Effects of diazinon on pseudocholinesterase activity and haematological indices in rats: The protective role of Vitamin E

Diazinon (DZN) is an organophosphate insecticide has been used in agriculture and domestic for several years. Vitamin E (200mg/kg, twice a week), diazinon (10mg/kg, per day) and Vitamin E (200mg/kg, twice a week)+diazinon (10mg/kg, per day) combination were given to rats orally via gavage for 7 weeks. Pseudocholinesterase in serum and haematological indices were investigated at the end of the 1st, 4th and 7th weeks comparatively with control group. At the end of 1st, 4th and 7th weeks, statistically significant decrease of pseudocholinesterase activity in serum were detected when diazinon- and Vitamin E+diazinon-treated groups compared to control group. When diazinon- and Vitamin E+diazinon-treated groups were compared to each other there were no significant changes. When diazinon-treated group was compared to control group, body weight decreased significantly at the end of the 4th and 7th weeks. It was observed that at the end of 1st, 4th and 7th weeks, there was a statistically significance in haematological indices except mean corpuscular hemoglobin (MCH) when diazinon-treated group was compared to control group. At the end of 1st week increase of thrombocyte, at the end of the 4th week increase of hemoglobin and thrombocyte and at the end of the 7th week increase of red blood cell (RBC), hemoglobin, hematocrit, mean corpuscular hemoglobin concentration (MCHC) and thrombocyte were observed statistically significant when Vitamin E+diazinon treated group was compared with diazinon treated group. According to the present study, we conclude that Vitamin E reduces diazinon toxicity, but it does not protect completely.     

Dichlorvos-induced hepatotoxicity in rats and the protective effects of vitamins C and E

Dichlorvos is an organophosphate insecticide that is widely used in pest control. Vitamin C (200mg/kg)+vitamin E (200mg/kg), dichlorvos (1.6mg/kg), or a combination of vitamin C (200mg/kg)+vitamin E (200mg/kg)+dichlorvos (1.6mg/kg) was given to rats via oral gavage for 7 weeks. When rats of the dichlorvos-treated group and the vitamins+dichlorvos-treated group were compared with the control group, body weights were decreased and liver weights were increased significantly at the end of the 4th and 7th week. Serum total protein, albumin, triglyceride, low density lipoprotein-cholesterol (VLDL-cholesterol) levels were decreased, and serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl-transferase (GGT), lactate dehydrogenase (LDH), and total cholesterol levels were increased significantly at the end of the 4th and 7th week in the dichlorvos- and vitamins+dichlorvos-treated rats. There was a statistically significant difference for all biochemical parameters when the vitamins+dichlorvos-treated group was compared with the dichlorvos-treated group at the end of the 4th and 7th week. In an electron microscopic investigation, swelling of mitochondria and dilatation of endoplasmic reticulum were observed in liver cells of the dichlorvos- and vitamins+dichlorvos-treated rats at the end of the 4th and 7th week. As a result, vitamins C and E reduced dichlorvos hepatotoxicity, but vitamins C and E did not confer complete protection.     

Sub-acute effects of diazinon on biochemical indices and specific biomarkers in rats: Protective effects of crocin and safranal

In this study, the effects of crocin and safranal were studied against sub-acute toxicity of diazinon (DZN) on specific biomarkers, biochemical indices and enzymes levels in rats. Vitamin E (200 IU/kg), safranal at doses 0.025, 0.05 and 0.1 ml/kg and crocin at doses 50, 100 and 200 mg/kg were injected intraperitoneally three times per week alone or with DZN (20 mg/kg/day, orally) for 4 weeks. The parameters were evaluated at the end of 4 weeks. Diazinon did not change serum urea, creatinine, cholesterol, triglyceride, total and direct bilirubin levels. Total protein and albumin concentrations were decreased by diazinon. Crocin, safranal and vitamin E prevented the effect of diazinon on some biochemical indices and enzymes levels. The levels of serum TNF-α, direct 8-iso-prostaglandin F_2α and soluble protein-100 β (S100β) were increased significantly by diazinon. The augmentation of direct 8-iso-prostaglandin F_2α and S100β levels by diazinon was significantly decreased by crocin, safranal and vitamin E. TNF-α level was significantly decreased in diazinon plus crocin 50 and 100 mg/kg treated groups compared to the diazinon group. This study showed that vitamin E, safranal and crocin could prevent diazinon induced enzymes elevation and augmentation of some specific biomarkers.     

