Epigallocatechin-3-gallate prevents cardiac apoptosis by modulating the intrinsic apoptotic pathway in isoproterenol-induced myocardial infarction.

(-)Epigallocatechin-gallate (EGCG) is an emerging natural therapy. This study examined the cardioprotective effect of EGCG on isoproterenol-induced myocardial damage and apoptosis and EGCG's role in modulating the expression of apoptotic signaling proteins. Experimental myocardial infarction was induced in albino Westar rats by isoproterenol (ISO) administration (100mg/kg, s.c.) at an interval of 24h on the 6th and 7th day. EGCG (15mg/kg, i.p.) was administered seven days before ISO. EGCG pretreatment significantly showed an anti-lipidemic effect and protected the cell membrane integrity, as shown by the blocking of changes in serum levels of CK-MB, LDH, ALP, ALT and troponin T. EGCG also maintained the redox balance by preventing the inhibition of the activity of SOD and CAT while limiting lipid peroxidation. Pretreatment with EGCG inhibited the stimulation of the pro-inflammatory cytokine, TNF-α, in the serum. In animals treated with EGCG, tissue Bcl-2 expression exceeded the values observed after ISO treatment and down-regulated the expression of pro-apoptotic signaling proteins, including Bax, caspase-9 and 3. This is accompanied by the protection of genomic integrity by inhibiting DNA fragmentation coincident with the down-regulation of P53. In conclusion, EGCG protected against cardiac damage by decreasing apoptosis in myocardium tissue by 1) maintaining the balance of anti-apoptotic / pro-apoptotic signaling proteins in the mitochondrial pathway of cell death, 2) limiting oxidative stress while performing antioxidant and anti-inflammatory effects, and 3) protecting DNA integrity, sustaining cardiac health. Therefore, EGCG is potentially beneficial as an early intervention in cardiac attack.

Laparoscopic Single Site Surgery for Repair of Retrocaval Ureter in a Morbidly Obese Patient.

This is to describe a case of a morbidly obese (BMI = 40) female with retrocaval ureter treated with laparoendoscopic single-site surgery. A JJ stent was positioned. A 2 cm umbilical access was created. A single port platform was positioned. The entire ureter was mobilized posterior to the vena cava and transected where the dilated portion ended. The distal ureter was repositioned lateral to the inferior vena cava. Anastomosis was done. A 3 mm trocar was used to assist suturing. At 4-month follow-up, CT revealed no evidence of obstruction of the right kidney and the patient was symptomless. Although challenging, in a morbidly obese patient, LESS repair for retrocaval ureter is feasible.

Ottelione A inhibited proliferation of Ehrlich ascites carcinoma cells in mice.

While the main target of chemotherapy in cancer treatment is the induction of apoptosis and cell death, natural products provide a wealth to medicine and are considered great sources of new drugs for cancer treatment. We aimed to determine the antitumor effect of ottelione A (OTTE) on the growth and proliferation of Ehrlich ascites carcinoma cells (EACs) implanted i.p. in female mice. Animals were inoculated with EAC cells to serve as the control group. In the OTTE group, animals were implanted with EAC followed by i.p. administration of OTTE. Antitumor activity was evaluated 15days after tumor implantation. The administration of OTTE significantly reduced ascetic volume, viability of EAC cells and increased the survival of tumor-bearing animals. Flow cytometric analysis indicated that OTTE induced G(0)/G(1) cell cycle arrest and apoptosis. These findings were associated with an alteration of redox state of EAC cells, which might impact cascade effects leading to cell cycle arrest at G(0)/G(1) phase. These effects include a decreased expression of cyclin D1, increased p53 expression and down-regulation of rRNA level, stimulation of CD8+ infiltrating T-lymphocytes. In addition, OTTE normalized oxidative stress in the liver of mice-bearing EAC cells evidenced by increased the levels of glutathione, superoxide dismutase, and catalase. In conclusion, the differential expression of p53, cyclin D1, and rRNA in EAC cells as well as the infiltration of CD8+ after OTTE treatment may play critical roles in the G(0)/G(1) cell cycle arrest that blocks cell proliferation and induce apoptosis of cancer cells. The potent antitumor property of the ottelione A can be exploited further to develop therapeutic protocols for treatment of cancer.

Assessment of biological changes of continuous whole body exposure to static magnetic field and extremely low frequency electromagnetic fields in mice.

