucose, lactate, and pyruvate levels in the interstitial space within striatum and in peripheral subcutaneous tissue. A brief convulsive seizure was associated with marked changes in striatal and peripheral metabolism during the post-ictal state that lasted up to 1 h. There were significant central and peripheral elevations of glucose, pyruvate, and lactate, reflecting increased glucose metabolism. Interestingly, the lactate-to-pyruvate ratio increased significantly in the periphery but remained unchanged in the striatum. Thus, there appears to be brain mechanisms that maintain adequate energy sources and prevent anaerobic shift during the post-ictal state.

Blood lactate accumulation in top level swimmers following competition.

PubMed

Bonifazi, M; Martelli, G; Marugo, L; Sardella, F; Carli, G

1993-03-01

The purposes of this study were to evaluate the significance of blood lactate values after competitions and the blood lactate-swimming speed relationship to swimming performances. Auricular blood samples (N = 421) were collected in 203 top level Italian swimmers (116 males and 87 females) at the end of competitions performed in a 25 m swimming pool. The distribution of all lactate values differed between males and females. The lowest lactate values occurred in swimmers performing the longest distances both in males (1500 m) and females (800 m). In swimmers performing freestyle events a relationship between V-4 mM (swimming speed at 4 mmol/l blood lactate value) and competition velocities was observed, in males, at 200, 400 and 1500 m and, in females, at 400 and 800 m. The predicted velocity corresponding to the competition lactate value assessed by the individual blood lactate-swimming speed relationship was found to be highly related to the actual competition velocity. Results suggest that blood lactate values in swimmers are a useful indication of individual aptitudes.

Neonatal treatment with scopolamine butylbromide prevents metabolic dysfunction in male rats

PubMed Central

Malta, Ananda; Souza, Aline Amenencia de; Ribeiro, Tatiane Aparecida; Francisco, Flávio Andrade; Pavanello, Audrei; Prates, Kelly Valério; Tófolo, Laize Peron; Miranda, Rosiane Aparecida; Oliveira, Júlio Cezar de; Martins, Isabela Peixoto; Previate, Carina; Gomes, Rodrigo Mello; Franco, Claudinéia Conationi da Silva; Natali, Maria Raquel Marçal; Palma-Rigo, Kesia; Mathias, Paulo Cezar de Freitas

2016-01-01

We tested whether treatment with a cholinergic antagonist could reduce insulin levels in early postnatal life and attenuate metabolic dysfunctions induced by early overfeeding in adult male rats. Wistar rats raised in small litters (SLs, 3 pups/dam) and normal litters (NLs, 9 pups/dam) were used in models of early overfeeding and normal feeding, respectively. During the first 12 days of lactation, animals in the SL and NL groups received scopolamine butylbromide (B), while the controls received saline (S) injections. The drug treatment decreased insulin levels in pups from both groups, and as adults, these animals showed improvements in glucose tolerance, insulin sensitivity, vagus nerve activity, fat tissue accretion, insulinemia, leptinemia, body weight gain and food intake. Low glucose and cholinergic insulinotropic effects were observed in pancreatic islets from both groups. Low protein expression was observed for the muscarinic M3 acetylcholine receptor subtype (M3mAChR), although M2mAChR subtype expression was increased in SL-B islets. In addition, beta-cell density was reduced in drug-treated rats. These results indicate that early postnatal scopolamine butylbromide treatment inhibits early overfeeding-induced metabolic dysfunctions in adult rats, which might be caused by insulin decreases during lactation, associated with reduced parasympathetic activity and expression of M3mAChR in pancreatic islets. PMID:27561682

Glymphatic clearance controls state-dependent changes in brain lactate concentration.

PubMed

Lundgaard, Iben; Lu, Minh Lon; Yang, Ezra; Peng, Weiguo; Mestre, Humberto; Hitomi, Emi; Deane, Rashid; Nedergaard, Maiken

2017-06-01

Brain lactate concentration is higher during wakefulness than in sleep. However, it is unknown why arousal is linked to an increase in brain lactate and why lactate declines within minutes of sleep. Here, we show that the glymphatic system is responsible for state-dependent changes in brain lactate concentration. Suppression of glymphatic function via acetazolamide treatment, cisterna magna puncture, aquaporin 4 deletion, or changes in body position reduced the decline in brain lactate normally observed when awake mice transition into sleep or anesthesia. Concurrently, the same manipulations diminished accumulation of lactate in cervical, but not in inguinal lymph nodes when mice were anesthetized. Thus, our study suggests that brain lactate is an excellent biomarker of the sleep-wake cycle and increases further during sleep deprivation, because brain lactate is inversely correlated with glymphatic-lymphatic clearance. This analysis provides fundamental new insight into brain energy metabolism by demonstrating that glucose that is not fully oxidized can be exported as lactate via glymphatic-lymphatic fluid transport.

Glymphatic clearance controls state-dependent changes in brain lactate concentration

PubMed Central

Lu, Minh Lon; Yang, Ezra; Peng, Weiguo; Mestre, Humberto; Hitomi, Emi; Deane, Rashid; Nedergaard, Maiken

2016-01-01

Brain lactate concentration is higher during wakefulness than in sleep. However, it is unknown why arousal is linked to an increase in brain lactate and why lactate declines within minutes of sleep. Here, we show that the glymphatic system is responsible for state-dependent changes in brain lactate concentration. Suppression of glymphatic function via acetazolamide treatment, cisterna magna puncture, aquaporin 4 deletion, or changes in body position reduced the decline in brain lactate normally observed when awake mice transition into sleep or anesthesia. Concurrently, the same manipulations diminished accumulation of lactate in cervical, but not in inguinal lymph nodes when mice were anesthetized. Thus, our study suggests that brain lactate is an excellent biomarker of the sleep–wake cycle and increases further during sleep deprivation, because brain lactate is inversely correlated with glymphatic-lymphatic clearance. This analysis provides fundamental new insight into brain energy metabolism by demonstrating that glucose that is not fully oxidized can be exported as lactate via glymphatic-lymphatic fluid transport. PMID:27481936

Normal lactate concentration range in the neonatal brain.

PubMed

Tomiyasu, Moyoko; Aida, Noriko; Shibasaki, Jun; Tachibana, Yasuhiko; Endo, Mamiko; Nozawa, Kumiko; Shimizu, Eiji; Tsuji, Hiroshi; Obata, Takayuki

2016-11-01

Lactate peaks are occasionally observed during in vivo magnetic resonance spectroscopy (MRS) scans of the neonatal brain, even in healthy patients. The purpose of this study was to investigate the normal range of neonatal brain lactate concentration, as a definitive normal range would be clinically valuable. Using a clinical 3T scanner (echo/repetition times, 30/5000ms), single-voxel MRS data were obtained from the basal ganglia (BG) and centrum semiovale (CS) in 48 healthy neonates (postconceptional age (PCA), 30-43weeks), nine infants (age, 1-12months old), and 20 children (age, 4-15years). Lactate concentrations were calculated using an MRS signal quantification program, LCModel. Correlations between regional lactate concentration and PCA (neonates), or age (all subjects) were investigated. Absolute lactate concentrations of the BG and CS were as follows: neonates, 0.77mM (0-2.02) [median (range)] and 0.77 (0-1.42), respectively; infants, 0.38 (0-0.79) and 0.49 (0.17-1.17); and children, 0.17 (0-0.76) and 0.22 (0-0.80). Overall, subjects' lactate concentrations decreased significantly with age (Spearman: BG, n=61, ρ=-0.38, p=0.003; CS, n=68, ρ=-0.57, p<0.001). However, during the neonatal period no correlations were detected between lactate concentration in either region and PCA. We determined normal ranges of neonatal lactate concentration, which may prove useful for diagnostic purposes. Further studies regarding changes in brain lactate concentration during development would help clarify the reasons for higher concentrations observed during the neonatal period, and contribute to improvements in diagnoses. Copyright © 2016 Elsevier Inc. All rights reserved.

Targeting the lactate transporter MCT1 in endothelial cells inhibits lactate-induced HIF-1 activation and tumor angiogenesis.

PubMed

Sonveaux, Pierre; Copetti, Tamara; De Saedeleer, Christophe J; Végran, Frédérique; Verrax, Julien; Kennedy, Kelly M; Moon, Eui Jung; Dhup, Suveera; Danhier, Pierre; Frérart, Françoise; Gallez, Bernard; Ribeiro, Anthony; Michiels, Carine; Dewhirst, Mark W; Feron, Olivier

2012-01-01

Switching to a glycolytic metabolism is a rapid adaptation of tumor cells to hypoxia. Although this metabolic conversion may primarily represent a rescue pathway to meet the bioenergetic and biosynthetic demands of proliferating tumor cells, it also creates a gradient of lactate that mirrors the gradient of oxygen in tumors. More than a metabolic waste, the lactate anion is known to participate to cancer aggressiveness, in part through activation of the hypoxia-inducible factor-1 (HIF-1) pathway in tumor cells. Whether lactate may also directly favor HIF-1 activation in endothelial cells (ECs) thereby offering a new druggable option to block angiogenesis is however an unanswered question. In this study, we therefore focused on the role in ECs of monocarboxylate transporter 1 (MCT1) that we previously identified to be the main facilitator of lactate uptake in cancer cells. We found that blockade of lactate influx into ECs led to inhibition of HIF-1-dependent angiogenesis. Our demonstration is based on the unprecedented characterization of lactate-induced HIF-1 activation in normoxic ECs and the consecutive increase in vascular endothelial growth factor receptor 2 (VEGFR2) and basic fibroblast growth factor (bFGF) expression. Furthermore, using a variety of functional assays including endothelial cell migration and tubulogenesis together with in vivo imaging of tumor angiogenesis through intravital microscopy and immunohistochemistry, we documented that MCT1 blockers could act as bona fide HIF-1 inhibitors leading to anti-angiogenic effects. Together with the previous demonstration of MCT1 being a key regulator of lactate exchange between tumor cells, the current study identifies MCT1 inhibition as a therapeutic modality combining antimetabolic and anti-angiogenic activities.

Targeting the Lactate Transporter MCT1 in Endothelial Cells Inhibits Lactate-Induced HIF-1 Activation and Tumor Angiogenesis

PubMed Central

Sonveaux, Pierre; Copetti, Tamara; De Saedeleer, Christophe J.; Végran, Frédérique; Verrax, Julien; Kennedy, Kelly M.; Moon, Eui Jung; Dhup, Suveera; Danhier, Pierre; Frérart, Françoise; Gallez, Bernard; Ribeiro, Anthony; Michiels, Carine

2012-01-01

Switching to a glycolytic metabolism is a rapid adaptation of tumor cells to hypoxia. Although this metabolic conversion may primarily represent a rescue pathway to meet the bioenergetic and biosynthetic demands of proliferating tumor cells, it also creates a gradient of lactate that mirrors the gradient of oxygen in tumors. More than a metabolic waste, the lactate anion is known to participate to cancer aggressiveness, in part through activation of the hypoxia-inducible factor-1 (HIF-1) pathway in tumor cells. Whether lactate may also directly favor HIF-1 activation in endothelial cells (ECs) thereby offering a new druggable option to block angiogenesis is however an unanswered question. In this study, we therefore focused on the role in ECs of monocarboxylate transporter 1 (MCT1) that we previously identified to be the main facilitator of lactate uptake in cancer cells. We found that blockade of lactate influx into ECs led to inhibition of HIF-1-dependent angiogenesis. Our demonstration is based on the unprecedented characterization of lactate-induced HIF-1 activation in normoxic ECs and the consecutive increase in vascular endothelial growth factor receptor 2 (VEGFR2) and basic fibroblast growth factor (bFGF) expression. Furthermore, using a variety of functional assays including endothelial cell migration and tubulogenesis together with in vivo imaging of tumor angiogenesis through intravital microscopy and immunohistochemistry, we documented that MCT1 blockers could act as bona fide HIF-1 inhibitors leading to anti-angiogenic effects. Together with the previous demonstration of MCT1 being a key regulator of lactate exchange between tumor cells, the current study identifies MCT1 inhibition as a therapeutic modality combining antimetabolic and anti-angiogenic activities. PMID:22428047

Lactate biosensors: current status and outlook.

PubMed

Rassaei, Liza; Olthuis, Wouter; Tsujimura, Seiya; Sudhölter, Ernst J R; van den Berg, Albert

2014-01-01

Many research efforts over the last few decades have been devoted to sensing lactate as an important analytical target in clinical care, sport medicine, and food processing. Therefore, research in designing lactate sensors is no longer in its infancy and now is more directed toward viable sensors for direct applications. In this review, we provide an overview of the most immediate and relevant developments toward this end, and we discuss and assess common transduction approaches. Further, we critically describe the pros and cons of current commercial lactate sensors and envision how future sensing design may benefit from emerging new technologies.

Lactational mastitis caused by Streptococcus lactarius.

PubMed

Tena, Daniel; Fernández, Cristina; López-Garrido, Beatriz; Pérez-Balsalobre, Mercedes; Losa, Cristina; Medina-Pascual, María José; Sáez-Nieto, Juan Antonio

2016-08-01

Human infections caused by Streptococcus lactarius have not been previously reported. In the present report, we describe a lactational mastitis caused by this organism. The infection occurred in a 28-year-old breast-feeding female, with a 10-days history of moderate pain on the right breast. The patient was cured after antibiotic treatment with levofloxacin for 21 days. Our case shows that S. lactarius should be considered as a cause of lactational mastitis. The introduction of molecular microbiology techniques can be extremely useful for knowing the implication of streptococci in lactational mastitis. Copyright © 2016 Elsevier Inc. All rights reserved.

Lactate rescues neuronal sodium homeostasis during impaired energy metabolism.

PubMed

Karus, Claudia; Ziemens, Daniel; Rose, Christine R

2015-01-01

Recently, we established that recurrent activity evokes network sodium oscillations in neurons and astrocytes in hippocampal tissue slices. Interestingly, metabolic integrity of astrocytes was essential for the neurons' capacity to maintain low sodium and to recover from sodium loads, indicating an intimate metabolic coupling between the 2 cell types. Here, we studied if lactate can support neuronal sodium homeostasis during impaired energy metabolism by analyzing whether glucose removal, pharmacological inhibition of glycolysis and/or addition of lactate affect cellular sodium regulation. Furthermore, we studied the effect of lactate on sodium regulation during recurrent network activity and upon inhibition of the glial Krebs cycle by sodium-fluoroacetate. Our results indicate that lactate is preferentially used by neurons. They demonstrate that lactate supports neuronal sodium homeostasis and rescues the effects of glial poisoning by sodium-fluoroacetate. Altogether, they are in line with the proposed transfer of lactate from astrocytes to neurons, the so-called astrocyte-neuron-lactate shuttle.