Protective effects of glycyrrhizin on sub-chronic diazinon-induced biochemical,hematological alterations and oxidative stress indices in male Wistar rats

The aim of this study was to elucidate the protective effect of glycyrrhizin on diazinon-induced changes in body and organ weights, blood hematology, lipid profile, biochemistry parameters and tissue markers of oxidative stress in male Wistar rats over a 7-week period. Rats were orally given sublethal dose of diazinon (10?mg/kg daily; 0.008 LD50), while glycyrrhizin (25?mg kg^?1 daily) was given alone or in combination with diazinon. At the end of 7th week, statistically significant decrease of pseudocholinesterase activity was detected when diazinon- and glycyrrhizin?+?diazinon-treated groups were compared to the control group. Diazinon treated rats showed weight loss and organ weight changes which were comparable to other groups. There was a statistically significance in hematological indices except mean corpuscular hemoglobin (MCH) when diazinon treated group was compared to glycyrrhizin?+?diazinon treated rats. Glycyrrhizin protected the liver and kidney from diazinon toxic effects with significantly decrease in serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase activities as well as ameliorated hepatic and renal function indices (such as bilirubin, total protein, albumin, BUN, creatinine glucose). In addition, glycyrrhizin minimized the hazardous effect of diazinon on plasma lipids and lipoproteins. The protective effects of glycyrrhizin were confirmed by tissue markers of oxidative stress analysis as glycyrrhizin in combination diminished malondialdehyde and glycyrrhizin alone or in combination enhanced thiol group and the ferric reducing power. In accordance to these results, our observations demonstrated the beneficial effects of glycyrrhizin in reducing the toxicity of diazinon.     

Malathion-induced hepatotoxicity in rats: The effects of vitamins C and E

Mature male Wistar rats (weighing 300–320 g and each group six animals) were given malathion (27 mg/kg; 1/50 of the LD50 for an oral dose), vitamin C (200 mg/kg) + vitamin E (200 mg/kg), or both daily via gavage for 4 weeks. At the end of the fourth week, the malathion-treated group and the malathion plus vitamin-treated group both had significantly higher white blood cell (WBC) and thrombocyte counts than the control group. Compared to the control group, the two groups also had significantly higher serum total cholesterol, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels, and significantly lower triglyceride and very low density lipoprotein (VLDL) levels. The malathion-treated rats also had significantly lower serum total protein and albumin levels, but the malathion plus vitamin-treated group did not differ from the control group in terms of these parameters. Moreover, concomitant vitamin treatment significantly normalized, at least partially, all of the other hematological and biochemical parameters that were altered by malathion. Light microscopic analyses revealed that both the malathion-treated and malathion plus vitamin-treated groups exhibited histopathological changes in liver tissues, although some pathological features were only observed in the malathion-treated group. Thus, vitamins C and E can reduce malathion hepatotoxicity, although the degree of protection they provide is limited.     

Endosulfan-induced cardiotoxicity and free radical metabolism in rats: the protective effect of vitamin E

Endosulfan is widely used in insect control and it is absorbed by both humans and animals through ingestion, inhalation and percutaneously. The aim of this work was to study antioxidant enzyme system which include superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) and malondialdehyde (MDA), the end product of lipid peroxidation and ultrastructural changes that might occur in the heart tissue of adult male Wistar rats as a result of endosulfan intoxication. Vitamin E (200 mg/kg, twice a week), endosulfan (2 mg/kg, per day, once a day in corn oil) and vitamin E (200 mg/kg, twice a week)+endosulfan (2 mg/kg, per day, once a day in corn oil) combination were given to rats (n = 10/group) orally via gavage for 6 weeks. SOD, GPx, CAT activities and MDA level increased in the endosulfan-treated group heart tissue compared to control group (P < 0.01, P < 0.01, P < 0.05 and P < 0.01, respectively). SOD, GPx activities and MDA level decreased in the vitamin E + endosulfan-treated group compared to endosulfan-treated group (P < 0.05, P < 0.05 and P < 0.05, respectively). Decrease of CAT activity was not significant statistically in the vitamin E + endosulfan-treated group compared to endosulfan-treated group. CAT activity increased in the vitamin E + endosulfan treated group compared to control group (P < 0.05). Increase of SOD, GPx activities and MDA levels were not significant statistically in the vitamin E + endosulfan-treated group compared to control group. In electron microscopic investigations while cytoplasmic edema and swelling and vacuolization of mitochondria of myocardial cells in endosulfan-treated group was observing, only a weak swelling of mitochondria of myocardial cells in vitamin E + endosulfan-treated group was observed. We conclude that vitamin E significantly reduce endosulfan-induced cardiotoxicity in rats.     

