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.

Protective effect of thymoquinone against lung intoxication induced by malathion inhalation

“…These adverse effects on the hematological parameters were greatly ameliorated by TQ supplementation. These results are consistent with Ghazy et al 28 , the alleviation of anemia induced by diazinon toxicity by TQ administration. The improved hematological parameters may be www.nature.com/scientificreports/ attributed to the ameliorative effect of TQ against free radicals caused by malathion inhalation 32,33 .…”

“…These results are compatible with Kanu et al 27 and Ghazy et al 28 who reported that other OPs are associated with a significant decrease in the hematological parameters, especially RBCs, hemoglobin, and platelet counts, and with a significant increase in the WBCs count. Moreover, Ghazy et al 28 reported decreases in erythrocytes could be as a result of either direct erythrocytes destruction by the pesticide or indirect through its bad effects on the bone marrow. Coles 29 stated www.nature.com/scientificreports/ that low packed cell volume promotes reticulocyte released from bone marrow, which increases the MCV.…”

“…These results are in harmony with El-Sheikh et al 44 who reported that TQ has hepatorenal protection against methotrexate-induced toxicity in the rats through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms. Moreover, Ghazy et al 28 reported the protective effect of TQ against the hepatotoxic effect of diazinon in male rats. In addition, Aboubakr et al 45 and Farid et al 46 recorded the antioxidant protective effect of the natural substances against tilmicosin and Carbon tetrachloride toxicity in the rats, respectively.…”

Ameliorative Effect of Thymoquinone and Thymoquinone Nanoparticles against Diazinon-Induced Hepatic Injury in Rats: A Possible Protection Mechanism

“…The findings are consistent with these results [ 77 ]. DZN was found to increase the amount of apoptotic cells in hepatic tissues and produce toxic damage to hepatocytes [ 78 ]. DZN causes mitochondrial damage by increasing membrane permeability and generating ROS [ 79 ].…”

“…Caspase-3 expression, an indicator of apoptosis, was also shown to be suppressed by TQ, as was previously reported that caspase-3 expression was also shown to be stifled by TQ [ 84 ]. In addition, the molecular analysis indicated that TQ inhibits apoptosis by showing a significant drop in Caspase-3 and Bax gene mRNA expression by inhibiting the release of cytochrome c, a cornerstone of the intrinsic apoptotic cascade [ 78 ].…”