Lactate rescues neuronal sodium homeostasis during impaired energy metabolism

PubMed Central

Karus, Claudia; Ziemens, Daniel; Rose, Christine R

2015-01-01

Recently, we established that recurrent activity evokes network sodium oscillations in neurons and astrocytes in hippocampal tissue slices. Interestingly, metabolic integrity of astrocytes was essential for the neurons' capacity to maintain low sodium and to recover from sodium loads, indicating an intimate metabolic coupling between the 2 cell types. Here, we studied if lactate can support neuronal sodium homeostasis during impaired energy metabolism by analyzing whether glucose removal, pharmacological inhibition of glycolysis and/or addition of lactate affect cellular sodium regulation. Furthermore, we studied the effect of lactate on sodium regulation during recurrent network activity and upon inhibition of the glial Krebs cycle by sodium-fluoroacetate. Our results indicate that lactate is preferentially used by neurons. They demonstrate that lactate supports neuronal sodium homeostasis and rescues the effects of glial poisoning by sodium-fluoroacetate. Altogether, they are in line with the proposed transfer of lactate from astrocytes to neurons, the so-called astrocyte-neuron-lactate shuttle. PMID:26039160

Lactate dehydrogenase-A is indispensable for vascular smooth muscle cell proliferation and migration.

PubMed

Kim, Ji-Hyun; Bae, Kwi-Hyun; Byun, Jun-Kyu; Lee, Sungwoo; Kim, Jung-Guk; Lee, In Kyu; Jung, Gwon-Soo; Lee, You Mie; Park, Keun-Gyu

2017-10-07

The proliferation and migration of vascular smooth muscle cells (VSMCs) have been implicated in the pathogenesis of atherosclerosis. Increased aerobic glycolysis is a key feature of cellular phenotypes including cancer and immune cells. However, the role of aerobic glycolysis in the atherogenic phenotype of VSMCs remains largely unknown. Here, we investigated the role of lactate dehydrogenase-A (LDHA), which is a key enzyme for glycolysis, in the proliferation and migration of VSMCs. Activation of primary rat VSMCs with fetal bovine serum (FBS) or platelet-derived growth factor (PDGF) increased their proliferation and migration, glycolytic activity, and expression of LDHA. Wound healing and transwell migration assays demonstrated that small interfering RNA-mediated knockdown of LDHA and pharmacological inhibition of LDHA by oxamate both effectively inhibited VSMC proliferation and migration. Inhibition of LDHA activity by oxamate reduced PDGF-stimulated glucose uptake, lactate production, and ATP production. Taken together, this study shows that enhanced glycolysis in PDGF- or FBS-stimulated VSMCs plays an important role in their proliferation and migration and suggests that LDHA is a potential therapeutic target to prevent vessel lumen constriction during the course of atherosclerosis and restenosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Anti-Diabetic Activity and Metabolic Changes Induced by Andrographis paniculata Plant Extract in Obese Diabetic Rats.

PubMed

Akhtar, Muhammad Tayyab; Bin Mohd Sarib, Mohamad Syakir; Ismail, Intan Safinar; Abas, Faridah; Ismail, Amin; Lajis, Nordin Hj; Shaari, Khozirah

2016-08-09

Andrographis paniculata is an annual herb and widely cultivated in Southeast Asian countries for its medicinal use. In recent investigations, A. paniculata was found to be effective against Type 1 diabetes mellitus (Type 1 DM). Here, we used a non-genetic out-bred Sprague-Dawley rat model to test the antidiabetic activity of A. paniculata against Type 2 diabetes mellitus (Type 2 DM). Proton Nuclear Magnetic Resonance (¹H-NMR) spectroscopy in combination with multivariate data analyses was used to evaluate the A. paniculata and metformin induced metabolic effects on the obese and obese-diabetic (obdb) rat models. Compared to the normal rats, high levels of creatinine, lactate, and allantoin were found in the urine of obese rats, whereas, obese-diabetic rats were marked by high glucose, choline and taurine levels, and low lactate, formate, creatinine, citrate, 2-oxoglutarate, succinate, dimethylamine, acetoacetate, acetate, allantoin and hippurate levels. Treatment of A. paniculata leaf water extract was found to be quite effective in restoring the disturbed metabolic profile of obdb rats back towards normal conditions. Thisstudy shows the anti-diabetic potential of A. paniculata plant extract and strengthens the idea of using this plant against the diabetes. Further classical genetic methods and state of the art molecular techniques could provide insights into the molecular mechanisms involved in the pathogenesis of diabetes mellitus and anti-diabetic effects of A. paniculata water extract.

Blood lactate clearance after maximal exercise depends on active recovery intensity.

PubMed

Devlin, J; Paton, B; Poole, L; Sun, W; Ferguson, C; Wilson, J; Kemi, O J

2014-06-01

High-intensity exercise is time-limited by onset of fatigue, marked by accumulation of blood lactate. This is accentuated at maximal, all-out exercise that rapidly accumulates high blood lactate. The optimal active recovery intensity for clearing lactate after such maximal, all-out exercise remains unknown. Thus, we studied the intensity-dependence of lactate clearance during active recovery after maximal exercise. We constructed a standardized maximal, all-out treadmill exercise protocol that predictably lead to voluntary exhaustion and blood lactate concentration>10 mM. Next, subjects ran series of all-out bouts that increased blood lactate concentration to 11.5±0.2 mM, followed by recovery exercises ranging 0% (passive)-100% of the lactate threshold. Repeated measurements showed faster lactate clearance during active versus passive recovery (P<0.01), and that active recovery at 60-100% of lactate threshold was more efficient for lactate clearance than lower intensity recovery (P<0.05). Active recovery at 80% of lactate threshold had the highest rate of and shortest time constant for lactate clearance (P<0.05), whereas the response during the other intensities was graded (100%=60%>40%>passive recovery, P<0.05). Active recovery after maximal all-out exercise clears accumulated blood lactate faster than passive recovery in an intensity-dependent manner, with maximum clearance occurring at active recovery of 80% of lactate threshold.

Maternal high fat diet and its consequence on the gut microbiome: A rat model.

PubMed

Mann, Phyllis E; Huynh, Kevin; Widmer, Giovanni

2017-11-14

The biological changes that occur during pregnancy in the female mammal include shifts in hormonal regulation in preparation for parturition and lactation, and changes in energy metabolism. In women, studies have also shown that during pregnancy there is a reduction in bacterial species richness in the gut. In the current experiment rats were used to model the interaction of diet, reproductive status, and intestinal bacterial microbiota during pregnancy and lactation. In Experiment 1 rats were exposed to either standard chow or high-fat chow (60%) and were divided into two groups: unmated (NULL) or mated (RE). In Experiment 2, both NULL and RE rats were exposed to high-fat chow for a 30-day period. High-throughput sequencing of the 16S rRNA gene revealed that pregnancy impacted the gut microbiota in a similar manner to humans. The impact of reproductive status on microbiota composition, however, was stronger in rats fed a high-fat (HF) diet. Diet-induced changes replicated some of the changes observed in humans, such as increasing the Firmicutes/Bacteroidetes ratio. However, in contrast to humans, pregnancy in rats did not increase β-diversity between microbiota from different animals. These results indicate that during pregnancy in rats, the gut microbiota is altered in a similar manner to that which occurs in women, and that these changes are further exaggerated by exposure to a HF diet. Thus, the rat may allow modelling the effects of consumption of HF food during pregnancy and enable future studies to determine the risks of HF diets during pregnancy and its consequences on the offspring.

Lactate response to different volume patterns of power clean.

PubMed

Date, Anand S; Simonson, Shawn R; Ransdell, Lynda B; Gao, Yong

2013-03-01

The ability to metabolize or tolerate lactate and produce power simultaneously can be an important determinant of performance. Current training practices for improving lactate use include high-intensity aerobic activities or a combination of aerobic and resistance training. Excessive aerobic training may have undesired physiological adaptations (e.g., muscle loss, change in fiber types). The role of explosive power training in lactate production and use needs further clarification. We hypothesized that high-volume explosive power movements such as Olympic lifts can increase lactate production and overload lactate clearance. Hence, the purpose of this study was to assess lactate accumulation after the completion of 3 different volume patterns of power cleans. Ten male recreational athletes (age 24.22 ± 1.39 years) volunteered. Volume patterns consisted of 3 sets × 3 repetition maximum (3RM) (low volume [LV]), 3 sets × 6 reps at 80-85% of 3RM (midvolume [MV]), and 3 sets × 9 reps at 70-75% of 3RM (high volume [HV]). Rest period was identical at 2 minutes. Blood samples were collected immediately before and after each volume pattern. The HV resulted in the greatest lactate accumulation (7.43 ± 2.94 mmol·L) vs. (5.27 ± 2.48 and 4.03 ± 1.78 mmol·L in MV and LV, respectively). Mean relative increase in lactate was the highest in HV (356.34%). The findings indicate that lactate production in power cleans is largely associated with volume, determined by number of repetitions, load, and rest interval. High-volume explosive training may impose greater metabolic demands than low-volume explosive training and may improve ability to produce power in the presence of lactate. The role of explosive power training in overloading the lactate clearance mechanism should be examined further, especially for athletes of intermittent sport.

Enhanced responsiveness to selective serotonin reuptake inhibitors during lactation.

PubMed

Jury, Nicholas J; McCormick, Betsy A; Horseman, Nelson D; Benoit, Stephen C; Gregerson, Karen A

2015-01-01

The physiology of mood regulation in the postpartum is poorly understood despite the fact that postpartum depression (PPD) is a common pathology. Serotonergic mechanisms and their dysfunction are widely presumed to be involved, which has led us to investigate whether lactation induces changes in central or peripheral serotonin (5-HT) systems and related affective behaviors. Brain sections from lactating (day 10 postpartum) and age-matched nulliparous (non-pregnant) C57BL/6J mice were processed for 5-HT immunohistochemistry. The total number of 5-HT immunostained cells and optical density were measured. Lactating mice exhibited lower immunoreactive 5-HT and intensity in the dorsal raphe nucleus when compared with nulliparous controls. Serum 5-HT was quantified from lactating and nulliparous mice using radioimmunoassay. Serum 5-HT concentrations were higher in lactating mice than in nulliparous controls. Affective behavior was assessed in lactating and non-lactating females ten days postpartum, as well as in nulliparous controls using the forced swim test (FST) and marble burying task (MBT). Animals were treated for the preceding five days with a selective serotonin reuptake inhibitor (SSRI, citalopram, 5mg/kg/day) or vehicle. Lactating mice exhibited a lower baseline immobility time during the FST and buried fewer marbles during the MBT as compared to nulliparous controls. Citalopram treatment changed these behaviors in lactating mice with further reductions in immobility during the FST and decreased marble burying. In contrast, the same regimen of citalopram treatment had no effect on these behaviors in either non-lactating postpartum or nulliparous females. Our findings demonstrate changes in both central and peripheral 5-HT systems associated with lactation, independent of pregnancy. They also demonstrate a significant interaction of lactation and responsiveness to SSRI treatment, which has important implications in the treatment of PPD. Although recent evidence

Enhanced Responsiveness to Selective Serotonin Reuptake Inhibitors during Lactation

PubMed Central

Jury, Nicholas J.; McCormick, Betsy A.; Horseman, Nelson D.; Benoit, Stephen C.; Gregerson, Karen A.

2015-01-01

The physiology of mood regulation in the postpartum is poorly understood despite the fact that postpartum depression (PPD) is a common pathology. Serotonergic mechanisms and their dysfunction are widely presumed to be involved, which has led us to investigate whether lactation induces changes in central or peripheral serotonin (5-HT) systems and related affective behaviors. Brain sections from lactating (day 10 postpartum) and age-matched nulliparous (non-pregnant) C57BL/6J mice were processed for 5-HT immunohistochemistry. The total number of 5-HT immunostained cells and optical density were measured. Lactating mice exhibited lower immunoreactive 5-HT and intensity in the dorsal raphe nucleus when compared with nulliparous controls. Serum 5-HT was quantified from lactating and nulliparous mice using radioimmunoassay. Serum 5-HT concentrations were higher in lactating mice than in nulliparous controls. Affective behavior was assessed in lactating and non-lactating females ten days postpartum, as well as in nulliparous controls using the forced swim test (FST) and marble burying task (MBT). Animals were treated for the preceding five days with a selective serotonin reuptake inhibitor (SSRI, citalopram, 5mg/kg/day) or vehicle. Lactating mice exhibited a lower baseline immobility time during the FST and buried fewer marbles during the MBT as compared to nulliparous controls. Citalopram treatment changed these behaviors in lactating mice with further reductions in immobility during the FST and decreased marble burying. In contrast, the same regimen of citalopram treatment had no effect on these behaviors in either non-lactating postpartum or nulliparous females. Our findings demonstrate changes in both central and peripheral 5-HT systems associated with lactation, independent of pregnancy. They also demonstrate a significant interaction of lactation and responsiveness to SSRI treatment, which has important implications in the treatment of PPD. Although recent evidence

Feeding a Mixture of Choline Forms to Lactating Dams Improves the Development of the Immune System in Sprague-Dawley Rat Offspring.

PubMed

Richard, Caroline; Lewis, Erin D; Goruk, Susan; Wadge, Emily; Curtis, Jonathan M; Jacobs, René L; Field, Catherine J

2017-06-02

Dietary choline is essential during lactation, but few studies have examined the implications of feeding a mixture of choline forms on immune function. This study investigates the impact of feeding lactating dams different mixtures of choline forms, similar to those in human diets, on the development and later immune function of suckled offspring. Sprague-Dawley lactating dams ( n = 6/diet) were randomized to consume one of three diets, containing 1 g/kg choline: Control (100% free choline (FC)), Mixed Choline (MC: 50% phosphatidylcholine (PC), 25% FC, 25% glycerophosphocholine (GPC)), or High GPC (HGPC: 75% GPC, 12.5% PC, 12.5% FC). At weaning, female pups ( n = 2/dam) were fed the Control diet until 10 weeks. At 3 weeks, MC and HGPC pups were heavier and their splenocytes had a higher proportion of helper T cells expressing CD25 and CD28 and produced less interferon gamma (IFN-γ) and tumor-necrosis factor-α (TNF-α) after Concanavalin A stimulation vs. Control pups ( p < 0.05). At 10 weeks, MC and HGPC offspring had a lower proportion of macrophages and dendritic cells and produced less interleukin (IL)-1β but more IL-10 after lipopolysaccharide stimulation vs. Control pups ( p < 0.05). In summary, feeding mixed choline diets during lactation improved T cell phenotype/function at the end of suckling and programmed a less inflammatory response later in life.

Feeding a Mixture of Choline Forms to Lactating Dams Improves the Development of the Immune System in Sprague-Dawley Rat Offspring

PubMed Central

Richard, Caroline; Lewis, Erin D.; Goruk, Susan; Wadge, Emily; Curtis, Jonathan M.; Jacobs, René L.; Field, Catherine J.

2017-01-01

Dietary choline is essential during lactation, but few studies have examined the implications of feeding a mixture of choline forms on immune function. This study investigates the impact of feeding lactating dams different mixtures of choline forms, similar to those in human diets, on the development and later immune function of suckled offspring. Sprague-Dawley lactating dams (n = 6/diet) were randomized to consume one of three diets, containing 1 g/kg choline: Control (100% free choline (FC)), Mixed Choline (MC: 50% phosphatidylcholine (PC), 25% FC, 25% glycerophosphocholine (GPC)), or High GPC (HGPC: 75% GPC, 12.5% PC, 12.5% FC). At weaning, female pups (n = 2/dam) were fed the Control diet until 10 weeks. At 3 weeks, MC and HGPC pups were heavier and their splenocytes had a higher proportion of helper T cells expressing CD25 and CD28 and produced less interferon gamma (IFN-γ) and tumor-necrosis factor-α (TNF-α) after Concanavalin A stimulation vs. Control pups (p < 0.05). At 10 weeks, MC and HGPC offspring had a lower proportion of macrophages and dendritic cells and produced less interleukin (IL)-1β but more IL-10 after lipopolysaccharide stimulation vs. Control pups (p < 0.05). In summary, feeding mixed choline diets during lactation improved T cell phenotype/function at the end of suckling and programmed a less inflammatory response later in life. PMID:28574475

Effect of Exercise-Induced Lactate Elevation on Brain Lactate Levels During Hypoglycemia in Patients With Type 1 Diabetes and Impaired Awareness of Hypoglycemia.