The ameliorating effects of vitamin E on hepatic antioxidant system and xenobiotic-metabolizing enzymes in fenvalerate-exposed iodine-deficient rats

This study investigated the effects of vitamin E (VE) on hepatic antioxidant system and drug-metabolizing enzymes in fenvalerate (FEN)-exposed iodine-deficient (ID) Wistar rats. ID was produced by perchlorate containing drinking water. VE was introduced by a loading dose of 100?mg/kg/d, i.g. for the first three days in the last week of feeding period; then with a single maintenance dose of 40?mg/kg on the 4th day. During last week, FEN groups (F) received 100?mg/kg/d, i.p. FEN. VE alone did not significantly affect thyroid hormones and antioxidant parameters; however, significantly increased total cytochrome P450 (38%) and cytochrome b5 levels (36%). In all ID groups, plasma thyroid-stimulating hormone (TSH) levels increased markedly, but remained at control level in vitamin E plus FEN receiving iodine-deficient group (IDVF) group. Glutathione peroxidase activity showed marked increases in F (19%) and FEN-exposed iodine-deficient group (IDF, 48%) groups. FEN treatment significantly increased total cytochrome P450 (28%) and thiobarbituric acid reactive substance levels (36%), as well as 7-ethoxyresorufin O-deethylase (120%), 7-penthoxyresorufin O-deethylase (139%) and glutathione S-transferase (15%) activities and decreased total glutathione concentrations (28%) versus control. Overall results suggest that vitamin E has ameliorating effects on the measured parameters in ID and/or FEN exposure.     

Evaluating the protective effects of vitamin E and selenium on hematology and liver,lung and uterus histopathology of rabbits with cypermethrin toxicity

Abstract

The objective of this study was to determine the efficacy of vitamin E and selenium as protective agents against cypermethrin (CY)-induced toxicity by evaluating hematology parameters along with liver, lung and uterus histopathology of female rabbits. Thirty female rabbits were randomly divided into five equal groups with six animals in each group (designated A, B, C, D and E). Animals in group A were control animals that did not receive CY, vitamin E, nor selenium. Animals in groups B–E were injected intraperitoneally with CY at 75?mg/kg body weight once every5 days over a 32?day period, while animals in the control group received saline. Animals in group C were also given vitamin E (150?mg/kg b.wt) orally and animals in group D were given selenium (0.45?mg/kg b.wt) orally. Group E was given both vitamin E at a dose of 150?mg/kg and selenium at a dose of 0.45?mg/kg. In group B (CY only), the values of PCV were decreased at the 12th day of gestation when compared to group A. The mean value of PCV was significantly higher in group E on the 12 and 24th day when compared to the other groups. The mean values of hemoglobin (Hb) were not significantly different among groups on the 12th and 24th day of gestation. On the 12th day of the gestation period, there were nonsignificant differences in the total number of erythrocytes among all the groups. However, on the 24thdayof the gestation period, there was a significant decrease in the total number of erythrocytes in group B compared to the control group. Total leukocytes were also increased in the animals of group B on the 12th day of gestation, whereas the total leukocytes were increased on the 24th day of gestation in all groups (A–D) compared to control. Histopathological studies of tissues of liver, lungs and uterus revealed that CY altered the normal parenchyma of these tissues and this was partially ameliorated by the vitamin E and selenium treatments. In conclusion, combined use of vitamin E and selenium partially ameliorated the toxicity of CY in female rabbits.     

Modification of diazinon-induced changes in carbohydrate metabolism by adrenalectomy in rats

Treatment with diazinon (40 mg/kg, i.p.) resulted in hyperglycemia and depletion of glycogen from cerebral and peripheral tissues 2 hr after its administration in rats. The activities of the glycogenolytic enzymes glycogen phosphorylase and phosphoglucomutase were increased significantly in brain and liver, whereas that of glucose-6-phosphatase was not altered. The activities of the glycolytic enzymes hexokinase and lactate dehydrogenase were increased only in the brain. The cholinesterase activity of the brain was reduced by treatment with diazinon. The activities of the hepatic gluconeogenic enzymes fructose 1,6-diphosphatase and phosphoenolpyruvate carboxykinase were also increased significantly in diazinon-treated animals. The level of lactate was increased in brain and blood, whereas that of pyruvate was not changed. The activity of glucose-6-phosphate dehydrogenase was not changed significantly. The cholesterol and ascorbic acid contents of adrenals were depleted in diazinon-treated animals. The hyperglycemia and changes in carbohydrate metabolism were abolished by adrenalectomy, suggesting the possible involvement of the adrenals in the induced changes in diazinon-treated animals.     

