Distribution of mercury 203 in pregnant rats and their fetuses following systemic infusions with thiol-containing amino acids and glutathione during late gestation

To investigate the effect of amino acids and the tripeptide glutathione (GSH) on tissue uptake of methylmercury (MeHg) in the developing rat fetus in utero, pregnant rats were continuously infused into the external jugular vein with 0.1 mM L-cysteine, 0.1 mM L-leucine, 0.1 mM GSH or saline commencing on day 17 of gestation. This was followed at 24, 48, and 72 hours by external jugular infusion of 50 microM [203Hg]-MeHgCl administered in 1 ml over 1 hour. Pups were surgically removed from the uterus on gestational day 21. Whole body, brain, kidney, liver, and placental 203Hg radioactivity was measured by means of gamma-spectrometry. Brain 203Hg concentration in pups exposed in utero to L-cysteine was significantly higher compared with pups exposed to saline (P less than 0.05). Brain 203Hg concentration in pups exposed in utero to L-leucine and GSH was significantly depressed compared with pups exposed to saline (P less than 0.05). Kidney 203Hg concentration was not significantly changed in all treatment groups compared with controls. Liver 203Hg concentration was significantly depressed in L-leucine- and GSH-treated pups compared with controls (P less than 0.05). Placental 203Hg concentration was not affected by any treatment compared with controls. These effects occurred despite no difference in total 203Hg body burden among pups, irrespective of the treatment. In addition, infusion with L-cysteine resulted in a significant increase in 203Hg brain concentration in dams compared with controls, and 203Hg brain concentration in L-leucine- and GSH-treated dams was significantly depressed compared with controls. Thus 203Hg distribution in both adult and developing animals is altered by chronic amino acid or GSH infusions and suggests that MeHg uptake may be mediated through the formation of a cysteine-MeHg complex which is transported across the blood-brain barrier by the neutral amino acid carrier transport system.     

The interaction of adrenochrome with some thiol-containing amino acids isolation of some products

The interactions of adrenochrome with some thiol-containing amino acid derivatives, namely, N-acetylcysteine and N-acetylpenicillamine, have been studied. The 5,6-dihydroxy-1-methylindole thioethers which were formed in these reactions were isolated and characterized. The structures of these products were analogous to those of similar compounds which had been obtained from the reactions of aminochromes with some simple thiols. Reactions of this type may be important in the formation of melanoproteins.     

Differential expression of uterine NO in pregnant and nonpregnant rats with intrauterine bacterial infection

Previous studies have demonstrated that nitric oxide (NO) is involved in the uterine host defense against bacterial infection. In nonpregnant rats, NO production in the uterus was shown to be lower, and inducible NO synthase (NOS) expression was undetectable. However, studies in pregnant rats show abundant expression of inducible NOS with significant elevation in NO production in the uterus. We have recently reported that intrauterine Escherichia coli infection caused a localized increase in uterine NO production and inducible NOS expression in the nonpregnant rat. In our present study, we examined whether the uterine NO production, NOS expression, and uterine tumor necrosis factor-alpha protein are increased in pregnant rats with intrauterine pathogenic Escherichia coli infection. Unlike the nonpregnant state, the NO production in the infected uterine horn of pregnant rats was not significantly elevated after bacterial inoculation compared with the contralateral uterine horn. The expression of uterine NOS (types II and III) also did not show significant upregulation in the infected horn. This is in contrast to that in nonpregnant animals, in which type II NOS was induced in the uterus on infection. Moreover, intrauterine infection induced an elevated expression of tumor necrosis factor-alpha protein in the infected horn both of nonpregnant and of pregnant rats. These data suggest that the sequential stimulation of NOS expression, especially the inducible isoform, and generation of uterine NO are lacking during pregnancy despite an elevated tumor necrosis factor-alpha after infection. In summary, NO synthesis response may be maximal at pregnancy, and infection may not further induce the NO system. Present studies, together with our previous report that intrauterine infection-induced lethality in pregnancy rats was amplified with the inhibition of NO, suggest that pregnancy is a state predisposed for increased complications associated with intrauterine infection and that the constitutively elevated uterine NO during pregnancy may help contain or even reduce the risk of infection-related complications.     