The question whether static magnetic fields (SMFs) and extremely low frequency electromagnetic fields (ELF-EMF) cause biological effects is of special interest. We investigated the effects of continuous whole body exposure to both fields for 30 days on some liver and blood parameters in mice. Two exposure systems were designed; the first produced a gradient SMF while the second generated uniform 50 Hz ELF-EMF. The results showed a gradual body weight loss when mice were exposed to either field. This is coupled with a significant decrease (P<0.05) in the levels of glucose, total protein and the activity of alkaline phosphatase in serum. A significant increase in lactate dehydrogenase activity was demonstrated in serum and liver paralleled with a significant elevation in hepatic γ-glutamyl transferase activity. The glutathione-S-transferase activity and lipid peroxidation level in the liver were significantly increased while a significant decrease in hepatic gluthathione content was recorded. A significant decrease in the counts of monocytes, platelets, peripheral lymphocytes as well as splenic total, T and B lymphocytes levels was observed for SMF and ELF-EMF exposed groups. The granulocytes percentage was significantly increased. The results indicate that there is a relation between the exposure to SMF or ELF-EMF and the oxidative stress through distressing redox balance leading to physiological disturbances.

Ameliorative effect of melatonin against gamma-irradiation-induced oxidative stress and tissue injury.

While radiation hazards, due to free radical generation, present an enormous challenge for biological and medical safety, melatonin is a potent scavenger of a variety of free radicals. The aim of this study was to investigate the radioprotective effect of melatonin against oxidative stress and tissue injury induced by gamma radiation. Rats were subjected to two doses of 2 and 4Gy from cesium-137 source. Four days prior to irradiation, animals received melatonin daily (10mg/kg body weight i.p.). In the irradiated animals, the oxidative stress markers malondialdehyde (MDA) and protein carbonyl were significantly increased in the liver, while a marked decrease in hepatic contents of DNA, RNA, and glutathione (GSH) as well as activity of glutathione-S-transferase (GST) was demonstrated. In addition, catalase (CAT) activity was increased in the liver 5 days after irradiation. The levels of total lipids, cholesterol, triglyceride (TG), low-density lipoprotein (LDL), urea, and creatinine, as well as activities of aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT), were significantly increased in sera of the irradiated rats. This is coupled with decreased serum levels of high-density lipoprotein (HDL), total protein and albumin, and total globulins by irradiation. The administration of melatonin alone daily for 4 days caused significant decreases in MDA and protein carbonyl content and produced significant elevations of GSH content and GST activity in the liver. Moreover, significant decreases in total lipids, cholesterol, and TG without change in LDL or HDL levels in serum were demonstrated. Treatment with melatonin for 4 days before acute irradiation significantly abolished radiation-induced elevations in MDA and protein carbonyl levels in the liver and significantly maintained hepatic GSH content, GST, and CAT activities close to the control values. Preirradiation treatment with melatonin showed significantly higher hepatic DNA and RNA contents than irradiated rats. The levels of total lipids, cholesterol, TG, HDL, LDL, total proteins, albumin, total globulins, creatinine, and urea, as well as the activities of AST, ALT, and GGT in serum were significantly ameliorated when melatonin was injected before irradiation. In conclusion, the increase in oxidative stress markers and the concomitant change in antioxidant levels indicate the role of oxidative stress in radiation-induced tissue damage. Moreover, melatonin shows a radioprotective impact against ionizing-radiation-induced oxidative stress and organ injury.

Role of melatonin in ameliorating lead induced haematotoxicity.

