PUNICA GRANATUM MITIGATES 7, 12-DIMETHYLBENZ[A]ANTHRACENE AND CCL4-INDUCED OXIDATIVE STRESS AND HEPATIC PRECANCEROUS LESIONS IN WISTAR RATS
This study is designed to assess the preventive effects Punica granatum aril juice, aqueous extracts of seeds and husk and their mixture on the hepatic injury and hepatocarcinogenesis induced by 7,12-dimethylbenz(a)anthracene (DMBA) and carbon tetrachloride (CCl4) administration in male Wistar rats. DMBA/CCl4-administered rats were orally treated with Punica granatum aril juice at 10 ml/kg b.w./day, seeds and husk aqueous extracts at 400 mg/kg b.w./day and their mixture for 16 weeks to rats. The treatments with Punica granatum aril juice, seeds and husk aqueous extracts successfully attenuate the deleterious effects of DMBA/CCl4 on serum ALT, AST, ALP and GGT activities as well as serum total bilirubin, albumin and globulin levels. The elevated oxidative stress and the deteriorated antioxidant defense system were markedly improved by treatments. The increased mRNA expressions of hepatic NF-κB, TNF-α and COX-2 in liver of DMBA/CCl4-administered rats were significantly decreased by treatments. In contrast, the lowered p53 and Bcl-2 were significantly increased. The liver histological lesions, represented by inflammatory cell infiltration, necrosis of hepatocytes and emergence of pre-cancerous oval cells, in DMBA/CCl4-administered rats, were amended by treatments with Punica granatum aril juice, seeds and husk extracts and their mixture. In conclusion, Punica granatum aril juice, aqueous extracts of seeds and husk and their mixture successfully mitigate DMBA and CCl4-induced liver deleterious changes and precancerous lesions via their anti-oxidant, anti-inflammatory and anti-apoptotic actions.