Physiological studies on nonpregnant and pregnant uterus in experimentally diabetic rats]

Spontaneous intraluminal pressure waves of diabetic nonpregnant uterus and contractile responses to oxytocin and prostaglandin F2 alpha (PGF 2 alpha) of both diabetic nonpregnant and diabetic pregnant uterus were investigated in vitro. Diabetes was induced by streptozotocin (STZ), 60 mg/kg for nonpregnant and 50 mg/kg for pregnant rats. Frequency of spontaneous intraluminal pressure waves of nonpregnant uterus was reduced in diabetic rats when compared with normal, but amplitude was slightly larger in diabetic than in normal uterus. Pressure-volume curves revealed that the compliance of nonpregnant diabetic uterus was remarkably reduced. Normal tubal side-circular muscle was significantly more sensitive to oxytocin and PGF 2 alpha than cervical one in contractile responses. This tendency was lost in diabetic nonpregnant uterus. Contractile responses of both tubal and cervical circular muscles to oxytocin were lower in nonpregnant diabetic than in normal rats, but those of longitudinal muscles were higher in diabetic nonpregnant than in normal rats. Cervical circular muscle of pregnant diabetic rats was more sensitive to both agents than those of normal. However, contractile responses of diabetic longitudinal muscle to both agents were higher than those of normal as in the case of nonpregnant uterus. The mechanism of diabetic changes of the nonpregnant and pregnant uterus was discussed.     

Effect of L-propargylglycine on metabolism of sulfur-containing amino acids in pregnant rats and their fetuses

Cystathionine accumulated in several tissues of dams and fetuses by a single intraperitoneal administration of L-proparglyglycine to pregnant rats. Cystathionine in the liver of dams reached its maximal level at about 15 hrs after L-proparglyglycine injection (10 mg/300g), while that in the kidney and brain of dams, and in the liver, kidney, and brain of fetuses reached a maximum at about 21 hrs. The content of cystine in the liver of fetuses decreased gradually in proportion to the amount of L-proparglyglycine administered. Cystathionine gamma-lyase activity in the liver of dams and fetuses decreased to about 2-4% of that of control rats at 15 hrs after L-proparglyglycine injection, and that in the kidney and pancreas of dams to about 10-20% of that of control rats. On the other hand, cystathionine beta-synthase activity did not show significant changes from that of control rats.     

Element variations in pregnant and nonpregnant female rats orally intoxicated by aluminum lactate

Pregnant or nonpregnant female rats were orally intoxicated by aluminum lactate (400 mg Al/kg/d) from d 0–19 of gestation to determine the treatment's influence on element variations in the females and their fetuses. The aluminum levels of plasma, liver, spleen, and kidneys were significantly higher in treated pregnant rats than non-pregnant female rats. Differences of P, Ca, Cu, Zn, or Mg levels were observed among the four groups of female rats in the tissues and plasma. The aluminum content of the 20-d-old fetuses did not significantly differ between the treated and control groups. On the contrary, calcium and magnesium levels in the whole fetuses from treated or nontreated dams are significantly different.     

Vascular function in alcohol-treated pregnant and nonpregnant mice

The effect of alcohol on maternal vascular adaptations to pregnancy is unknown. This study was designed to determine the effect of alcohol consumption on nitric oxide-mediated vascular function in mice during pregnancy. Female pregnant or nonpregnant C57BL/6J mice were fed a control diet or a liquid diet of 25% ethanol-derived calories for 13 days (from gestational days 6-18). Phenylephrine vasoconstriction was blunted in pregnancy compared with the nonpregnant state due to enhanced nitric oxide modulation, which was impaired by ethanol exposure. Although the EC50 and maximal responses to methacholine were not different in nonpregnant vs. pregnant mice, the nitric oxide component to methacholine-induced vasorelaxation was greater in the pregnant mice. Interestingly, alcohol affected only the pregnant animals in their response to methacholine. These data indicate that alcohol reduced the nitric oxide modulation of vascular response, which was more pronounced during pregnancy. These studies provide novel information regarding the effects of alcohol on the maternal vascular system during pregnancy and thereby contribute to further understanding of the adverse effects associated with prenatal alcohol exposure.     

