Hepatoprotective effects of vitamin E against hexachlorobenzene-induced hepatotoxicity and oxidative stress in rats: histological,biochimical and antioxidant status changes

The protective effects of α-Tocopherol (vitamin E) on liver injury induced by hexachlorobenzene (HCB) were investigated in adult male rats of Wistar strain. Animals were randomly divided into six groups of eight rats each. Group 1 and 2 have received HCB, dissolved in olive oil, at a dose of 4?mg or 16?mg/kg b.w., respectively. Group 3 and 4 were treated by the same doses of HCB (4?mg and 16?mg/kg b.w.) after 1?h of pretreatment with α-tocopherol at a dose of 100?mg kg^?1 b.w. The other two groups served as controls; which received either olive oil only, a solvent of HCB, or α-tocopherol. A significant increase in hepatic lipid peroxidation (LPO) and GSH activity were observed following HCB administration. The activities of antioxidant enzymes like superoxide dismutase and catalase were significantly decreased while glutathione peroxidase was significantly increased following HCB administration. Similarly, a significant increase in plasma levels of various marker enzymes [aminotransferase (aspartate aminotransférase (AST) and alanine aminotransferase (ALT)), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH)] and a decrease of total protein level were observed. Pretreatment with vitamin E of HCB treated rats ameliorated all biochemical parameters to near normal values. Liver histological study confirmed biochemical parameters and the beneficial role of vitamin E.     

Hepatoprotective effects of zingerone on carbon tetrachloride- and dimethylnitrosamine-induced liver injuries in rats

In this study, we investigated the hepatoprotective and anti-fibrotic effects of zingerone, one of the active components of ginger, against carbon tetrachloride (CCl₄)- and dimethylnitrosamine (DMN)-induced liver injuries in rats, respectively. Oral administration of zingerone (10 mg/kg) reduced CCl₄-induced abnormalities in liver histology, serum alanine aminotransferase and aspartate aminotransferase levels, and liver malondialdehyde levels. Zingerone treatment attenuated CCl₄-induced increases in inflammatory mediators, including tumor necrosis factor-α, interleukin-1β, cyclooxygenase-2, and inducible nitric oxide synthase mRNA levels. Western blot analysis showed that zingerone suppressed activation of nuclear factor-kappa B (NF-κB) p65 and phosphorylation of extracellular signal-regulated kinase, c-Jun NH₂-terminal kinase, and p38 mitogen-activated protein kinases (MAPKs). Liver fibrosis induced by DMN (10 mg/kg, intraperitoneally) was ameliorated by administration of zingerone (10 and 20 mg/kg, orally). Zingerone treatment reduced DMN-induced elevation of hydroxyproline content and hepatic stellate cell activation. In conclusion, zingerone showed antioxidative and anti-inflammatory effects in CCl₄-intoxicated rats by inhibiting oxidative stress and NF-κB activation via blockade of the activation of upstream MAPKs. Moreover, zingerone had hepatoprotective and anti-fibrotic effects against DMN-induced liver injury suggesting its usefulness in the prevention of liver inflammation and the development of hepatic fibrosis.     

Hepatoprotective and antioxidant effects of baicalin against CCl4-induced hepatotoxicity

Scutellaria baicalensis is widely cultivated in eastern Asia, particularly in China. In the present study, we isolated baicalin from this plant and studied for its hepatoprotective activity against CCl₄-induced oxidative damage in rats. Our findings revealed that baicalin exhibited strong antioxidant activity in vitro. In established in vivo tests, baicalin showed effective protective effects by reducing the elevated levels of glutamate pyruvate transaminase(ALT), aspartate aminotransferase(AST), alkaline phosphatase (ALP), total bilirubin (TB) and malondialdehyde (MDA) against CCl₄-induced damage, and it restored the activities antioxidant defense substances, such as superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH), toward their normal levels. These data were supplemented with histopathological examination of rat liver sections. The results demonstrated that baicalin could be proposed to protect the liver against CCl₄-induced oxidative damage in rats, and the possible underlying mechanism of the activity could be due to its free radical-scavenging and antioxidant activity.     

