Carnosine supplementation protects rat brain tissue against ethanol-induced oxidative stress

Ethanol causes oxidative stress and tissue damage. The aim of this study was to investigate the effect of antioxidant carnosine on the oxidative stress induced by ethanol in the rat brain tissue. Forty male rats were divided equally into four groups as control, carnosine (CAR), ethanol (EtOH), and ethanol plus carnosine (EtOH + CAR). Rats in the control group (n = 10) were injected intraperitoneally (i.p.) with 0.9% saline; EtOH group (n = 10) with 2 g/kg/day ethanol, CAR group (n = 10) received carnosine at a dose of 1 mg/kg/day and EtOH + CAR group (n = 10) received carnosine (orally) and ethanol (i.p.). All animals were sacrificed using ketamine and brain tissues were removed. Malondialdehyde (MDA), protein carbonyl (PCO) and tissue carnosine levels, and superoxide dismutase (SOD) activities were measured. Endogenous CAR levels in the rat brain tissue specimens were significantly increased in the CAR and EtOH groups when compared to the control animals. MDA and PCO levels in the EtOH group were significantly increased as compared to the other groups (P < 0.05). CAR treatment also decreased MDA levels in the CAR group as compared to the control group. Increased SOD activities were obtained in the EtOH + CAR group as compared to the control (P < 0.05). CAR levels in the rat brain were significantly increased in the CAR, EtOH and CAR + EtOH groups when compared to the control animals. These findings indicated that carnosine may appear as a protective agent against ethanol-induced brain damage.     

Protective effect of Cassia fistula Linn. on diethylnitrosamine induced hepatocellular damage and oxidative stress in ethanol pretreated rats

Diethylnitrosamine (DEN), found in many commonly consumed foods, is widely reported to induce cancer in animals and humans. The aim of the present study was to investigate the hepatoprotective and antioxidant activities of the leaf extract of the medicinal plant Cassia fistula Linn. against diethylnitrosamine induced liver injury in ethanol pretreated rats. Albino Wistar rats, pretreated with ethanol for 15 days, were administered a single dose of DEN. Thirty days after DEN administration, hepatotocellular damage was observed histologically, along with elevated levels of serum AST, ALT, ALP, LDH, γ-GT and bilirubin and a simultaneous fall in the levels of the marker enzymes in the liver tissue. Liver oxidative stress was confirmed by elevated levels of lipid peroxidation (LPO) and a decrease in enzymic and non-enzymic antioxidants activities. Oral administration of the ethanolic leaf extract (ELE) of Cassia fistula for 30 days to ethanol + DEN treated rats significantly improved the above alterations in the markers of hepatotoxicity and oxidative stress, resulting in the reversal of most of the parameters studied and were comparable to the standard hepatoprotective drug silymarin.     

The hepatoprotective effects of Hypericum perforatum L. on hepatic ischemia/reperfusion injury in rats

Little is known about the effective role of Hypericum perforatum on hepatic ischemia–reperfusion (I/R) injury in rats. Hence, albino rats were subjected to 45 min of hepatic ischemia followed by 60 min of reperfusion period. Hypericum perforatum extract (HPE) at the dose of 50 mg/kg body weight (HPE₅₀) was intraperitonally injected as a single dose, 15 min prior to ischemia. Rats were sacrificed at the end of reperfusion period and then, biochemical investigations were made in serum and liver tissue. Liver tissue homogenates were used for the measurement of malondialdehyde (MDA), catalase (CAT) and glutathione peroxidase (GPx) levels. At the same time alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were assayed in serum samples and compared statistically. While the ALT, AST, LDH activities and MDA levels were significantly increased, CAT and GPx activities significantly decreased in only I/R-induced control rats compared to normal control rats (p < 0.05). Treatment with HPE₅₀ significantly decreased the ALT, AST, LDH activities and MDA levels, and markedly increased activities of CAT and GPx in tissue homogenates compared to I/R-induced rats without treatment–control group (p < 0.05). In oxidative stress generated by hepatic ischemia–reperfusion, H. perforatum L. as an antioxidant agent contributes an alteration in the delicate balance between the scavenging capacity of antioxidant defence systems and free radicals in favour of the antioxidant defence systems in the body.     