PubMed

Wiegers, Evita C; Rooijackers, Hanne M; Tack, Cees J; Groenewoud, Hans J M M; Heerschap, Arend; de Galan, Bastiaan E; van der Graaf, Marinette

2017-12-01

Since altered brain lactate handling has been implicated in the development of impaired awareness of hypoglycemia (IAH) in type 1 diabetes, the capacity to transport lactate into the brain during hypoglycemia may be relevant in its pathogenesis. High-intensity interval training (HIIT) increases plasma lactate levels. We compared the effect of HIIT-induced hyperlacticacidemia on brain lactate during hypoglycemia between 1 ) patients with type 1 diabetes and IAH, 2 ) patients with type 1 diabetes and normal awareness of hypoglycemia, and 3 ) healthy participants without diabetes ( n = 6 per group). All participants underwent a hypoglycemic (2.8 mmol/L) clamp after performing a bout of HIIT on a cycle ergometer. Before HIIT (baseline) and during hypoglycemia, brain lactate levels were determined continuously with J-difference-editing 1 H-MRS, and time curves were analyzed using nonlinear mixed-effects modeling. At the beginning of hypoglycemia (after HIIT), brain lactate levels were elevated in all groups but most pronounced in patients with IAH. During hypoglycemia, brain lactate decreased ∼30% below baseline in patients with IAH but returned to baseline levels and remained there in the other two groups. Our results support the concept of enhanced lactate transport as well as increased lactate oxidation in patients with type 1 diabetes and IAH. © 2017 by the American Diabetes Association.

Genetic improvement of total milk yield and total lactation persistency of the first three lactations in dairy cattle.

PubMed

Togashi, K; Lin, C Y

2008-07-01

The objective of this study was to compare 6 selection criteria in terms of 3-parity total milk yield and 9 selection criteria in terms of total net merit (H) comprising 3-parity total milk yield and total lactation persistency. The 6 selection criteria compared were as follows: first-parity milk estimated breeding value (EBV; M1), first 2-parity milk EBV (M2), first 3-parity milk EBV (M3), first-parity eigen index (EI(1)), first 2-parity eigen index (EI(2)), and first 3-parity eigen index (EI(3)). The 9 selection criteria compared in terms of H were M1, M2, M3, EI(1), EI(2), EI(3), and first-parity, first 2-parity, and first 3-parity selection indices (I(1), I(2), and I(3), respectively). In terms of total milk yield, selection on M3 or EI(3) achieved the greatest genetic response, whereas selection on EI(1) produced the largest genetic progress per day. In terms of total net merit, selection on I(3) brought the largest response, whereas selection EI(1) yielded the greatest genetic progress per day. A multiple-lactation random regression test-day model simultaneously yields the EBV of the 3 lactations for all animals included in the analysis even though the younger animals do not have the opportunity to complete the first 3 lactations. It is important to use the first 3 lactation EBV for selection decision rather than only the first lactation EBV in spite of the fact that the first-parity selection criteria achieved a faster genetic progress per day than the 3-parity selection criteria. Under a multiple-lactation random regression animal model analysis, the use of the first 3 lactation EBV for selection decision does not prolong the generation interval as compared with the use of only the first lactation EBV. Thus, it is justified to compare genetic response on a lifetime basis rather than on a per-day basis. The results suggest the use of M3 or EI(3) for genetic improvement of total milk yield and the use of I(3) for genetic improvement of total net merit H

Hippocampal 3alpha,5alpha-THP may alter depressive behavior of pregnant and lactating rats.

PubMed

Frye, Cheryl A; Walf, Alicia A

2004-07-01

The 5alpha-reduced metabolite of progesterone (P), 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), may mediate progestins' effects to reduce depressive behavior of female rats in part through actions in the hippocampus. To investigate, forced swim test behavior and plasma and hippocampal progestin levels were assessed in groups of rats expected to differ in their 3alpha,5alpha-THP levels due to endogenous differences (pregnant and postpartum), administration of a 5alpha-reductase inhibitor (finasteride; 50 mg/kg sc), and/or gestational stress [prenatal stress (PNS)], an animal model of depression. Pregnant rats had higher plasma and hippocampal 3alpha,5alpha-THP levels and less depressive behavior (decreased immobility, increased struggling and swimming) in the forced swim test than did postpartum rats. Finasteride, compared to vehicle-administration, reduced plasma and hippocampal 3alpha,5alpha-THP levels and increased depressive behavior (increased immobility, decreased struggling and swimming). PNS was associated with lower hippocampal, but not plasma, 3alpha,5alpha-THP levels and increased swimming compared to that observed in control rats. Together, these data suggest that 3alpha,5alpha-THP in the hippocampus may mediate antidepressive behavior of female rats.

Isozyme composition of lactate dehydrogenase of rat skeletal muscles after flight in Kosmos-690 biosatellite. [Effects of radiation on lactate dehydrogenase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petrova, N.V.

1978-01-01

Rats in a ground-based model experiment, in which all flight conditions with the exception of weightlessness and accelerations and intact animals maintained under vivarium conditions served as a control. On the 10th day of flight and of the ground-based model experiments, the rats were exposed to 800 rad radiation for 24 h. Samples of soleus and plantaris muscles were taken for examination on the 2d and 27th days after landing and termination of the ground-based model experiment. Intact animals were sacrificed on the same days as experimental ones. Samples of muscle tissue were frozen in dry ice and stored formore » several days at a temperature of -70/sup 0/ before they were studied. This investigation of isozyme spectrum of LDH of skeletal muscles of rats from the Kosmos-690 satellite indicates that the changes in proportion of isozyme fractions of LDH on the 2d day after the flight are due to the effects of weightlessness; subsequent changes (27th day) in correlation between LDH fraction activity are related to the effects of radiation.« less

Peritoneal lavage with povidone-iodine solution in colorectal cancer-induced rats.

PubMed

Song, Hua-Li; Zhang, Dong-Mei; Wen, Heng; Wang, Meng; Zhao, Na; Gao, Yu-Hua; Ding, Ni

2018-08-01

Although peritoneal lavage with povidone-iodine (PVPI) is frequently performed after surgery on the gastrointestinal tract, the effects of PVPI on the intestinal epithelial barrier are unknown. The purpose of this study was to investigate the effects of abdominal irrigation with PVPI on the intestinal epithelial barrier in a colorectal cancer (CRC)-induced rat model. The CRC model was induced in rats with azoxymethane and dextran sodium sulfate. Next, a total of 24 male CRC-induced rats were randomly divided into three groups (n = 8): (1) a sham-operated group, (2) an NS group (peritoneal lavage 0.9% NaCl), and (3) a PVPI group (peritoneal lavage with 0.45%-0.55% PVPI). The mean arterial pressure was continuously monitored throughout the experiment. The levels of plasma endotoxin and D-lactate, blood gases, and protein concentration were measured. The ultrastructural changes of the epithelial tight junctions were observed by transmission electron microscopy. The mean arterial pressure after peritoneal lavage was lower in the PVPI group than that in the NS group. The protein concentration and levels of endotoxin and D-lactate were higher in the PVPI group than they were in the PVPI group. In addition, PVPI treatment resulted in a markedly severe metabolic acidosis and intestinal mucosal injury compared with NS rats. Peritoneal lavage with PVPI dramatically compromises the integrity of the intestinal mucosa barrier and causes endotoxin shock in CRC rats. It is unsafe for clinical applications to include peritoneal lavage with PVPI in colorectal operations. Copyright © 2018 Elsevier Inc. All rights reserved.

Oleuropein and hydroxytyrosol protect rats' pups against bisphenol A induced hypothyroidism.

PubMed

Mahmoudi, Asma; Ghorbel, Hèla; Feki, Ines; Bouallagui, Zouhaier; Guermazi, Fadhel; Ayadi, Lobna; Sayadi, Sami

2018-04-27

Bisphenol A (BPA) can disturb the endocrine system and the organs that respond to endocrine signals in organisms, indirectly exposed during prenatal and/or early postnatal life. The present study was designed to assess the protective effect of phenolic compounds from olive leaves against BPA induced thyroid dysfunction and growth perturbation in young rats during lactation. The BPA disrupting effect on thyroid function was investigated by measuring changes in plasma levels of thyroid hormones. Free triiodothyronine (FT3) and thyroxine (FT4) were decreased in young rats breast-fed from mothers treated with bisphenol A. This effect was associated with an increase in the plasma level of thyroid-stimulating hormone (TSH). The histological and immunohistochemical study of the thyroid gland revealed a disturbance in morphological structure and thyroid cells function. Thyroid dysfunction led to a disruption in the skeletal bone growth of young rats. In fact, the infrared microspectroscopic analysis and histological examination of femoral bone showed significant changes in their histoarchitecture associated with a perturbation in the mechanism of bone tissue mineralization. The administration of oleuropein or hydroxytyrosol in BPA treated lactating mothers improved the thyroid cells function by enhancing thyroid hormone levels. Moreover, these phenolics increased the body growth characterized by an amelioration in the structure and the microstructure of femoral bone tissue. HPLC analysis of rats-breast milk indicated the presence of oleuropein and hydroxytyrosol, which could contribute to the protective effect against bisphenol A induced hypothyroidism in pups rats. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Hypothyroxinemia Induced by Mild Iodine Deficiency Deregulats Thyroid Proteins during Gestation and Lactation in Dams

PubMed Central

Wei, Wei; Wang, Yi; Dong, Jing; Wang, Yuan; Min, Hui; Song, Binbin; Shan, Zhongyan; Teng, Weiping; Xi, Qi; Chen, Jie

2013-01-01

The main object of the present study was to explore the effect on thyroidal proteins following mild iodine deficiency (ID)-induced maternal hypothyroxinemia during pregnancy and lactation. In the present study, we established a maternal hypothyroxinemia model in female Wistar rats by using a mild ID diet. Maternal thyroid iodine content and thyroid weight were measured. Expressions of thyroid-associated proteins were analyzed. The results showed that the mild ID diet increased thyroid weight, decreased thyroid iodine content and increased expressions of thyroid transcription factor 1, paired box gene 8 and Na+/I− symporter on gestational day (GD) 19 and postpartum days (PN) 21 in the maternal thyroid. Moreover, the up-regulated expressions of type 1 iodothyronine deiodinase (DIO1) and type 2 iodothyronine deiodinase (DIO2) were detected in the mild ID group on GD19 and PN21. Taken together, our data indicates that during pregnancy and lactation, a maternal mild ID could induce hypothyroxinemia and increase the thyroidal DIO1 and DIO2 levels. PMID:23917811

Analytical performance of three whole blood point-of-care lactate devices compared to plasma lactate comparison methods and a flow-injection mass spectrometry method.

PubMed

Tolan, Nicole V; Wockenfus, Amy M; Koch, Christopher D; Crews, Bridgit O; Dietzen, Dennis J; Karon, Brad S

2017-03-01

Point of care (POC) whole blood lactate testing may facilitate rapid detection of sepsis. We evaluated three POC methods against both plasma lactate comparison methods and a flow-injection mass spectrometric (MS) method. Nova StatStrip, Abbott i-STAT CG4+ and Radiometer ABL90 POC lactate methods were evaluated against the mean of Cobas Integra 400 and Vitros 350 plasma lactate. POC methods were also compared to a flow-injection mass spectrometric assay measuring lactate in ZnSO 4 -precipitated whole blood extracts. Intra- and inter-assay precision was determined using quality control material. Method comparison included specimens from normal donors at rest, after exertion, and after spiking with lactic acid. Intra- and inter-assay coefficient of variation was <5% for i-STAT and ABL90; but ranged from 3.1-8.2% on two StatStrip meters. Mean (±SD) bias between POC and plasma lactate ranged from -0.2±0.9 (i-STAT and ABL90) to -0.4±1.2 (StatStrip) mmol/L. At concentrations >6mmol/L, all POC methods showed proportional negative bias compared to plasma methods; but this bias was not observed when compared to the MS method. Despite proportional negative bias, all POC methods demonstrated acceptable concordance (94-100%) with plasma lactate within the reference interval (<2.3mmol/L) and >4mmol/L, commonly used clinical cut-offs for detection of sepsis. POC lactate methods demonstrate acceptable concordance with plasma lactate across commonly used clinical cut-offs for detection of sepsis. Due to systematic negative bias at higher lactate concentrations, POC and plasma lactate should not be used interchangeably to monitor patients with elevated lactate concentrations. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

In Vivo Evidence for a Lactate Gradient from Astrocytes to Neurons.

PubMed

Mächler, Philipp; Wyss, Matthias T; Elsayed, Maha; Stobart, Jillian; Gutierrez, Robin; von Faber-Castell, Alexandra; Kaelin, Vincens; Zuend, Marc; San Martín, Alejandro; Romero-Gómez, Ignacio; Baeza-Lehnert, Felipe; Lengacher, Sylvain; Schneider, Bernard L; Aebischer, Patrick; Magistretti, Pierre J; Barros, L Felipe; Weber, Bruno

2016-01-12

Investigating lactate dynamics in brain tissue is challenging, partly because in vivo data at cellular resolution are not available. We monitored lactate in cortical astrocytes and neurons of mice using the genetically encoded FRET sensor Laconic in combination with two-photon microscopy. An intravenous lactate injection rapidly increased the Laconic signal in both astrocytes and neurons, demonstrating high lactate permeability across tissue. The signal increase was significantly smaller in astrocytes, pointing to higher basal lactate levels in these cells, confirmed by a one-point calibration protocol. Trans-acceleration of the monocarboxylate transporter with pyruvate was able to reduce intracellular lactate in astrocytes but not in neurons. Collectively, these data provide in vivo evidence for a lactate gradient from astrocytes to neurons. This gradient is a prerequisite for a carrier-mediated lactate flux from astrocytes to neurons and thus supports the astrocyte-neuron lactate shuttle model, in which astrocyte-derived lactate acts as an energy substrate for neurons. Copyright © 2016 Elsevier Inc. All rights reserved.

Flexible graphene bio-nanosensor for lactate.