Comparative effects of diazinon and malathion in Najdi sheep.

The comparative effects of diazinon and malathion on Najdi sheep were described in sheep allotted as untreated controls, diazinon-treated at 25 mg/kg/d or 50 mg/kg/d, and malathion-treated at 25 mg/kg/d or 50 mg/kg/d. Although serum cholinesterase (ChE) activity was reduced, neither significant clinical signs nor severe pathological changes were produced in sheep dosed orally with 25 or 50 mg diazinon/kg/d for 21 d. Both oral dose levels of malathion were lethal to sheep between 1 and 6 d and caused, prior to death, hyperexcitability, tremors, clonic convulsions, salivation, nasal discharge, incoordination of movement, paresis of the limbs and recumbency. Lesions were widespread congestion and hemorrhage, patchy pulmonary cyanosis, gastroenteritis and hepatonephropathy. These changes were accompanied by increases in the activities of serum SDH and AST, in the concentrations of urea, triglyceride and cholesterol, and decreases in ChE activity and in RBC, PCV and Hb values.     

Effects of Phyllanthus reticulatus on lipid profile and oxidative stress in hypercholesterolemic albino rats

Objective:

This study was designed to investigate the effect of Phyllanthus reticulatus on lipid profile and oxidative stress in hypercholesterolemic albino rats.

Materials and Methods:

Hypercholesterolemia was induced in albino rats by administration of atherogenic diet for 2 weeks. Experimental rats were divided into different groups: normal, hypercholesterolemic control and P. reticulatus treated (250 and 500 mg/kg body weight doses for 45 days). After the treatment period of 45^th day triglyceride, VLDL-cholesterol, HDL-cholesterol, total cholesterol (TC), LDL-cholesterol and oxidative stress (protein carbonyl) were assayed and compared with hypercholesterolemic control.

Results:

The aqueous extract of P. reticulatus (250 mg and 500 mg/kg) produced significant reduction (P < 0.05) in triglyceride, VLDL-cholesterol, total cholesterol (TC), LDL-cholesterol and oxidative stress (protein carbonyl) while increased HDL-cholesterol in atherogenic diet-induced hypercholesterolemic rats at the end of the treatment period (45 days). However, the reduction in the above parameters was comparable with hypercholesterolemic control. Thus, aqueous extract of P. reticulatus is effective in controlling TC, lipid profile and oxidative stress in hypercholesterolemic animals.

Conclusion:

The results suggest the aqueous extract of P. reticulatus can be utilized for prevention of atherosclerosis in hypercholesterolemic patients.     

Changes in cerebral glycogenolysis and related enzymes in diazinon treated hyperglycaemic animals

Effect of diazinon (10,20 and 40 mg/kg, i.p.) on the level of blood glucose in rats was investigated. Hyperglycaemia peaked 2 h after i.p. treatment with 40 mg/kg diazinon. The cerebral acetylcholinesterase activity was significantly reduced. The blood level of pyruvic acid was unchanged while that of lactic acid was significantly increased. Convulsions and biochemical changes caused by diazinon (40 mg/kg) were prevented by diazepam injected immediately after diazinon. In diazinon-treated hyperglycaemic animals, the glycogen content of the brain was depleted, the activities of glycogen phosphorylase, phosphoglucomutase and hexokinase were significantly increased and the activity of glucose-6-phosphatase remained unchanged. Lactate dehydrogenase activity was also increased by treatment with diazinon. The induced changes may compensate for the energy requirement of stimulatory effects caused by diazinon.     