Owing to the risks of heavy metals-induced severe haematopoietic disorders, it is important to investigate these chemicals for their haematotoxicity and the possible ways to ameliorate their toxicity. The effects of melatonin on lead-induced haematotoxicity have, therefore, been examined in rat blood and bone marrow. When adult male rats were injected intramuscularly with lead acetate (10 mg kg(-1)) daily for 7 days, the erthrocytic count, haematocrite value and haemoglobin content were significantly decreased. The counts of platelets, total leucocytes and lymphocytes in the peripheral blood were also significantly lower in lead-treated rats than in control animals. The total granulocyte count was significantly elevated in the peripheral blood of the same lead-treated rats. Significant decreases in polychromatic and pyknotic erythroid series as well as lymphocytes in bone marrow of the lead-intoxicated rats were also demonstrated. Meanwhile, the neutrophiles were increased in the same treated rats. The erythropoietin level was significantly decreased and the lead concentration was increased in the plasma of the lead-treated rats compared with the control rats. Bone marrow examination of the rats treated with lead for 7 days showed erythroid hyperplasia with a sign of dyserythropoiesis and demonstrated ringed sideroblasts in varying proportions. Daily pretreatment with melatonin (30 mg kg(-1)) intragastricaly, concurrently with lead injection for 7 days significantly prevented the changes recorded in the peripheral blood parameters. The changes observed in the bone marrow polychromatic erythroid, lymphocytes and the neutrophiles were significantly ameliorated by coadministration of melatonin and lead compared with lead-treated rats, while the pyknotic erythroid series was still significantly low. The levels of erythropoietin and lead in plasma were not changed in melatonin+lead-treated group compared with lead only treated rats. In addition, melatonin administration ameliorated the decrease in erythroid cell count in bone marrow. Less dyserythropoiesis and megaloblastic changes were observed in bone marrow film when melatonin was concurrently administered with lead. In the same animals, iron staining of the bone marrow cells showed absence of ringed sideroblasts. In conclusion, the present results indicate that melatonin has the ability to protect the haematopoietic cells from the damaging effects of exposure to lead. This protection might be attributed to the antioxidative power of melatonin.

L-Arginine ameliorates oxidative stress in alloxan-induced experimental diabetes mellitus.

Oxidative stress occurs in diabetic patients and experimental models of diabetes. The ability of l-arginine to ameliorate the oxidative stress and metabolic changes after treatment with alloxan was investigated in rats. Adult male rats were injected intraperitoneally with 100 mg kg(-1) of alloxan to produce experimental oxidative stress characteristic of diabetes mellitus. Hyperglycaemia and hypercholesterolaemia were observed in serum after 7 days of alloxan treatment. This was associated with a depression of glutathione (GSH) concentration as well as superoxide dismutase (SOD) and catalase (CAT) activities in the liver and brain. In addition, the thiobarbituric acid-reactive substances (TBARS) were significantly elevated, indicating increased lipid peroxidation and oxidative stress in the same tissues. Administration of 100 mg kg(-1) l-arginine for 7 days either before or after alloxan injection significantly ameliorated the oxidative stress evidenced by a lower TBARS and a higher level of the endogenous GSH concentration and SOD and CAT activities than alloxan-treated rats. These effects were paralleled by marked protection and partial prophylaxis against alloxan-induced hyperglycaemia and cholesterolaemia. Thus, these results showed that exogenously administered l-arginine might improve the clinical manifestation of diabetes mellitus and decrease the oxidative stress in the liver and brain. In addition, the study supports the beneficial effect of l-arginine, which might be attributed to its direct, NO-dependent antioxidant capacity and/or NO-independent pathways.

Potential protective role of angiotensin-converting enzyme inhibitors captopril and enalapril against adriamycin-induced acute cardiac and hepatic toxicity in rats.

Captopril and enalapril-angiotensin-converting enzyme (ACE) inhibitors-were evaluated for their antioxidative protective action against adriamycin-induced cardiac and hepatic toxicity. Rats were treated with either captopril (10 mg kg(-1)) or enalapril (2 mg kg(-1)) intragastrically (i.g.) daily for 7 days before single intraperitoneal (i.p.) injection with adriamycin (15 mg kg(-1)). The animals were killed 30 h after adriamycin administration. Adriamycin produced significant elevation in thiobarbituric acid reactive substances (TBARS), which is an indicator of lipid peroxidation, and significantly inhibited the activity of superoxide dismutase (SOD) in heart and liver tissues, with a significant rise in the serum levels of glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), creatine kinase isoenzyme (CK-MB) and lactic dehydrogenase (LDH), indicating acute cardiac toxicity. A single injection of adriamycin did not affect the cardiac or hepatic glutathione (GSH) content or cardiac catalase (CAT) activity, but hepatic CAT activity was elevated. Pretreatment with ACE inhibitors significantly reduced the TBARS concentration in both heart and liver and ameliorated the inhibition of cardiac and hepatic SOD activity. In addition, the ACE inhibitors significantly improved the serum levels of GOT, GPT, CK-MB and LDH in adriamycin-treated rats. Thus, these results suggest that captopril and enalapril possess antioxidative potential that may protect the heart against adriamycin-induced acute oxidative toxicity. This protective effect might be mediated, at least in part, by the limitation of culprit free radicals and the amelioration of oxidative stress.

Protection by metal complexes with SOD-mimetic activity against oxidative gastric injury induced by indomethacin and ethanol in rats.

