الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 196 |  |  |
| | | from | 196 | | |
Abstract
N-acetyl-p-aminophenol (APAP) or acetaminophen is one of the widely used and most popular drugs for the therapy of pain and fever. Although APAP is considered as a safe drug, its overdose could result in severe liver and kidney injuries, and even death. APAP is especially dangerous on the liver when it is taken over long periods.
Thus, this study was designed to assess the preventive effects and to suggest the mechanisms of action of navel orange peel hydroethanolic extract, naringin and naringenin in APAP-induced hepatotoxicity and nephrotoxicity in male Wistar rats. APAP was administered to male Wistar rats at dose level of 0.5 g/kg body weight (b.w.) by oral gavage every other day for 4 weeks. APAP-administered rats were treated with navel orange peel hydroethanolic extract (50 mg/kg b.w.), naringin (20 mg/kg b.w.) and naringenin (20 mg/kg b.w.) by oral gavage every other day during the same period of APAP administration. The treatments of APAP-administered rats with peel extract, naringin and naringenin produced a significant decrease in the elevated serum urea, Cr, uric acid, AST, ALT, ALP, LDH and GGT levels as well as total bilirubin and TNF-α levels while they induced a significant increase in the lowered serum albumin and IL-4 levels. The treatments also resulted in a significant decrease in the elevated liver and kidney lipid peroxidation and enhanced the liver and kidney GSH content and SOD, GST and GPx activities as compared with APAP-administered control; the peel extract was the most potent in improving the LPO, GSH content and GPx activity. In addition, the three treatments significantly downregulated the elevated hepatic pro-apoptotic mediators p53, Bax and caspase-3 and significantly upregulated the suppressed anti-apoptotic protein, Bcl-2, in APAP-administered rats. In association, the treatments markedly amended the APAP-induced liver and kidney histopathological deteriorations that include hepatocytes steatosis, cytoplasmic vacuolization, hydropic degeneration and necrosis together with mononuclear leucocytic and fibroblastic inflammatory cells’ infiltration. In conclusion, the navel orange peel hydroethanolic extract, naringin and naringenin may exert their hepatopreventive and nephropreventive effects in APAP-administered rats via enhancement of antioxidant defense system and suppression of inflammation and apoptosis.