Metabolism of amino acids in protein-calorie-deficient rats

The overall oxidative degradation of leucine and phenylalanine, measured in vivo in rats fed on a 2%-casein diet for 8 weeks, is markedly decreased as compared with controls, whereas that of glutamate and alanine is apparently unaffected. The decrease in leucine degradation is due, at least in part, to a block before the formation of 3-methylbutyryl-CoA (isovaleryl-CoA) in the catabolic pathway. This phenomenon is accompanied by increased incorporation of [¹⁴C]leucine into liver proteins, decreased urinary excretion of leucine and increased urinary excretion of 4-methyl-2-oxopentanoate (α-oxoisocaproate) by protein-depleted animals. The results suggest the existence of adaptive mechanisms that function to conserve an indispensable carbon skeleton.     

No significant net uptake of branched chain amino acids by the liver of fed-mid pregnant rats

The hepatic balance for valine, leucine and isoleucine has been measured in anaesthetized virgin controls and 9 and 12-day pregnant rats. The liver of non gravid animals show fractional extraction rates of over 11.6% for valine, 17.6% for leucine and 16.8% for isoleucine. Fed mid-pregnant rats do not show either a significant net uptake nor a release of these amino acids. It is proposed that higher intestinal amino acid requirements for protein synthesis during mid pregnancy than before impregnation may be, in part, the cause of a decreased hepatic uptake and, thus, a different role for the liver in the amino acid inter-organ relationships during this period is suggested.     

Branched-chain amino acids improve glucose metabolism in rats with liver cirrhosis

It is well established that impaired glucose metabolism is a frequent complication in patients with hepatic cirrhosis. We previously showed that leucine, one of the branched-chain amino acids (BCAA), promotes glucose uptake under insulin-free conditions in isolated skeletal muscle from normal rats. The aim of the present study was to evaluate the effects of BCAA on glucose metabolism in a rat model of CCl(4)-induced cirrhosis (CCl(4) rats). Oral glucose tolerance tests were performed on BCAA-treated CCl(4) rats. In the CCl(4) rats, treatment with leucine or isoleucine, but not valine, improved glucose tolerance significantly, with the effect of isoleucine being greater than the effect of leucine. Glucose uptake experiments using isolated soleus muscle from the CCl(4) rats revealed that leucine and isoleucine, but not valine, promoted glucose uptake under insulin-free conditions. To clarify the mechanism of the blood glucose-lowering effects of BCAA, we collected soleus muscles from BCAA-treated CCl(4) rats with or without a glucose load. These samples were used to determine the subcellular location of glucose transporter proteins and glycogen synthase (GS) activity. Oral administration of leucine or isoleucine without a glucose load induced GLUT4 and GLUT1 translocation to the plasma membrane. GS activity was augmented only in leucine-treated rats and was completely inhibited by rapamycin, an inhibitor of mammalian target of rapamycin. In summary, we found that leucine and isoleucine improved glucose metabolism in CCl(4) rats by promoting glucose uptake in skeletal muscle. This effect occurred as a result of upregulation of GLUT4 and GLUT1 and also by mammalian target of rapamycin-dependent activation of GS in skeletal muscle. From these results, we consider that BCAA treatment may have beneficial effects on glucose metabolism in cirrhotic patients.     

Plasma vitamin D metabolite levels in pregnant and nonpregnant ewes

1. Maternal calcium homeostasis during pregnancy is strained due to fetal mineral requirements for bone formation. 2. In most species, the mother adjusts to the mineral requirements of the fetus with alterations in her metabolism of vitamin D that include a decrease in plasma 25-(OH)D levels and an increase in circulating levels of the hormone, 1,25-(OH)2D. 3. Plasma 25-(OH)D and 1,25-(OH)2D levels in adult male, adult female and pregnant sheep were measured by specific radioreceptor binding assays. 4. Pregnancy did not alter circulating levels of 25-(OH)D or 1,25-(OH)2D in the sheep. 5. The pregnant ewe differs from all species studied to date in that maternal plasma 1,25-(OH)2D levels do not rise as a result of pregnancy.