Antioxidant enzymes, hydrogen peroxide metabolism, and respiration in rat heart during experimental hyperammonemia

The effects of toxic ammonia doses on H₂O₂ metabolism, energy metabolism, and antioxidant enzyme activities in rat heart were studied. Ammonium acetate administration to animals proved to increase total superoxide dismutase (SOD), catalase, and glutathione peroxidase activities in the heart cytoplasmic fraction as well as Mn-SOD, catalase, and glutathione reductase in heart mitochondria. Conversely, ammonia inhibited the same activities in the brain, liver, and erythrocytes. Hyperammonemia had no effect on the levels of ATP, ADP and total adenine nucleotides in the heart but decreased them in the brain. Ammonia impaired oxidative phosphorylation and increased the rate of H₂O₂ production in heart and brain mitochondria. The ammonia concentration inhibiting antioxidant enzymes in the liver and brain can be insufficient for such effect in the heart.     

Blocking NMDA receptors prevents the oxidative stress induced by acute ammonia intoxication

Acute ammonia intoxication diminishes the activities of antioxidant enzymes and increases superoxide formation in brain. These effects could play a role in the mechanism of ammonia toxicity. It has been shown that ammonia toxicity is mediated by activation of NMDA receptors. The aim of this work was to assess whether ammonia-induced changes in antioxidant enzymes and in superoxide formation are mediated by activation of NMDA receptors. It is shown that MK-801, an antagonist of NMDA receptors prevents ammonia-induced changes in superoxide dismutase, glutathione peroxidase and catalase. Ammonia intoxication also induces a depletion of glutathione and an increase in lipid peroxidation. Both effects, as well as ammonia-induced increase in superoxide formation are prevented by MK-801. These results indicate that ammonia-induced oxidative stress in brain is mediated by excessive activation of NMDA receptors and support the idea that oxidative stress can play a role in the mechanism of ammonia toxicity.     

Influence of subacute treatment of some plant growth regulators on serum marker enzymes and erythrocyte and tissue antioxidant defense and lipid peroxidation in rats

This study aims to investigate the effects of the plant growth regulators (PGRs) (2,3,5-triiodobenzoic acid (TIBA), Naphthaleneacetic acid (NAA), and 2,4-dichlorofenoxyacetic acid (2,4-D)) on serum marker enzymes (aspartate aminotransferase (AST), alanin aminotransferase (ALT), creatine phosphokinase (CPK), and lactate dehydrogenase (LDH)), antioxidant defense systems (reduced glutathione (GSH), glutathione reductase (GR), superoxide dismutase (SOD), glutathione-S-transferase (GST), and catalase (CAT)), and lipid peroxidation content (malondialdehyde = MDA) in various tissues of rats. 50 and 100 ppm of PGRs as drinking water were administered orally to rats (Sprague-Dawley albino) ad libitum for 25 days continuously. The PGRs treatment caused different effects on the serum marker enzymes, antioxidant defense systems, and the MDA content in experimented rats compared to controls. Results showed that TIBA caused a significant decrease in serum AST activity with both the dosage whereas serum CPK was significantly increased with 100 ppm dosage of TIBA. Meanwhile, serum AST, CPK, and LDH activities were significantly increased with both dosage of NAA and 2,4-D. The lipid peroxidation end-product MDA significantly increased in the all tissues treated with both dosages of PGRs without any change in the brain and erythrocyte of rats treated with both the dosages of 2,4-D. The GSH depletion in the kidney and brain tissues of rats treated with both dosages of PGRs was found to be significant. Furthermore, the GSH depletion in the erythrocyte of rats treated with both dosages of PGRs except 50 ppm dosage of 2,4-D was significant too. Also, the GSH level in the liver was significantly depleted with 50 ppm of 2,4-D and NAA, whereas the GSH depletion in the same tissue did not significantly change with the treatment. The activity of antioxidant enzymes was also seriously affected by PGRs; SOD significantly decreased in the liver, heart, kidney, and brain of rats treated with both dosages of NAA, whereas the SOD activity in the erythrocytes, liver, and heart was either significantly decreased or not changed with two doses of 2,4-D and TIBA. Although the CAT activity significantly increased in the erythrocyte and brain of rats treated with both doses of PGRs, it was not changed in the liver, heart, and kidney. Meanwhile, the ancillary enzyme GR activity significantly increased in the brain, heart, and liver but decreased in the erythrocyte and kidney of rats treated with both doses of PGRs. The drug-metabolizing enzyme GST activity significantly increased in the heart and kidney but decreased in the brain and erythrocytes of rats treated with both dosages of PGRs. As a conclusion, the results indicate that PGRs might affect antioxidant potential enzymes, the activity of hepatic damage enzymes, and lipid peroxidation dose independently. Also, the rats resisted to oxidative stress via antioxidant mechanism but the antioxidant mechanism could not prevent the increases in lipid peroxidation in rat's tissues. These data, along with the determined changes, suggest that PGRs produced substantial systemic organ toxicity in the erythrocyte, liver, brain, heart, and kidney during the period of a 25-day subacute exposure.     