Preventive role of gallic acid on hepatic ischemia and reperfusion injury in rats

There is little information about the hepatoprotective effects of gallic acid against ischemia–reperfusion (I/R) damage. Animals were subjected to I/R. Gallic acid at doses of 50 and 100 mg/kg body weight (bw) were injected as a single dose prior to ischemia. Liver tissue homogenates were used for the measurement of malondialdehyde (MDA), catalase (CAT) and glutathione peroxidase (GPx) levels. At the same time alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were assayed in serum samples and compared statistically. While the ALT, AST, LDH activities and MDA levels were significantly increased, CAT and GPx activities significantly decreased in only I/R-induced control rats compared to normal control rats (P < 0.05). Treatment with gallic acid at a dose of 100 mg/kg bw significantly decreased the ALT, AST, LDH activities and MDA levels, and markedly increased activities of CAT and GPx in tissue homogenates compared to I/R-induced rats with no treatment group (P < 0.05). In oxidative stress generated by hepatic ischemia–reperfusion, gallic acid contributes partially an alteration in the delicate balance between the scavenging capacity of antioxidant defense systems and free radicals in favour of the antioxidant defense systems in the body.     

Protective effects of ascorbic acid, dl-α-tocopherol acetate, and sodium selenate on ethanol-induced liver damage of rats

In this study, the effect of a combination of vitamin C (ascorbic acid), vitamin E (dl-α-tocopherol acetate), and selenium (sodium selenate) on ethanol-induced liver damage in rats was investigated, morphologically and biochemically. The ethanol-induced injury was produced by the administration of 1 mL of absolute ethanol to each rat. Animals received vitamin C (250 mg/kg), vitamin E (250 mg/kg), and selenium (0.5 mg/kg) (ViCESe) for 3 d 1 h prior to the administration of absolute ethanol. In the liver of the animals given ethanol, the degenerative changes such as extreme hyperemia, vacuolization in cells of portal areas, a dilation in sinusoids, mononuclear cell infiltration, a swelling in cisternae of granular endoplasmic reticulum and in mitochondrial cristae, an increase in smooth endoplasmic reticulum, many lipid vacuoles were observed both light and electron microscopically. A similar structure was usually distinguished when compared with control animals, in rats given ethanol+ViCESe. In this group, the findings indicating cellular damage were either not observed at all or were decreased. In the group administered ethanol, a reduction of the blood glutathione (GSH) level and increases in serum values of alanine aminotranserase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and γ-glutamyl transferase (GGT) activities were observed, whereas in the control group, the reverse was found to occur. On the other hand, in the group in which ethanol+ViCESe was administered, it was observed that the blood GSH value and serum ALP and ALT activities increased and serum AST, LDH, and GGT activities decreased. As a result, the present study indicates that ViCESe because of their antioxidant activity against ethanol damage have a protective effect on the liver.     

Green tea catechins, alleviate hepatic lipidemic-oxidative injury in Wistar rats fed an atherogenic diet

In the present study, the efficacy of green tea catechins (GTC from the plant Camellia sinensis), with epigallocatechin gallate (EGCG), as the major component, was studied in relation to hepatic oxidative abnormalities in atherosclerotic rats. When male albino Wistar rats were fed an atherogenic diet for 30 days and then treated with saline for 7 or 15 days, there was a significant decline in hepatic mean activities of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase and glutathione-S-transferase), and non-enzymatic antioxidants (reduced glutathione, vitamins C and E) while there was a significant elevation in the mean level of hepatic malondialdehyde (MDA), in comparison to the values noted in control rats fed a normal diet. In addition, a concomitant increase in the activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) was noted, when compared to the values in control rats. Following intraperitoneal administration of GTC (100 mg/kg) for 7 or 15 days to rats fed the atherogenic diet, significantly higher mean activities of enzymatic and non-enzymatic antioxidants and lower mean levels of MDA in hepatic tissue and lower mean activities of AST, ALT, ALP and LDH in serum were observed, compared to the values in the rats fed the atherogenic diet and treated with saline. Histopathological studies were performed to provide direct evidence of the atherogenic diet-induced hepatic changes and of the hepatoprotective effect of GTC. These results suggest that EGCG as a major component of green tea catechins may protect against the hepatic abnormalities occurring in Wistar rats fed an atherogenic diet.     

