Modulatory Role of Gallic Acid and Vitamin C on Amoxicillin/Clavulanic Acid Combination Induced Hepatotoxicity in Adult Albino Rats

Abstract

KEYWORDSAmoxicillin, Clavulanate, Gallic acid, Vitamin C, Hemoxygenase gene.Amoxicillin/ Clavulanate (AC) combination has become one of the antibiotics most widely prescribed used in the treatment of several bacterial infections, associated with liver injury. This study aimed to investigate amoxicillin/clavulanic acid induced hepatotoxicity and the modulatory effect of gallic acid (GA)/ vitamin C (VTC) individually and in combination on oxidative stress-related liver damage. Sixty-four male albino rats were randomly separated into eight groups; negative control; GA group; VTC group; GA +VTC group; AC-treated group; AC + GA-treated group; AC + VTC treated group and AC+ GA + VTC treated group. A twice daily dose of AC (31.83 mg/kg) and a single daily dose of both GA (60 mg/kg) and VTC (200 mg/kg/day) were introduced to rats orally for 7 consecutive days. After sacrificed, blood was collected for biochemical analysis of aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum tumor necrosis factor alpha (TNF-α), caspase-3, RNA of heme oxygenase-1 gene (HMOX-1) and liver sample for lipid peroxidation and histopathological study. The serum levels of AST, ALT and TNF-α were significantly increased and upregulation of caspase-3 protein in rats treated with AC. Hepatic contents of malondialdehyde (MDA) were markedly increased following AC administration but produced a significant decrease in the levels of reduced glutathione (GSH) and glutathione-S-transferase (GST) along with down regulated the expression of HMOX-1. These findings were in accordance with the histopathological findings. Co-administration of GA and/or VTC along with AC to rats reduced liver injury, oxidative stress, apoptosis and histopathological alterations. So, we concluded that GA and VTC pose a positive modulatory effect against AC induced hepatotoxicity.

The Possible Ameliorative Effect of Vitamin C Against Amoxicillin-Clavulanic Acid Toxicity in the liver of Adult Male Albino Rats

“…Additionally, their effects on oxidant markers can reduce oxidative stress. (12) Collagen fibers between the hepatocyte cords were nearly identical to those found in the control groups, with a little distribution around the central vein and portal tract. Studies indicate the positive effect of vitamin C intake in preventing both lipid peroxidation and type I collagen production.…”

“…Hussein et al (12) who attributed the observed distortion in the liver architecture including vacuolation, necrosis and inflammatory changes the cytotoxic action of AC on the liver, which interferes with the liver's regular role in detoxifying and other processes. As a form of cellular defense mechanism against toxic substances, vacuolation in hepatocytes has been recognized as ballooning degeneration.…”

“…(11)  Assessment of oxidative stress in liver tissue: To measure oxidant/antioxidant status, liver tissues from each group were frozen at -80°C and homogenized for MDA and GSH levels. (12) Light microscopic study:…”