Neuroprotective effect of vitamin e supplementation in wistar rat treated with acrylamide

Male wistar rats (weighting 160-180 g) were divided into six groups of six animals per group. Groups A and F served as control. Groups B, C, D, and E received acrylamide at 20 mg/kg body weight for 28 days and groups C and E received additionally vitamin E (50 IU/kg body weight) for 1 to 28 days and 29 to 42 days of experiment, respectively. The animals from groups A, B, and C were sacrificed on day 28 of experiment and from groups D, E, and F on day 42 of experiment, respectively. The FOB (Functional Observational Battery) and histopathological changes were investigated at the end of 4(th) week and 6(th) week. FOB at the end of 4(th) week, of rats given acrylamide alone, or in combination with vitamin E, revealed a significant change in CNS, neuromuscular, and autonomic domains. A marked decrease in grip strength was recorded. A significant increase in foot splay, reduction in width and angle of sequential stride was noticed. Degenerative changes, necrosis, congestion, and kupffer cell proliferation in liver while vacuolar degenerative changes in tubular epithelium, coagulative necrosis, and hemorrhages in kidney were constant findings in acrylamide intoxicated rats. Neuronal degeneration, severe gliosis, congestion were found in brain. Spinal cord revealed demyelination. Acute microscopic softening of lumbar cord, bilateral necrosis with malacia and liquefaction of white matter, and loss of myelin from grey matter were seen. In the recovery period, vitamin E-treated rats revealed improvement in remyelination of spinal cord. In brain mild gliosis was seen. Thus, it appears that vitamin E is not able to protect them from acrylamide toxicity during active feeding, but after cessation of acrylamide feeding treatment with vitamin E revealed faster recovery as compared to the non-treated group.     

Effect of adrenalectomy on diazinon-induced changes in carbohydrate metabolism

Treatment with diazinon resulted in hyperglycaemia and depletion of glycogen from cerebral and peripheral tissues 2 h after its administration in rats; the changes were maximal after 40 mg/kg diazinon, administered intraperitoneally. The activities of glycogen phosphorylase and phosphoglucomutase were significantly increased in brain and liver, while that of glucose-6-phosphatase was not altered. The activities of the glycolytic enzymes hexokinase and lactate dehydrogenase were increased only in brain. The cholinesterase activity of the brain was reduced by treatment with diazinon. The activities of hepatic gluconeogenic enzymes (fructose 1,6 diphosphatase and phosphoenolpyruvate carboxykinase) were also significantly increased in diazinon-treated animals. The level of lactate was increased in brain and blood while that of pyruvate was not changed. The activity of glucose-6-phosphate dehydrogenase was not significantly changed. Cholesterol and ascorbic acid contents of adrenals were depleted in diazinon-treated animals. Adrenalectomy abolished the hyperglycaemia and changes in carbohydrate metabolism, suggesting the possible involvement of adrenals in the induced changes in diazinon-treated animals.     

Evaluation of subchronic chlorpyrifos poisoning on hematological and serum biochemical changes in mice and protective effect of vitamin C

Chlorpyrifos (CPF) is one of the most widely used organophosphorous insecticides in agriculture with its attendant adverse health outcomes. This study aimed at evaluating the effect of subchronic oral CPF administration on hematological and serum biochemical indices, and the possible ameliorating effect of vitamin C on the indices in mice. Thirty mice divided into 3 groups of 10 mice each were used for this study. Mice in group I (control) were dosed with vegetable oil, while those in group II were given CPF (21.3 mg/kg~ 1/5(th) LD(50)) only. Mice in group III were pretreated with vitamin C (100 mg/kg) prior to dosing with CPF 30 min later (Vitamin C + CPF-treated group). This regime was given to each group of mice three times a week for a period of ten weeks. During the study period, mice were examined for signs of toxicity, and weight of each mouse was measured every week. At the end of the study period, blood samples were collected from the mice and analyzed for packed cell volume (PCV), total red blood cell (RBC), white blood cell (WBC) and total protein (TP). Serum obtained from the blood was analyzed for Na( +, K+ and Cl-), urea, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). The results showed that mice in the vitamin C + CPF-treated group exhibited milder signs of toxicity and significant increase in weight gain (p<0.01) compared to the CPF-treated group. No significant increase in weight in the CPF-treated group was observed compared to the control. There was a significant increase in PCV, RBC, Hb, TP and creatinine, but a significant decrease was obtained in WBC, ALT and AST in the CPF-treated group compared to the control. All the parameters with the exception of WBC, ALT and AST (which increased significantly), were significantly decreased in the vitamin C + CPF-treated group compared to CPF-treated group. ALP was significantly elevated in the CPF-treated group compared to both the control and vitamin C + CPF-treated group. No significant changes in urea and the measured electrolytes in all three groups, except a significant decrease in the concentration of Na(+) was observed in the CPF-treated group compared to the control. The study demonstrated that pretreatment of CPF-administered mice with vitamin C significantly altered some important hematological and serum biochemical parameters, revealing the protective action of the vitamin against some organ damage induced by CPF.     