Antioxidant activity and hepatoprotective potential of Hammada scoparia against ethanol-induced liver injury in rats

The present work was aimed at studying the antioxidative activity and hepatoprotective effects of methanolic extract (ME) of Hammada scoparia leaves against ethanol-induced liver injury in male rats. The animals were treated daily with 35 % ethanol solution (4 g?kg^?1?day^?1) during 4 weeks. This treatment led to an increase in the lipid peroxidation, a decrease in antioxidative enzymes (catalase, superoxide dismutase, and glutathione peroxidase) in liver, and a considerable increase in the serum levels of aspartate and alanine aminotransferase and alkaline phospahatase. However, treatment with ME protects efficiently the hepatic function of alcoholic rats by the considerable decrease in aminotransferase contents in serum of ethanol-treated rats. The glycogen synthase kinase-3 β was inhibited after ME administration, which leads to an enhancement of glutathione peroxidase activity in the liver and a decrease in lipid peroxidation rate by 76 %. These biochemical changes were consistent with histopathological observations, suggesting marked hepatoprotective effect of ME. These results strongly suggest that treatment with methanolic extract normalizes various biochemical parameters and protects the liver against ethanol induced oxidative damage in rats.     

Gastroprotective,cytoprotective and antioxidant effects of Oleum cinnamomi on ethanol induced damage

Peptic ulcer disease is a gastrointestinal disorder defined by mucosal damage and free oxygen radicals associated with peptic ulcer and gastritis. Cinnamon is a traditional herb used for many diseases and it has also effects as an antioxidant, anti-inflammatory, antispasmodic and anti-ulcerative. Our research is based on oxidative stress and effects of Oleum cinnamomi on stomach, liver and kidney disorders induced by ethanol. In our experiment, 2–3 month old male Sprague–Dawley rats were used. One hour before the mucosal damage induced by 70 % ethanol, O. cinnamomi (2.5 ml/kg) was added into the groups. Gastric pH, analysis of gastric mucus and ulcer index were calculated from samples obtained from the stomach. Superoxide dismutase (SOD), malondialdehyde and catalase (CAT) levels were determined in stomach, liver and kidney homogenates and erythrocyte hemolysate. Histopathological examination of stomach, liver and kidney were determined with H&E staining. The non-treated ulcerative group showed higher scores than the control group which was treated with O. cinnamomi, when ulcer scores, gastric mucus and pH level of stomach are compared. Increased lipid peroxidation levels were observed in the liver, kidney and erythrocyte hemolysate. SOD activity was decreased in liver whereas increased in stomach of ethanol treated ulcerative groups. CAT levels were increased in stomach and liver of ethanol treated rats. Histopathological findings showed that ethanol treatment cause multiply organ damage such as stomach, liver and kidney injury. O. cinnamomi treatment protected these tissues from ethanol-induced damage. Consequently, the current investigation shows that O. cinnamomi has protective effects on ethanol-induced oxidative and mucosal damage.     

The effect of Myrtus communis L. ethanol extract on the small intestine and lungs in experimental thermal burn injury

