Selenium and Vitamin E Modulates Cigarette Smoke Exposure-Induced Oxidative Stress in Blood of Rats

Cigarette smoke contains about 5,000 chemicals that include organic and metallic compounds. The current study was undertaken to investigate the effects of selenium and vitamin E on oxidative stress-induced damage in rats exposed to cigarette smoke. Forty male rats were equally divided into four groups. The first and second groups were used as control and cigarette smoke groups, respectively. Selenium was administered to rats constituting the third group for 27 days. The Se and vitamin E combination was given to animals in fourth group for 27 days. All groups except the control, were exposed to cigarette smoke starting at the third day of the experiment and continuing for 27 days. The blood samples from all groups were taken at the end of 27 days. Plasma lipid peroxidation, triacylglycerol, and total cholesterol levels were higher in the cigarette smoke group than in the control, although erythrocytic superoxide dismutase and glutathione peroxidase activities were lower in the cigarette smoke group than in the control. The plasma lipid peroxidation, triacylglycerol, and total cholesterol levels were lower in cigarette smoke+Se+VE group than in the cigarette smoke group, although erythrocytic superoxide dismutase activity and glutathione peroxidase activity in selenium and vitamin E-administered groups were higher than in the exposed to cigarette smoke group. High-density lipoprotein-cholesterol level was not affect by selenium and vitamin E administrations. In conclusion, selenium and vitamin E seem to have protective effects on the cigarette smoke-induced blood toxicity by supporting the enzymatic antioxidant redox systems.     

Antioxidant Enzyme and Element Status in Heroin Addiction or Heroin Withdrawal in Rats: Effect of Melatonin and Vitamin E Plus Se

Heroin use, withdrawal syndrome, and heroin-related deaths are still the most serious public health problems. Antioxidants and bio-elements are essential for metabolism in living organisms. To our knowledge, there are no data about the effect of antioxidant therapy on the levels of bio-elements and antioxidant enzymes in the naloxone (NX)-induced heroin withdrawal syndrome. Therefore, in the present study for the first time, we have investigated the role of antioxidant therapy, melatonin, and vitamin E plus Se, on the trace and major elements and antioxidant enzymes in the heroin addiction or heroin withdrawal in rats. Glutathione peroxidase levels were increased and catalase levels were decreased in the all study groups when compared to the sham group. The level of superoxide dismutase (SOD) in the fixed dose of heroin (FDH) given group was lower; however, in the variable doses of heroin (VDH) given group SOD level was higher. Furthermore, in withdrawal syndrome, Fe, Mg, Mn, and Ti levels were diminished and Al, Ca, and Cu levels were increased in the FDH+NX group. Moreover, Mg, Mn, and Se levels were also diminished and Al level was increased in the VDH+NX group. In conclusion, our results obviously indicated that heroin effected both bio-element status and antioxidant enzyme activities and, exogenous melatonin or vE+Se therapy might relieve on the element and antioxidant enzyme the destructive activity caused by heroin.     

Effects of Selenium with Vitamin E and Melatonin on Cadmium-Induced Oxidative Damage in Rat Liver and Kidneys

The present study was performed to determine the protective effects of melatonin alone and vitamin E with selenium combination against cadmium-induced oxidative damage in rat liver. A total of 60 male rats were equally divided into five groups, one of which acted as control receiving subcutaneous injections of physiological saline. The remaining four groups were treated with subcutaneous injections of cadmium chloride at a dose of 1 mg/kg weight. The first study group received no treatment. The second group was treated with a combination of 60 mg/kg vitamin E and 1 mg/kg sodium selenite. Group 3 was treated with 10 mg/kg melatonin, and the four group received a combination of vitamin E, sodium selenite, and melatonin at the doses mentioned above. After 1 month, the animals were killed, and liver and kidneys were excised for histopathological inspection and determination of tissue malondialdehyde and the activity of superoxide dismutase. The animals receiving no treatment showed significantly higher malondialdehyde levels and reduced activity of superoxide dismutase (p < 0.05). Treatment with antioxidants resulted in a significant reduction in malondialdehyde when compared to nontreated animals (p < 0.05) and increase in the enzyme activity that was almost the same as the controls. The pathological findings were also in parallel with the results of the biochemical analysis. In conclusion, all the agents tested had protective effects against cadmium-induced oxidative damage.     