Cyclophosphamide treatment causes impairment of sperm and its fertilizing ability in mice

This study is focused on the toxicological effect of cyclophosphamide on male mice reproductive system. In the present study, cyclophosphamide was injected intraperitoneally (ip) at the level of 50-200mg/kg body weight into 6-weeks old ICR male mice once in a week for a period of 5 weeks. The animals were sacrificed after 1st and 5th week of last injection. Reduction in weight of testis and epididymis were observed both in 1st and 5th week group mice after administration with increasing concentration of cyclophosphamide. The weight of the body significantly decreased in both 1st and 5th week group in mice treated with 200mg/kg cyclophosphamide. The weight of the testis significantly decreased with all doses of cyclophosphamide in 1st week group, whereas, in 5th week group significant reduction was observed only in 200mg/kg dose of cyclophosphamide. The sperm motility was analyzed with Computer-Assisted Sperm Analysis (CASA). The motility of caudal sperm decreased with increasing concentration of cyclophosphamide in the 1st week group, whereas, it revived after 5th week. The total sperm counts in the epididymis of 1st week group mice declined significantly while significant restoration of the same was observed with mice treated with 50,100 and 150 mg/kg doses in the 5th week group. The intact acrosome was lower with 150 and 200mg/kg doses in both 1st and 5th week group. The live sperm was reduced to 29% in mice treated with 200mg/kg in the 5th week group. The decrease in the pregnancy rate of female mice was 17, 50, 58 and 100% when mated with male mice injected with 50, 100, 150 and 200mg/kg dose, respectively. Seminiferous tubules of mouse testis were severely damaged in the 1st week group. However, reinstate of sperm within the seminiferous tubules was observed in the 5th week group mice. Significant decrease in serum luteinizing hormone (LH) was observed in the 1st week group treated with 50, 100, 150 and 200mg/kg dose of cyclophosphamide. However, no significant difference was observed in the serum follicle-stimulating hormone (FSH), whereas, a decrease of about 98% in serum testosterone level was observed in cyclophosphamide treated mice. The decrease in the mean testosterone levels of cyclophosphamide treated mice served as proof for the damage of testis. These results demonstrate that cyclophosphamide caused temporary interference of normal male reproductive system with low dose treatment, but might be permanent dysfunction in high dose treatment.     

Protection against chronic cadmium toxicity by glycine.

A Japanese drug containing glycine, glycyrrhizin, and cysteine (Stronger Neo-Minophagen C) has been reported to protect against chronic cadmium (Cd) toxicity. The present study was conducted to evaluate which of the three constituents of this drug was the main antagonist for Cd toxicity and whether the mechanism of protection involved antioxidant action. Adult female Sprague-Dawley rats were injected sc with 5 micromol CdCl2/kg per day, five times per week, for 15 weeks. Four groups of Cd-injected animals received co-treatments with either 10 mg glycyrrhizin/kg, 100 mg glycine/kg, 5 mg cysteine/kg, or with a mixture of all three compounds, five times per week, starting from week 7. An additional Cd-injected group was co-treated with vitamin E (100 mg/kg, five times per week, starting from week 7) as a positive control. Only those animals that received vitamin E, Minophagen mixture, or glycine were protected against Cd-induced hepatotoxicity as well as nephrotoxicity. All three co-treatments suppressed Cd-induced hepatic and renal lipid peroxidation. We conclude that the reported beneficial effects of Stronger Neo-Minophagen C are due to glycine, which appears to protect against chronic Cd toxicity by reducing oxidative stress.     