Thermal trauma can damage organs away from the skin burn site and lead to multiple organ dysfunction. Following thermal injury, all tissues are exposed to ischemia, and as a result, resuscitation and reperfusion occur during the burning shock. Burn damage starts systemic inflammatory reactions that produce toxins and reactive oxygen radicals that lead to peroxidation. This study aimed to investigate, for the first time, the possible antioxidant effects of Myrtus communis ethanol extract on burn-induced oxidative distant organ injury orally. The thermal trauma was generated under ether anesthesia by exposing the dorsum of rats to 90 ^°C water bath for 10 s. 100 mg/kg/day Mrytus communis ethanol extract was applied orally for two days. Malondialdehyde (MDA) and glutathione (GSH) levels, glutatinone-S-transferase (GST), superoxidedismutase (SOD) and catalase (CAT) activities were determined to detect the possible antioxidant effects of myrtle on small intestine and lung tissues. Burn damage significantly increased MDA levels in lung and small intestine tissues, and significantly decreased GSH levels, CAT and GST activities in the small intestine and lung tissues compared to control group. Mrytus communis ethanol extract decreased MDA level and increased GSH level, SOD, CAT and GST activities significantly in either small intestine or lung tissues. Mrytus communis extract may be an ideal candidate to be used as an antioxidant adjunct to improve oxidative distant organ damage to limit the systemic inflammatory response and decreasing the recovery time after thermal injury.     

Betaine prevents ethanol-induced oxidative stress and reduces total homocysteine in the rat cerebellum

Oxidative stress is a hypothesis for the association of reactive oxygen species with cerebrovascular and neurodegenerative diseases. Thus, we examined whether oral betaine can act as a preventive agent in ethanol-induced oxidative stress on the cerebellum of rats. Thirty-two adult male Sprague–Dawley rats were divided into four equal groups (control, ethanol, betaine, and betaine plus ethanol) with different dietary regimens and were followed up for 1 month. Total homocysteine (tHcy) of plasma and cerebellum homogenate was determined by an Axis^® homocysteine EIA kit, and antioxidant enzyme (glutathione peroxidase (GPx), SOD, and CAT) activities of cerebellum homogenate were measured chemically by a spectrophotometer. Lipid peroxidation of cerebellum was shown by the measurement of thiobarbituric reactive substances (TBARS) via a spectrophotometer. Ethanol-induced hyperhomocysteinemia was manifested by an increase in the concentrations of tHcy in the plasma and cerebellum homogenates of the ethanol group, while ethanol-induced oxidative stress was indicated via an increase in lipid peroxidation marker (TBARS) in cerebellum homogenates of ethanol-treated rats. In contrast, betaine prevented hyperhomocysteinemia and oxidative stress in the betaine plus ethanol group as well as the betaine group. The results of the present investigation indicated that the protective effect of betaine is probably related to its ability to strengthen the cerebellum membrane cells by enhancement of antioxidant enzyme activity principally GPx, while the methyl donor effect of betaine to reduce hyperhomocysteinemia has been explained previously and confirmed in the present study.     

Mast cell stabilizator and antioxidant effects of epidermal growth factor (EGF) on gastric mucosal injury induced by ethanol in rats

The role of epidermal growth factor (EGF), a polypeptide containing 53 amino acids, on protection and repair of ethanol-induced gastric mucosal injury was investigated in rats. In addition, the effects of EGF on the gastric damage were evaluated histopathologically. We used 48 Spraque-Dawley rats which were divided into [corrected] three groups as control rats, ethanol treated rats and ethanol+EGF treated rats. The ethanol group was given a gastric gavage containing 1 ml of 80% ethanol (v/v) prepared in distilled water. EGF (100 microg/kg) was given by intragastric gavage 30 min before the administration of ethanol. We studied histopathological evaluation and the histochemical heterogeneity of mast cells and its degree of degranulation. Besides, gastric tissue malondialdehyde (MDA), protein sulfhydryl groups (SH), and protein carbonyl levels were measured. EGF treatment stabilized mast cells degranulation and had lower polymorphonuclear leukocytes (PMNL) infiltration, ulcer index, histamine, and MDA; protein carbonyl levels were also lower, compared to the non-treated animals. EGF exerts a protective effect on gastric mucosa to ethanol-induced gastric injury probably through antioxidant and mast cell stabilizing mechanism.     