Morin a flavonoid exerts antioxidant potential in chronic hyperammonemic rats: a biochemical and histopathological study

Plant flavonoids are emerging as potent therapeutic drugs effective against a wide range of free radical-mediated diseases. Morin (3,5,7,2′,4′-pentahydroxyflavone), a member of flavonols, is an important bioactive compound by interacting with nucleic acids, enzymes and protein. In this study, we found that morin (30 mg/kg body weight) by oral administration offers protection against hyperammonemia by means of reducing blood ammonia, oxidative stress and enhancing antioxidant status in ammonium chloride-induced (100 mg/kg body weight; i.p) hyperammonemic rats. Enhanced blood ammonia, plasma urea, lipid peroxidation in circulation and tissues (liver and brain) of ammonium chloride-treated rats was accompanied by a significant decrease in the tissues levels of superoxide dismutase (SOD), catalase, reduced glutathione (GSH) and glutathione peroxidase (GPx). Morin administered rats showed a significant reduction in ammonia, urea, lipid peroxidation with a simultaneous elevation in antioxidant levels. Cotreatment with morin prevented the elevation of liver marker enzymes induced by ammonium chloride. The body weight of the animals decreased significantly on ammonium chloride administration when compared with control group. However, cotreatment with morin significantly prevented the decrease of the body weight caused by ammonium chloride. Hyperammonemic rats show liver fibrosis, steatosis, sinusoidal dilatation, etc., along with necrosis, microcystic degeneration in brain. All these changes were reduced in hyperammonemic rats treated with Morin, which too correlated with the biochemical observations. In conclusion, these findings indicate that morin exert antioxidant potential and offer protection against ammonium chloride-induced hyperammonemia. But the exact underlying mechanism needs to be elucidated.     

Reactive oxygen species generation is modulated by mitochondrial kinases: correlation with mitochondrial antioxidant peroxidases in rat tissues

Mitochondrial hexokinase (mt-HK) and creatine kinase (mt-CK) activities have been recently proposed to reduce the rate of mitochondrial ROS generation through an ADP re-cycling mechanism. Here, we determined the role of mt-HK and mt-CK activities in regulate mitochondrial ROS generation in rat brain, kidney, heart and liver, relating them to the levels of classical antioxidant enzymes. The activities of both kinases were significantly higher in the brain than in other tissues, whereas the activities of catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) were higher in both liver and kidney mitochondria. In contrast, manganese superoxide dismutase (Mn-SOD) activity was not significantly different among these tissues. Activation of mitochondrial kinases by addition of their substrates increased the ADP re-cycling and thus the respiration by enhancing the oxidative phosphorylation. Succinate induced hydrogen peroxide (H(2)O(2)) generation was higher in brain than in kidney and heart mitochondria, and the lowest in liver mitochondria. Mitochondrial membrane potential (DeltaPsi(m)) and H(2)O(2) production, decreased with additions of 2-DOG or Cr to respiring brain and kidney mitochondria but not to liver. The inhibition of H(2)O(2) production by 2-DOG and Cr correspond to almost 100% in rat brain and about 70% in kidney mitochondria. Together our data suggest that mitochondrial kinases activities are potent preventive antioxidant mechanism in mitochondria with low peroxidase activities, complementing the classical antioxidant enzymes against oxidative stress.     

