Comparison of melatonin, vitamin E and L-carnitine in the treatment of neuro- and hepatotoxicity induced by thioacetamide

This study was designed to evaluate and compare the effect of melatonin, vitamin E and L-carnitine on brain and liver oxidative stress and liver damage. Oxidative stress and hepatic failure were produced by a single dose of thioacetamide (TAA) (150 mg kg(-1)) in Wistar rats. A dose of either melatonin (3 mg kg(-1)) vitamin E (20 mg kg(-1) ) or L-carnitine (100 mg kg(-1)) was used. Blood samples were taken from the neck vasculature in order to determine ammonium, blood urea nitrogen (BUN) and liver enzymes. Lipid peroxidation products, glutathione (GSH) content and antioxidative enzymes were determined in cerebral and hepatic homogenates. The results showed a decrease in BUN and in the antioxidant enzymes activities and GSH in the brain and liver. Likewise, TAA induced significant enhancement of lipid peroxidation products levels in both liver and brain, as well as in ammonia values. Melatonin, vitamin E and L-carnitine, although melatonin more significantly, decreased the intensity of the changes produced by the administration of TAA alone. Furthermore melatonin combined with TAA, decreased the ammonia levels and increased the BUN values compared with TAA animals. Also it was more effective than vitamin E or L-carnitine in these actions. These data show the protective effect of these agents, especially melatonin, against oxidative stress and hepatic damage present in fulminant hepatic failure.     

Propolis protects CYP 2E1 enzymatic activity and oxidative stress induced by carbon tetrachloride

Induction of CYP 2E1 by carbon tetrachloride (CCl₄) is one of the central pathways by which CCl₄ generates oxidative stress in hepatocytes. Experimental liver injury was induced in rats by CCl₄ to determine toxicological actions on CYP 2E1 by microsomal drug metabolizing enzymes. In this report, ethanolic extract of propolis at a dose of 200 mg/kg (po) was used after 24 h of toxicant administration to validate its protective potential. Intraperitoneal injection of CCl₄ (1.5 ml/kg) induced hepatotoxicity after 24 h of its administration that was associated with elevated malonyldialdehyde (index of lipid peroxidation), lactate dehydrogenase and γ-glutamyl transpeptidase release (index of a cytotoxic effect). Hepatic microsomal drug metabolizing enzymes of CYP 2E1 showed sharp depletion as assessed by estimating aniline hydroxylase and amidopyrine N-demethylase activity after CCl₄ exposure. Toxic effect of CCl₄ was evident on CYP 2E1 activity by increased hexobarbitone induced sleep time and bromosulphalein retention. Propolis extract showed significant improvement in the activity of both enzymes and suppressed toxicant induced increase in sleep time and bromosulphalein retention. Choleretic activity of liver did not show any sign of toxicity after propolis treatment at a dose of 200 mg/kg (id). Histopathological evaluation of the liver revealed that propolis reduced the incidence of liver lesions including hepatocyte swelling and lymphocytic infiltrations induced by CCl₄. Electron microscopic observations also showed improvement in ultrastructure of liver and substantiated recovery in biochemical parameters. Protective activity of propolis at 200 mg/kg dose was statistically compared with positive control silymarin (50 mg/kg, po), a known hepatoprotective drug seems to be better in preventing hepatic CYP 2E1 activity deviated by CCl₄. These results lead us to speculate that propolis may play hepatoprotective role via improved CYP 2E1 activity and reduced oxidative stress in living system.     

