Modulation of Nrf2/HO1 Pathway by Thymoquinone to Exert Protection Against Diazinon-induced Myocardial Infarction in Rats

Abstract

Background Modern strategies to alleviate the harmful effects of organophosphate pesticide diazinon (DN) abnormalities were focused mainly on using natural compounds or their derivatives. DN is an organophosphate compound that causes many health abnormalities in humans due to its usage as an insecticide in agriculture. TQ is one of the beneficiary active principles derived from plant sources that has pharmacological benefits. Aim This research reveals the therapeutic potential of thymoquinone (TQ) on DN-induced myocardial infarction (MI) in rats. Materials and Methods Male Sprague–Dawley rats were procured, acclimatized, and divided into four groups of six animals each with feed and water ad libitum. MI was induced in rats with a dose of 25 mg/kg DN by oral gavage and TQ in a dose of 20 mg/kg p.o. for the treatment. After animal sacrifice at the end of the experimental period, serum and heart tissue samples were collected and processed appropriately for various analyses such as changes in the body weight, heart weight, marker enzymes, oxidative markers, non-enzymatic and enzymatic antioxidants, inflammatory cytokines, histopathological studies, and cardiac-specific markers. Results DN-induced toxicity depicted decreased body weight (167.83 ± 4.62), heart weight (0.9 ± 0.06), and heart-to-body weight ratio (0.54 ± 0.03). Also, elevated marker enzymes (147.33 ± 20.85, 407.5 ± 31.3, and 110.67 ± 9.65 for CK-MB, AST, and ALT, respectively), elevated oxidative markers (12.87 ± 1.34, 125.17 ± 9.95, and 80.17 ± 5.78 for serum MDA, heart MDA, and heart GSSG, respectively), decreased enzymatic- and non-enzymatic antioxidants (3.15 ± 0.42, 12.23 ± 1.02, 5.75 ± 0.46, 2.02 ± 0.26, 0.72 ± 0.07, 18.05 ± 1.04, 8.62 ± 0.65, and 45.8 ± 2.43 for SOD, CAT, GST, GPx, heart GSH, serum GSH, vit.E, and vit.C, respectively), damaged cellular architecture, elevated inflammatory cytokines, and cardiac-specific markers were noticed. Discussion TQ significantly reduced the toxicities produced by DN in almost all the above parameters. The beneficial effect of DN could be attributed to the influential effect of DN on cardiac-specific Nrf2/HO1-related pathways. Conclusion These results suggest that TQ exerts protection against MI and could serve as a promising candidate for drug development.