ABSTRACT
The aim of the study was to investigate the antiinflammatory effects of naringenin in rats induced liver damage by exposure to ethanol. Rats were divided into four groups, groups 1 and 2 received isocaloric glucose; groups 3 and 4 received 20% ethanol equivalent to 6 g/kg body weight everyday for the total experimental period of 60 days. In addition, groups 2 and 4 were supplemented with naringenin (50 mg/kg p.o.) everyday for the last 30 days of the experiment. The results showed significantly elevated levels/activities/expression of serum aspartate and alanine transaminases, iron, ferritin, transforming growth factor-alpha (TNF-α), interleukin-6 (IL-6), nuclear factor-kappa B (NF-κB), cyclooxygenase-2 (COX-2), macrophage inflammatory protein 2 (MIP-2) and CD14 in ethanol fed rats as compared to those of the control. Ethanol-fed rats exhibited increased staining for the presence of inducible nitric oxide (iNOS) protein adducts in the liver. Supplementation with naringenin for the last 30 days to ethanol-fed rats, significantly decreased the levels/activities/expression of serum aspartate and alanine transaminases, iron, ferritin, TNF-α, IL-6, NF-κB, COX-2, MIP-2, CD14 and iNOS protein adducts in the liver as compared to the untreated ethanol fed rats. The inhibition of TNF-α, IL-6, NF-κB, COX-2, MIP-2, iNOS and CD14 by naringenin may contribute to its antiinflammatory activity in ethanol fed rats.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Ethanol/toxicity , Flavanones/therapeutic use , Liver Diseases, Alcoholic/prevention & control , Liver/drug effects , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Biomarkers/metabolism , Ferritins/metabolism , Flavanones/administration & dosage , Immunohistochemistry , Iron/metabolism , Liver/enzymology , Liver/immunology , Liver/metabolism , Liver Diseases, Alcoholic/enzymology , Liver Diseases, Alcoholic/immunology , Liver Diseases, Alcoholic/metabolism , Liver Function Tests , Male , Nitric Oxide Synthase Type II/metabolism , Rats , Rats, Wistar , Real-Time Polymerase Chain ReactionABSTRACT
We have investigated the modulatory efficacy of naringenin on circulatory lipid peroxidation and anti-oxidant status, hepatic alcohol metabolizing enzymes in rats with ethanol induced hepatotoxicity. Rats were divided into four groups: groups 1 and 2 received isocaloric glucose and 0.5% carboxymethyl cellulose; groups 3 and 4 received 20% ethanol equivalent to 6 g/kg body weight everyday for the total experimental period of 60 days. In addition, groups 2 and 4 were given naringenin (50 mg/kg) everyday for the last 30 days of the experiment. The results showed significantly elevated levels/activities of bilirubin, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH), conjugated dienes (CD) and phase I enzymes, and significantly lowered the activities of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), superoxide dismutase (SOD), catalase (CAT) and phase II enzymes in ethanol-fed rats as compared to those of the control. Supplementation with naringenin for the last 30 days of the experiment to ethanol-fed rats, significantly decreased the levels/activities of bilirubin, ALP, LDH, TBARS, LOOH, CD and phase I enzymes, and significantly elevated the activities of ADH, ALDH, SOD, CAT and phase II enzymes as compared to control rats. These findings suggest that naringenin can effectively modulate the hepatic alcohol metabolizing enzymes in rats with ethanol induced liver injury.
Subject(s)
Antioxidants/metabolism , Ethanol/toxicity , Flavanones/pharmacology , Liver Diseases, Alcoholic/prevention & control , Animals , Ethanol/administration & dosage , Lipid Peroxidation/drug effects , Liver/drug effects , Liver/enzymology , Liver Diseases, Alcoholic/physiopathology , Male , Rats , Rats, WistarABSTRACT
OBJECTIVES: The aim was to study the effect of naringenin, a biologically active compound, on tissue antioxidant status and lipid peroxidation in ethanol-induced hepatotoxicity in rats. METHODS: Rats were divided into four groups: Groups 1 and 2 received isocaloric glucose and 0.5% carboxymethyl cellulose; groups 3 and 4 received 20% ethanol equivalent to 6 g/kg daily for 60 days. In addition, groups 2 and 4 were given naringenin (50 mg/kg) daily for the last 30 days of the experiment. KEY FINDINGS: The results showed significantly elevated levels of serum aspartate and alanine transaminases, gamma-glutamyl transpeptidase, tissue thiobarbituric acid reactive substances, conjugated dienes, lipid hydroperoxides and protein carbonyl content, and significantly lowered activities/levels of antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, reduced glutathione and vitamins C and E in ethanol-treated rats compared with control rats. Administration of naringenin to rats with ethanol-induced liver injury significantly decreased the levels of serum aspartate and alanine transaminases, gamma-glutamyl transpeptidase, tissue thiobarbituric acid reactive substances, conjugated dienes, lipid hydroperoxides and protein carbonyl content and significantly elevated the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase, and the levels of reduced glutathione and vitamins C and E in the tissues compared with unsupplemented ethanol-treated rats. Histological changes observed in the liver correlated with the biochemical findings. CONCLUSIONS: Taken together these findings suggest that naringenin has a therapeutic potential in the abatement of ethanol-induced hepatotoxicity.