Long-term administration of aqueous garlic extract (AGE) alleviates liver fibrosis and oxidative damage induced by biliary obstruction in rats

The aim of this study was to assess the antioxidant and antifibrotic effects of chronic administration of aqueous garlic extract on liver fibrosis induced by biliary obstruction in rats. Liver fibrosis was induced in male Wistar albino rats by bile duct ligation and scission (BDL). Aqueous garlic extract (AGE, 1 ml/kg, i.p., corresponding to 250 mg/kg) or saline was administered for 28 days. At the end of the experiment, rats were killed by decapitation. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels were determined to assess liver functions and tissue damage, respectively. Tumor necrosis factor-alpha (TNF-alpha) was also assayed in serum samples. Liver tissues were taken for determination of the free radicals, renal malondialdehyde (MDA) levels, an end product of lipid peroxidation; glutathione (GSH) levels, a key antioxidant; and myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration. Hepatic collagen content, as a fibrosis marker was also determined. Serum AST, ALT, LDH, and TNF- alpha levels were elevated in the BDL group as compared to control group, while this increase was significantly decreased by AGE treatment. Hepatic GSH levels, significantly depressed by BDL, were elevated back to control levels in AGE-treated BDL group. Increases in tissue free radical and MDA levels and MPO activity due to BDL were reduced back to control levels by AGE treatment. Similarly, increased hepatic collagen content in the BDL rats was reduced to the level of the control group with AGE treatment. Since AGE administration alleviated the BDL-induced oxidative injury of the liver and improved the hepatic structure and function, it seems likely that AGE with its antioxidant and antifibrotic properties, may be of potential therapeutic value in protecting the liver fibrosis and oxidative injury due to biliary obstruction.     

The Effect of Different Oral Doses of Hydroalcoholic Extract of Silymarin on the Blood Oxidative Stress Indicators in Streptozotocin Induced Diabetic Rats

The effect of oral administration of different doses of hydroalcoholic extract of silymarin on body weight, glucose concentration and indicators of oxidative stress superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT) and malondialdehyde (MDA) was investigated in the present study. Fifty adult male Wistar rats were used. The animals were divided into five groups and oral route of administration was used in control group (0.9 %, NaCl), control group patients (0.9 %, NaCl), diabetic group (100 mg/kg, silymarin), diabetic group (125 mg/kg, silymarin), diabetic group (250 mg/kg, silymarin) for 14 days with gavage. Diabetes was induced by a single injection of streptozotocin (45 mg/kg, i.p.). Before and 3 days after injection, and at 7 and 14 days of treatment, the fasting glucose level and weight were measured. At the end of 14 days, animals were anesthetized with ether and blood samples were taken by heart puncture and were analyzed for oxidative stress indicators. The results showed that hydroalcoholic extract of silymarin can increase the average body weight and decrease glucose and, at the end of 14 days, decrease MDA level and increase the level of antioxidant enzymes (SOD, GPX, CAT) in red blood cells in a dose-dependent manner (P < 0.05). In conclusion, the hydroalcoholic extract of silymarin has an overall beneficial effect on body weight, glucose level and oxidative stress. Therefore, silymarin may reduce oxidative stress via increasing antioxidant enzyme activity.     

Effects of Selenium-Enriched Agaricus blazei Murill on Liver Metabolic Dysfunction in Mice,a Comparison with Selenium-Deficient Agaricus blazei Murill and Sodium Selenite

In the present study, we investigated the effects of Se-enriched Agaricus blazei Murill (Se-AbM) on liver injury in mice induced by acute alcohol administration. Mice received ethanol (5 g/kg body weight (BW)) by gavage every 12 h for a total of 3 doses. Se-AbM was administrated before ethanol administration. Subsequent serum alanine aminotransferase (ALT) level, aspartate aminotransaminase (AST) level, maleic dialdehyde (MDA) level, hepatic total antioxidant status (TAOS), nuclear factor kappa B (NF-κB) level, polymorphonuclear cells (PMN) level, interleukin-1β (IL-1β) level, inducible nitric oxide synthase (iNOS) level, tumor necrosis factor-α (TNF-α) level, intercellular adhesion molecule 1 (ICAM-1), and cyclooxygenase-2 (COX-2) were determined by ELISA and immunohistochemistry, respectively. Se-AbM administration markedly (p?<?005) decreased serum ALT, AST, and MDA levels, hepatic IL-1β and TNF-α levels, as well as PMN infiltration and the expression of ICAM-1, COX-2, iNOS, and NF-κB compared with alcohol administration. In conclusion, we observed that Se-AbM supplementation could restrain the hepatic damage caused by acute alcohol exposure.     