Melatonin Prevents Oxidative Stress and Hepatocyte Cell Death Induced by Experimental Cholestasis

The induction of oxidative stress precedes liver injury during experimental obstructive jaundice (OJ). In this sense, different evidences suggest that melatonin (MEL), as antioxidant, may be useful in the protection against apoptosis and necrosis during experimental cholestasis. In addition, we will also assess if MEL-dependent protection is related to a recovery of antioxidant status disturbances induced by OJ. Cholestasis was achieved by double ligature and sectioning of the principal bile duct. MEL was injected intraperitoneally (500?μg/kg/day). Lipid peroxidation was evaluated by the measurement of malondialdehyde (MDA) content in liver. Different parameters related to antioxidant status, such as reduced glutathione (GSH), glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD) were determined in liver. Liver injury was assessed by alanine aminotransferase (ALT) in serum, histological examination, DNA fragmentation and TUNEL assay. The activation of perisinusoidal stellate cells was evaluated by immunohistochemical measurement of α-smooth muscle actin in liver sections. The induction of OJ increased all the parameters related to apoptosis and necrosis in liver. The induction of liver injury was associated with stellate cell activation, as well as an increase in MDA (p<0.0001) and a reduction in GSH, GPx, catalase and SOD content (p<0.0001) in liver. MEL reduced hepatic apoptosis and necrosis (p<0.004) with a significant improvement in all oxidative stress markers. In conclusion, our results showed that MEL recovered the antioxidant status and reduced apoptosis and necrosis induced by experimental cholestasis.     

N-Acetylcysteine and Selenium Modulate Oxidative Stress,Antioxidant Vitamin and Cytokine Values in Traumatic Brain Injury-Induced Rats

It has been suggested that oxidative stress plays an important role in the pathophysiology of traumatic brain injury (TBI). N-acetylcysteine (NAC) and selenium (Se) display neuroprotective activities mediated at least in part by their antioxidant and anti-inflammatory properties although there is no report on oxidative stress, antioxidant vitamin, interleukin-1 beta (IL)-1β and IL-4 levels in brain and blood of TBI-induced rats. We investigated effects of NAC and Se administration on physical injury-induced brain toxicity in rats. Thirty-six male Sprague–Dawley rats were equally divided into four groups. First and second groups were used as control and TBI groups, respectively. NAC and Se were administrated to rats constituting third and forth groups at 1, 24, 48 and 72 h after TBI induction, respectively. At the end of 72 h, plasma, erythrocytes and brain cortex samples were taken. TBI resulted in significant increase in brain cortex, erythrocytes and plasma lipid peroxidation, total oxidant status (TOS) in brain cortex, and plasma IL-1β values although brain cortex vitamin A, β-carotene, vitamin C, vitamin E, reduced glutathione (GSH) and total antioxidant status (TAS) values, and plasma vitamin E concentrations, plasma IL-4 level and brain cortex and erythrocyte glutathione peroxidase (GSH-Px) activities decreased by TBI. The lipid peroxidation and IL-1β values were decreased by NAC and Se treatments. Plasma IL-4, brain cortex GSH, TAS, vitamin C and vitamin E values were increased by NAC and Se treatments although the brain cortex vitamin A and erythrocyte GSH-Px values were increased through NAC only. In conclusion, NAC and Se caused protective effects on the TBI-induced oxidative brain injury and interleukin production by inhibiting free radical production, regulation of cytokine-dependent processes and supporting antioxidant redox system.     

Effects of Oxidative Stress on Immunosuppression Induced by Selenium Deficiency in Chickens