The ameliorating effects of selenium and vitamin C against fenitrothion-induced blood toxicity in Wistar rats

Fenitrothion is widely used organophosphate pesticide in agriculture and health programs, but besides, it causes several toxic effects. The present study was designed to evaluate the possible protective effects of selenium (0.5 mg/kg b.w.) and vitamin C (100 mg/kg b.w) on altered haematological, biochemical and oxidative stress parameters in the blood of rats orally treated with fenitrothion (20 mg/kg b.w) for 30 days. Fenitrothion caused changes in body weight, food and water intake, and some haematological and biochemical parameters. Fenitrothion altered the glutathione redox status (GSH and GSSG) and decreased activity of antioxidant enzymes (GSH-Px, GST, SOD and CAT), leading to a lipid peroxidation. Selenium and vitamin C, by improving the activity of antioxidants, reduced oxidative stress and a lipid peroxidation, maintaining the values of examined parameters to optimal levels. Therefore, selenium and vitamin C could be useful in providing protection of exposed non-target organisms including people from fenitrothion.     

Hepatoprotective and antioxidant activity of Leucas aspera against d-galactosamine induced liver damage in rats

Context: Whole plant of Leucas aspera (LA) Willd. (Labiatae) is traditionally used in Siddha medicine for hepatic ailments.

Objective: LA was investigated for its hepatoprotective, antioxidant, and protective effect on microsomal drug metabolizing enzymes (MDMEs).

Materials and methods: LA aqueous extract (200 and 400 mg/kg, p.o.) was evaluated for its hepatoprotective and antioxidant activity in d-galactosamine (d-GalN)-induced hepatotoxicity in rats. Biochemical and histopathological studies were performed to assess hepatoprotective activity. Hexobarbitone-induced sleeping time model was used to study the protective effect of LA on MDMEs.

Results: d-GalN administration induced hepatotoxicity in rats which was manifested by increased levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total cholesterol, triglycerides, total bilirubin and oxidative stress. Pretreatment with LA extract significantly protected the liver in d-GalN administered rats. LA extract significantly elevated antioxidant enzymes like superoxide dismutase, catalase, glutathione peroxidase and decreased lipid peroxidation levels in liver. The total phenolic and flavonoid content in LA aqueous extract was found to be 28.33 ± 0.19 gallic acid equivalents mg/g of extract and 3.96 ± 0.57 rutin equivalent mg/g of extract, respectively. LA extract (200 and 400 mg/Kg) treatment with CCl₄ decreased the hexobarbitone-induced sleeping time in mice by 56.67 and 71.30%, respectively, which indicated the protective effect of LA on hepatic MDMEs. Histological studies showed that LA at 400 mg/kg attenuated the hepatocellular necrosis in d-GalN intoxicated rats.

Conclusion: Our results contribute towards validation of the traditional use of LA in hepatic disorders.     

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.     

Influence of vitamin E and selenium on glutathione-dependent protection against microsomal lipid peroxidation

A GSH-dependent microsomal protein which inhibits lipid peroxidation has been described [R. F. Burk, Biochim. biophys. Acta 757, 21 (1983)]. Studies of its mechanism indicate that it scavenges free radicals. Vitamin E (alpha-tocopherol) and selenium are micronutrients which protect against lipid peroxidation. The effect of nutritional deficiencies of these substances on the GSH-dependent protection against rat liver microsomal lipid peroxidation was studied to determine whether GSH, selenium and alpha-tocopherol function through separate or shared mechanisms. In the ascorbate-iron microsomal lipid peroxidation system, there is a 1-3 min lag phase before lipid peroxidation begins. The length of the lag correlated well (r = 0.87) with the microsomal alpha-tocopherol content as measured by high pressure liquid chromatography. Thus, the selenium-deficient microsomes, which had a shorter lag than controls, had a somewhat lower alpha-tocopherol content. The vitamin E-deficient microsomes, which had no detectable alpha-tocopherol, had the shortest lag, but a distinct lag was present. Addition of 0.1 mM GSH to control microsomes prolonged the lag by 270%. In selenium-deficient and vitamin E-deficient microsomes, which had shorter initial lags, GSH addition caused 345 and 280% increases respectively. This suggests that the function of the GSH-dependent protective mechanism is unimpaired in these deficiencies. Trypsin digestion of microsomes, which abolished the lag completely and destroyed the GSH-dependent protection, had no effect on microsomal alpha-tocopherol content, however. These experiments illustrate the importance of two defenses against microsomal lipid peroxidation: the GSH-dependent protein which is responsible for the existence of the lag, and alpha-tocopherol which affects the length of the lag. They suggest that these defenses function separately to prevent peroxidation of membrane polyunsaturated fatty acids. Selenium appears to affect microsomal alpha-tocopherol content but to have no other effect on the microsomal lipid peroxidation system.     