Effects of angiotensin II type 1 receptor blockade on the oxidative stress in spontaneously hypertensive rat tissues

The aim of this work was to investigate the production of oxidative damage in homogenized kidney, liver and brain of spontaneously hypertensive rats (SHR), as well as the involvement of angiotensin (Ang) II in this process. Groups of 12-week-old SHR and Wistar Kyoto rats (WKY) were given 10 mg/kg/day losartan in the drinking water during 14 days. Other groups of WKY and SHR without treatment were used as controls. The production of thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and the activity of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (Gpx) were determined. No significant difference in TBARS was observed between untreated SHR or WKY rats; GSH content was lower in the liver but higher in the brain of SHR compared to WKY rats. In tissues from the SHR group, SOD and Gpx activities were reduced, whereas CAT activity was slightly increased in kidney. TBARS levels did not change in WKY rats after losartan administration, but were reduced in SHR liver and brain. Losartan treatment decreased GSH content in WKY kidney, but increased GSH in SHR liver. The activity of the antioxidant enzymes was not modified by losartan in WKY rats; however, their activities increased in tissues from treated SHR. The lower activity of antioxidant enzymes in tissues from hypertensive rats compared to those detected in normotensive controls, indicates oxidative stress production. Ang II seems to play no role in this process in normotensive animals, although AT1 receptor blockade in SHR enhances the enzymatic activity indicating that Ang II is implicated in oxidative stress generation in the hypertensive animals.     

Expression of antioxidant enzymes in rat kidney during ischemia-reperfusion injury

The effect of ischemia-reperfusion on activity, protein and m-RNA levels of catalase, copper-zinc and manganese containing superoxide dismutases and glutathione peroxidase, the enzymes that are involved in free radical detoxification was studied in rat kidney. Ischemia alone did not alter either the activities or protein levels of superoxide dismutase and glutathione peroxidase. However, catalase activity was found to be inhibited to 82% of control. The inhibition of catalase was due to the inactivation of the enzyme as there was no significant change in enzyme protein level. Reperfusion following ischemia, however, led to a significant decrease in both the activities as well as the protein levels of all the antioxidant enzymes. The observed overall decrease in total superoxide dismutase activity was the net effect of a decrease in copper-zinc superoxide dismutase while manganese superoxide dismutase activity was found to be increased following reperfusion. This observed increased manganese superoxide dismutase activity was the result of its increased protein level. The mRNA levels for catalase, superoxide dismutases, and glutathione peroxidase were observed to be increased (100–145% of controls) following ischemia; reperfusion of ischemic kidneys, however, resulted in a significant decrease in the levels of mRNAs coding for all the enzymes except manganese superoxide dismutase which remained high. These results suggest that in tissue, the down regulation of the antioxidant enzyme system could be responsible for the pathophysiology of ischemia-reperfusion injury.     