Hepatoprotective effect of bis(4‐methylbenzoyl) diselenide against CCl4‐induced oxidative damage in mice

From a pharmacological point of view, organoseleniums are compounds with important and interesting antioxidant and biological activities. The aim of this study was to evaluate the hepatoprotective effect of bis(4‐methylbenzoyl) diselenide (BMD) against carbon tetrachloride (CCl₄)–induced oxidative damage in mice. The animals received BMD (25 mg/kg p.o., for 3 days), and after 1 day, CCl₄ (1 mg/kg body weight) was administered by intraperitoneal route. One day after the CCl₄ exposure, the animals were euthanized for biochemical and histological analysis. Treatment with BMD (25 mg/kg p.o.) protected against aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma‐glutamyl transferase and lactate dehydrogenase activity increases induced by CCl₄ plasma exposure. Treatment with BMD (25 mg/kg) protected against increases in thiobarbituric reactive species and decreasing non‐protein thiols and ascorbic acid levels in liver of mice. Catalase and superoxide dismutase activity inhibition in the liver caused by CCl₄ were protected by treatment with BMD (25 mg/kg). Glutathione S‐transferase activity was inhibited by CCl₄ and remained unaltered even after treatment with BMD. Sections of liver from CCl₄‐exposed mice presented an intense infiltration of inflammatory cells and loss of the cellular architecture. BMD (25 mg/kg) attenuated CCl₄‐induced hepatic histological alterations. The results demonstrated the hepatoprotective effects of BMD in the mouse liver, possibly by modulating the antioxidant status. Copyright © 2012 John Wiley & Sons, Ltd.     

Protective effects of L-carnosine on CCl4 -induced hepatic injury in rats

The present study was undertaken to investigate the possible protective effect of L-carnosine (CAR), an endogenous dipeptide of alanine and histidine, on carbon tetrachloride (CCl₄)-induced hepatic injury. Liver injury was induced in male Sprague-Dawley rats by intraperitoneal (i.p.) injections of CCl₄, twice weekly for six weeks. CAR was administered to rats daily, at dose of 250 mg/kg, i.p. At the end of six weeks, blood and liver tissue specimens were collected. Results show that CAR treatment attenuated the hepatic morphological changes, necroinflammation and fibrosis induced by CCl₄, as indicated by hepatic histopathology scoring. In addition, CAR treatment significantly reduced the CCl₄-induced elevation of liver-injury parameters in serum. CAR treatment also combated oxidative stress; possibly by restoring hepatic nuclear factor erythroid 2-related factor 2 (Nrf-2) levels. Moreover, CAR treatment prevented the activation of hepatic stellate cells (HSCs), as indicated by reduced α-smooth muscle actin (α-SMA) expression in the liver, and decreased hepatic inflammation as demonstrated by a reduction in hepatic tumor necrosis factor-α (TNF-α) and restoration of interleukin-10 (IL-10) levels. In conclusion, CCl₄-induced hepatic injury was alleviated by CAR treatment. The results suggest that these beneficial, protective effects are due, at least in part, to its anti-oxidant, anti-inflammatory and anti-fibrotic activities.     

3-Alkynyl selenophene protects against carbon-tetrachloride-induced and 2-nitropropane-induced hepatic damage in rats

The aim of this study was to investigate the protective effect of 3-alkynyl selenophene (3-ASP) on acute liver injury induced by carbon tetrachloride (CCl₄) and 2-nitropropane (2-NP) in rats. On the first day of treatment, the animals received 3-ASP (25 mg/kg, p.o.). On the second day, the rats received CCl₄ (1 mg/kg, i.p.) or 2-NP (100 mg/kg, p.o.). Twenty-four hours after CCl₄ or 2-NP administration, the animals were euthanized, and their plasma and liver were removed for biochemical and histological analyses. The histological analysis revealed extensive injury in the liver of CCl₄-exposed and 2-NP-exposed rats, which was attenuated by 3-ASP. 3-ASP significantly attenuated (1) the increase in plasmatic aspartate and alanine aminotransferase activities and lipid peroxidation levels induced by CCl₄ and 2-NP; (2) the inhibition of δ-aminolevulinic dehydratase activity caused by 2-NP; and (3) the decrease in ascorbic acid (AA) levels and catalase (CAT) activity caused by CCl₄. AA levels and CAT activity remained unaltered in the liver of rats exposed to 2-NP. The protective effect of 3-ASP on acute liver injury induced by CCl₄ and 2-NP in rats was demonstrated.     