Selenium (Se) is an important nutritional trace element possessing immune-stimulatory properties. The aim of this 75-day study was to investigate effect of oxidative stress on immunosuppression induced by selenium deficiency by determining antioxidative function, morphological changes, DNA damage, and immune function in immune organ of chickens. One hundred sixty 1-day-old chickens (egg-type birds) were randomly assigned to two groups of 80 each and were fed on a low-Se diet (0.032?mg/kg Se) or a control diet (0.282?mg/kg Se, sodium selenite), respectively. Se contents in blood and immune organ (thymus, spleen, bursa of Fabricius) were determined on days 30, 45, 60, and 75, respectively. Antioxidative function was examined by total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and xanthine oxidase (XOD), and oxidative damage was examined by malondialdehyde (MDA) detection. DNA damage was measured by comet assay, and immune function was examined by determining serum interleukin-1?? (IL-1??), interleukin-2 (IL-2), and tumor necrosis factor (TNF) contents. The results showed that Se concentrations in the low-Se group were significantly lower (P?<?0.05) than in the control group. Low-Se diet caused a decrease in the activities of T-AOC, SOD, GSH-Px, and an increase in XOD activity and MDA content. Pathological lesions and DNA damage of immune tissues were observed in low-Se group, while the serum IL-1?? and IL-2 contents decreased, and TNF content increased. The present study demonstrated that chickens fed deficient in Se diets exhibited lesions in immune organs, decreased serum IL-1??, IL-2 content, and serum TNF content, indicating that oxidative stress inhibited the development of immune organs and finally impaired the immune function of chickens.     

Melatonin Prevents Oxidative Stress in Ovariectomized Rats Treated with Aluminium

This study is designed to determine the simultaneous effect of aluminium (Al) and melatonin (Mel) treatment in intact and ovariectomized (Ovx) female rats on oxidative stress and their inter-organ relationship in the kidney and liver. Al-treated rats received an intra-peritoneal injection of solution of aluminium lactate (0.575?mg Al/100?g of body weight, three times a week), during 12?weeks. Mel groups received intra-peritoneal injections of melatonin at a dose of 10?mg/kg/day, 5?days/week, during 12?weeks. The results of this study showed that Al treatment in female rats modifies homeostasis of glutathione and the antioxidant capacity of the rat liver and kidney. The alteration of glutathione homeostasis and oxidative status was not associated with an increased lipid peroxidation in both organs with the exception of the increase observed in the liver of Ovx rats. Al also induced modifications in the activity of some enzymes related to the glutathione cycle: GSH-Px in the liver and kidney and glutathione reductase only in the kidney. Al exposure decreased CAT activity in both the kidney and liver of intact and Ovx groups. The administration of Mel in the intact and castrated females treated with Al seems to reduce oxidative changes in the liver and kidney of intact and Ovx rats.     

Effects of Exogenous Selenium on Nicotine-Induced Oxidative Stress in Rats

The effect of two different doses of selenium [1 and 50 μg selenium/100 g body weight (wt)] on nicotine-induced oxidative damage in liver was investigated in experimental rats. Male albino rats were maintained for 60 days as follows: (1) control group (normal diet), (2) nicotine group (0.6 mg/kg body wt)/day, (3) high-dose selenium (50 μg/100 g body wt)/day, (4) high-dose selenium (50 μg/100 g body wt) + nicotine (0.6 mg/kg body wt)/day, (5) low-dose selenium (1 μg/100 g body wt)/day, and (6) low-dose selenium (1 μg/100 g body wt) + nicotine (0.6 mg/kg body wt)/day. Nicotine administration caused a decrease in the activity of antioxidant enzymes, an increase in the concentration of lipid peroxidation products and protein carbonyls and an increase in the activity of nitric oxide synthase compared to the control group. Coadministration of nicotine and selenium reduced the concentration of lipid peroxidation products and increased the activity of antioxidant enzymes compared to the nicotine group. Selenium also enhanced the metabolism of nicotine. The antioxidant effect was more significant in the group administered a low dose of selenium.     

Attenuating Effect of Zinc and Vitamin E on the Intestinal Oxidative Stress Induced by Silver Nanoparticles in Broiler Chickens

The aim of this study was to assess the relationship between magnesium status and oxidative stress in obese and nonobese women. This cross-sectional study included 83 women, aged between 20 and 50 years, who were divided into two groups: the obese group (n = 31) and the control group (n = 52). The control group was age-matched with the obese group. Magnesium intake was monitored using 3-day food records and NutWin software version 1.5. The plasma and erythrocyte magnesium concentrations were determined by flame atomic absorption spectrophotometry. Plasma levels of thiobarbituric acid reactive substances (TBARS) were determined as biomarkers for lipid peroxidation and therefore of oxidative stress. The mean values of the magnesium content in the diet were found to be lower than those recommended, though there was no significant difference between groups (p > 0.05). The mean concentrations of plasma and erythrocyte magnesium were within the normal range, with no significant difference between groups (p > 0.05). The mean concentration of plasma TBARS was higher in obese woman, and the difference between the groups was statistically different (p < 0.05). There was a positive correlation between erythrocyte magnesium and plasma TBARS in the obese group (p = 0.021). Obese patients ingest low dietary magnesium content, which does not seem to affect the plasma and erythrocyte concentrations of the mineral. The study showed a negative correlation between erythrocyte magnesium concentrations and plasma TBARS, suggesting the influence of magnesium status on the parameters of oxidative stress in obese women.     