Endogenous antioxidant defence system in rat liver following mercury chloride oral intoxication

Mercury is a highly toxic metal which induces oxidative stress. Superoxide dismutases, catalase, and glutathion peroxidase are proteins involved in the endogenous antioxidant defence system. In the present study rats were administered orally, by gavage, a single daily dose of HgCl2 for three consecutive days. In order to find a relation between the proteins involved in the antioxidant defence and mercury intoxication, parameters of liver injury, redox state of the cells, as well as intracellular protein levels and enzyme activities of Mn-dependent superoxide dismutase (MnSOD), Cu-Zn-dependent superoxide dismutase (CuZnSOD), catalase, and glutathione peroxidase (GPx) were assayed both in blood and in liver homogenates. HgCl2 at the doses of 0.1 mg/kg produced liver damage which that was detected by a slight increase in serum alanine aminotransferase and gamma glutamyl transferase. Hepatic GSH/GSSG ratio was assayed as a parameter of oxidative stress and a significant decrease was detected, as well as significant increases in enzyme activities and protein levels of hepatic antioxidant defence systems. Changes in both MnSOD and CuZnSOD were parallel to those of liver injury and oxidative stress, while the changes detected in catalase and GPx activities were progressively increased along with the mercury intoxication. Other enzyme activities related to the glutathione redox cycle, such as glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PDH), also increased progressively. We conclude that against low doses of mercury that produce a slight oxidative stress and liver injury, the response of the liver was to induce the synthesis and activity of the enzymes involved in the endogenous antioxidant system. The activities of all the enzymes assayed showed a rapidly induced coordinated response.     

Antioxidant levels in tissues of young and adult camels (Camelus dromedarius)

In this study, we measured the concentration of some antioxidant substances in erythrocytes hemolysate, liver, kidney and brain in young and adult camels. It has been found that the activity of the antioxidant enzymes glutathione peroxidase (GSH-Px), catalase (CAT), superoxide dismutase (SOD) and the concentration of glutathione, ascorbic acid and alpha-tocopherol are high in both young and adult camels. GSH-Px and CAT activities were higher in adult camels than in the young whereas no significant difference in the activity of SOD between young and adult camels was noticed. Glutathione was present in all tissues studied. Ascorbic acid was found to have significantly higher values in young camels. From this study it could be concluded that, as in other mammals, camel tissues contain a powerful antioxidant system. The liver has the highest contents of antioxidants and antioxidant enzymes indicating that it plays an important role in pro-oxidants detoxification. Age has a variable effect on the antioxidant system in camels.     

Nitric oxide is involved in abscisic acid-induced antioxidant activities in Stylosanthes guianensis

Previous studies suggest that abscisic acid (ABA) stimulates the activities of antioxidant enzymes under normal and chilling temperature and enhanced chilling resistance in Stylosanthes guianensis. The objective of this study was to test whether nitric oxide (NO) is involved in the ABA-induced activities of the antioxidant enzymes in Stylosanthes guianensis due to its nature as a second messenger in stress responses. Plants were treated with NO donors, ABA, ABA in combination with NO scavengers or the nitric oxide synthase (NOS) inhibitor and their effects on the activity of antioxidant enzymes and NO production were compared. The results showed that ABA increased the activities of superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX). The effect of ABA on antioxidant enzyme activities was suppressed by the NOS inhibitor, N(omega)-nitro-L-arginine (L-NNA), and the NO scavenger, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl3-oxide (PTIO). NO content increased after 5 h of ABA treatment. The NO-scavenger, PTIO, and the NOS-inhibitor, L-NNA, inhibited the accumulation of NO in ABA-treated Stylosanthes guianensis. NO donor treatment enhanced the activities of SOD, CAT, and APX. The results suggested that NO was involved in the ABA-induced activities of SOD, CAT, and APX in Stylosanthes guianensis. ABA triggered NO production that may lead to the stimulation of antioxidant enzyme activities.     

