الفهرس 
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Abstract
Dox is widely used as anticancer drug. However, it was found that it produced significant hepatotoxicity, nephrotoxicity and cardiotoxicity. Therefore, the present study aimed to assess the preventive effects of green tea aqueous extract and epicatechin on liver, kidney and heart injuries in Dox-injected male Wistar rats.
The Dox was interperitoneally injected as total cumulative doses, each of 24 mg/kg b. wt divided into 6 equal doses, each of 4 mg/kg b. wt once weekly for 6 weeks The Dox-injected rats were treated with green tea aqueous extract (200 mg/kg b. wt) or epicatechin (25 mg/kg b. wt) by oral gavage every other day for 6 weeks.
The treatment of Dox-injected rats with green tea aqueous extract and epicatechin for 6 weeks produced marked improvements in liver function and histological integrity and architecture. Serum ALT, AST, ALP and γ-GT activities as well as total bilirubin and AFP levels were signifantly decreased by treatment of Dox-injected rats with green tea aqueous extract and epicatechin while serum albumin level was significantly increased. Most of the deleterious liver histological changes including vacuolization of hepatocytes, fibroblast proliferation, fibrosis of hepatic capsules and fibroplasia of bile ductules were markedly improved after treatments of Dox-injected rats with green aqueous extract and epicatechin.
The impaired kidney function and deleterious kidney histological changes in Dox-administered rats were remarkably ameriolated as a result of treatments with green tea aqueous extract and epicatechin. The elevated serum creatinine, urea and uric acid levels in Dox-injected rats were significantly improved by treatments. Kidney histological lesions including focal inflammatory cell infiltration, perivascular odema, atrophy of glomerular tufts, congestion of blood hemorrhage observed in the kidney of Dox-injected rats were noticeably amended as a result of treatments with green tea aqueous extract and epicatechin.
The heart dysfunction and deleterious heart histological changes were markedly alleviated as a result of treatments of Dox-injected rats with green tea aqueous extract and epicatechin. The elevated serum CK-MB and LDH activities in Dox-injected rats were significantly decreased as a result of treatments with green tea aqueous extract and epicatechin. The mononuclear cell infiltration, hemorrhage and vacuolation of cardiomyocytes observed in Dox-administered rats disappeared as a result of treatments with green tea aqueous extract and epicatechin.
The levels of serum proinflammatory cytokine, TNF-α, was significantly increased in Dox-administered rats while serum level of anti-inflammatory cytokine, IL-4, was reduced. The treatment of Dox-administered rats with green tea aqueous extract and epicatechin induced a significant ameriolation of these deleterious changes.
The deteriorated liver, kidney and heart lipid peroxidation, GSH content and the antioxidant enzyme activities including SOD, GPx and GST activities in Dox-administered rats were detectably improved as a result of treatments with green tea aqueous extract and epicatechin.
The elevated mRNA expression of liver apoptotic marker p53 and inflammatory mediator (NF-κB) in Dox-injected rats were significantly decreased as a result of treatment with green tea aqueous extract and epicatechin while mRNA expression of anti-apoptoic mediator (Bcl-2) was significantly increased.
The immunohistochemically detected liver COX-2 and caspase-3 were observably increased in Dox-injected rats while they exhibited weak positive expression in Dox-injected rats treated with green tea aqueous and epicatechin.
In conclusion, the green tea aqueous extract extract and epicatechin have potential preventive effects against liver, kidney and heart injures. These preventive effects may be mediated via enhancement of antioxidant defense system and suppression of oxidative stress, inflammatory effects and apoptotic actions.