Efficacy of Vanadyl Sulfate and Selenium Tetrachloride as Anti-Diabetic Agents against Hyperglycemia and Oxidative Stress Induced by Diabetes Mellitus in Male Rats

The use of metals in medicine has grown in popularity in clinical and commercial settings. In this study, the immune-protecting effects and the hypoglycemic and antioxidant activity of vanadyl sulfate (VOSO₄) and/or selenium tetrachloride (Se) on oxidative injury, DNA damage, insulin resistance, and hyperglycemia were assessed. Fifty male albino rats were divided into five groups, and all treatments were administrated at 9:00 a.m. daily for 60 successive days: control, STZ (Streptozotocin; 50 mg/kg of STZ was given to 6 h fasted animals in a single dose, followed by confirmation of diabetic state occurrence after 72 h by blood glucose estimation at >280 mg/dl), STZ (Diabetic) plus administration of VOSO₄ (15 mg/kg) for 60 days, STZ (Diabetic) plus administration of selenium tetrachloride (0.87 mg/Kg), and STZ plus VOSO₄ and, after 1/2 h, administration of selenium tetrachloride at the above doses. The test subjects’ blood glucose, insulin hormone, HbA1C, C-peptide, antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, myeloperoxidase, and xanthine oxidase), markers of lipid peroxidation (MDA), and histological sections of pancreatic tissues were evaluated, and a comet assay was performed. Histological sections in pancreas tissues were treated as indicators of both VOSO₄ and selenium tetrachloride efficacy, either alone or combined, for the alleviation of STZ toxicity. The genotoxicity of diabetes mellitus was assessed, and the possible therapeutic roles of VOSO₄ or selenium tetrachloride, or both, on antioxidant enzymes were studied. The findings show that the administration of VOSO₄ with selenium tetrachloride reduced oxidative stress to normal levels, lowered blood glucose levels, and elevated insulin hormone. Additionally, VOSO₄ with selenium tetrachloride had a synergistic effect and significantly decreased pancreatic genotoxicity. The data clearly show that both VOSO₄ and selenium tetrachloride inhibit pancreatic and DNA injury and improve the oxidative state in male rats, suggesting that the use of VOSO₄ with selenium tetrachloride is a promising synergistic potential ameliorative agent in the diabetic animal model.     

Antioxidant Effects of SelegilIne in Oxidative Stress Induced by Iron Neonatal Treatment in Rats

Increased levels of iron in specific brain regions have been reported in neurodegenerative disorders. It has been postulated that iron exerts its deleterious effects on the nervous system by inducing oxidative damage. In a previous study, we have shown that iron administered during a particular period of the neonatal life induces oxidative damage in brain regions in adult rats. The aim of the present study was to evaluate the possible protective effect of selegiline, a monoamino-oxidase B (MAO-B) inhibitor used in pharmacotherapy of Parkinson’s disease, against iron-induced oxidative stress in the brain. Results have shown that selegiline (1.0 and 10.0 mg/kg), when administered early in life was able to protect the substantia nigra as well as the hippocampus against iron-induced oxidative stress, without affecting striatum. When selegiline (10.0 mg/kg) was administered in the adult life to iron-treated rats, oxidative stress was reduced only in the substantia nigra.     