We have investigated the protective effect of oral administration of copper and manganese complexes with superoxide dismutase (SOD)-mimetic activity against oxidative gastric mucosal injury induced by the non-steroidal anti-inflammatory drug indometacin with ethanol in the rat. The total area of the gastric lesions and lipid peroxidation were significantly increased 1 h after oral administration of indometacin (15 mg/kg) and ethanol, indicating an acute oxidative injury. The activities of SOD, catalase (CAT), glutathione-S-transferase (GST) and glutathione content were significantly decreased in the gastric mucosa by indometacin plus ethanol. Manganese or copper complexes showed SOD-mimetic activity. Pretreatment with these complexes protected against gastric mucosal lesions and decreased lipid peroxides, as well as attenuating the decrease in the activities of SOD, CAT and GST in gastric mucosa. These findings suggest that active oxygen species and lipid peroxidation play an important role in the pathogenesis of gastric mucosal injury induced by indometacin. In addition, we have shown that Mn and Cu complexes have gastroprotective properties against ulceration induced by indometacin plus ethanol. The present results suggest that appropriate copper or manganese complex supplementation may potentially provide prophylaxis or therapy for some pathologies associated with excessive free radical production and inhibited SOD activity.

The protective action of melatonin on indomethacin-induced gastric and testicular oxidative stress in rats.

Reactive oxygen species and lipid peroxidation play a role in the pathogenesis induced by the non-steroidal anti-inflammatory drug indomethacin. Melatonin (MLT) protection against indomethacin-induced oxidative tissue injury was investigated in gastric mucosa and testis of rats. MLT was administered intragastrically (i.g.) 30 min before the administration to fasted rats of 20 mg indomethacin/kg rat given i.g.. The area of gastric lesion as well as thiobarbituric acid reactive substances (TBARS) and lactate dehydrogenase (LDH) activity were found to be significantly increased 4 h after administration of indomethacin in rat gastric mucosa and testis indicating acute oxidative injury. MLT pretreatment reduced gastric lesion area to 80% of the indomethacin-treated rats and reduced the rise in TBARS concentration. MLT treatment reduced the LDH activity increase in testis but not in gastric mucosa. In indomethacin-treated rats, both the cytosolic Cu,Zn superoxide dismutase (Cu,Zn-SOD) and mitochondrial Mn-SOD activities were significantly diminished in gastric mucosa as well as the total SOD activity in testis. In addition, glutathione (GSH) content in both tissues was markedly decreased following indomethacin treatment. Pretreatment with MLT significantly ameliorated both the inhibition of SOD activity and the decreased GSH content in both tissues. Thus, these results show the effective antiperoxidative and preventive actions of MLT against indomethacin-induced gastric mucosal damage and testicular oxidative injury and we propose that this action might be relevant for its use with other free radical generating drugs.

Attenuation of the acute adriamycin-induced cardiac and hepatic oxidative toxicity by N-(2-mercaptopropionyl) glycine in rats.

The protective effect of the synthetic aminothiol, N-(2-mercaptopropionyl) glycine (MPG) on adriamycin (ADR) induced acute cardiac and hepatic oxidative toxicity was evaluated in rats. ADR toxicity, induced by a single intraperitoneal injection (15 mg/kg), was indicated by an elevation in the level of serum glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), creatine kinase isoenzyme (CK-MB), and lactic dehydrogenase (LDH). ADR produced significant elevation in thiobarbituric acid reactive substances (TBARS), indicating lipid peroxidation, and significantly inhibited the activity of superoxide dismutase (SOD) in heart and liver tissues. In contrast, a single injection of ADR did not affect the cardiac or hepatic glutathione (GSH) content and cardiac catalase (CAT) activity but elevated hepatic CAT. Pretreatment with MPG, (2.5 mg/kg) intragastrically, significantly reduced TBARS concentration in both heart and liver and ameliorated the inhibition of cardiac and hepatic SOD activity. In addition, MPG significantly decreased the serum level of GOT, GPT, CK-MB, and LDH of ADR treated rats. These results suggest that MPG exhibited antioxidative potentials that may protect heart and liver against ADR-induced acute oxidative toxicity. This protective effect might be mediated, at least in part, by the high redox potential of sulfhydryl groups that limit the activity of free radicals generated by ADR.

Amelioration of alloxan induced diabetes mellitus and oxidative stress in rats by oil of Eruca sativa seeds.