PubMed

Labroo, Pratima; Cui, Yue

2013-03-15

The development of a flexible nanosensor for detecting lactate could expand opportunities for using graphene, both in fundamental studies for a variety of device platforms and in practical applications. Graphene is a delicate single-layer, two-dimensional network of carbon atoms with ultrasensitive sensing capabilities. Lactic acid is important for clinical analysis, sports medicine, and the food industry. Recently, wearable and flexible bioelectronics on plastics have attracted great interest for healthcare, sports and defense applications due to their advantages of being light-weight, bendable, or stretchable. Here, we demonstrate for the first time the development of a flexible graphene-based bio-nanosensor to detect lactate. Our results show that flexible lactate biosensors can be fabricated on a variety of plastic substrates. The sensor can detect lactate sensitively from 0.08 μM to 20 μM with a fast steady-state measuring time of 2s. The sensor can also detect lactate under different mechanical bending conditions, the sensor response decreased as the bending angle and number of bending repetitions increased. We anticipate that these results could open exciting opportunities for fundamental studies of flexible graphene bioelectronics by using other bioreceptors, as well as a variety of wearable, implantable, real-time, or on-site applications in fields ranging from clinical analysis to defense. Copyright © 2012 Elsevier B.V. All rights reserved.

[Temperature-switched high-efficiency D-lactate production from glycerol].

PubMed

Tian, Kangming; Zhou, Li; Chen, Xianzhong; Shen, Wei; Shi, Guiyang; Singh, Suren; Lu, Fuping; Wang, Zhengxiang

2013-01-01

Glycerol from oil hydrolysis industry is being considered as one of the abundent raw materials for fermentation industry. In present study, the aerobic and anaerobic metabolism and growth properties on glycerol by Esherichia coli CICIM B0013-070, a D-lactate over-producing strain constructed previously, at different temperatures were investigated, followed by a novel fermentation process, named temperature-switched process, was established for D-lactate production from glycerol. Under the optimal condition, lactate yield was increased from 64.0% to 82.6%. Subsequently, the yield of D-lactate from glycerol was reached up to 88.9% while a thermo-inducible promoter was used to regulate D-lactate dehydrogenase transcription.

21 CFR 73.165 - Ferrous lactate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Ferrous lactate. 73.165 Section 73.165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.165 Ferrous lactate. (a) Identity. The color additive ferrous...

21 CFR 73.165 - Ferrous lactate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Ferrous lactate. 73.165 Section 73.165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.165 Ferrous lactate. (a) Identity. The color additive ferrous...

21 CFR 73.165 - Ferrous lactate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Ferrous lactate. 73.165 Section 73.165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.165 Ferrous lactate. (a) Identity. The color additive ferrous...

21 CFR 73.165 - Ferrous lactate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Ferrous lactate. 73.165 Section 73.165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.165 Ferrous lactate. (a) Identity. The color additive ferrous...

21 CFR 73.165 - Ferrous lactate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Ferrous lactate. 73.165 Section 73.165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.165 Ferrous lactate. (a) Identity. The color additive ferrous...

Cocaine- and Amphetamine-Regulated Transcript (CART) Expression is Differentially Regulated in the Hypothalamic Para ventricular Nucleus of Lactating Rats Exposed to Suckling or Cold Stimulation

PubMed Central

Sánchez, Edith; Fekete, Csaba; Lechan, Ronald M.; Joseph-Bravo, Patricia

2007-01-01

Neural stimuli, such as suckling or cold exposure, increase TRH mRNA in the paraventricular nucleus (PVN) of the rat hypothalamus, yet only suckling induces prolactin secretion. As TRH co-localizes with cocaine-and amphetamine-regulated transcript (CART) in hypophysiotropic neurons of the PVN, and CART inhibits TRH-induced prolactin release but not TRH-induced TSH release in adenohypophyseal cell cultures, we raised the possibility that differential regulation of CART gene expression in the PVN may explain the differences in prolactin secretion following each of the two stimuli. Primiparous female rats were mated and handled daily during the pre- and postpartum periods. After delivery, the litter was adjusted to 8 pups and at mid-lactation, dams were separated from their pups for 8 hours and exposed to either 1h of cold or 30 min of suckling. Long term effects of suckling were studied by separating pups from their mothers for 24h, followed by a 12h period of continuous suckling. Serum TSH levels increased in response to cold exposure, while prolactin levels were increased by suckling and diminished by cold exposure. CART mRNA levels increased in rostral and mid parts of the medial parvocellular PVN following cold exposure but not after suckling stimulation. These data demonstrate a differential regulation of CART gene expression in hypophysiotropic neurons in response to stimuli that increase TRH mRNA levels, and suggest that CART activation in the PVN may contribute to the decrease in PRL release when the thyroid axis is activated by cold exposure. Section: Regulatory systems PMID:17174283

Fertilization and early embryonic development in heifers and lactating cows in summer and lactating and dry cows in winter.

PubMed

Sartori, R; Sartor-Bergfelt, R; Mertens, S A; Guenther, J N; Parrish, J J; Wiltbank, M C

2002-11-01

Two experiments in two seasons evaluated fertilization rate and embryonic development in dairy cattle. Experiment 1 (summer) compared lactating Holstein cows (n = 27; 97.3 +/- 4.1 d postpartum [dppl; 40.0 +/- 1.5 kg milk/d) to nulliparous heifers (n = 28; 11 to 17 mo old). Experiment 2 (winter) compared lactating cows (n = 27; 46.4 +/- 1.6 dpp; 45.9 +/- 1.4 kg milk/d) to dry cows (n = 26). Inseminations based on estrus included combined semen from four high-fertility bulls. Embryos and oocytes recovered 5 d after ovulation were evaluated for fertilization, embryo quality (1 = excellent to 5 = degenerate), nuclei/embryo, and accessory sperm. In experiment 1, 21 embryos and 17 unfertilized oocytes (UFO) were recovered from lactating cows versus 32 embryos and no UFO from heifers (55% vs. 100% fertilization). Embryos from lactating cows had inferior quality scores (3.8 +/- 0.4 vs. 2.2 +/- 0.3), fewer nuclei/embryo (19.3 +/- 3.7 vs. 36.8 +/- 3.0) but more accessory sperm (37.3 +/- 5.8 vs. 22.4 +/- 5.5/embryo) than embryos from heifers. Sperm were attached to 80% of UFO (17.8 +/- 12.1 sperm/UFO). In experiment 2, lactating cows yielded 36 embryos and 5 UFO versus 34 embryos and 4 UFO from dry cows (87.8 vs. 89.5% fertilization). Embryo quality from lactating cows was inferior to dry cows (3.1 +/- 0.3 vs. 2.2 +/- 0.3), but embryos had similar numbers of nuclei (27.2 +/- 2.7 vs. 30.6 +/- 2.1) and accessory sperm (42.0 +/- 9.4 vs. 36.5 +/- 6.3). From 53% of the flushings from lactating cows and 28% from dry cows, only nonviable embryos were collected. Thus, embryos of lactating dairy cows were detectably inferior to embryos from nonlactating females as early as 5 d after ovulation, with a surprisingly high percentage of nonviable embryos. In addition, fertilization rate was reduced only in summer, apparently due to an effect of heat stress on the oocyte.

Metabolism and Clearance of T-2 Mycotoxin in Perfused Rat Livers

DTIC Science & Technology

1986-02-10

nucleottde system in rat liver. B5ochem. J. 117, 499-503. 4ALLACE, E. 4., PATHRE, S. V., MIROCHA, C. J., ROSISON, T. S., AND FENTON , S. W. (1977). Synthesis...lactating cow. Food Cosmet . Toxicol. 19, 31- 39. YOSHIZAWA, T., SAKAMOTO, T., AND KUWAMWA, K. (1985). Structures of Deepoxytrichothecene mecabolites

Effect of L-arginine supplementation on the hepatic phosphatidylinositol 3-kinase signaling pathway and gluconeogenic enzymes in early intrauterine growth-restricted rats

PubMed Central

Luo, Kaiju; Chen, Pingyang; Li, Suping; Li, Wen; He, Mingfeng; Wang, Tao; Chen, Juncao

2017-01-01

The present study aimed to investigate the response of the phosphatidylinositol 3-kinase (PI3K) signaling pathway and gluconeogenic enzymes in intrauterine growth-restricted rats to dietary L-arginine (L-Arg) supplementation during the lactation period early in life. Pregnant Sprague-Dawley rats were randomly divided into a control group (CON), an intrauterine growth restriction group (IUGR) and an L-Arg group (LA). The pregnant rats in the CON group were fed a 21% protein diet, and those in the IUGR and LA groups were fed a 10% low protein diet, and all rats were fed a 21% protein diet after delivery. Water was available ad libitum to the pregnant rats during the 21-day lactation period, and the water provided to the LA group included 200 mg/kg/day L-Arg. Blood glucose, serum insulin, homeostasis model of assessment for insulin resistance (HOMA-IR), PI3K and protein kinase B (PKB) protein expression, and phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase) mRNA expression in the offspring rats were measured postnatally at 1, 3 and 8 weeks. No significant difference in blood glucose, serum insulin and HOMA-IR were identified at any time point among the three groups. PI3K and PKB expression was lower in the IUGR group offspring compared with that in the CON group offspring, but both were increased by dietary L-Arg supplementation. PEPCK mRNA and G-6-Pase mRNA expression levels in the offspring of the IUGR group were higher compared with those in the CON group but were downregulated following L-Arg supplementation. These results suggest that dietary L-Arg supplementation during the early lactation period promoted catch-up growth and reversed abnormalities in hepatic insulin signaling and gene expression of gluconeogenic enzymes in IUGR offspring rats. PMID:28962167

Lactate promotes glutamine uptake and metabolism in oxidative cancer cells

PubMed Central

Pérez-Escuredo, Jhudit; Dadhich, Rajesh K; Dhup, Suveera; Cacace, Andrea; Van Hée, Vincent F; De Saedeleer, Christophe J; Sboarina, Martina; Rodriguez, Fabien; Fontenille, Marie-Joséphine; Brisson, Lucie; Porporato, Paolo E; Sonveaux, Pierre

2016-01-01

ABSTRACT Oxygenated cancer cells have a high metabolic plasticity as they can use glucose, glutamine and lactate as main substrates to support their bioenergetic and biosynthetic activities. Metabolic optimization requires integration. While glycolysis and glutaminolysis can cooperate to support cellular proliferation, oxidative lactate metabolism opposes glycolysis in oxidative cancer cells engaged in a symbiotic relation with their hypoxic/glycolytic neighbors. However, little is known concerning the relationship between oxidative lactate metabolism and glutamine metabolism. Using SiHa and HeLa human cancer cells, this study reports that intracellular lactate signaling promotes glutamine uptake and metabolism in oxidative cancer cells. It depends on the uptake of extracellular lactate by monocarboxylate transporter 1 (MCT1). Lactate first stabilizes hypoxia-inducible factor-2α (HIF-2α), and HIF-2α then transactivates c-Myc in a pathway that mimics a response to hypoxia. Consequently, lactate-induced c-Myc activation triggers the expression of glutamine transporter ASCT2 and of glutaminase 1 (GLS1), resulting in improved glutamine uptake and catabolism. Elucidation of this metabolic dependence could be of therapeutic interest. First, inhibitors of lactate uptake targeting MCT1 are currently entering clinical trials. They have the potential to indirectly repress glutaminolysis. Second, in oxidative cancer cells, resistance to glutaminolysis inhibition could arise from compensation by oxidative lactate metabolism and increased lactate signaling. PMID:26636483

Effects of Chronic Central Arginine Vasopressin (AVP) on Maternal Behavior in Chronically Stressed Rat Dams

PubMed Central

Coverdill, Alexander J.; McCarthy, Megan; Bridges, Robert S.; Nephew, Benjamin C.

2012-01-01

Exposure of mothers to chronic stressors during pregnancy or the postpartum period often leads to the development of depression, anxiety, or other related mood disorders. The adverse effects of mood disorders are often mediated through maternal behavior and recent work has identified arginine vasopressin (AVP) as a key neuropeptide hormone in the expression of maternal behavior in both rats and humans. Using an established rodent model that elicits behavioral and physiological responses similar to human mood disorders, this study tested the effectiveness of chronic AVP infusion as a novel treatment for the adverse effects of exposure to chronic social stress during lactation in rats. During early (day 3) and mid (day 10) lactation, AVP treatment significantly decreased the latency to initiate nursing and time spent retrieving pups, and increased pup grooming and total maternal care (sum of pup grooming and nursing). AVP treatment was also effective in decreasing maternal aggression and the average duration of aggressive bouts on day 3 of lactation. Central AVP may be an effective target for the development of treatments for enhancing maternal behavior in individuals exposed to chronic social stress. PMID:24349762

Preventive effects of Lactobacillus mixture on experimental E. coli urinary tract infection in infant rats.

PubMed

Lee, Jung Won; Lee, Jee Hyun; Sung, Sun Hee; Lee, Seung Joo

2013-03-01

Urinary tract infection (UTI) is an ascending infection of fecal uropathogens, urogenital lactobacilli are suggested to play a role in the prevention of UTI. This study was to investigate whether lactobacillus mixture (LM) could prevent the experimental infantile UTI. The LM were composed of three lactobacillus strains (L. gasseri, L. rhamnosus, and L. reuteri). Mother rats were grouped as lactobacillus (LB) group I (LB I, n=22), II (LB II, n=24) and control (n=20). LB I and LB II were fed with LM (1 mL/day) and control with phosphate-buffered saline (PBS) from late pregnancy through lactation. All newborn rats were breast-fed and their urine and stool were collected at the end of the 3rd week to compare lactobacillus colony. Then, infant rats from LB II were treated with intravesical instillation of LM. Infant rats from LB I and control were instilled with PBS. Twenty-four hours later, experimental UTI was introduced by intravesical instillation of standard E. coli strain. After 72 hours later, the infant rats were sacrificed for histologic examination. Lactobacilli colonies in urine and stool were not statistically different among the three groups. The incidence of pyelonephritis in the LB II was 16.7% (4/24), LB I 72.7% (16.22) and control 75.0% (15/20) (p=0.015). The incidence of cystitis was not significantly different among the three groups. The intravesically instilled LM significantly prevented experimental pyelonephritis in infant rats, however, LM administered orally to the pregnant and lactating mother rats did not.

Metabolic differentiation and classification of abnormal Savda Munziq's pharmacodynamic role on rat models with different diseases by nuclear magnetic resonance-based metabonomics.

PubMed

Mamtimin, Batur; Xia, Guo; Mijit, Mahmut; Hizbulla, Mawlanjan; Kurbantay, Nazuk; You, Li; Upur, Halmurat

2015-01-01

Abnormal Savda Munziq (ASMq) is a traditional Uyghur herbal preparation used as a therapy for abnormal Savda-related diseases. In this study, we investigate ASMq's dynamic effects on abnormal Savda rat models under different disease conditions. Abnormal Savda rat models with hepatocellular carcinoma (HCC), type 2 diabetes mellitus (T2DM), and asthma dosed of ASMq. Serum samples of each animal tested by nuclear magnetic resonance spectroscopy and analyzed by orthogonal projection to latent structure with discriminant analysis. Compared with healthy controls, HCC rats had higher concentrations of amino acids, fat-related metabolites, lactate, myoinositol, and citrate, but lower concentrations of α-glucose, β-glucose, and glutamine. Following ASMq treatment, the serum acetone very low-density lipoprotein (VLDL), LDL, unsaturated lipids, acetylcysteine, and pyruvate concentration decreased, but α-glucose, β-glucose, and glutamine concentration increased (P < 0.05). T2DM rats had higher concentrations of α- and β-glucose, but lower concentrations of isoleucine, leucine, valine, glutamine, glycoprotein, lactate, tyrosine, creatine, alanine, carnitine, and phenylalanine. After ASMq treated T2DM groups showed reduced α- and β-glucose and increased creatine levels (P < 0.05). Asthma rats had higher acetate, carnitine, formate, and phenylalanine levels, but lower concentrations of glutamine, glycoprotein, lactate, VLDL, LDL, and unsaturated lipids. ASMq treatment showed increased glutamine and reduced carnitine, glycoprotein, formate, and phenylalanine levels (P < 0.05). Low immune function, decreased oxidative defense, liver function abnormalities, amino acid deficiencies, and energy metabolism disorders are common characteristics of abnormal Savda-related diseases. ASMq may improve the abnormal metabolism and immune function of rat models with different diseases combined abnormal Savda.