The role of vitamin C, vitamin E, and selenium on cadmium-induced renal toxicity of rats

The aim of this study was to determine whether vitamin C, vitamin E, and selenium have protective effects against cadmium-induced renal toxicity of rats. Vitamin C (250 mg/kg/day), vitamin E (250 mg/kg/day), and sodium selenate (0.25 mg/kg/day) were given to rats orally for 8 days. Cadmium (2 mg/kg/day CdCl2) was given to rats intraperitoneally. Vitamin C, vitamin E, and selenium (in the same dose and time) were given 1 h prior to the administration of cadmium every day. The tissue and blood samples were taken from the rats for histological evaluation and biochemical analyses on the Day 9. Lipid peroxidation (LPO) and glutathione (GSH) determination were made in kidney tissue. In addition, urea and creatinine levels were determined in serum. The damage to the kidney tissue was moderate in the rats given cadmium. In this group, the distinctive changes in the proximal tubules were observed. Degenerative changes in kidney tissue were also observed in rats given vitamin C, vitamin E, selenium, and cadmium. LPO levels significantly increased and GSH levels decreased in kidney tissues following cadmium administration. Serum urea and creatinine levels were also increased in rats given cadmium. The administration of vitamin C, vitamin E, and selenium caused a significant decrease in LPO levels and an increase in GSH levels in the kidney of rats given cadmium. Serum urea and creatinine levels were decreased in rats given both the antioxidant and cadmium. It is concluded that vitamin C, vitamin E, and selenium showed some protective effect on the rat kidney.     

Hepatoprotective and antioxidant effects of porcine plasma protein hydrolysates on carbon tetrachloride-induced liver damage in rats

Porcine plasma protein hydrolysate (PPH) prepared by alcalase for 5 h was fractioned by ultrafiltration. Four fractions, H₁ (MW > 10k), H₂ (MW 6-10k), H₃ (MW 3-6k) and H₄ (MW < 3k), were obtained. H₄ possessed the highest antioxidant activity as indicated by thiobarbituric acid-reactive substance values and hydroxyl radical scavenging activity (P < 0.01). Male rats were pretreated with H₄ at dose of 50, 100, and 200 mg/kg of body weight orally once daily for 12 days, then they were treated intraperitoneally with a single dose of CCl₄ (2 mL/kg of body weight). The results showed that oral feeding of H₄ could significantly lower (P < 0.01) the serum levels of hepatic enzyme markers (aspartate transaminase and alanine transaminase). Compared with the CCl₄-only treatment group, levels of hepatic superoxide dismutase, glutathione peroxidase, catalase and total antioxidant capacity were significantly increased, and the malondialdehyde levels were sharply decreased (P < 0.01) in rats treated by all doses of PPH fraction H₄. A histological examination of the liver showed that lesions, including necrosis, lymphocyte infiltration and fatty degeneration, were partially healed by treatment with H₄ fractions. These data suggest that in rats, PPH can protect the liver against CCl₄-induced oxidative damage.     