Selenium and vitamin E for prostate cancer: post-SELECT (Selenium and Vitamin E Cancer Prevention Trial) status

Various formulations of selenium and vitamin E, both essential human dietary components, have been shown to possess a therapeutic and preventive effect against prostate cancer. Fortuitous results of clinical trials also implied a risk-reduction effect of selenium and vitamin E supplements. The Selenium and Vitamin E Cancer Prevention Trial (SELECT), using oral selenium and vitamin E supplementation in disease-free volunteers, was designed to test a prostate cancer chemoprevention hypothesis. SELECT was terminated early because of both safety concerns and negative data for the formulations and doses given. Here, we review and discuss the studies done before and since the inception of SELECT, as well as the parameters of the trial itself. We believe that there is a lack of appropriate in vivo preclinical studies on selenium and vitamin E despite many promising in vitro studies on these agents. It seems that the most effective doses and formulations of these agents for prostate cancer chemoprevention have yet to be tested. Also, improved understanding of selenium and vitamin E biology may facilitate the discovery of these doses and formulations.     

The Influence of Selenium on Root Growth and Oxidative Stress Induced by Lead in Vicia faba L. minor Plants

The effect of selenium (Se) on Vicia faba L. minor roots subjected to lead (Pb) stress was studied by investigating root growth, root viability, and antioxidant enzyme activity. The experiments were carried out on plants grown for 2 weeks on Hoagland medium supplied with 50 μM Pb in the form of lead nitrate Pb(NO(3))(2) and/or Se concentrations of 1.5 and 6 μM in the form of sodium selenite Na(2)SeO(3). It was shown that Pb reduced the root growth and caused serious damage in the roots, which was accompanied by metal accumulation in these tissues. The exposition of roots to Pb led to significant changes in the biochemical parameters: the MDA and T-SH content and glutathione peroxidase (GSH-Px) activity increased but the guaiacol peroxidase (GPOX) activity decreased. Moreover, Pb intensified O(2)(·-) production in the roots. Selenium at a lower concentration alleviated Pb toxicity which was accompanied by a decreased O(2)(·-) production in the apical parts of roots and increased the T-SH content and GPOX activity. However, higher Se concentration intensified MDA and T-SH accumulation and GPOX and GSH-Px activity in Pb-treated plant roots. At low concentration, Se improved cell viability whereas at high concentration it was pro-oxidant and enhanced the lipid peroxidation and cell membrane injury.     

Vitamin E Protects Against Oxidative Damage Caused by Formaldehyde in the Liver and Plasma of Rats

Abstract Background: During myocardial ischemia, accumulation of end products from anaerobic glycolysis (hydrogen ions (H⁺), lactate) can cause cellular injury, consequently affecting organ function. The cells' ability to buffer H⁺ (buffering capacity (BC)) plays an important role in ischemic tolerance. Age related differences in myocardial lactate and H⁺ accumulation (one hour of ischemia) as well as differences in BC, myoglobin (Mb) and histidine (His) contents in the left (LV) and right (RV) ventricles were assessed in neonatal compared to adult pigs. The BC of the septum was also compared. Methods and Results: Neonatal RV and LV had lactate accumulations of 43% and 63% and significantly greater H⁺ (p < 0.004) compared to the adult. In the neonate LV, BC was 17% significantly poorer (p = 0.0001), had 33% lower Mb (p = 0.0002) and 15% lower His content (p = 0.0004) when compared to the adult. In the RV, despite similar BC between the neonate and adult, myoglobin content was 36% (p = 0.0004) lower in the neonate. The neonate septum had a BC that was 11% lower than that of the adult. With maturation, the adult LV had a BC that was 10% greater (p < 0.01) than the RV while the septum mirrored that of the LV. Conclusions: During maturation to adulthood, the BC of the septum begins to closely resemble the LV. Neonatal hearts have a potentially greater vulnerability to acid-base disturbances during ischemia in both ventricles when compared to hearts of adults. This is due to lower levels of myoglobin and histidine in the young, which could render them more susceptible to injury during ischemia.Condensed Abstract During myocardial ischemia, H⁺ and lactate accumulation may pose deleterious effects on the heart. The ability to buffer H⁺ (buffering capacity, BC) affects ischemic tolerance. Although lactate accumulation during 1 h of global ischemia was similar between ventricles of neonatal and adult swine, H⁺ accumulation was greater and BC, Mb and His content were lower. With maturation, LV BC was higher than the RV while septum developmentally resembled the LV. Thus, hearts of neonates may be at a greater risk of ischemic injury compared to hearts of adults. (Mol Cell Biochem xxx: 1–7, 2005)     

