THE ROLE OF THYMOQUINONE IN AMELIORATING THE HEPATOXIC EFFECT OF DIAZINON IN MALE RATS

Abstract

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.Key words: diazinon; thymoquinone; oxidative stress; hepatotoxicity