Combined effects of vitamin C, vitamin E, and sodium selenate supplementation on absolute ethanol-induced injury in various organs of rats

In this study, the effect of combination of vitamin C (ascorbic acid), vitamin E (alpha -tocopherol), and selenium (sodium selenate) on ethanol-induced liver and intestine injury in rats was investigated. The ethanol-induced injury was produced by the administration of 1 ml of absolute ethanol to each rats. Animals received vitamin C (250 mg/kg), vitamin E (250 mg/kg), and sodium selenate (Se) (0.5 mg/kg) for 3 days; 1 h after the final antioxidant administration, they were sacrificed. Lipid peroxidation and glutathione levels, catalase (CAT), lactate dehydrogenase (LDH), superoxide dismutase (SOD), and glutathione peroxidase (GP(x)) activities were determined in liver and intestine tissues. Myeloperoxidase (MPO), aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT) were determined in liver tissue. Also, CAT activity, urea, creatinine, uric acid, and total lipid levels were determined in serum samples. In the ethanol group, serum urea, creatinine, uric acid, and total lipid levels; liver and intestine LDH; liver MPO, AST, ALP, ALT, and GGT activities; and liver and intestine LPO levels increased, whereas serum CAT activity, liver and intestine GSH levels, and CAT, SOD, and GP(x) activities decreased. On the other hand, treatment with vitamin C, vitamin E, and Se reversed these effects. As a result of these findings, we can say that the combination of vitamin C, vitamin E, and selenium has a protective effect on ethanol-induced changes in lipid peroxidation, glutathione levels, and antioxidant enzyme activities in liver and intestine tissues, and in some serum parameters of rats.     

Effects of vitamin C and E on liver enzymes and biochemical parameters of rabbits exposed to aflatoxin B1

Hepatotoxic substances such as aflatoxin B1 (AFB1) produce free radical reactions during biotransformation damage to liver cells. Vitamins C and E are important natural antioxidants suppressing free radicals. This study investigated the effects of vitamins C and E on liver enzymes and other biochemical parameters in rabbits experimentally exposed to AFB1. The first group was control and fed the diet with dimethyl sulfoxide; the second group received 0.1 mg AFB1/kg diet; the third group received vitamin C (100 mg L-ascorbic acid/kg diet); the fourth group received vitamin E (100 mg alpha-tocopherol/kg diet); and the fifth group received vitamin C+vitamin E (100 mg L-ascorbic acid/kg diet+100 mg alpha-tocopherol/kg diet). Diets of the second, third, fourth and fifth groups were mixed with 0.1 mg AFB/kg diet) and feedings were continued for 10 w. Levels of aspartate transaminase, alanine transaminase, alkaline phosphatase, creatine phosphokinase and lactate dehydrogenase after receiving AFB1 were significantly increased, while activities of aspartate transaminase, alanine transaminase, amylase, creatine phosphokinase and lactate dehydrogenase in groups receiving AFB1 + vitamins C, E or C+E were significantly lower than that of the AFB1-alone group. Although of the activity of alkaline phosphatase increased with AFB1 exposure, it decreased with vitamin C administration. Levels of urea, triglyceride, cholesterol and albumin were affected by AFB1 and AFB1+vitaminC. AFB1 affected some liver enzymes and other biochemical parameters, but vitamins C, E and C+E partially prevented an increase in these liver enzymes and some the biochemical parameters induced by AFB1.     

Oren-gedoku-to and Keishi-bukuryo-gan-ryo inhibit the progression of atherosclerosis in diet-induced hypercholesterolemic rabbits

In this study, we examined whether the Kampo formulas Oren-gedoku-to (OGT, Huanglian-jie-du-tang in Chinese) and Keishi-bukuryo-gan-ryo (KBG, Gui-zhi-fu-ling-wan in Chinese) could prevent the progression of atherosclerosis in cholesterol-fed rabbit, an animal model for hypercholesterolemia in vivo. Twenty-four male Japanese white rabbits (2 kg body weight) were divided into four groups. The control group was fed standard rabbit chow containing 1% cholesterol, the OGT group was fed standard rabbit chow containing 1% cholesterol and 1% OGT, the KBG group was fed standard rabbit chow containing 1% cholesterol and 1% KBG, and the vitamin E group was fed standard rabbit chow containing 1% cholesterol and vitamin E (450 mg/1000 g). All four groups were kept on these diets for 8 weeks. At the end of the experiments, the percentage of surface area of the total thoracic aorta with visible plaque was significantly reduced in the OGT and KBG groups. The serum thiobarbituric acid reactive substances of the vitamin E group showed a significantly low value compared with the control group, whereas the serum lipid peroxide levels of the OGT and KBG groups were considerably lower than that of the control groups as well as that of the vitamin E group. Furthermore, the urinary 8-hydroxydeoxyguanosine levels of the OGT and KBG groups were considerably lower than that of the vitamin E group. These results suggest that OGT and KBG prevent the progression of atheromatous plaque by creating a sounder antioxidant defense system than vitamin E.