Clinical research has confirmed the efficacy of several plant extracts in the modulation of oxidative stress associated with diabetes mellitus (DM). Oil of Eruca sativa seeds (ESS) is tried for prevention and treatment of DM induced experimentally by alloxan injection. A single dose of alloxan (100 mg/kg) produced a decrease in insulin level, hyperglycemia, elevated total lipids, triglycerides and cholesterol, decreased high-density lipoprotein and hepatic glycogen contents and elevated hepatic glucose-6-phosphatase activity. Concurrent with these changes, there was an increase in the concentration of malondialdehyde and 4-hydroxynonenal in the liver. This oxidative stress was related to a decreased glutathione (GSH) content and superoxide dismutase activity in the liver of alloxan-diabetic rats. ESS oil (0.06 ml/kg) on its own increased significantly hepatic GSH. Daily oral administration of ESS oil 2 weeks before or after diabetes induction ameliorated hyperglycemia, improved lipid profile, blunted the increase in malondialdehyde and 4-hydroxynonenal and stimulated the GSH production in the liver of alloxan-treated rats. We suggested that ESS oil could be used as antidiabetic complement in case of DM. This may be related to its antioxidative properties and to the increase in hepatic GSH.

Role of beta-carotene in ameliorating the cadmium-induced oxidative stress in rat brain and testis.

The role of oxidative stress in chronic cadmium (Cd) toxicity and its prevention by cotreatment with beta-carotene was investigated. Adult male rats were intragastrically administered 2 mg CdCl2/kg body weight three times a week intragastrically for 3 and 6 weeks. Brain and testicular thiobarbituric acid reactive substances (TBARS) was elevated after 3 and 6 weeks of Cd administration, indicating increased lipid peroxidation (LPO) and oxidative stress. Cellular damage was indicated by inhibition of adenosine triphosphatase (ATPase) activity and increased lactate dehydrogenase (LDH) activity in brain and testicular tissues. Chronic Cd administration resulted in a decline in glutathione (GSH) content and a decrease of superoxide dismutase (SOD) and glutathione S-transferase (GST) activity in both organs. Administration of beta-carotene (250 IU/kg i.g.) concurrent with Cd ameliorated Cd-induced LPO. The brain and testicular antioxidants, SOD, GST, and GSH, decreased by Cd alone, were restored by beta-carotene cotreatment. Concurrent treatment with beta-carotene also ameliorated the decrease in ATPase activity and the increase in LDH activity in brain and testis of Cd-treated rats, indicating a prophylactic action of beta-carotene on Cd toxicity. Therefore, the results indicate that the nutritional antioxidant beta-carotene ameliorated oxidative stress and the loss of cellular antioxidants and suggest that beta-carotene may control Cd-induced brain and testicular toxicity.

Photosensitization induced reactive oxygen species and oxidative damage in human erythrocytes.

Generation of reactive oxygen species by photosensitization is the corner stone of photodynamic therapy of tumors. Cell damage may be mediated by free radical species and lipid peroxidation of their membranes. The effects of oxygen active species (.OH and O(2)(.-) radicals) photogenerated by the novel photosensitizer m-chloroperbenzoic acid (m-CPBA) on human erythrocyte integrity and stability were studied. The biological toxicity of the reactive oxygen species on human red blood cells (RBCs) was evident by increased osmotic fragility, spherocytosis and haemolysis. The haemolysis was increased in concentration and time dependent manner. The lipid peroxidation product thiobarbituric acid reactive substances (TBARS) was elevated in m-CPBA photosensitized RBCs indicating increased oxidative stress. This was accompanied with a depletion of erythrocyte glutathione (GSH). These effects were blunted by hydroxyl radical scavengers, thiourea and mannitol, which might indicate the production of (.)OH radical by photosensitization with m-CPBA. The antioxidant enzyme activities such as superoxide dismutase (SOD), catalase (CAT), peroxidase (Px) and glutathione peroxidase (GSH-Px) were elevated in RBCs treated with m-CPBA in the presence and absence of hydroxyl radical scavengers, mannitol and thiourea. These results suggested that the main oxygen radical photogenerated from m-CPBA is O(2)(&z.rad;-) radical, which is transformed to (.)OH radical probably by hydrogen abstraction. This is probably the main damaging oxygen species and played an essential role in oxidative haemolysis mediated by peroxidation of membrane lipids of human erythrocytes. This study provides an investigational promising data for photodynamic therapy.