Simvastatin and vitamin E effects on cardiac and hepatic oxidative stress in rats fed on high fat diet

High fat diet (HFD) is a common cause of metabolic syndrome and type 2 diabetes mellitus. Published data showed that HFD and subsequent dyslipidemia are major triggers for oxidative stress. Forty-eight male Sprague–Dawley rats, weighing 170–200 g, were divided into six groups: control, control with vitamin E (100 mg/kg/day, i.p.), control with simvastatin (SIM) (10 mg/kg of body weight/day), HFD, HFD with vitamin E, and HFD with SIM. Standard and high cholesterol diets were given for 15 weeks and SIM and vitamin E were added in the last 4 weeks. In all rats, serum vitamin E, total cholesterol (TC), triglycerides (TG), low (LDL) and high (HDL) density lipoproteins, alanine (ALT) and aspartate (AST) transaminases, alkaline phosphatase (ALP), and gamma glutamyl transpeptidase (GGT) as well as cardiac and hepatic thiobarbituric acid-reactive substances (TBARS) and antioxidants (reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT)) were measured. Also, electrocardiogram (ECG) was recorded. HFD significantly increased QTc interval, heart rate (HR), serum TC, TG, LDL, ALT, AST, ALP, GGT, liver TG, and cardiac and hepatic TBARS but decreased antioxidants and HDL, while SIM decreased HR, liver TG, serum TC, TG, and LDL and increased HDL in HFD rats. Vitamin E had no effect. Moreover, SIM and vitamin E decreased QTc interval, serum ALT, AST, ALP, GGT, and cardiac and hepatic TBARS and increased antioxidants in HFD rats. Histopathological observations confirm the biochemical parameters. SIM and vitamin E slow progression of hypercholesterolemia-induced oxidative stress in liver and heart and improve their functions.     

Protective Effect of Cornuside against Carbon Tetrachloride-Induced Acute Hepatic Injury

This study elucidated the effects of cornuside on carbon tetrachloride (CCl₄)-induced hepatotoxicity. Rats were treated intraperitoneally with 0.5 mL/kg of CCl₄. Sixteen h after CCl₄ treatment, the levels of serum aminotransferases, tumor necrosis factor-α (TNF-α), and lipid peroxidation were significantly elevated, whereas the hepatic antioxidative enzyme activities were decreased. These changes were attenuated by cornuside. Histological studies also indicated that cornuside inhibited CCl₄-induced liver damage. Furthermore, the contents of hepatic nitrite, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were elevated after CCl₄ treatment, while cytochrome P450 2E1 (CYP2E1) expression was suppressed. Cornuside treatment inhibited the formation of liver nitrite, and reduced the overexpression of iNOS and COX-2 proteins, but restored the liver CYP2E1 content as compared with the CCl₄-treated rats. Our data indicate that cornuside protects the liver from CCl₄-induced acute hepatotoxicity, perhaps due to its ability to restore the CYP2E1 function and suppress inflammatory responses, in combination with its capacity to reduce oxidative stress.     

S-allyl cysteine prevents CCl4-induced acute liver injury in rats

Aged garlic extract (AGE) possesses multiple biological activities. We evaluated the protective effect of S-allyl cysteine (SAC), one of the organosulfur compounds of AGE, against carbon tetrachloride (CCl₄)-induced acute liver injury in rats. SAC was administrated intraperitoneally (50–200 mg/kg). SAC significantly suppressed the increases of plasma ALT and LDH levels. SAC also attenuated histological liver damage. CCl₄ administration induced lipid peroxidation accompanied by increases in the plasma malondialdehyde and hepatic 4-hydroxy-2-nonenal levels, and SAC dose-dependently attenuated these increases. The hepatic total level of hydroxyoctadecadienoic acid (HODE), a new oxidative stress biomarker, was closely correlated with the amount of liver damage. These results suggest that SAC decreased CCl₄-induced liver injury by attenuation of oxidative stress, and may be a better therapeutic tool for chronic liver disease.     