Selenium and Vitamin E Deficiency in Pigs

The effect of selenium (Se) and vitamin E (Vit. E) on reproductive performance, growth and health was studied in pigs. Two levels of Se were used, 0.03 and 0.06 nag per kg feed. The major component of the experimental diets was barley originating from soil which had formerly produced crops with a very low content of Se. Prior to seeding, the area was divided into 2 plots, 1 of which was treated with Se in the form of sodium selenite, 100 g Se per ha. The use of Se enriched fertilizer was an effective way of increasing the Se concentration of the grain. Thus the concentration of Se in the barley produced on the treated area was 5 times higher than in barley from the untreated one. Vit. E was added at a level of 30 i.u. per kg feed, and the concentrations were approx. 15 and 45 i.u. in the basal and experimental diets, respectively. The higher level of Se or Vit. E was not significantly associated with milk yield of the sow, litter size, birth weight or haemoglobin levels. However, there was a tendency to an increase in milk yield of the sows following additions of Se plus Vit. E, and litter size was slightly higher from sows which had received an addition of Vit. E. The concentration of Se and Vit. E was much higher in colostrum than in sow milk, and additions of dietary Se and Vit. E were associated with marked increases in the concentrations of these compounds in both colostrum and sow milk. There was a moderately improving effect of a high Se concentration in feed on growth rate and feed utilization. Low dietary levels of Se and Vit. E were followed by increased mortality rate in piglets; iron toxicity in connection with iron treatment was observed in piglets on low dietary Vit. E. Symptoms characteristic of PSE were not observed in the Se and Vit. E deficient pigs.     

Melatonin Modulates Hippocampus NMDA Receptors, Blood and Brain Oxidative Stress Levels in Ovariectomized Rats

We investigated the effects of melatonin administration on ovariectomy-induced oxidative toxicity and N-methyl-d-aspartate receptor (NMDAR) subunits in the blood of rats. Thirty-two rats were studied in three groups. The first and second groups were control and ovariectomized rats. Melatonin was daily administrated to the ovariectomized rats in the third group for 30 days. Blood, brain cortical and hippocampal samples were taken from the three groups after 30 days. Brain cortical, erythrocyte and plasma lipid peroxidation (LP) levels were higher in the ovariectomized group than in controls, although the LP level was decreased in the ovariectomized group with melatonin treatment. Brain cortical and plasma concentrations of vitamins A, C and E as well as the NMDAR 2B subunit were lower in the ovariectomized group than in controls, although, except for plasma vitamin C, they were increased by the treatment. Brain cortical and erythrocyte reduced glutathione (GSH) levels were lower in the ovariectomized group than in controls, although erythrocyte GSH levels were higher in the melatonin group than in the ovariectomized group. Brain cortical and erythrocyte glutathione peroxidase activity and NMDAR 2A subunit concentrations were not found to be different in all groups statistically. Oxidative stress has been proposed to explain the biological side effect of experimental menopause. Melatonin prevents experimental menopause–induced oxidative stress to strengthen antioxidant vitamin and NMDAR 2A subunit concentrations in ovariectomized rats.     

Zinc Deficiency and Oxidative Stress Involved in Valproic Acid Induced Hepatotoxicity: Protection by Zinc and Selenium Supplementation

Valproic acid (VPA) is an antiepileptic drug, which its usage is limited due to its hepatotoxicity. The present study was conducted to investigate the efficacy of zinc (Zn) and selenium (Se), necessary trace elements, against VPA-induced hepatotoxicity in Wistar rats. The animals were divided into five groups: control, VPA 200 mg/kg, VPA + Zn (100 mg/kg), VPA + Se (100 mg/kg), and VPA + Zn + Se. The administration of VPA for four consecutive weeks resulted in decrease in serum level of Zn in rats. Also, an increase in liver marker enzymes (ALT and AST) and also histological changes in liver tissue were shown after VPA administration. Oxidative stress was evident in VPA group by increased lipid peroxidation (LPO), protein carbonyl (PCO), glutathione (GSH) oxidation, and reducing total antioxidant capacity. Zn and Se (100 mg/kg) administration was able to protect against deterioration in liver enzyme, abrogated the histological change in liver tissue, and suppressed the increase in oxidative stress markers. Zn and combination of Zn plus Se treatment showed more protective effects than Se alone. These results imply that Zn and Se should be suggested as effective supplement products for the prevention of VPA-induced hepatotoxicity.