Moderate grade hyperammonemia induced concordant activation of antioxidant enzymes is associated with prevention of oxidative stress in the brain slices

Acute hyperammonemia (HA) induced oxidative stress in the brain is considered to play critical roles in the neuropathology of end stage hepatic encephalopathy (HE). Moderate grade HA led minimal/moderate type HE is more common in the patients with chronic liver failure. However, implication of oxygen free radical ( \textO ₂ ^- {\text{O}}_{ 2}^{ - } ) based oxidative mechanisms remain to be defined during moderate grade HA. This article describes profiles of all the antioxidant enzymes Vis a Vis status of oxidative stress/damage in the brain slices exposed to 0.1–1 mM ammonia, reported to exist in the brain of animals with chronic liver failure and in liver cirrhotic patients. Superoxide dismutase catalyzes the first step of antioxidant mechanism and, with concerted activity of catalase, neutralizes \textO ₂ ^- {\text{O}}_{ 2}^{ - } produced in the cells. Both these enzymes remained unchanged up to 0.2–0.3 mM ammonia, however, with significant increments (P < 0.01–0.001) in the brain slices exposed to 0.5–1 mM ammonia. This was consistent with the similar pattern of production of reactive oxygen species in the brain slices. However, level of lipid peroxidation remained unchanged throughout the ammonia treatment. Synchronized activities of glutathione peroxidase and glutathione reductase regulate the level of glutathione to maintain reducing equivalents in the cells. The activities of both these enzymes also increased significantly in the brain slices exposed to 0.5–1 mM ammonia with concomitant increments in GSH/GSSG ratio and in the levels of total and protein bound thiol. The findings suggest resistance of brain cells from ammonia induced oxidative damage during moderate grade HA due to concordant activations of antioxidant enzymes.     

Effect of cigarette smoke on lipid peroxidation and antioxidant enzymes in albino rat

Effect of cigarette smoke on lipid peroxidation (LPX) and antioxidant enzymes like catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione-S-transferase (GST) in various organs like brain, heart, lung, liver and kidney of the albino rats exposed to cigarette smoke for 30 min/day for a period of 30 days were assayed. It was observed that the lipid peroxide levels in liver, lung and kidney were enhanced in case of animals exposed to cigarette smoke, whereas brain and heart did not show any change as compared to control animals. The activity of the antioxidant enzymes was also elevated in liver, lung and kidney of the test animals whereas, brain and heart did not show any change in the activities of all of these antioxidant enzymes except glutathione-s-transferase which was increased in brain also. The level of reduced glutathione (GSH) was lowered in liver, lung and kidney of the tested animals when compared with the control animals but there was no significant change in brain and heart. The results of our study suggest that cigarette smoke induces lipid peroxidation in liver, lung and kidney, and the antioxidant enzymes levels were enhanced in order to protect these tissues against the deleterious effect of the oxygen derived free radicals. The depletion of reduced glutathione in these organs could be due to it's utilization by the tissues to mop off the free radicals.     

Aluminium increases xanthine oxidase activity and disturbs antioxidant status in the rat.

The mechanisms responsible for the neurotoxic effects of Al remain poorly understood. In order to determine whether Al promotes oxidative stress in vivo, we measured the enzymatic activity of xanthine oxidase (XO), superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione-S-transferase (GST) and glutathione reductase (GR) in four groups of rats after eight days of intraperitoneal administration of variable concentrations of Al (0, 5, 10, and 15 mg/kg body weight, respectively). XO activity was measured in both plasma and liver samples, and the activities of the remaining enzymes were further determined in the brain and red blood cells (RBC). The most significant changes were observed in XO and GPX activities, that were enhanced and depressed, respectively. In both instances, the enzyme activities were correlated with Al concentrations, either positively (XO) or negatively (GPX). Enhancement of XO and inhibition of GPX activity may lead to the accumulation of intermediate toxic compounds such as hydrogen peroxide and hydroxyl radicals, since SOD activity is increased as well. The latter finding must be taken with some caution because previous studies have shown contradictory results in this field. Our data suggest that Al toxicity could be mediated by its action on both pro- and anti-oxidant enzymes. The biological significance of these findings remains to be established.     

Ethanol and the antioxidant defense in the gastrointestinal tract.

