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 8 th day 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 CYP2E1 and 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.

Diazinon (DZN) is one of most dangerous hepatotoxic organophosphorous insecticides used in veterinary practices which induces oxidative stress. The present study aimed to evaluate the ameliorative role of thymoquinone (TQ) in diazinon toxicity. Forty nine male albino rats and were divided into seven groups (n =7 for each). The first group (c-ve group) orally received saline daily all over the experiment (8 weeks). The second group (c+ve1) orally received DZN (15 mg/kg body weight, b-w) for the first four weeks and saline for the next four weeks. The third group (c+ve2) orally received saline for the first four weeks and DZN (15 mg /kg b-w) for the following four weeks. The fourth group (DZN-TQ 10 mg group) received DZN (15 mg/kg b-w) daily for the first four weeks then TQ (10 mg/kg b-w) for the next four weeks. The fifth group (TQ 10 mg-DZN) orally treated with TQ (10 mg/kg b-w) and DZN (15 mg/kg b-w) for the next for weeks. The sixth group (DZN-TQ 5 mg group) received DZN (15 mg/kg b-w) for first four weeks and TQ (5 mg/kg b-w) for the following four weeks 5 mg. The seventh group treated by TQ (5 mg/kg b-w) daily for the first four weeks and DZN (15 mg/kg b-w) for the following four weeks (TQ 5 mg-DZN group). DZN intoxicated groups showed macrocytic hypochromic anemia and serum biochemical alteration related to liver injury, including elevation of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and a significant decrease in total protein and albumin. Furthermore, these groups also exhibited a significant increase in liver tissue malondialdehyde (MDA), significant decrease in total antioxidant capacity (TAC) and catalase (CAT) activities and over-expression of the two apoptotic hepatic genes Bax and caspase 3. Administration of DZN also resulted in hepatic vacuolation, necrosis and congestion of hepatic sinusoids. Thymoquinone ameliorated the most deleterious effect of diazinon on hematological, biochemical, antioxidant, molecular and histopathological parameters in a dose dependent manner and a prophylactic strategy is better than therapeutic one.