Effects of vitamin E, vitamin C, and selenium on gastric fundus in cadmium toxicity in male rats

Cadmium (Cd) is a highly toxic metal. It has an indirect role in the generation of various free radicals. Antioxidants such as vitamin E, vitamin C, and selenium are important for preventing the damage caused by reactive oxygen species. This study was undertaken to examine the effect of acute cadmium and/or antioxidants on serum lipid metabolism, tissue glutathione, and lipid peroxidation (LPO) levels, and ghrelin and metallothionein production in the gastric fundus mucosa of rats. Cd (2 mg/kg/day CdCl(2)) was administered to rats for 8 days, intraperitoneally. Vitamin E (250 mg /kg/day) + vitamin C (250 mg/kg/day) + sodium selenate (0.25 mg /kg/day) were administered to rats orally at the same time. The animals were treated by antioxidants 1 h prior to treatment with Cd every day. Gastric tissue homogenates were used for protein and glutathione and LPO levels. Phospholipid and total lipid levels were determined in serum. Gastric fundus sections examined for histopathological changes and by immunohistochemistry for expression of ghrelin and metallothionein. In the group treated with Cd, degenerative changes such as discontinuity in the surface epithelium were observed. The degenerative changes induced by Cd were decreased in the group given vitamin E + vitamin C + selenium. There was no significant change in ghrelin- and metallothionein-immunoreactive cells in fundus mucosa. Stomach glutathione levels insignificantly decreased in the Cd groups, but in the Cd group given antioxidant, stomach glutathione levels were significantly increased. Serum phospholipid and total lipid levels were significantly increased in the Cd groups. On the other hand, treatment with antioxidants reversed these effects. These results indicate that antioxidants partly prevent the toxicity of Cd in rat gastric fundus.     

Hepatoprotective effects of cod liver oil against sodium nitrite toxicity in rats

Abstract

Context: Exposure to high levels of nitrites for a prolonged time have adverse health effects on several organs especially the liver due to oxidative properties. Meanwhile, cod liver oil has been reported to ameliorate organ dysfunction in animal models that involve oxidative stress.

Objective: Examine the impact of dietary cod liver oil on sodium nitrite-induced liver damage.

Materials and methods: Thirty-two adult male Sprague-Dawely rats were daily treated with sodium nitrite (80?mg/kg) in presence or absence of cod liver oil (5?ml/kg). Morphological changes were assessed in liver sections. Oxidative stress and antioxidant markers were measured in serum and liver homogenates. Liver samples were used for measurements of MCP-1, DNA fragmentation and mitochondrial function.

Results: The hepatoprotective effect of cod liver oil was proved by significant reduction of elevated liver enzymes and normal appearance of hepatocytes. Cod liver oil significantly reduced hepatic malondialdehyde, hydrogen peroxide and superoxide anion (224.3?±?18.9?nmol/g, 59.3?±?5.1 and 62.5?±?5.1?µmol/g, respectively) compared with sodium nitrite (332.5?±?25.5?nmol/g, 83.1?±?8.1 and 93.9?±?6.5?µmol/g, respectively). Cod liver oil restored hepatic cytochrome c oxidase activity after 38% reduction by sodium nitrite. Furthermore, cod liver oil significantly reduced hepatic MCP-1 (79.8?pg/mg) and DNA fragmentation (13.8%) compared with sodium nitrite (168.7?pg/mg and 41.3%, respectively).

Discussion and conclusion: Cod liver oil ameliorates sodium nitrite induced hepatic impairment through several mechanisms including attenuation of oxidative stress, blocking MCP-1, reactivation of mitochondrial function and reduction of DNA fragmentation.     

Hepatoprotective role and antioxidant capacity of pomegranate (Punica granatum) flowers infusion against trichloroacetic acid-exposed in rats