Effect of vitamin D3 supplementation on hepatic lipid dysregulation associated with autophagy regulatory AMPK/Akt-mTOR signaling in type 2 diabetic mice

Vitamin D₃ has been reported to protect liver against non-alcoholic fatty liver disease (NAFLD) by attenuating hepatic lipid dysregulation in type 2 diabetes mellitus (T2DM). However, the mechanism of vitamin D₃ on hepatic lipid metabolism-associated autophagy in hyperglycemia-induced NAFLD remains yet to be exactly elucidated. C57BL/6J mice were intraperitoneally injected with 30 mg/kg of streptozotocin and fed a high-fat diet for induction of diabetes. All mice were administered with vehicle or vitamin D₃ (300 ng/kg or 600 ng/kg) by oral gavage for 12 weeks. Histological demonstrations of the hepatic tissues were obtained by H&E staining and the protein levels related to lipid metabolism and autophagy signaling were analyzed by Western blot. Treatment with vitamin D₃ improved insulin resistance, liver damage, and plasma lipid profiles, and decreased hepatic lipid content in the diabetic mice. Moreover, vitamin D₃ administration ameliorated hepatic lipid dysregulation by downregulating lipogenesis and upregulating lipid oxidation under diabetic condition. Importantly, vitamin D₃ treatment induced autophagy by activating AMP-activated protein kinase (AMPK), inactivating Akt and ultimately blocking mammalian target of rapamycin (mTOR) activation in the T2DM mice. Additionally, vitamin D₃ was found to be effective in anti-apoptosis and anti-fibrosis in the liver of diabetic mice. The results suggested that vitamin D₃ may ameliorate hepatic lipid dysregulation by activating autophagy regulatory AMPK/Akt-mTOR signaling in T2DM, providing insights into its beneficial effects on NAFLD in type 2 diabetic patients.     

Anti-apoptotic and antioxidant effect of leptin on CCl4-induced acute liver injury in rats

The aim of this study is to investigate the effect of leptin in rats on carbon tetrachloride (CCl₄) induced acute liver damage using immunohistochemical methods for apoptosis and biochemical parameters. In this experimental study, 18 Spraque-Dawley rats were divided into three groups viz; control, CCl₄ and CCl₄+leptin treatment. 0.8 ml/kg olive oil was administered intraperitoneally (i.p.) to the control group and 0.8 ml/kg CCl₄ (1:1 dissolved in olive oil) was administered i.p. to the CCl₄ and CCl₄+leptin treatment groups, respectively. After 6 h of administrating CCl₄, CCl₄+leptin treatment group was given i.p. leptin (10 μg/kg). Twenty-four hours after administrating CCl₄ all of the groups were euthanized. Biochemical assessments were performed using serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), plasma tumor necrosis factor alpha (TNF-α) levels and tissue malondialdehyde (MDA), and TNF-α levels. Histological assessments were then performed using Hematoxylin&Eosin (H&E) staining in light microscope and apoptosis assessment using Terminal Transferase dUTP Nick End Labeling (TUNEL)-staining. Serum AST, ALT, ALP and plasma TNF-α levels, tissue MDA and TNF-α levels had all increased in CCl₄ group, but were found to be significantly decreased in CCl₄+leptin treatment group. Moreover, TUNEL-positive cell counts in liver had significantly increased in CCl₄ group, but decreased in CCl₄+leptin treatment group (P < 0.05). The results of our study the biochemical, histological and TUNEL-staining showed that leptin has treatment effects on liver CCl₄ induced injury. It plays a role as a potent free radical scavenger, a powerful antioxidant and it also has anti-apoptotic effects.     

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.     