Bioavailability of soy isoflavones through placental/lactational transfer and soy food

DOE Office of Scientific and Technical Information (OSTI.GOV)

Doerge, Daniel R., E-mail: daniel.doerge@fda.hhs.gov

2011-07-15

Isoflavones are non-nutritive components of soy responsible for estrogenic responses observed in vitro and in experimental animals. Possible beneficial effects (e.g., reduction of serum lipids, increased bone mineral density, relief of hot flashes and other menopausal symptoms, mammary and prostate cancer chemoprevention) in humans have been attributed to consumption of isoflavones but evidence for potential adverse effects (e.g., stimulation of estrogen-dependent mammary tumors and aberrant perinatal development) has also been reported in experimental animal models. Bioavailability from appropriate food matrices and exposure during different life stages are both critical determinants of isoflavone effects. For these reasons, it is important tomore » compare isoflavone bioavailability in adults to that in fetal and neonatal animals for a more complete understanding of potential susceptibility issues. Studies of the major soy isoflavone genistein were conducted in pregnant and lactating Sprague-Dawley rats to quantify placental and lactational transfer to plasma and brain to understand better biological effects observed in multigenerational studies. In addition, studies were conducted with genistein in adult Balb/c mice to define absolute bioavailability from both gavage and soy protein isolate (SPI)-containing food. The information derived from these studies makes it possible to predict internal exposures of children to genistein from soy infant formula, which is manufactured using SPI.« less

[Bone loss in lactating women and post-pregnancy osteoporosis].

PubMed

Hirata, Go; Chaki, Osamu

2011-09-01

Measurement of the bone mineral density have shown that lactating women had 1 to 3% decrease in bone mineral density. Post pregnancy osteoporosis is rare condition that causes fragile fracture mostly in vertebrae. The bone loss in lactating women is caused by calcium loss, decrease in estrogen level, and increase in PTHrP (parathyroid hormone related protein) level. Some data have shown that extended lactation and amenorrhea had an association with the degree of bone loss. Mostly, the bone loss of the lactating women recovers to the baseline level, soon after the weaning, and there is no long term effect. Post pregnancy osteoporosis should be concerned, when we see a lactating woman with fragile fracture of the vertebrae.

Developmental Neurotoxicity Study of Dietary Bisphenol A in Sprague-Dawley Rats

PubMed Central

Stump, Donald G.; Beck, Melissa J.; Radovsky, Ann; Garman, Robert H.; Freshwater, Lester L.; Sheets, Larry P.; Marty, M. Sue; Waechter, John M.; Dimond, Stephen S.; Van Miller, John P.; Shiotsuka, Ronald N.; Beyer, Dieter; Chappelle, Anne H.; Hentges, Steven G.

2010-01-01

This study was conducted to determine the potential of bisphenol A (BPA) to induce functional and/or morphological effects to the nervous system of F1 offspring from dietary exposure during gestation and lactation according to the Organization for Economic Cooperation and Development and U.S. Environmental Protection Agency guidelines for the study of developmental neurotoxicity. BPA was offered to female Sprague-Dawley Crl:CD (SD) rats (24 per dose group) and their litters at dietary concentrations of 0 (control), 0.15, 1.5, 75, 750, and 2250 ppm daily from gestation day 0 through lactation day 21. F1 offspring were evaluated using the following tests: detailed clinical observations (postnatal days [PNDs] 4, 11, 21, 35, 45, and 60), auditory startle (PNDs 20 and 60), motor activity (PNDs 13, 17, 21, and 61), learning and memory using the Biel water maze (PNDs 22 and 62), and brain and nervous system neuropathology and brain morphometry (PNDs 21 and 72). For F1 offspring, there were no treatment-related neurobehavioral effects, nor was there evidence of neuropathology or effects on brain morphometry. Based on maternal and offspring body weight reductions, the no-observed-adverse-effect level (NOAEL) for systemic toxicity was 75 ppm (5.85 and 13.1 mg/kg/day during gestation and lactation, respectively), with no treatment-related effects at lower doses or nonmonotonic dose responses observed for any parameter. There was no evidence that BPA is a developmental neurotoxicant in rats, and the NOAEL for developmental neurotoxicity was 2250 ppm, the highest dose tested (164 and 410 mg/kg/day during gestation and lactation, respectively). PMID:20164145

Adaptations in the Microarchitecture and Load Distribution of Maternal Cortical and Trabecular Bone in Response to Multiple Reproductive Cycles in Rats

PubMed Central

de Bakker, Chantal M. J.; Altman-Singles, Allison R.; Li, Yihan; Tseng, Wei-Ju; Li, Connie; Liu, X. Sherry

2017-01-01

Pregnancy, lactation, and weaning result in dramatic changes in maternal calcium metabolism. In particular, the increased calcium demand during lactation causes a substantial degree of maternal bone loss. This reproductive bone loss has been suggested to be largely reversible, as multiple clinical studies have found that parity and lactation history have no adverse effect on post-menopausal fracture risk. However, the precise effects of pregnancy, lactation, and post-weaning recovery on maternal bone structure are not well understood. Our study aimed to address this question by longitudinally tracking changes in trabecular and cortical bone microarchitecture at the proximal tibia in rats throughout three cycles of pregnancy, lactation, and post-weaning using in vivo μCT. We found that the trabecular thickness underwent a reversible deterioration during pregnancy and lactation, which was fully recovered after weaning, while other parameters of trabecular microarchitecture (including trabecular number, spacing, connectivity density, and structure model index) underwent a more permanent deterioration which recovered minimally. Thus, pregnancy and lactation resulted in both transient and long-lasting alterations in trabecular microstructure. In the meantime, multiple reproductive cycles appeared to improve the robustness of cortical bone (resulting in an elevated cortical area and polar moment of inertia), as well as increase the proportion of the total load carried by the cortical bone at the proximal tibia. Taken together, changes in the cortical and trabecular compartments suggest that while rat tibial trabecular bone appears to be highly involved in maintaining calcium homeostasis during female reproduction, cortical bone adapts to increase its load-bearing capacity, allowing the overall mechanical function of the tibia to be maintained. PMID:28109138

21 CFR 184.1768 - Sodium lactate.

Code of Federal Regulations, 2014 CFR

2014-04-01

....1768 Sodium lactate. (a) Sodium lactate (C3H5O3Na, CAS Reg. No. 72-17-3) is the sodium salt of lactic acid. It is prepared commercially by the neutralization of lactic acid with sodium hydroxide. (b) The... ingredient is used in food at levels not to exceed current good manufacturing practice. (d) Prior sanctions...

Effects of Urtica dioica on hepatic ischemia-reperfusion injury in rats.

PubMed

Kandis, Hayati; Karapolat, Sami; Yildirim, Umran; Saritas, Ayhan; Gezer, Suat; Memisogullari, Ramazan

2010-01-01

To evaluate the effects of Urtica dioica on hepatic ischemia-reperfusion injury. Thirty adult male Wistar albino rats were divided into three groups: sham group (group 1), control group (group 2), and Urtica dioica group (group 3). All the rats were exposed to hepatic ischemia for 60 min, followed by 60 min of reperfusion. In group 2, a total of 2 ml/kg 0.9% saline solution was given intraperitoneally. In group 3, a total of 2 ml/kg Urtica dioica was given intraperitoneally. At the end of the procedure, liver tissue and blood samples were taken from all rats. Serum aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, ceruloplasmin, catalase, paraoxonase, arylesterase, and lipid hydroperoxide levels were measured. Liver tissue histopathologies were also evaluated by light microscopy. Serum aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase levels were significantly higher in group 2 than in group 1, and significantly lower in group 3 than in group 2. Also, group 2 had higher serum lipid hydroperoxides and ceruloplasmin levels but lower catalase, paraoxonase, and arylesterase levels than group 1. In group 3, serum lipid hydroperoxides and ceruloplasmin levels were significantly lower, and catalase, paraoxonase, and arylesterase levels were higher than those in group 2. Histopathological examination showed that liver tissue damage was significantly decreased in group 3 compared with group 2. Urtica dioica has a protective effect on the liver in hepatic ischemia-reperfusion-injured rats.

Effects of Urtica dioica on hepatic ischemia‐reperfusion injury in rats

PubMed Central

Kandis, Hayati; Karapolat, Sami; Yildirim, Umran; Saritas, Ayhan; Gezer, Suat; Memisogullari, Ramazan

2010-01-01

OBJECTIVES: To evaluate the effects of Urtica dioica on hepatic ischemia‐reperfusion injury. METHODS: Thirty adult male Wistar albino rats were divided into three groups: sham group (group 1), control group (group 2), and Urtica dioica group (group 3). All the rats were exposed to hepatic ischemia for 60 min, followed by 60 min of reperfusion. In group 2, a total of 2 ml/kg 0.9% saline solution was given intraperitoneally. In group 3, a total of 2 ml/kg Urtica dioica was given intraperitoneally. At the end of the procedure, liver tissue and blood samples were taken from all rats. Serum aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, ceruloplasmin, catalase, paraoxonase, arylesterase, and lipid hydroperoxide levels were measured. Liver tissue histopathologies were also evaluated by light microscopy. RESULTS: Serum aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase levels were significantly higher in group 2 than in group 1, and significantly lower in group 3 than in group 2. Also, group 2 had higher serum lipid hydroperoxides and ceruloplasmin levels but lower catalase, paraoxonase, and arylesterase levels than group 1. In group 3, serum lipid hydroperoxides and ceruloplasmin levels were significantly lower, and catalase, paraoxonase, and arylesterase levels were higher than those in group 2. Histopathological examination showed that liver tissue damage was significantly decreased in group 3 compared with group 2. CONCLUSIONS: Urtica dioica has a protective effect on the liver in hepatic ischemia‐reperfusion‐injured rats. PMID:21340227

Social preference and maternal defeat-induced social avoidance in virgin female rats: sex differences in involvement of brain oxytocin and vasopressin.

PubMed

Lukas, Michael; Neumann, Inga D

2014-08-30

Research concerning non-reproductive sociability in rodents is mainly restricted to assessing the effects of oxytocin (OXT) and arginine-vasopressin (AVP) in male rats and mice. Comparable studies on natural social preference and social avoidance in females are substantially lacking. Here, we adapted a behavioral paradigm for monitoring social preference of female rats consisting of two consecutive exposures to either non-social or social stimuli. Further, to induce stimulus-specific social avoidance, female rats were exposed to a single 10-min maternal defeat by a lactating dam. Social preference towards same-sex conspecifics in female rats was shown to be independent of the estrous cycle and even more pronounced than in male rats. Intracerebroventricular (icv) application of OXT, AVP, or their selective receptor antagonists or agonists, did not alter naturally-occurring social preference in female rats. Stimulus-specific social avoidance could be induced by prior exposure to a lactating rat: an effect that could not be reversed/overcome by icv OXT. The female social preference paradigm for rats established in this study detected subtle sex differences in social preference behavior of rats. Further, stimulus-specific social deficits could be induced in female rats using an acute exposure to social defeat - as previously observed in male rodents. Female rats show strong social preference behavior, which can be prevented by social defeat, but does not seem to be regulated by the OXT or AVP systems. Accordingly, icv application of synthetic OXT does not reverse maternal defeat-induced social avoidance in female rats. Copyright © 2014 Elsevier B.V. All rights reserved.

COMPARATIVE TISSUE DISTRIBUTION OF MIREX AND CHLORDECONE IN FETAL AND NEONATAL RATS

EPA Science Inventory

The transport of mirex and chlordecone (Kepone) across the placental during late gestation and through the milk during lactation was investigated in the rat. In the placental transport study, doses of 5 mg/kg were administrered on Day 15, 18 or 20 of gestation and animals were ki...

Mechanisms driving the lactate switch in Chinese hamster ovary cells.

PubMed

Hartley, Fiona; Walker, Tracy; Chung, Vicky; Morten, Karl

2018-03-31

The metabolism of Chinese Hamster Ovary (CHO) cells in a production environment has been extensively investigated. However, a key metabolic transition, the switch from lactate production to lactate consumption, remains enigmatic. Though commonly observed in CHO cultures, the mechanism(s) by which this metabolic shift is triggered is unknown. Despite this, efforts to control the switch have emerged due to the association of lactate consumption with improved cell growth and productivity. This review aims to consolidate current theories surrounding the lactate switch. The influence of pH, NAD + /NADH, pyruvate availability and mitochondrial function on lactate consumption are explored. A hypothesis based on the cellular redox state is put forward to explain the onset of lactate consumption. Various techniques implemented to control the lactate switch, including manipulation of the culture environment, genetic engineering, and cell line selection are also discussed. © 2018 Wiley Periodicals, Inc.

Changes in dietary intake and body weight in lactating and non-lactating women: prospective study in northern coastal Croatia.

PubMed

Dujmović, Mihela; Kresić, Greta; Mandić, Milena L; Kenjerić, Daniela; Cvijanović, Olga

2014-03-01

Postpartum weight retention is a risk factor for the development of midlife obesity. Since dietary intake and breastfeeding practice could be promoters of weight loss during postpartum, the objective of this study was to investigate their influence on weight retention during six months postpartum. The study sample consisted of 83 lactating and 76 non-lactating Croatian women who were examined at three measurement waves: at 1 month +/- 1 week, 3 months +/- 1 week and 6 months +/- 1 week postpartum. At each measurement wave, two consecutive 24-hour dietary recalls were collected, and body weight measurements were made. Both groups had a daily energy intake lower by about 25% than recommended. Although both groups continuously decreased energy and macronutrient intake, lactating women had energy intake higher by 205 kcal (p = 0.048) and 370 kcal (p < 0.001) after one and three months, respectively. At six months postpartum lactating women had a higher intake of fat (p = 0.036) but a lower intake of protein (p = 0.009) compared with non-lactating mothers. After six months, lactating women retained 101.9% of pre-pregnancy weight, which was significantly less than the percentage of weight retained among non-lactating women (p = 0.014). Multiple regression analysis showed that weight retention were predicted by: type of feeding (beta = -0.281; p <0.001), and time since parturition (beta = -0.151; p < 0.001), while gestational weight gain (P = 0.491; p < 0.001), energy intake (b = 0.157; p < 0.001) and energy derived from fat (beta = 0.122; p = 0.035) were positive predictors. We concluded that the dietary intake of Croatian women and breastfeeding practice over six months significantly influence their weight loss.

Fortified tuna bone powder supplementation increases bone mineral density of lactating rats and their offspring.