This study was designed to investigate the protective and antioxidant properties of Punica granatum (PG) beverage against trichloroacetic acid (TCA)-exposure in rats. The hepatopreventive and antioxidant potential of the plant’s infusion was evaluated by measuring level of serum enzymes, antioxidant defense systems (ADS) and lipid peroxidation content in various organs of rats. Three experimental groups: A (untreated = control), B (only TCA-treated) and C (TCA+PG treated). According to the results, while the levels of AST and ALT increased significantly in B groups’ they decreased significantly in the C groups’. LDH and CK did not change significantly in B groups’ whereas decreased significantly in the C groups’. Liver, brain, kidney and heart tissues MDA content significantly increased in B groups’, whereas no significant changes were observed in the C groups’. On the other hand, SOD decreased significantly in liver of the B group but did not change significantly in the C groups’. GST activity increased significantly in liver, brain and spleen of C group while significant decrease was observed for kidney as compared to those of control. Hence, the study reveals that constituents present in PG impart protection against carcinogenic chemical induced oxidative injury that may result in development of cancer during the period of a 52-day protective exposure.     

Hepatoprotective and antioxidant activity of N-acetyl cysteine in carbamazepine-administered rats

Objectives:

The present study evaluates the hepatoprotective activity of N-acetyl cysteine (NAC) against carbamazepine (CBZ)-induced hepatotoxicity.

Materials and Methods:

Rats were treated with CBZ (50 mg/kg p.o.) and CBZ supplemented with NAC 50, 100 and 200 mg/kg for 45 days, after which blood samples were collected and subjected to liver function tests. Animals were killed, liver was separated, weighed and the levels of antioxidants and liver enzymes were estimated. In addition, histopathological investigation was also performed.

Results:

Serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate (SGOT) transaminase, alkaline phosphatase (ALP), bilirubin, lipid peroxidation, absolute and relative liver weights were significantly (P < 0.05) elevated, whereas serum levels of albumin, total protein and body weight were decreased in the CBZ-treated animals. CBZ also produced vacuolar degeneration, centrilobular congestion and hepatic necrosis as evidenced from histopathological report. NAC significantly reduced the levels of serum transaminase, ALP, bilirubin and liver weight and increased the levels of total protein, albumin and body weight.

Conclusion:

It was observed that NAC increased the glutathione (GSH) content, reduced lipid peroxidation and reversed the CBZ-induced histopathological abnormalities. CBZ-induced hepatotoxicity may be due its toxic epoxide metabolite-induced oxidative stress.KEY WORDS: Carbamazepine, hepatotoxicity, N-acetyl cysteine, oxidative stress     

The interactive effects of mercury and selenium on metabolic profiles,gene expression and antioxidant enzymes in halophyte Suaeda salsa

Suaeda salsa is the pioneer halophyte in the Yellow River Delta and was consumed as a popular vegetable. Mercury has become a highly risky contaminant in the sediment of intertidal zones of the Yellow River Delta. In this work, we investigated the interactive effects of mercury and selenium in S. salsa on the basis of metabolic profiling, antioxidant enzyme activities and gene expression quantification. Our results showed that mercury exposure (20 μg L^?1) inhibited plant growth of S. salsa and induced significant metabolic responses and altered expression levels of INPS, CMO, and MDH in S. salsa samples, together with the increased activities of antioxidant enzymes including SOD and POD. Overall, these results indicated osmotic and oxidative stresses, disturbed protein degradation and energy metabolism change in S. salsa after mercury exposures. Additionally, the addition of selenium could induce both antagonistic and synergistic effects including alleviating protein degradation and aggravating osmotic stress caused by mercury. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 440–451, 2016.     

Protective effects of vitamin E and selenium against dimethoate‐induced cardiotoxicity in vivo: Biochemical and histological studies