The Effects of Levosimendan Exposure on Oxidant/Antioxidant Status and Trace Element Levels in the Pulmonary Artery of Rats

We investigated both the effect of levosimendan and the role of oxidant/antioxidant status and trace element levels in the pulmonary artery of rats. Fourteen male Wistar albino rats were randomly divided into two groups of seven animals each. Group 1 was not exposed to levosimendan and served as a control. Levosimendan (12 μg/kg) diluted in 10 ml 0.9 % NaCl was administered intraperitoneally to group 2. Animals of both groups were killed after 3 days, and their pulmonary arteries were harvested to determine changes in tissue oxidant/antioxidant status and trace element levels. The animals in both groups were killed 72 h after the levosimendan exposure treatment, and pulmonary arteries were harvested to determine levels of the lipid peroxidation product MDA and the antioxidant GSH as well as the decreased activity of antioxidant enzymes such as SOD, GSH-Px and CAT. It was found that MDA levels increased in pulmonary artery tissues of rats after levosimendan administration. The GSH level decreased in the pulmonary artery of rats after levosimendan treatment. Co, Mn, Fe, Cd and Pb levels were significantly higher (P < 0.001) and Mg, Zn and Cu levels significantly lower (P < 0.001) in the levosimendan group compared to the control group. These results suggest that levosimendan treatment caused an increase in free radical production and a decrease in antioxidant enzyme activity in the pulmonary artery of levosimendan-treated rats. It also caused a decrease or increase in the levels of many minerals in the pulmonary artery, which is an undesirable condition for normal pharmacological function.     

Paraquat-induced lipid peroxidation: effects of ovariectomy and estrogen receptor antagonist

Estrogen protects females against cardiovascular diseases in both receptor-dependent, genomic or non-genomic manner. Although part of the protective effects is attributed to its enhancement of nitric oxide (NO) production and antioxidant properties, in vivo evidence is difficult to establish. We thus employed paraquat (PQ)-treated rats as a model for oxidative stress and to compare oxidative damage determined by malondialdehyde (MDA) contents as index for lipid peroxidation of various tissues. Samples from aorta, lung, and liver exhibited low but detectable MDA level in intact control rats; sham operation did not but PQ-treatment significantly enhanced the MDA levels of all tissues. Different hormonal status were achieved by comparing sham-operated (sham), sham treated with estrogen receptor antagonist ICI182,780 (ICI), and ovariectomized (OVX) rats. OVX significantly reduced plasma estrogen level, ICI effectively blocked estrous cycle without reducing estrogen level. Derived from rats subjected to identical PQ treatment, MDA level was significantly higher in OVX rats than that of sham in isolated aortic rings. In lung tissues, MDA level were similar in all groups. In liver tissues, ICI rats exhibited higher level of MDA than both sham and OVX rats. These data indicated that hormonal status could affect the degree of lipid peroxidation under similar oxidative stress induced by PQ, and that not all tissues responded identically.     

Hepatoprotective Potentials of Onion and Garlic Extracts on Cadmium-Induced Oxidative Damage in Rats

The hepatoprotective effect of onion and garlic extracts on cadmium (Cd)-induced oxidative damage in rats is reported. Control group received double-distilled water alone. Cd group was challenged with 3CdSO₄·8H₂O (as Cd; 1.5 mg/kg bw per day per oral) alone, while extract-treated groups were pretreated with varied doses of onion and/or garlic extract (0.5 and 1.0 ml/100 g bw per day per oral) for a week and thereafter co-treated with Cd (1.5 mg/kg bw per day per oral) for 3 weeks. Cd caused a marked (p?<?0.001) increase in the levels of lipid peroxidation and glutathione S-transferase, whereas glutathione, superoxide dismutase, and catalase levels were decreased in the liver. We also observed a decrease in hepatic activities of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase and a concomitant increase in the plasma activities of ALT and AST. Onion and garlic extracts significantly attenuated these adverse effects of Cd. Onion extract proffered a dose-dependent hepatoprotection. Our study showed that Cd-induced oxidative damage in rat liver is amenable to attenuation by high dose of onion and moderate dose of garlic extracts possibly via reduced lipid peroxidation and enhanced antioxidant defense system that is insufficient to prevent and protect Cd-induced hepatotoxicity.     