PubMed

Suntornsaratoon, Panan; Charoenphandhu, Narattaphol; Krishnamra, Nateetip

2018-03-01

Breastfeeding leads to bone calcium loss for milk production, resulting in progressive maternal osteopenia. Calcium supplement from natural sources has been postulated to be more beneficial to bone health than purified CaCO 3 because natural sources also contain other nutrients such as certain amino acids that might enhance calcium metabolism. Herein, we examined the effect of calcium supplementation from tuna bone powder and CaCO 3 on bones of dams and the offspring. Both forms of calcium supplement, i.e. tuna bone powder and CaCO 3 , increased maternal bone mineral density (BMD). However, bone histomorphometry revealed that only tuna bone had beneficial effect on maternal bone microstructure, i.e. increased bone formation, decreased bone resorption and increased in bone volume. Regarding the mechanical properties, the decreased ultimate load in non-supplement lactating mothers was restored to the load seen in nulliparous animals by calcium supplementation. Moreover, both tuna bone and CaCO 3 supplementation in mothers led to increased milk calcium concentration and consequently increased BMD in the growing offspring. Calcium supplement from tuna bone powder was effective in preventing maternal osteopenia. Tuna bone, which is a readily available fishing industrial waste, is a good alternative source of calcium supplement that increases BMD in both lactating mothers and the neonates. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Cinnamic Acid Derivatives Enhance the Efficacy of Transarterial Embolization in a Rat Model of Hepatocellular Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilkins, Luke R., E-mail: lrw6n@virginia.edu; Brautigan, David L., E-mail: db8g@virginia.edu; Wu, Hanping, E-mail: hanpingwumd@gmail.com

IntroductionWe hypothesize that the combination of transarterial embolization (TAE) plus inhibition of lactate export will limit anaerobic metabolism and reduce tumor survival compared to TAE alone. The purpose of this study was to test this hypothesis in a rat model of hepatocellular carcinoma (HCC).MethodsRat N1-S1 hepatoma cells were assayed in vitro using the Seahorse XF analyzer to measure extracellular acidification (lactate excretion) comparing effects of the addition of caffeic acid (CA) or ferulic acid (FA) or UK-5099 with control. Monocarboxylate transporter Slc16a3 was knocked down by RNAi. N1S1 tumors were orthotopically implanted in rats and 4 groups evaluated: (1) Control,more » (2) TAE-only, (3) TAE plus CA, and (4) TAE plus FA. Tumor size was determined by ultrasound and analyzed by repeated measures statistics. Tumors harvested at 4 weeks were examined by microscopy.ResultsSeahorse assays showed that CA and FA caused a significant reduction by >90% in lactate efflux by N1S1 tumor cells (p < 0.01). Knockdown of Slc16a3 prevented inhibition by CA. In vivo tumors grew 30-fold in volume over 4 weeks in untreated controls. By comparison, TAE resulted in near cessation of growth (10% in 4-week time period). However, both TAE + CA and TAE + FA caused a significant reduction of tumor volumes (87 and 72%, respectively) compared to control and TAE (p < 0.05). Pathologic evaluation revealed residual tumor in the TAE group but no residual viable tumor cells in the TAE + CA and TAE + FA groups.ConclusionAddition of CA or FA enhances the effectiveness of TAE therapy for HCC in part by blocking lactate efflux.« less

Effect of short-term ornithine alpha-ketoglutarate pretreatment on intestinal ischemia-reperfusion in rats.

PubMed

Gonçalves, Eduardo Silvio Gouveia; Rabelo, Camila Menezes; Prado Neto, Alberico Ximenes do; Garcia, José Huygens Parente; Guimarães, Sérgio Botelho; Vasconcelos, Paulo Roberto Leitão de

2011-01-01

To investigate the effects of preventive enteral administration of ornithine alpha-ketoglutarate (OKG) in an ischemia-reperfusion rat model. Sixty rats were randomized into five groups (G1-G5, n = 12). Each group was divided into two subgroups (n = 6) and treated with calcium carbonate (CaCa) or OKG by gavage. Thirty minutes later, the animals were anesthetized with xylazine 15mg + ketamine 1mg ip and subjected to laparotomy. G1-G3 rats served as controls. Rats in groups G4 and G5 were subjected to ischemia for 30 minutes. Ischemia was achieved by clamping the small intestine and its mesentery, delimiting a segment of bowel 5 cm long and 5 cm apart from the ileocecal valve. In addition, G5 rats underwent reperfusion for 30 minutes. Blood samples were collected at the end of the laparotomy (G1), after 30 minutes (G2, G4) and 60 minutes (G3, G5) to determine concentrations of metabolites (pyruvate, lactate), creatine phosphokinase (CPK), thiobarbituric acid reactive substances (TBARS) and glutathione (GSH). There was a significant decrease in tissue pyruvate and lactate and plasma CPK levels in OKG-treated rats at the end of reperfusion period. GSH levels did not change significantly in ischemia and reperfusion groups. However, TBARS levels increased significantly (p<0.05) in tissue samples in OKG-treated rats subjected to ischemia for 30 minutes. Short-term pretreatment with OKG before induction of I/R decreases tissue damage, increases pyruvate utilization for energy production in the Krebs cycle and does not attenuate the oxidative stress in this animal model.

Resveratrol Intake During Pregnancy and Lactation Modulates the Early Metabolic Effects of Maternal Nutrition Differently in Male and Female Offspring.

PubMed

Ros, Purificación; Díaz, Francisca; Freire-Regatillo, Alejandra; Argente-Arizón, Pilar; Barrios, Vicente; Argente, Jesús; Chowen, Julie A

2018-02-01

Poor maternal nutrition can have detrimental long-term consequences on energy homeostasis in the offspring. Resveratrol exerts antioxidant and antiobesity actions, but its impact during development remains largely unknown. We hypothesized that resveratrol intake during pregnancy and lactation could improve the effects of poor maternal nutrition on offspring metabolism. Wistar rats received a low-fat diet (LFD; 10.2% kcal from fat) or high-fat diet (HFD; 61.6% kcal from fat), with half of each group receiving resveratrol in their drinking water (50 mg/L) during pregnancy and lactation. Body weight (BW) of dams was measured at treatment onset and weaning [postnatal day (PND) 21] and of pups at birth and PND21, at which time dams and pups were euthanized. Although HFD dams consumed more energy, their BW at the end of lactation was unaffected. Mean litter size was not modified by maternal diet or resveratrol. At birth, male offspring from HFD and resveratrol (HFD + R) dams weighed less than those from LFD and resveratrol (LFD + R) dams. On PND21, pups of both sexes from HFD dams weighed more, had more visceral adipose tissue (VAT) and subcutaneous adipose tissue (SCAT), and had higher serum leptin levels than those from LFD dams. Resveratrol reduced BW, leptin, VAT, and SCAT, with females being more affected, but increased glycemia. Neuropeptide levels were unaffected by resveratrol. In conclusion, resveratrol intake during pregnancy and lactation decreased BW and adipose tissue content in offspring of dams on an HFD but did not affect offspring from LFD-fed dams, suggesting that the potential protective effects of resveratrol during gestation/lactation are diet dependent. Copyright © 2018 Endocrine Society.

The clinical diagnostic significance of cerebrospinal fluid D-lactate for bacterial meningitis.

PubMed

Chen, Zengqiang; Wang, Yumin; Zeng, Aibing; Chen, Lijiang; Wu, Ruihao; Chen, Bicheng; Chen, Mengquan; Bo, Jinshuang; Zhang, Hu; Peng, Qian; Lu, Jianxin; Meng, Qing H

2012-10-09

To study the clinical and laboratory significance of D‐lactate in the diagnosis of bacterial meningitis (BM). The levels of D‐lactate, L‐lactate, IL-6, IL-8, and other biochemical markers were determined in 83 CSF samples from different types of meningitis and the controls. The CSF values of D‐lactate, L‐lactate, IL-6, IL-8, erythrocytes, leukocytes, and protein were higher in patients with BM than those in the controls and patients with viral meningitis. The levels of D‐lactate, L‐lactate, IL-6, and erythrocytes in the BM group were higher than those in the tuberculous meningitis group. At the cutoff 12.8 μmol/l, D‐lactate showed the diagnostic sensitivity of 94.7%. D‐lactate gave the area under the curve (AUC) 0.905, which was higher than those of other markers. Using multiple marker detection, the AUC reached 0.956, which was the highest among all the parameters. Pearson correlation analysis revealed that D‐lactate was positively correlated to IL-6 and L‐lactate (r=0.727, 0.789 and P=0.000, 0.000, respectively). THE CSF concentrations of D‐lactate are significantly increased in the presence of BM. Measurement of D‐lactate provides a rapid diagnosis and differential diagnosis for BM. Combination of D‐lactate with other biochemical markers improves the specificity. Copyright © 2012 Elsevier B.V. All rights reserved.

[Study of rat blood serum biochemical indicators of cardiotoxic action of novel antitumor 4-thiazolidinone derivatives and doxorubicin in complexes with polyethylene glycol-containing polymeric carrier in the rat blood serum].

PubMed

Kobylyns'ka, L I; Havryliuk, D Ia; Riabtseva, A O; Mitina, N Ie; Zaichenko, O S; Zimenkovskyĭ, B S; Stoĭka, R S

2014-01-01

The aim of this study was to measure the activity of enzymes which reflect cardiotoxic action in rats of novel synthetic 4-thiazolidone derivatives--3882, 3288 and 3833 that demonstrated antineoplastic effect in vitro towards 60 lines of human tumor cells tested in the framework of the program of screening new anticancer drugs at the National Cancer Institute (USA). Such action of these compounds was compared with the effect of well known anticancer agent doxorubicin and after conjugation of all above mentioned substances with new polyethylenglycol-containing polymeric comb-like carrier that was synthesized by the authors. Among the biochemical indicators of cardiotoxic action of anticancer agents, activity of the following enzymes in rat blood serum showed to be the most informative: creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransterase. Tenfold injection of doxorubicin in a dose of 5.5 mg/kg of weight caused rats' death, while 3882, 3288 and 3833 preparations had not such action. Application of the doxorubicin in combination with polymeric carrier prolonged the survival time to 20 days. Thus, the injection of anticancer agents in a complex with polymeric carrier provides a significant decrease in their cardiotoxicity that was confirmed by the corresponding changes in the activity of marker enzymes: creatine kinase, lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase in blood serum of treated rats.

Monochloroacetic acid lethality in the rat in relation to lactic acid accumulation in the cerebrospinal fluid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mitroka, J.G.

1989-01-01

Potential antidotes for human exposure to monochloroacetic acid (MCA) were evaluated using a rodent model. Dichloroacetic acid (DCA) and phenobarbital (PB) but not ethanol or phenytoin, were found to be effective antidotes to monochloroacetic acid (MCA) in rats. DCA (110 mg/kg, ip), administered to rats 15 minutes after a LD-80 of MCA (80 mg/kg, iv), consistently reduced mortality to 0%, while PB reduced mortality to less than 20%. Both DCA and PB were found to be similarly effective in mice. The hypothesis that PB reduces mortality in MCA treated rats by altering the metabolic disposition of MCA was evaluated andmore » rejected. Administration of PB to rats treated with a lethal dose of ({sup 14}C)MCA did not alter the concentrations of MCA or its metabolites in plasma or cerebrospinal fluid (CSF), or the extent of covalent binding between radioactivity equivalent to ({sup 14}C)MCA and brain proteins. The relationship between altered blood-brain barrier permeability and death in MCA treated rats was investigated. Treatment with MCA (80 mg/kg, iv) was associated with a significant (50%) increase in the permeability of the rat blood-brain barrier to ({sup 125}I)BSA. The effect was not altered by treatment with PB, however, suggesting that altered blood-brain barrier permeability does not have an important role in the lethal effect of MCA in rats. The effect of MCA on brain carbohydrate metabolism in vivo was investigated. CSF and blood lactic acid concentrations increased in MCA treated rats, and the increase in CSF levels was dose related. In individual MCA treated rats, CSF lactate concentrations paralleled the time course of ataxia and a discrete threshold for death (18 mmol/L) was observed. The relationship between excess brain lactate levels and death in MCA treated rats was investigated further.« less

Lactate Clearance and Normalization and Prolonged Organ Dysfunction in Pediatric Sepsis.

PubMed

Scott, Halden F; Brou, Lina; Deakyne, Sara J; Fairclough, Diane L; Kempe, Allison; Bajaj, Lalit

2016-03-01

To evaluate whether lactate clearance and normalization during emergency care of pediatric sepsis is associated with lower rates of persistent organ dysfunction. This was a prospective cohort study of 77 children <18 years of age in the emergency department with infection and acute organ dysfunction per consensus definitions. In consented patients, lactate was measured 2 and/or 4 hours after an initial lactate; persistent organ dysfunction was assessed through laboratory and physician evaluation at 48 hours. A decrease of ≥ 10% from initial to final level was considered lactate clearance; a final level < 2 mmol/L was considered lactate normalization. Relative risk (RR) with 95% CIs, adjusted in a log-binomial model, was used to evaluate associations between lactate clearance/normalization and organ dysfunction. Lactate normalized in 62 (81%) patients and cleared in 70 (91%). The primary outcome, persistent 48-hour organ dysfunction, was present in 32 (42%). Lactate normalization was associated with decreased risk of persistent organ dysfunction (RR 0.46, 0.29-0.73; adjusted RR 0.47, 0.29-0.78); lactate clearance was not (RR 0.70, 0.35-1.41; adjusted RR 0.75, 0.38-1.50). The association between lactate normalization and decreased risk of persistent organ dysfunction was retained in the subgroups with initial lactate ≥ 2 mmol/L and hypotension. In children with sepsis and organ dysfunction, lactate normalization within 4 hours was associated with decreased persistent organ dysfunction. Serial lactate level measurement may provide a useful prognostic tool during the first hours of resuscitation in pediatric sepsis. Copyright © 2016 Elsevier Inc. All rights reserved.

Antioxidant effect of vitamin E and 5-aminosalicylic acid on acrylamide induced kidney injury in rats.

PubMed

Rajeh, Nisreen A; Al-Dhaheri, Najlaa M

2017-02-01

To explore renal toxicity caused by sub-acute exposure of acrylamide and to study the protective effect of 5-Aminosalicylic acid (5-ASA) and Vitamin E (vit-E)on Acrylamide (ACR) induced renal toxicity. Methods: This study was conducted at King Fahad Medical Research Centre, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia, between August and November 2015. A total of 49 adult Wistar rats (250 ± 20g) aged 60 days were kept in a controlled environment and used in the present study. The rats were divided into 7 groups (control, ACR alone, ACR+5-ASA, ACR+vit-E, ACR+ASA+vit-E, vit-E alone, and ASA alone). After 5 days of ACR oral gavage treatment, the rats were observed for 24 hours then killed. Histopathology for the kidney and lactate dehydrogenase assay were carried out.  Results: Acrylamide produced significant pathological changes in the kidney with acute tubular necrosis in the distal tubules that could be reversed by concomitant injection of rat with 5-ASA. Together with vitamin E, 5-ASA, showed maximum renal protection. No statistically significant difference was observed in either body weights or lactate dehydrogenase activity of ACR treated rats.  Conclusion: Acrylamide exposure leads to adverse clinical pathologies of renal tubules, which were reversed by a concomitant treatment with 5-ASA and vitamin-E.