Chicory (Cichorium intybus L.) Root Extract Regulates the Oxidative Status and Antioxidant Gene Transcripts in CCl4-Induced Hepatotoxicity

The ability of Cichorium intybus root extract (chicory extract) to protect against carbon tetrachloride (CCl₄)-induced oxidative stress and hepatotoxicity was evaluated in male rats. The rats were divided into four groups according to treatment: saline (control); chicory extract (100 mg/kg body weight daily, given orally for 2 weeks); CCl₄ (1 ml/kg body weight by intraperitoneal injection for 2 consecutive days only); or chicory extract (100 mg/kg body weight daily for 2 weeks) + CCl₄ injection on days 16 and 17. The levels of hepatic lipid peroxidation, antioxidants, and molecular biomarkers were estimated twenty-four hours after the last CCl₄ injection. Pretreatment with chicory extract significantly reduced CCl₄-induced elevation of malondialdehyde levels and nearly normalized levels of glutathione and activity of glutathione S-transferase, glutathione peroxidase (GPx), glutathione reductase, catalase (CAT), paraoxonase-1 (PON1), and arylesterase in the liver. Chicory extract also attenuated CCl₄-induced downregulation of hepatic mRNA expression levels of GPx1, CAT and PON1 genes. Results of DNA fragmentation support the ability of chicory extract to ameliorate CCl₄-induced liver toxicity. Taken together, our results demonstrate that chicory extract is rich in natural antioxidants and able to attenuate CCl₄-induced hepatocellular injury, likely by scavenging reactive free radicals, boosting the endogenous antioxidant defense system, and overexpressing genes encoding antioxidant enzymes.     

Alterations in susceptibility to carbon tetrachloride toxicity and hepatic antioxidant/detoxification system in streptozetocin-induced short-term diabetic rats: Effects of insulin and Schisandrin B treatment

The streptozotocin-induced short-term (2 week) diabetic rats showed an increase in susceptibility to carbon tetrachloride (CCl4)-induced hepatocellular damage. This diabetes-induced change was associated with a marked impairment in the hepatic glutathione antioxidant/detoxification response to CCl₄ challenge, as indicated by the abrogation of the increases in hepatic reduced glutathione (GSH) level, glucose-6-phosphate dehydrogenase and microsomal glutathione S-transferases (GST) activities upon challenge with increasing doses of CCl₄. While the hepatic GSH level was increased in diabetic rats, the hepatic mitochondrial GSH level and Se-glutathione peroxidase activity were significantly reduced. Insulin treatment could reverse most of the biochemical alterations induced by diabetes. Both insulin and schisandrin B (Sch B) pretreatments protected against the CCl₄ hepatotoxicity in diabetic rats. The hepatoprotection was associated with improvement in hepatic glutathione redox status in both cytosolic and mitochondrial compartments, as well as the increases in hepatic ascorbic acid level and microsomal GST activity. The ensemble of results suggests that the diabetes-induced impairment in hepatic mitochondrial glutathione redox status may at least in part be attributed to the enhanced susceptibility to CCl4 hepatotoxicity. Sch B may be a useful hepatoprotective agent against xenobiotics-induced toxicity under the diabetic conditions. (Mol Cell Biochem 175: 225–232, 1997)     

Hepatoprotective potential of Ferula communis extract for carbon tetrachloride induced hepatotoxicity and oxidative damage in rats

ABSTRACT

We investigated the hepatoprotective potential of Ferula communis extract for CCI₄ induced liver damage. We used six groups of rats: group 1, untreated control; group 2, CCl₄ treated (hepatotoxic); group 3, treated with 150 mg/kg F. communis; group 4, treated with 300 mg/kg F. communis; group 5, treated with CCl₄ + 150 mg/kg F. communis; and group 6, treated with CCl₄ + 300 mg/kg F. communis. Liver damage was produced by injection of 1 ml/kg CCI₄ twice/week. Extracts of F. communis, 150 and 300 mg/kg/day, were administered for 8 weeks. The effects of F. communis were assessed by measuring aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transferase (GGT) and total bilirubin (T-BIL) levels, and the activities of antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the liver. The histology and immunohistochemistry of liver tissue were evaluated using hematoxylin and eosin staining, and caspase 3 and 8-OHdG immunostaining. F. communis extract produced significant reductions in elevated levels of ALT, AST, GGT and T-BIL and increased levels of GPx and SOD in rats treated with CCl₄. F. communis extract decreased CCl₄ induced 8-OHdG formation and caspase 3 activation significantly in hepatocytes, especially at the 150 mg/kg dose. Our findings demonstrate the potential efficacy of F. communis for attenuating CCl₄ induced hepatotoxicity and oxidative damage.     