Protective effects of ascorbic acid, dl-alpha-tocopherol acetate, and sodium selenate on ethanol-induced liver damage of rats

In this study, the effect of a combination of vitamin C (ascorbic acid), vitamin E (dl-alpha-tocopherol acetate), and selenium (sodium selenate) on ethanol-induced liver damage in rats was investigated, morphologically and biochemically. The ethanol-induced injury was produced by the administration of 1 mL of absolute ethanol to each rat. Animals received vitamin C (250 mg/kg), vitamin E (250 mg/kg), and selenium (0.5 mg/kg) (ViCESe) for 3 d 1 h prior to the administration of absolute ethanol. In the liver of the animals given ethanol, the degenerative changes such as extreme hyperemia, vacuolization in cells of portal areas, a dilation in sinusoids, mononuclear cell infiltration, a swelling in cisternae of granular endoplasmic reticulum and in mitochondrial cristae, an increase in smooth endoplasmic reticulum, many lipid vacuoles were observed both light and electron microscopically. A similar structure was usually distinguished when compared with control animals, in rats given ethanol + ViCESe. In this group, the findings indicating cellular damage were either not observed at all or were decreased. In the group administered ethanol, a reduction of the blood glutathione (GSH) level and increases in serum values of alanine aminotranserase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) activities were observed, whereas in the control group, the reverse was found to occur. On the other hand, in the group in which ethanol + ViCESe was administered, it was observed that the blood GSH value and serum ALP and ALT activities increased and serum AST, LDH, and GGT activities decreased. As a result, the present study indicates that ViCESe because of their antioxidant activity against ethanol damage have a protective effect on the liver.     

Downregulation of matrix metalloproteinase-9 by melatonin during prevention of alcohol-induced liver injury in mice

Matrix metalloproteinases (MMPs) have been implicated in inflammatory and degradative processes in several diseases. The study aims to explore the mechanism of MMP-9 regulation in alcohol-induced acute liver injury and its protection by melatonin in mice. Alcohol-induced acute liver injury was induced in female Balb/C mice by ethanol administration and protection studies were carried out with a well-known antioxidant molecule, melatonin. Degree of liver injury was monitored by histological and biochemical analysis of liver tissues. Oral administration of ethanol in mouse caused significant increase in alanine amino transferase (ALT) activity in serum. Depletion of glutathione and enhancement of lipid peroxidation as well as protein oxidation was observed in liver tissues following ethanol treatment. However, melatonin exhibited potent hepatoprotective activity by inhibiting ALT activity and oxidative stress. Additionally, MMP-9 expression was increased by ethanol in a dose and time dependent manner in liver tissue and serum. Increased secretion of proMMP-9 was strongly correlated with the expression of proinflammatory cytokines e.g., tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL6. Melatonin showed hepatoprotective role by downregulation of MMP-9 and upregulation of tissue inhibitor of metalloproteases (TIMP-1) expression in liver tissue. Nuclear factor (NF)-κB, plays an important role in inducing inflammatory genes during oxidative stress, thus the role of NF-κB in ethanol-induced liver injury was investigated. Ethanol induced nuclear translocation of NF-κB and increased degradation of inhibitor of NF-κB (IκBα) in liver tissues. Moreover, ethanol-induced NF-κB translocation into nucleus was inhibited significantly by melatonin. This is the first study to elucidate the induction of MMP-9 expression by NF-κB-dependent pathway in ethanol-induced acute liver injury in mice. This study also identifies the novel role of melatonin in hepatoprotection via MMP-9 down regulation.