Minimizing the effects of oxygen interference on l-lactate sensors by a single amino acid mutation in Aerococcus viridansl-lactate oxidase.

PubMed

Hiraka, Kentaro; Kojima, Katsuhiro; Lin, Chi-En; Tsugawa, Wakako; Asano, Ryutaro; La Belle, Jeffrey T; Sode, Koji

2018-04-30

l-lactate biosensors employing l-lactate oxidase (LOx) have been developed mainly to measure l-lactate concentration for clinical diagnostics, sports medicine, and the food industry. Some l-lactate biosensors employ artificial electron mediators, but these can negatively impact the detection of l-lactate by competing with the primary electron acceptor: molecular oxygen. In this paper, a strategic approach to engineering an AvLOx that minimizes the effects of oxygen interference on sensor strips was reported. First, we predicted an oxygen access pathway in Aerococcus viridans LOx (AvLOx) based on its crystal structure. This was subsequently blocked by a bulky amino acid substitution. The resulting Ala96Leu mutant showed a drastic reduction in oxidase activity using molecular oxygen as the electron acceptor and a small increase in dehydrogenase activity employing an artificial electron acceptor. Secondly, the Ala96Leu mutant was immobilized on a screen-printed carbon electrode using glutaraldehyde cross-linking method. Amperometric analysis was performed with potassium ferricyanide as an electron mediator under argon or atmospheric conditions. Under argon condition, the response current increased linearly from 0.05 to 0.5mM l-lactate for both wild-type and Ala96Leu. However, under atmospheric conditions, the response of wild-type AvLOx electrode was suppressed by 9-12% due to oxygen interference. The Ala96Leu mutant maintained 56-69% of the response current at the same l-lactate level and minimized the relative bias error to -19% from -49% of wild-type. This study provided significant insight into the enzymatic reaction mechanism of AvLOx and presented a novel approach to minimize oxygen interference in sensor applications, which will enable accurate detection of l-lactate concentrations. Copyright © 2017 Elsevier B.V. All rights reserved.

In utero and lactational exposure to low-dose genistein-vinclozolin mixture affects the development and growth factor mRNA expression of the submandibular salivary gland in immature female rats.

PubMed

Kouidhi, Wided; Desmetz, Catherine; Nahdi, Afef; Bergès, Raymond; Cravedi, Jean-Pierre; Auger, Jacques; El May, Michèle; Canivenc-Lavier, Marie Chantal

2012-06-01

It has been suggested that hormonally controlled submandibular salivary gland (SSG) development and secretions may be affected by endocrine disruptor compounds. We investigated the effects of oral gestation-lactation exposure to 1 mg/kg body weight daily dose of the estrogenic soy-isoflavone genistein and/or the anti-androgenic food contaminant vinclozolin in female rats. The SSGs of female offspring were collected at postnatal day 35 to study gland morphogenesis and mRNA expression of sex-hormone receptors and endocrine growth factors as sex-dependent biomarkers. Because of high expression in neonatal SSG, mRNA expression of transforming growth factor α was also studied. Exposure to genistein, vinclozolin, or a genistein+vinclozolin mixture resulted in significantly lower numbers of striated ducts linked to an increase in their area and lower acinar proliferation (Ki-67-positive nuclei). Exposure to the mixture had the highest significant effects, which were particularly associated with repression of epidermal growth factor, nerve growth factor, and transforming growth factor α expression. In conclusion, early exposure to low doses of genistein and vinclozolin can affect glandular structure and endocrine gene mRNA expression in prepubertal SSG in female rats, and the effects are potentialized by the genistein+vinclozolin mixture. Our study provides the first evidence that SSG are targeted by both estrogenic and anti-androgenic disrupting compounds and are more sensitive to mixtures.

Biochemical and structural characterization of Cryptosporidium parvum Lactate dehydrogenase.

PubMed

Cook, William J; Senkovich, Olga; Hernandez, Agustin; Speed, Haley; Chattopadhyay, Debasish

2015-03-01

The protozoan parasite Cryptosporidium parvum causes waterborne diseases worldwide. There is no effective therapy for C. parvum infection. The parasite depends mainly on glycolysis for energy production. Lactate dehydrogenase is a major regulator of glycolysis. This paper describes the biochemical characterization of C. parvum lactate dehydrogenase and high resolution crystal structures of the apo-enzyme and four ternary complexes. The ternary complexes capture the enzyme bound to NAD/NADH or its 3-acetylpyridine analog in the cofactor binding pocket, while the substrate binding site is occupied by one of the following ligands: lactate, pyruvate or oxamate. The results reveal distinctive features of the parasitic enzyme. For example, C. parvum lactate dehydrogenase prefers the acetylpyridine analog of NADH as a cofactor. Moreover, it is slightly less sensitive to gossypol inhibition compared with mammalian lactate dehydrogenases and not inhibited by excess pyruvate. The active site loop and the antigenic loop in C. parvum lactate dehydrogenase are considerably different from those in the human counterpart. Structural features and enzymatic properties of C. parvum lactate dehydrogenase are similar to enzymes from related parasites. Structural comparison with malate dehydrogenase supports a common ancestry for the two genes. Copyright © 2014 Elsevier B.V. All rights reserved.

Disposable electrochemiluminescent biosensor for lactate determination in saliva.

PubMed

Ballesta Claver, J; Valencia Mirón, M C; Capitán-Vallvey, L F

2009-07-01

An electrochemiluminescence-based disposable biosensor for lactate is characterized. The lactate recognition system is based on lactate oxidase (LOx) and the transduction system consists of luminol. All the needed reagents, luminol, LOx, BSA, electrolyte and buffer have been immobilized by a Methocel membrane placed on the working electrode of the screen-printed electrochemical cell. The measurement of the electrochemiluminescence (ECL) is made possible via a photocounting head when 50 microl of sample is placed into the screen-printed cell with a circular container containing the disposable sensing membrane. The compositions of the membrane and reaction conditions have been optimized to obtain adequate sensitivity. The disposable biosensor responds to lactate after 20 s when two 1 s pulses at 0.5 V are applied to obtain the analytical parameter, the ECL initial rate. The linearized double logarithmic dependence for lactate shows a dynamic range from 10(-5) to 5 x 10(-4) M with a detection limit of 5 x 10(-6) M and a sensor-to-sensor repeatability, as relative standard deviation, RSD, of 3.30% at the medium level of the range. The ECL disposable biosensor was applied to the analysis of lactate in human saliva as an alternative procedure for obtaining the lactate level in a non-invasive way. Interferences coming from components of saliva were studied and eliminated in a simple way that was easy to handle. The procedure was validated for use in human saliva, comparing the results against an enzymatic reference procedure. The proposed method is quick, inexpensive, selective and sensitive and uses conventional ECL instrumentation.

Chronic consumption of trans fat can facilitate the development of hyperactive behavior in rats.

PubMed

Pase, C S; Roversi, Kr; Trevizol, F; Kuhn, F T; Dias, V T; Roversi, K; Vey, L T; Antoniazzi, C T; Barcelos, R C S; Bürger, M E

2015-02-01

In recent decades, the increased consumption of processed foods, which are rich in hydrogenated vegetable fat (HVF), has led to a decreased consumption of fish and oilseed, rich in omega-3 fatty acids. This eating habit provides an increased intake of trans fatty acids (TFA), which may be related to neuropsychiatric conditions, including inattention and hyperactivity. In this study, we evaluated the potential connection between prolonged trans fat consumption and development of hyperactivity-like symptoms in rats using different behavioral paradigms. Trans fat intake for 10 months (Experiment 1), as well as during pregnancy and lactation across two sequential generations of rats, (Experiment 4) induced active coping in the forced swimming task (FST). In addition, HVF supplementation was associated with increased locomotion before and after amphetamine (AMPH) administration (Experiment 2). Similarly, HVF supplementation during pregnancy and lactation were associated with increased locomotion in both young and adult rats (Experiment 3). Furthermore, trans fat intake across two sequential generations increased locomotor and exploratory activities following stressors (Experiment 4). From these results, we suggest that chronic consumption of trans fat is able to enhance impulsiveness and reactivity to novelty, facilitating hyperactive behaviors. Copyright © 2014 Elsevier Inc. All rights reserved.

Management of hyperthyroidism during pregnancy and lactation.

PubMed

Azizi, Fereidoun; Amouzegar, Atieh

2011-06-01

Poorly treated or untreated maternal overt hyperthyroidism may affect pregnancy outcome. Fetal and neonatal hypo- or hyper-thyroidism and neonatal central hypothyroidism may complicate health issues during intrauterine and neonatal periods. To review articles related to appropriate management of hyperthyroidism during pregnancy and lactation. A literature review was performed using MEDLINE with the terms 'hyperthyroidism and pregnancy', 'antithyroid drugs and pregnancy', 'radioiodine and pregnancy', 'hyperthyroidism and lactation', and 'antithyroid drugs and lactation', both separately and in conjunction with the terms 'fetus' and 'maternal.' Antithyroid drugs are the main therapy for maternal hyperthyroidism. Both methimazole (MMI) and propylthiouracil (PTU) may be used during pregnancy; however, PTU is preferred in the first trimester and should be replaced by MMI after this trimester. Choanal and esophageal atresia of fetus in MMI-treated and maternal hepatotoxicity in PTU-treated pregnancies are of utmost concern. Maintaining free thyroxine concentration in the upper one-third of each trimester-specific reference interval denotes success of therapy. MMI is the mainstay of the treatment of post partum hyperthyroidism, in particular during lactation. Management of hyperthyroidism during pregnancy and lactation requires special considerations and should be carefully implemented to avoid any adverse effects on the mother, fetus, and neonate.

Diammonium phosphate stimulates transcription of L-lactate dehydrogenase leading to increased L-lactate production in the thermotolerant Bacillus coagulans strain.

PubMed

Sun, Lifan; Li, Yanfeng; Wang, Limin; Wang, Yanping; Yu, Bo

2016-08-01

Exploration of cost-effective fermentation substrates for efficient lactate production is an important economic objective. Although some organic nitrogen sources are also cheaper, inorganic nitrogen salts for lactate fermentation have additional advantages in facilitating downstream procedures and significantly improving the commercial competitiveness of lactate production. In this study, we first established an application of diammonium phosphate to replace yeast extract with a reduced 90 % nitrogen cost for a thermotolerant Bacillus coagulans strain. In vivo enzymatic and transcriptional analyses demonstrated that diammonium phosphate stimulates the gene expression of L-lactate dehydrogenase, thus providing higher specific enzyme activity in vivo and increasing L-lactic acid production. This new information provides a foundation for establishing a cost-effective process for polymer-grade L-lactic acid production in an industrial setting.

Maternal low intensity physical exercise prevents obesity in offspring rats exposed to early overnutrition.

PubMed

Ribeiro, Tatiane Aparecida; Tófolo, Laize Peron; Martins, Isabela Peixoto; Pavanello, Audrei; de Oliveira, Júlio Cezar; Prates, Kelly Valério; Miranda, Rosiane Aparecida; da Silva Franco, Claudinéia Conationi; Gomes, Rodrigo Mello; Francisco, Flávio Andrade; Alves, Vander Silva; de Almeida, Douglas Lopes; Moreira, Veridiana Mota; Palma-Rigo, Kesia; Vieira, Elaine; Fabricio, Gabriel Sergio; da Silva Rodrigues, Marcos Ricardo; Rinaldi, Wilson; Malta, Ananda; de Freitas Mathias, Paulo Cezar

2017-08-09

Low intensity exercise during pregnancy and lactation may create a protective effect against the development of obesity in offspring exposed to overnutrition in early life. To test these hypotheses, pregnant rats were randomly assigned into 2 groups: Sedentary and Exercised, low intensity, on a rodent treadmill at 30% VO 2Max /30-minute/session/3x/week throughout pregnancy and the lactation. Male offspring were raised in small litters (SL, 3 pups/dam) and normal litters (NL, 9 pups/dam) as models of early overnutrition and normal feed, respectively. Exercised mothers showed low mesenteric fat pad stores and fasting glucose and improved glucose-insulin tolerance, VO 2max during lactation and sympathetic activity. Moreover, the breast milk contained elevated levels of insulin. In addition, SL of sedentary mothers presented metabolic dysfunction and glucose and insulin intolerance and were hyperglycemic and hyperinsulinemic in adulthood. SL of exercised mothers showed lower fat tissue accretion and improvements in glucose tolerance, insulin sensitivity, insulinemia and glycemia. The results suggest that maternal exercise during the perinatal period can have a possible reprogramming effect to prevent metabolic dysfunction in adult rat offspring exposed to early overnutrition, which may be associated with the improvement in maternal health caused by exercise.

Ameliorative effects of Spirulina platensis against lead-induced nephrotoxicity in newborn rats: Modulation of oxidative stress and histopathological changes

PubMed Central

Gargouri, Manel; Soussi, Ahlem; Akrouti, Amel; Magné, Christian; El Feki, Abdelfattah

2018-01-01

Our experimental work was aimed at evaluating the safety and protective effects of dietary spirulina supplementation on the kidney of newborn rats, the offspring of lead contaminated lactating mothers. Female rats were randomly divided into four groups: group I (control) was given a normal diet, group II (positive control, S) received a diet enriched with spirulina, group III received only lead through drinking water (Pb), and group IV received both a diet enriched with spirulina and lead contaminated water (S Pb). The treatment of pregnant rats with lead administrated in drinking water, from the 5th day of pregnancy until day 14 after delivery, induced an increased level of renal lipid peroxidation, protein carbonyl, hydrogen peroxide and advanced oxidation protein product, a decreased renal content of glutathione and antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase in newborns. A statistically significant increase of renal DNA, mRNA, hematological parameters as well as in plasma urea and creatinine serum levels and lactate dehydrogenase was seen in pups, while those of uric acid declined. Interestingly, these biochemical modifications were accompanied by a significant decrease of lactate dehydrogenase in kidney, plasma alkaline phosphatase and gamma glutamyl-transpeptidase levels, urinary levels of creatinine and urea. Conversely, supplementation of lead-treated mother's with spirulina alleviated hematotoxicity induced by lead as evidenced, by restoring the biochemical markers cited above to near normal levels. Nevertheless, the distorted histoarchitecture in rat kidney attenuated following spirulina supplementation. It can be then concluded that spirulina is an important protective source against kidney impairments. PMID:29743860

Carbohydrate metabolism in erythrocytes of copper deficient rats.

PubMed

Brooks, S P J; Cockell, K A; Dawson, B A; Ratnayake, W M N; Lampi, B J; Belonje, B; Black, D B; Plouffe, L J

2003-11-01

Dietary copper deficiency is known to adversely affect the circulatory system of fructose-fed rats. Part of the problem may lie in the effect of copper deficiency on intermediary metabolism. To test this, weanling male Long-Evans rats were fed for 4 or 8 weeks on sucrose-based diets containing low or adequate copper content. Copper deficient rats had significantly lower plasma and tissue copper as well as lower plasma copper, zinc-superoxide dismutase activity. Copper deficient rats also had a significantly higher heart:body weight ratio when compared to pair-fed controls. Direct measurement of glycolysis and pentose phosphate pathway flux in erythrocytes using (13)C NMR showed no differences in carbon flux from glucose or fructose to pyruvate but a significantly higher flux through the lactate dehydrogenase locus in copper deficient rats (approximately 1.3 times, average of glucose and glucose + fructose measurements). Copper-deficient animals had significantly higher erythrocyte concentrations of glucose, fructose, glyceraldehyde 3-phosphate and NAD(+). Liver metabolite levels were also affected by copper deficiency being elevated in glycogen and fructose 1-phosphate content. The results show small changes in carbohydrate metabolism of copper deficient rats.

