SESAME OIL MITIGATES INITIATION STAGE OF DIETHYNITROSAMINE HEPATOCARCINOGENESIS IN RATS

Abstract

Diethylnitrosamine (DEN) induced hepatocarcinogenesis in experimental animals through triggering reactive oxygen species (ROS) release and subsequent induction of oxidative stress dependant liver damage. This study was conducted to estimate the protective role of sesame oil (SO) in the initial phase of DEN induced hepatocarcinogenesis. Forty five male Wistar rats were randomly divided into five groups groups (n = 9 each). In the first group (control), rats were orally administrated normal saline. Rats of second group (DEN) were intraperitoneally (i.p) injected with a single dose of (200mg/kg body weight, DEN) at the 8thday of the experiment. The third, fourth, fifth groups orally administrated SO at a dose (2.5, 5, 10 mL/kg b.w), respectively 1 week before i.p injection of DEN and continued for 4 successive weeks. DEN- induced hepatotoxicity as detected by normocytic normochromic anemia with marked increase in white blood cells and significant increase in hepatic damage enzymatic markers (alanine transaminase (ALT), aspartate aminotransferase (AST), γ-glutamyl Transferase (γGT) and alkaline phosphatase (ALP)) with significant decrease in serum total protein. Hepatic malondialdehyde (MDA) was increased significantly while hepatic antioxidant biomarkers superoxide dismutase (SOD), catalase (CAT) and hepatic reduced glutathione (GSH) were significantly decreased. Histological examination of hepatic tissue of DEN treated rats proved centrolobular necrosis associated with bile duct and oval cell proliferation. This was accompanied with over expression of CYP2E1and down regulation in BAX gene expression in liver. Administration of SO minimized the harmful effects of DEN on hematological, biochemical, antioxidant and histopathological parameter as well as on gene expression. The degree of improvement was in dose dependant manner. Our findings revealed that SO supplementation can mitigate the toxic effects of DEN via their potent antioxidant and free radical-scavenging activities. Key words: diethylnitrosamine, sesame oil, antioxidant, gene expression, rats