Ethanol is known to have profound actions on the gastrointestinal tract. The present study was undertaken to examine the effects of ethanol on some of the natural antioxidant defensive enzymes in the gastrointestinal tract; the activities of these enzymes in the liver and the brain were also measured for comparison with those in the gastrointestinal tract. Oral administration of absolute ethanol induced severe gastric mucosal lesions and also damage in the small intestine, however the total superoxide dismutase was unaffected in the tissues measured. The glucose-6-phosphate dehydrogenase activity was reduced only in the stomach while the total glutathione was elevated in the small intestinal mucosa. The catalase activities were activated in the stomach, small and large intestines, and brain, but not in the liver which contained the highest concentration of the enzyme. The present findings indicate that endogenous hydrogen peroxide may be an important damaging agent towards biomolecules in different organs and the removal of this by catalase represents an important defensive mechanism against ethanol toxicity.     

Metabolic adaptations to nitrogen excess in late gestation in rat.

Pregnant rats of 19th and 21st days were given an acute nitrogen overload produced by an infusion of either 0.2 M ammonium acetate or 0.2 M glutamine. Metabolic adaptations to nitrogen excess were studied measuring--in fetomaternal unit--non-protein nitrogen content and the activities of enzymes related with ammonia metabolism. Maternal and fetal plasma urea levels were increased by ammonium acetate treatment. Glutamine overload increased more the amino acid content in the mothers than in conceptus. As response to ammonium acetate treatment, glutamate dehydrogenase activity in liver was more sensitive in pregnant than in nonpregnant rats, suggesting more nitrogen incorporation into amino acids in pregnancy. Regarding glutamine synthetase activity, both treatments had an opposite effect except in kidney. The adenylate deaminase activity of pregnant rats was inhibited similarly to nonpregnant rats by nitrogen overloads, but stronger after glutamine infusion. Placenta and fetal metabolism were adjusted, as the dams, to lack of ammonia production by nitrogen overloads and to glutamine synthesis by ammonium acetate infusion.     

茜素红S对中华倒刺鲃幼鱼不同组织抗氧化酶活性和脂质过氧化的影响

以中华倒刺鲃幼鱼[平均体长（12.3±0.6）cm,平均体重（41.8±3.6）g]为研究对象,通过测定不同浓度茜素红S溶液（ARS）浸泡24h后肝脏、脑和鳃组织中抗氧化酶（SOD、CAT、GSH-Px）的活性和丙二醛（MDA）含量,评估ARS对中华倒刺鲃幼鱼的生理生化影响。结果表明:除脑组织GSH-Px随着ARS浓度的升高而不断升高外,肝脏、鳃和脑组织的抗氧化酶活性均表现为低浓度被诱导而高浓度受抑制的规律,与ARS浓度呈抛物线型剂量效应关系。肝脏、鳃、脑组织抗氧化酶活性达到最大值所对应的浓度分别是300、300和400 mg/L。除鳃部MDA含量随着茜素红S浓度升高不断升高外,脑和肝脏组织的丙二醛含量随着ARS浓度的升高呈现出先降低后上升趋势。根据试验的结果,推荐120-200 mg/L为ARS染色标记中华倒刺鲃幼鱼（体长10 cm）的适宜浓度。     

Acute ammonia intoxication induces an NMDA receptor-mediated increase in poly(ADP-ribose) polymerase level and NAD metabolism in nuclei of rat brain cells

Acute ammonia toxicity is mediated by excessive activation of NMDA receptors. Activation of NMDA receptors leads to activation of poly(ADP-ribose) polymerase (PARP) which mediates NMDA excitotoxicity. PARP is activated following DNA damage and may lead to cell death via NAD+ and ATP depletion. The aim of the present work was to assess whether acute ammonia intoxication in vivo leads to increased PARP in brain cells nuclei and to altered NAD+ and superoxide metabolism and the contribution of NMDA receptors to these alterations. Acute ammonia intoxication increases PARP content twofold in brain cells nuclei.NAD+ content decreased by 55% in rats injected with ammonia. This was not due to decreased NAD+ synthetase nor increased NAD+ hydrolase activities and would be due to increased NAD+ consumption by PARP. Superoxide radical formation increased by 75% in nuclei of brains of rats injected with ammonia, that also induced protein nitrotyrosylation and DNA damage. Blocking NMDA receptors prevented ammonia-induced PARP, superoxide and nitrotyrosylation increase, DNA damage and NAD+ decrease. These results show that acute ammonia intoxication in vivo leads to activation of NMDA receptors, leading to increased superoxide formation and PARP content and depletion of NAD+ in brain cells nuclei that contribute to ammonia toxicity.     