Kinetics of lactate metabolism during acellular normothermic ex vivo lung perfusion.

PubMed

Koike, Terumoto; Yeung, Jonathan C; Cypel, Marcelo; Rubacha, Matthew; Matsuda, Yasushi; Sato, Masaaki; Waddell, Thomas K; Liu, Mingyao; Keshavjee, Shaf

2011-12-01

Plasma lactate has been used as a marker of poor prognosis in clinical conditions. However, the relationship between lactate production and lung function during acellular normothermic ex vivo lung perfusion (EVLP) is unclear. We investigated the kinetics of lactate metabolism during EVLP and the correlation of this marker with outcomes after transplant. Human donor lungs in our clinical EVLP trial (CLs; n = 28) and rejected donor lungs for experimental use (Els; n = 8) were perfused ex vivo using the Toronto technique. Lactate level, lactate/pyruvate (L/P) ratio, and glucose level in the perfusate were measured. In CLs, we examined the relationship between lactate metabolism during EVLP and early post-transplant outcomes. The hypoxia-inducible factor 1 sub-unit 1α (HIF-1α) level in lung tissue was examined in ELs. We performed double-lung EVLP in CLs and single-lung EVLP in ELs. In CLs, the lactate and L/P ratios at the end of EVLP had no correlation with early post-transplant outcomes despite lactate elevation during EVLP. Although lactate elevation was also present in all ELs, we were able to identify 2 groups based on L/P ratio at the end of EVLP. The group with the high L/P ratio had higher airway pressure during EVLP and higher HIF-1α in lung tissue at the end of EVLP. Lactate increases seen in the EVLP perfusate most often represent physiologic lactate production by the lung in a setting with reduced lactate clearance. Thus, patients who underwent transplantation after EVLP had good outcomes despite lactate elevation during EVLP. Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Age related rise in lactate and its correlation with lactate dehydrogenase (LDH) status in post-mitochondrial fractions isolated from different regions of brain in mice.

PubMed

Datta, Siddhartha; Chakrabarti, Nilkanta

2018-04-18

Rise in brain lactate is the hallmark of ageing. Separate studies report that ageing is associated with elevation of lactate level and alterations of lactate dehydrogenase (LDH)-A/B mRNA-expression-ratio in cerebral cortex and hippocampus. However, age related lactate rise in brain and its association with LDH status and their brain regional variations are still elusive. In the present study, level of lactate, LDH (A and B) activity and LDH-A expression were evaluated in post-mitochondrial fraction of tissues isolated from four different brain regions (cerebral cortex, hippocampus, substantia nigra and cerebellum) of young and aged mice. Lactate levels elevated in four brain regions with maximum rise in substantia nigra of aged mice. LDH-A protein expression and its activity decreased in cerebral cortex, hippocampus and substantia nigra without any changes of these parameters in cerebellum of aged mice. LDH-B activity decreased in hippocampus, substantia nigra and cerebellum whereas its activity remains unaltered in cerebral cortex of aged mice. Accordingly, the ratio of LDH-A/LDH-B-activity remains unaltered in hippocampus and substantia nigra, decreased in cerebral cortex and increased in cerebellum. Therefore, rise of lactate in three brain regions (cerebral cortex, hippocampus, substantia nigra) appeared to be not correlated with the alterations of its regulatory enzymes activities in these three brain regions, rather it supports the fact of involvement of other mechanisms, like lactate transport and/or aerobic/anaerobic metabolism as the possible cause(s) of lactate rise in these three brain regions. The increase in LDH-A/LDH-B-activity-ratio appeared to be positively correlated with elevated lactate level in cerebellum of aged mice. Overall, the present study indicates that the mechanism of rise in lactate in brain varies with brain regions where LDH status plays an important role during ageing. Copyright © 2018 Elsevier Ltd. All rights reserved.

Cerebrospinal fluid lactate and pyruvate concentrations and their ratio.

PubMed

Zhang, Wan-Ming; Natowicz, Marvin R

2013-05-01

Determinations of cerebrospinal fluid (CSF) lactate and pyruvate concentrations and CSF lactate:pyruvate (L/P) ratios are important in several clinical settings, yet published normative data have significant limitations. We sought to determine a large dataset of stringently-defined normative data for CSF lactate and pyruvate concentrations and CSF L/P ratios. We evaluated data from 627 patients who had determinations of CSF lactate and/or CSF pyruvate from 2001 to 2011 at the Cleveland Clinic. Inclusion in the normal reference population required normal CSF cell counts, glucose and protein and routine serum chemistries and absence of progressive brain disorder, epilepsy, or seizure within 24h. Brain MRI, if done, showed no evidence of tumor, acute changes or basal ganglia abnormality. CSF cytology, CSF alanine and immunoglobulin levels, and oligoclonal band analysis were required to be normal, if done. Various inclusion/exclusion criteria were compared. 92 patients fulfilled inclusion/exclusion criteria for a reference population. The 95% central intervals (2.5%-97.5%) for CSF lactate and pyruvate levels were 1.01-2.09mM and 0.03-0.15mM, respectively, and 9.05-26.37 for CSF L/P. There were no significant gender-related differences of CSF lactate or pyruvate concentrations or of CSF L/P. Weak positive correlations between the concentration of CSF lactate or pyruvate and age were noted. Using stringent inclusion/exclusion criteria, we determined normative data for CSF lactate and pyruvate concentrations and CSF L/P ratios in a large, well-characterized reference population. Normalcy of routine CSF and blood analytes are the most important parameters in determining reference intervals for CSF lactate and pyruvate. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Changes in Plasma Progesterone Levels in the Caudal Vena Cava and the Jugular Vein and Luteinizing Hormone Secretion Pattern After Feeding in Lactating and Non-lactating Dairy Cows

PubMed Central

ENDO, Natsumi; NAGAI, Kiyosuke; TANAKA, Tomomi; KAMOMAE, Hideo

2012-01-01

Abstract The present study was designed to assess progesterone profiles at the secreted (caudal vena cava) and circulating levels (jugular vein) and luteinizing hormone (LH) secretion pattern in lactating and non-lactating cows with reference to feeding. Four lactating and four non-lactating cycling Holstein cows were examined. Blood samples were collected simultaneously from the caudal vena cava (via a catheter inserted from the coccygeal vein) and the jugular vein every 15 min for 12 h (0500–1700 h) during the functional luteal phase. Cows were fed 50% of the daily diet 6 h after the start of blood sampling. During the 12-h sampling period, mean progesterone concentrations in the caudal vena cava did not differ between lactating and non-lactating cows (49.0 ± 2.9 and 53.3 ± 3.7 ng/ml; mean ± SE), whereas mean progesterone concentrations in the jugular vein in lactating cows were higher than those in non-lactating cows (6.4 ± 0.1 and 5.6 ± 0.1 ng/ml, P < 0.001). Lactating cows had a higher frequency of LH pulses than non-lactating cows (7.0 ± 0.7 and 4.3 ± 0.9 pulses/12 h, P<0.05). The influence of feeding was not observed on LH profiles but was observed on progesterone profiles in both veins. Progesterone concentrations in the caudal vena cava increased after feeding in both groups. Progesterone concentrations in the jugular vein decreased after feeding in lactating cows but not in non-lactating cows. These results indicate the difference in feeding-related changes in progesterone dynamics between lactating and non-lactating cows. PMID:23171608

Energy balance in lactating undernourished Indian women.

PubMed

Madhavapeddi, R; Rao, B S

1992-05-01

An energy balance study was conducted in eight lactating poor-income Indian women from delivery to 6 months. Energy intake and expenditure were assessed for 7 days every month (30-37 days). Every month, basal metabolic rate (BMR) and milk ingested by infants was measured. An energy balance was computed. As a group these women were in energy balance, indicated by small body weight changes with respect to time. However, only two of these women were in a positive energy balance. Women with higher body weight lost more weight. Estimated mean energy intake was higher than energy expenditure. BMR showed a slight but not significant fall during the second month of lactation and was not different from the BMR seen in 13 non-pregnant, non-lactating women matched for body weight from the staff of the Institute. The energy cost of lactation was 2.3 MJ (549 kcal), a figure that justifies the Recommended Dietary Allowance for energy recommended by FAO/WHO/UNU (1985) and ICMR (1989).

Regional analyses of CNS microdialysate glucose and lactate in seizure patients.

PubMed

Cornford, Eain M; Shamsa, Kamran; Zeitzer, Jamie M; Enriquez, Cathleen M; Wilson, Charles L; Behnke, Eric J; Fried, Itzhak; Engel, Jerome

2002-11-01

To correlate glucose (and lactate) results obtained from microdialysate to recent studies suggesting that glucose transporter activity may be significantly altered in seizures. We used a fluorometric technique to quantify glucose and lactate levels in microdialysates collected from two to four depth electrodes implanted per patient in the temporal and frontal lobes of a series of four patients. Hour-by-hour and day-to-day changes in brain glucose and lactate levels at the same site were recorded. Additionally we compared regional variations in lactate/glucose ratios around the predicted epileptogenic region. Lactate/glucose ratios in the range of 1-2:1 were the most commonly seen. When the lactate/glucose ratio was <1:1, we typically observed a relative increase in local glucose concentration (rather than decreased lactate), suggesting increased transport, perhaps without increased glycolysis. In some sites, lactate/glucose ratios of 3:1-15:1 were seen, suggesting that a circumscribed zone of inhibition of tricarboxylic acid cycle activity may have been locally induced. In these dialysates, collected from probes closer to the epileptogenic region, the large increase in lactate/glucose ratios was a result of both increased lactate and reduced glucose levels. We conclude that regional variations in brain extracellular glucose concentrations may be of greater magnitude than previously believed and become even more accentuated in partial seizure patients. Data from concomitant assays of microdialysate lactate and glucose may aid in understanding cerebral metabolism.

Amino acid and glucose uptake by rat brown adipose tissue. Effect of cold-exposure and acclimation.

PubMed Central

López-Soriano, F J; Fernández-López, J A; Mampel, T; Villarroya, F; Iglesias, R; Alemany, M

1988-01-01

The net uptake/release of glucose, lactate and amino acids from the bloodstream by the interscapular brown adipose tissue of control, cold-exposed and cold-acclimated rats was estimated by measurement of arteriovenous differences in their concentrations. In the control animals amino acids contributed little to the overall energetic needs of the tissue; glucose uptake was more than compensated by lactate efflux. Cold-exposure resulted in an enhancement of amino acid utilization and of glucose uptake, with high lactate efflux. There was a net glycine and proline efflux that partly compensated the positive nitrogen balance of the tissue; amino acids accounted for about one-third of the energy supplied by glucose to the tissue. Cold-acclimation resulted in a very high increase in glucose uptake, with a parallel decrease in lactate efflux and amino acid consumption. Branched-chain amino acids, however, were more actively utilized. This was related with a much higher alanine efflux, in addition to that of glycine and proline. It is suggested that most of the glucose used during cold-exposure is returned to the bloodstream as lactate under conditions of active lipid utilization, amino acids contributing their skeletons largely in anaplerotic pathways. On the other hand, cold-acclimation resulted in an important enhancement of glucose utilization, with lowered amino acid oxidation. Amino acids are thus used as metabolic substrates by the brown adipose tissue of rats under conditions of relatively scarce substrate availability, but mainly as anaplerotic substrates, in parallel to glucose. Cold-acclimation results in a shift of the main substrates used in thermogenesis from lipid to glucose, with a much lower need for amino acids. PMID:3421924

Exposure to mother's pregnancy and lactation in infancy is associated with sexual attraction to pregnancy and lactation in adulthood.

PubMed

Enquist, Magnus; Aronsson, Hanna; Ghirlanda, Stefano; Jansson, Liselotte; Jannini, Emmanuele A

2011-01-01

Several theories, including psychodynamic theories, sexual imprinting and early conditioning have been formulated to explain sexual development. Empirical data, however, remain insufficient for a thorough evaluation of these theories. In this study, we test the hypothesis that a critical period exists for the acquisition of sexual preferences, as suggested by empirical findings in birds and mammals (sexual imprinting). An Internet questionnaire was used. We gather data from individuals with a sexual preference for pregnant and/or lactating women, under the hypothesis that pregnancy or lactation may become sexually attractive in adulthood following an exposure to pregnant or lactating women in infancy. We find that these preferences are more common in older siblings, i.e., in individuals who have been exposed to more maternal pregnancy and lactation. This result is independent of respondent and sibling sex. In addition, only maternal pregnancies and lactations experienced between 1.5 and 5 years of age are associated with the preferences. We discuss our findings in relation to theories of sexual development and to earlier reports of birth order effects on sexual behavior. We suggest that this age range may constitute a sensitive period for the acquisition of sexual preferences. © 2010 International Society for Sexual Medicine.

Evolution of D-lactate dehydrogenase activity from glycerol dehydrogenase and its utility for D-lactate production from lignocellulose.

PubMed

Wang, Qingzhao; Ingram, Lonnie O; Shanmugam, K T

2011-11-22

Lactic acid, an attractive, renewable chemical for production of biobased plastics (polylactic acid, PLA), is currently commercially produced from food-based sources of sugar. Pure optical isomers of lactate needed for PLA are typically produced by microbial fermentation of sugars at temperatures below 40 °C. Bacillus coagulans produces L(+)-lactate as a primary fermentation product and grows optimally at 50 °C and pH 5, conditions that are optimal for activity of commercial fungal cellulases. This strain was engineered to produce D(-)-lactate by deleting the native ldh (L-lactate dehydrogenase) and alsS (acetolactate synthase) genes to impede anaerobic growth, followed by growth-based selection to isolate suppressor mutants that restored growth. One of these, strain QZ19, produced about 90 g L(-1) of optically pure D(-)-lactic acid from glucose in < 48 h. The new source of D-lactate dehydrogenase (D-LDH) activity was identified as a mutated form of glycerol dehydrogenase (GlyDH; D121N and F245S) that was produced at high levels as a result of a third mutation (insertion sequence). Although the native GlyDH had no detectable activity with pyruvate, the mutated GlyDH had a D-LDH specific activity of 0.8 μmoles min(-1) (mg protein)(-1). By using QZ19 for simultaneous saccharification and fermentation of cellulose to D-lactate (50 °C and pH 5.0), the cellulase usage could be reduced to 1/3 that required for equivalent fermentations by mesophilic lactic acid bacteria. Together, the native B. coagulans and the QZ19 derivative can be used to produce either L(+) or D(-) optical isomers of lactic acid (respectively) at high titers and yields from nonfood carbohydrates.

Evolution of D-lactate dehydrogenase activity from glycerol dehydrogenase and its utility for D-lactate production from lignocellulose