International Academic Journal of Innovative Research

  • ISSN 2454-390X

Influence of Sibinin on DMBA Induced Hepatotoxicity and Free-Radical Damage in Norwegian Rat, Rattus norvegicus

Vitthalrao B. Khyade

Abstract: 7,12-Dimethylbenz[a]anthracene (DMBA) is acting as immunosuppressor and it serves as a tumor initiator. Tumor promotion can be induced with treatments of 12-O-tetradecanoylphorbol-13- acetate (TPA) in some models of two-stage carcinogenesis. This allows for a greatly accelerated rate of tumor growth, making many cancer studies possible. The DMBA damages many internal organs including liver, by inducing the production of reactive oxygen species, DNA-adduct formation and affecting the activities of phase I, II, antioxidant and serum enzymes. The silibinin is a pharmacologically active constitute of Silybum marianum (L), with documented antioxidant activity. The aim of present attempt was to evaluate both histopathologically and biochemically whether silibinin is protective in DMBA induced liver damage. Thirty two Norwegian Rats ( Rattus norvegicus L) were divided into four groups, as follows: 1) control group - oral corn oil was given; 2) DMBA group – DMBA was administered orally 335 mg/kg in the corn oil solution; 3) Silibinin group - 100 mg/kg/day silibinin was given alone orally, every 24 hours for 7 days; 4) Silibinin + DMBA group - DMBA plus silibinin was given. All rats were sacrificed at the end of experiment. Superoxide dismutases (SOD), glutathione peroxidase (GPX), nitric oxide (NO) and myeloperoxidase (MPO) were investigated in serum and liver tissue. In addition, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzyme activities were evaluated. The liver tissue was evaluated histopathologically with Hematoxilin & Eosin dye. Biochemically, ALT, AST, NO, MPO in serum and NO, MPO in liver tissue were found to be significantly higher in DIMBA group, compared to control group (P < 0.001). In Group Silibinin + DMBA, serum AST, ALT, NO, MPO levels were significantly lower (P < 0.01), and both serum and tissue SOD activities were significantly higher, compared to DMBA group (P < 0.001). DMBA induced histopathological changes in liver tissue were: severe sinusoidal dilatation, moderate disruption of the radial alignment of hepatocytes around the central vein, severe vacuolization in the hepatocyte cytoplasm, inflammation around central vein and portal region. In rats receiving both DMBA and silibinin, the DMBA induced changes accounted for less sinusoidal dilatation, vacuolization in the hepatocyte cytoplasm and the inflammation around central vein and portal region (P < 0.05). The DMBA was found to induce liver damage by oxidative stress mechanisms. Silibinin reduced the oxidative stress by inducing antioxidant mechanisms, thereby showing protective effect against DMBA induced liver damage. Further studies with silibinin should be performed regarding DMBA toxicity

Keywords: DMBA; Oxidative Stress; Antioxidants; Histopathology; Liver

Page: 20-36

DOI: 10.9756/IAJIR/V6I1/1910002

Volume 6, Issue 1, 2019