Acetyl-<Emphasis Type="SmallCaps">l</Emphasis>-carnitine prevents carbon tetrachloride-induced oxidative stress in various tissues of Wistar rats

Acetyl-l-carnitine (ALCAR) has been shown to prevent experimental selenite cataractogenesis, a manifestation of oxidative stress, but little is known about its potential in other settings of oxidative stress. The present study was based on the hypothesis that ALCAR prevents carbon tetrachloride (CCl₄)-induced oxidative stress in vital tissues. Male albino Wistar rats were divided into three groups, each of six rats. Group I (control) rats received only vehicle (1 ml/kg b.w.) for 4 days; Group II (CCl₄-exposed, untreated) rats received CCl₄ (2 ml/kg b.w.) on the second and third days and vehicle on the first and fourth days; Group III (CCl₄-exposed, ALCAR-treated) rats received ALCAR (200 mg/kg b.w.) for 4 days and CCl₄ on the second and third days. All administrations were made intraperitoneally. After the experimental period, significantly (P < 0.05) elevated mean serum levels of aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase were observed in Group II rats when compared to Group I and Group III rats. The mean levels of vitamin C, vitamin E, and reduced glutathione and the mean activities of superoxide dismutase, catalase, and glutathione peroxidase were significantly (P < 0.05) lower in samples of hemolysate and of liver, kidney, and brain tissues of Group II rats than those in Group I and Group III rats. The mean level of lipid peroxidation was significantly (P < 0.05) higher in Group II rats than that in Group I and Group III rats. Moreover, the CCl₄-induced upregulation of inducible nitric oxide synthase expression was prevented by ALCAR in the liver and brain tissues. These results suggest that ALCAR is able to prevent the CCl₄-induced oxidative stress.     

Effects of Selenium and Vitamin E,in Addıtıon to Melatonin,Against Oxidative Stress Caused by Cadmium in Rats

The present study was carried to evaluate the protective effects of melatonin alone and vitamin E with selenium combination against high dose cadmium-induced oxidative stress in rats. The control group received subcutanous physiological saline. The first study group administered cadmium chloride (CdCl₂) by subcutaneous injection of dose of 1 mg/kg. The second study group administered cadmium plus vitamin E with selenium (1 mg/kg sodium selenite with 60 mg/kg vitamin E); the third study group administered cadmium plus 10 mg/kg melatonin (MLT); the fourth study group administered CdCl₂ plus a combination of melatonin in addition to vitamin E and selenium for a month. Determination levels of plasma malondialdehyde (MDA), glutathione peroxidase (GSH-Px), blood superoxide dismutase (SOD), creatinine alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), blood urea nitrogen (BUN), and urea were measured in serum. In only CdCl₂ administered group, the MDA, creatinine, ALT, AST, ALP, and urea levels in the serum were significantly higher than the control group (p < 0.05). Whereas in all other groups, this values were significantly lower than the only CdCl₂ administered group (p < 0.05). Erythrocytes GSH-Px, serum SOD activities of only CdCl₂ received group were significantly lower than the control group (p < 0.05). In conclusion, vitamin E + Se, melatonin and vitamin E, and Se, in addition to MLT combinations, had protective effects against high dose cadmium-induced oxidative damage.     