N-acetylcysteine exposure on lead-induced lipid peroxidative damage and oxidative defense system in brain regions of rats

Lead (Pb) is known to disrupt the pro-oxidant/antioxidant balance of tissues, which leads to biochemical and physiological dysfunction. Oxidative stress is considered a possible molecular mechanism involved in Pb neurotoxicity. Considering the vulnerability of the brain to oxidative stress under Pb neurotoxicity, this study investigated the effects of exposure of the thiol antioxidant N-acetylcysteine (NAC) on lead-induced oxidative damage and lipid peroxidation in brain regions of the rat. Wister strain rats were exposed to lead in the form of lead acetate (20 mg/kg body wt/d) for a period of 2 wk and the effects of NAC on lead-induced neurotoxicity in rat brain regions were assessed by postadministration of NAC (160 mg/kg body wt/d) for a period of 3 wk. The lipid peroxidation byproduct, malondialdehyde (MDA) increased following lead exposure in both of the regions, and the antioxidant capacities of the cell in terms of the activity of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) was diminished. Following NAC treatment, lead-induced lipid peroxidation decreased and antioxidant enzyme activities improved, with CAT showing enhancement in the cerebral region only and SOD showing enhancements in the cerebellar region. Our result suggests that thiol-antioxidant supplementation following Pb exposure might enhance the reductive status of brain regions by arresting the lipid peroxidative damage in brain regions.     

Influence of aminooxyacetate administration on ammonia-induced metabolic disturbances in the rat liver.

The purpose of the present report was to investigate the effects of aminooxyacetate administration to rats on the ammonia-induced disturbances in the substrate levels and in the activities of the enzymes involved in glutamine metabolism. 1.--Aminooxyacetate enhances the accumulation of ammonia following an ammonia load and prevents the other substrate level changes induced by ammonia. Thus, this transaminase inhibitor suppresses ammonia detoxication by formation of aminoacids as well as by urea synthesis. 2.--A significant decrease of glutamine synthetase activity is observed only after administration of both aminooxyacetate and ammonium chloride. 3.--Like in rats injected with ammonium chloride alone, an ammonia-induced activation of liver glutaminase I is found in inhibitor-pretreated rats. This result confirms the specific enhancement of glutaminase I activity by ammonia in excess.     

Dietary orotic acid affects antioxidant enzyme mRNA levels and oxidative damage to lipids and proteins in rat liver

We investigated the effects of the dietary addition of orotic acid on liver antioxidant enzymes, mRNA levels of these enzymes, and peroxidative products by comparing casein with soy protein as the source of dietary protein. Rats fed the casein diet accumulated more liver lipids than those fed the soy protein diet when orotic acid was added. The addition of orotic acid lowered both the activity of liver Cu, Zn-superoxide dismutase and the level of Cu, Zn-superoxide dismutase mRNA. The addition of orotic acid led to a significant increase in the contents of conjugated dienes and protein carbonyls in the liver. In addition, dietary soy protein protected the increase in the levels of lipids and proteins peroxide induced by orotic acid. The addition of orotic acid to the casein diet increased the activities of both serum ornithine carbamoyltransferase and alanine aminotransferase. Thus, liver damage might result from the increased superoxide anion due to the decrease in the activity of hepatic superoxide dismutase, as well as increase in the production of hepatic peroxidative products in rats fed the casein diet with orotic acid.