Influence of melatonin on proliferation and antioxidant system in Ehrlich ascites carcinoma cells.

The effects of oral supplementation of melatonin on growth of Ehrlich ascites carcinoma (EAC) cells implanted intraperitoneally in female mice were studied. Melatonin at 50 mg/kg body wt. reduced the viability and volume of Ehrlich ascites carcinoma cells and increased the survival of the treated mice. No significant change in intracellular reduced glutathione (GSH) content in EAC cells was observed indicating that GSH was not involved in the inhibitory effect of melatonin. The activity of glutathione-S-transferase in EAC cells was significantly increased. Flow cytometirc studies showed that melatonin not only delayed the progression of cells from G(0)/G(1) phase to S-phase of the cell cycle but also reduced DNA synthesis during cell cycle. In addition, the aneuploidy status was depressed in melatonin treated mice. Based on these data and the reduced viability in both in vitro and in vivo, it is suggested that melatonin might induce apoptosis in EAC cells.

Prophylactic effect of melatonin on lead-induced inhibition of heme biosynthesis and deterioration of antioxidant systems in male rats.

We studied the protective role of the pineal hormone melatonin on lead-induced suppression of the heme synthesis pathway as a consequence of reduced antioxidant systems in rat. We injected rats intramuscularly with lead acetate (10 mg/kg body weight) daily for 7 days, which significantly abolished heme synthesis as evidenced by decreased blood hemoglobin, liver delta-aminolevulinic acid synthetase, erythrocytic delta-aminolevulinic acid dehydratase, and hepatic iron content. These effects were accompanied with marked elevation of hepatic lipid peroxidation and decreased enzymatic antioxidants such as glutathione reductase, glutathione-S-transferase, superoxide dismutase, and catalase, as well as nonenzymatic antioxidants such as total sulfhydryl groups and glutathione. Furthermore, lead treatment caused hepatic deficiency in copper and zinc accompanied by a significant elevation of lead concentration in both plasma and liver. Daily pretreatment with melatonin (30 mg/kg body weight) intragastrically prevented the suppressive effects of lead on heme-synthesizing enzymes and iron deficiency. In addition, preadministration of melatonin reduced the inhibitory effect of lead on both enzymatic and nonenzymatic antioxidants. This was accompanied by marked normalization of lipid peroxidation and modulation of copper and zinc levels in liver. The action of melatonin on lead-induced changes was attributed to protection of the antioxidant capacity in cells in addition to the ability of melatonin to scavenge free radicals.

Enhanced testicular antioxidant system by ascorbic acid in alloxan diabetic rats.

The diabetic subject is at significantly increased risk of developing testicular changes. Its etiology may involve oxidative damage by free radicals and protection against such damage can be offered by antioxidant supplementation. Alloxan elicited significant inhibition of antioxidants including superoxide dismutase, catalase and glutathione reductase activities and decreased glutathione content in testis. These effects were accompanied by significant elevation of testicular lipid peroxidation, decreased plasma testosterone level and a drop in copper and zinc concentrations in testis. The administration of ascorbic acid after alloxan treatment interfered and prevented alloxan action. Ascorbic acid blunted the increased testicular lipid peroxidation and the decreased plasma testosterone level probably by protecting antioxidants and the loss of copper and zinc from testes. The data suggested that ascorbic acid has a protective effect on alloxan-induced damage by maintaining the activity of cellular antioxidants.

Role of selenium against lead toxicity in male rats.

Male albino rats were intramuscularly administered a single dose of lead acetate (100 micromol/kg b.wt). Another group of rats were injected with sodium selenite (10 micromol/kg b.wt) before lead intoxication. After 3 and 24 hours, lead treatment resulted in significant increases in acid and alkaline phosphatases, GOT and GPT, total proteins, and cholesterol in serum. The total triglycerides in serum was decreased after 24 hours of intoxication. Lead treatment also produced significant elevation of lipid peroxidation in liver and kidney. The antioxidant capacity of hepatic and renal cells in terms of the activities of superoxide dismutase, glutathione reductase, and glutathione content was diminished. It appears from these results that lead may exert its toxic effect via peroxidative damage to renal and hepatic cell membranes after 24 hours. Selenium administration prior to lead injection produced pronounced prophylactic action against lead effects, and it is observed that selenium enhances the endogenous antioxidant capacity of the cells by increasing the activities of the superoxide dismutase and glutathione reductase and the glutathione content. As a result, the lipid peroxidation was decreased in both liver and kidney.