Determination of DNA Damage in Experimental Liver Intoxication and Role of N-Acetyl Cysteine

The present study aimed at detecting DNA damage and fragmentation as well as histone acetylation depending on oxidative stress caused by CCl₄ intoxication. Also, the protective role of N-acetyl cysteine, a precursor for GSH, in DNA damage is investigated. Sixty rats were used in this study. In order to induce liver toxicity, CCl₄ in was dissolved in olive oil (1/1) and injected intraperitoneally as a single dose (2 ml/kg). N-acetyl cysteine application (intraperitoneal, 50 mg/kg/day) was started 3 days prior to CCl₄ injection and continued during the experimental period. Control groups were given olive oil and N-acetyl cysteine. After 6 and 72 h of CCl₄ injection, blood and liver tissue were taken under ether anesthesia. Nuclear extracts were prepared from liver. Changes in serum AST and ALT activities as well as MDA, TAS, and TOS levels showed that CCl₄ caused lipid peroxidation and liver damage. However, lipid peroxidation and liver damage were reduced in the N-acetyl cysteine group. Increased levels in 8-hydroxy-2-deoxy guanosine and histone acetyltransferase activities, decreased histone deacetylase activities, and DNA breakage detected in nuclear extracts showed that CCl₄ intoxication induces oxidative stress and apoptosis in rat liver. The results of the present study indicate that N-acetyl cysteine has a protective effect on CCl₄-induced DNA damage.     

Protective effect of Piper betle leaf extract against cadmium-induced oxidative stress and hepatic dysfunction in rats

The present study was undertaken to examine the attenuative effect of Piper betle leaf extract (PBE) against cadmium (Cd) induced oxidative hepatic dysfunction in the liver of rats. Pre-oral supplementation of PBE (200 mg/kg BW) treated rats showed the protective efficacy against Cd induced hepatic oxidative stress. Oral administration of Cd (5 mg/kg BW) for four weeks to rats significantly (P > 0.05) elevated the level of serum hepatic markers such as serum aspartate transaminase (AST), serum alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (GGT), bilirubin (TBRNs), oxidative stress markers viz., thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH), protein carbonyls (PC) and conjugated dienes (CD) and significantly (P > 0.05) reduced the enzymatic antioxidants viz., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PD) and non-enzymatic antioxidants Viz., reduced glutathione (GSH), total sulfhydryls (TSH), vitamin C and vitamin E in the liver. Pre-oral supplementation of PBE (200 mg/kg BW) in Cd intoxicated rats, the altered biochemical indices and pathological changes were recovered significantly (P > 0.05) which showed ameliorative effect of PBE against Cd induced hepatic oxidative stress. From the above findings, we suggested that the pre-administration of P. betle leaf extract exhibited remarkable protective effects against cadmium-induced oxidative hepatic injury in rats.     

Effects of melatonin on oxidative-antioxidative status of tissues in streptozotocin-induced diabetic rats

In view of the antioxidant properties of melatonin, the effects of melatonin on the oxidative-antioxidative status of tissues affected by diabetes, e.g. liver, heart and kidneys, were investigated in streptozotocin (STZ)-induced diabetic rats in the present study. Concentrations of malondialdehyde (MDA) and reduced glutathione (GSH), and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the tissues were compared in three groups of 10 rats each (control non-diabetic rats (group I), untreated diabetic rats (group II) and diabetic rats treated with melatonin (group III)). In the study groups, diabetes developed 3 days after intraperitoneal (i.p.) administration of a single 60 mg kg(-1) dose of STZ. Thereafter, while the rats in group II received no treatment, the rats in group III began to receive a 10 mg kg(-1) i.p. dose of melatonin per day. After 6 weeks, the rats in groups II and III had significantly lower body weights and higher blood glucose levels than the rats in group I (p < 0.001 and p < 0.001, respectively). MDA levels in the liver, kidney and heart of group II rats were higher than that of the control group (p < 0.01, p < 0.05, p < 0.01, respectively) and diabetic rats treated with melatonin (p < 0.05). The GSH, GSH-Px and SOD levels increased in diabetic rats. Treatment with melatonin changed them to near control values. Our results confirm that diabetes increases oxidative stress in many organs such as liver, kidney and heart and indicate the role of melatonin in combating the oxidative stress via its free radical-scavenging and antioxidant properties.