There is considerable interest in the study of free radical‐mediated damage to biological systems due to pesticide exposure. However, there is a lack of consensus as to which determinations are best used to quantify future risks arising from xenobiotic exposure and natural antioxidant interventions. Our study investigated the potential ability of selenium and/or vitamin E, used as nutritional supplements, to alleviate cardiotoxicity induced by dimethoate. Female Wistar rats were exposed for 30 days either to dimethoate (0.2 g L^?1 of drinking water), dimethoate+selenium (0.5 mg kg^?1 of diet), dimethoate+vitamin E (100 mg kg^?1 of diet), or dimethoate+selenium+vitamin E. The exposure of rats to dimethoate promoted oxidative stress with a rise in malondialdehyde, advanced protein oxidation, and protein carbonyl levels. An increase of glutathione peroxidase, superoxide dismutase, and catalase activities was also noted. A fall in acetylcholinesterase and Na⁺K⁺‐ATPase activities, glutathione, nonprotein thiols, vitamins C and E levels was observed. Plasma levels of cholesterol, triglycerides, and low density lipoprotein‐cholesterol increased and those of high density lipoprotein‐cholesterol decreased. Coadministration of selenium or vitamin E to the diet of dimethoate‐treated rats ameliorated the biochemical parameters cited above. The histopathological findings confirmed the biochemical results and the potential protective effects of selenium and vitamin E against cardiotoxicity induced by dimethoate. © 2011 Wiley Periodicals, Inc. Environ Toxicol 28:630–643, 2013.     

Co-consumption of selenium and vitamin E altered the reproductive and developmental toxicity of methylmercury in rats

Methylmercury (MeHg), an environmental contaminant primarily found in fish and seafood, may pose long-term health risks to pregnant women and their developing children. The objective of this study was to determine whether co-consumption of nutritional supplements would alter the effects of MeHg on reproductive and developmental toxicity using a rodent model. Adult female rats were fed a diet containing additional selenium (1 ppm), additional vitamin E (225 IU/kg) or a combination of the two for 4 weeks before oral dosing of MeHg (1.25 mg/kg/day). Treatment with MeHg and dietary supplementation continued throughout pregnancy after which the dams were allowed to deliver their offspring. In addition to routine evaluations including periodic body weight measurements and daily clinical signs observations, dams and pups were evaluated for auditory startle habituation and pups were evaluated for developmental landmarks and reflexology. The dams and offspring were euthanized approximately 4 weeks after birth of the offspring. Results indicated that treatment with MeHg caused adverse effects on both reproduction of the dams and decreased progeny survival. However, the dams showed significant improvement in body weight gain during lactation and average auditory startle response time when the diet was enriched with both selenium and vitamin E. The combination of both vitamin E and Se also resulted in a significant increase in post-natal survival when compared to MeHg-treated group. There was no nutrient effect on the MeHg toxicity shown in offspring physical landmarks, performance in reflex tests and assessment of simple auricular startle response. Also, accelerated development as indicated by earlier opening in the pups of the supplemental diet groups was observed. These results suggest that antioxidant nutrients in the diet may alter MeHg reproductive and developmental toxicity. The underlying and human health implications warrant further investigations.     

Excessive dietary selenium decreases the vitamin A storage and the enzymatic antioxidant defence in the liver of rats

This study investigated the influence of selenium intake, over 8 weeks, on vitamin A level and on enzymatic antioxidant defence in the liver of young rats. Deficient animals were fed a well-balanced diet but without selenite addition; the Se content of this diet which originated from natural Se content of ingredients was 0.05 mg/kg. Controls were fed the same diet with 0.40 mg/kg added Se. The two other groups received high levels of Se, 2.05 or 4.05 mg/kg. Excessive Se intake decreased the concentrations of retinol and retinyl palmitate in the liver. The linear regression analysis indicated a significant (P < 0.001) dose-dependent vitamin A decline. As expected, Se deficit lowered glutathione peroxidase activity. The highest Se excess decreased the enzymatic antioxidation: Zn,Cu Superoxide dismutase, catalase, glutathione peroxidase activities. Data showed that high dietary Se can sometimes enhance carcinogenesis and our results suggest that it is best to be cautious in administrating Se to humans with the aim of preventing diseases.     

Enzymatic defense against radiation damage in mice. Effect of selenium and vitamin E depletion

Radiation effects are mediated in part by the generation of oxygen-derived free radicals and hydrogen peroxide. Membrane polyunsaturated fatty acids are important biological targets of these toxic molecules which cause lipid peroxidation. Radiation damage to DNA is also known to result in base hydroperoxides, especially thymidine hydroperoxide. Glutathione (GSH) is known to inhibit lipid peroxidation both chemically and through its interaction with the selenium-dependent glutathione peroxidase (GSH-Px). Although cytosolic GSH-Px can metabolize organic lipid peroxides in solution, it cannot metabolize phospholipid peroxides in micelles. This may be due to the interference of phase differences between the aqueous cytosol and the membrane, or the result of steric hindrance. Recent studies have suggested the presence of a membrane-bound GSH-dependent peroxidase system. We examined the cytosolic versus membrane-associated GSH-Px, in various tissues of mice on a selenium and vitamin E deficient diet, and found significant differences among organs in the distribution of enzyme activity in these two subcellular fractions. The effect of single high-dose whole body irradiation did not appear to be related to the activity of these enzymes.     

Hepatoprotective effects of Portulaca oleracea extract against CCl4-induced damage in rats

Abstract

Context: Purslane (Portulaca oleracea L., Portulacaceae) has been traditionally used in folk medicine to afford protection against liver injury, although its actual efficacy remains uncertain.

Objective: To evaluate purslane as a hepatoprotective agent, we investigated the protective effect of its ethanol extract against carbon tetrachloride (CCl₄)-induced hepatic toxicity in rats.

Materials and methods: A total of 108 male Wistar rats were randomly divided into 12 groups. The first group was maintained as normal control, whereas CCl₄ (0.5?ml/kg bw, 50% CCl₄ in olive oil, i.p.), purslane extract (0.005, 0.01, 0.05, 0.1, and 0.15?g/kg bw, intragastrically), and purslane extract (five doses as above) along with CCl₄ were administered to the Groups II, III–VII, and VIII–XII, respectively. The rats were sacrificed on the 30th day, and blood was withdrawn by cardiac puncture. Liver damage was assessed by measuring hepatic marker enzymes (ALT, AST, ALP, GGT, and SOD) and histopathological observation.

Results: Treatment with CCl₄ resulted in increased serum activities of marker enzymes with a concomitant decrease in SOD. Histological alterations were also observed in the liver tissue upon CCl₄ treatment. Administration of purslane extract (0.01, 0.05, 0.1, and 0.15?g/kg b.w.) significantly showed a marked tendency towards normalization of all measured biochemical parameters in CCl₄-treated rats. Histopathological changes also paralleled the detected alteration in markers of liver function.

Discussion and conclusion: These results demonstrate that purslane exerts protective effects against CCl₄-induced damage in rat liver and supports a potential therapeutic use of purslane as an alternative for patients with liver diseases.     

Effects of melatonin and vitamin E on oxidative-antioxidative status in rats exposed to irradiation

Bone marrow is known to be particularly susceptible to radiation. In this study, the effects of treatment with Vitamin E and melatonin and irradiation-induced lipid peroxidation and its association with antioxidant enzymes in the total bone (bone and bone marrow) and skeletal muscle of rats subjected to total body irradiation was investigated. Wistar-Albino rats were intraperitoneally treated with 100mg/kg Vitamin E or melatonin before exposure to 720cGy irradiation. Control, irradiation, Vitamin E plus irradiation, melatonin plus irradiation groups were sacrificed by decapitation under ether anaesthesia on the 10th day after irradiation exposure. Application of total body irradiation elevated malondialdehyde (MDA) levels in rat skeletal muscle (p<0.001), but glutathione peroxidase (GSH-Px) and catalase activities remained unchanged. Application of Vitamin E with irradiation or melatonin decreased the MDA levels in skeletal muscle (p<0.01), but did not affect the GSH-Px and catalase activity. MDA levels were found elevated in total bone (p<0.001), GSH-Px activity decreased (p<0.001) and catalase activity remained unchanged in the group treated with irradiation. Application of Vitamin E with irradiation increased the GSH-Px activity in total bone (p<0.01), but the activity of MDA and catalase remained unchanged. Treatment of the animals with melatonin concurrent with total body irradiation reduced the degree of lipid peroxidation and elevation in antioxidant enzymes in total bone (p<0.01). We conclude that melatonin may protect the total bone from the damaging effects of irradiation exposure, and its actions protect total bone from oxidative stress. However, protective effects of Vitamin E were not observed in this study.