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Abstract Snake venoms are secretions of venomous snakes synthesized and stored in venomous glands ready for secretion upon biting their preys. Snake venom is a combination of many different proteins, peptides and enzymes that possess different toxicological effects on body tissues. Cardiotoxicity is a profound type of manifestations of most of crude venoms of cobra snakes e.g. Naja nubiae due to venom’s high level of cardiotoxins. Thymoquinone (TQ) is a bioactive compound with diverse reported therapeutic benefits dependent on its anti-oxidant properties against the buildup of reactive oxygen species in target tissues. Cardioprotective effects were among actions described in literature for thymoquinone against myocardial tissue injury. However, protective activity of thymoquinone against snake envenomation was never previously studied. The current study aimed to investigate the possibility of thymoquinone to exert its cardioprotective effects against myocardial necrosis induced by intravenous injections of snake venom into experimental animals. Furthermore, studying of changes of thioredoxin system in heart was evaluated as a possible candidate for the prospective cardioprotection of the drug. To achieve such aims, cardiotoxic effects of progressive sub-lethal doses of crude venom i.e. (1/8, 1/4, and 1/2 LD50 of venom) were challenged against previously administered daily thymoquinone oral doses on two levels (25, 50 mg/kg) for 7 days in experimental rats. Animals were anaesthetized 1 hr. after venom injection and were set to electrocardiogram (ECG) recording before scarification after 3 hrs. of envenomation. Histopathological examination of left ventricle and percentage survival, body weight, and heart weight changes were VI evaluated. Cardiac markers (creatine kinase of muscle and brain (ck-mb), lactate dehydrogenase (LDH), and troponin) concentrations were measured. Additionally, cardiac expressions of Thioredoxin (Trx), Thioredoxin-interacting protein (TXNIP), and single stranded DNA (SSDNA) were evaluated immunohistochemically. Activity of Thioredoxin reductase (TrxR) enzyme was measured in cardiac tissues. Venom insulted groups showed -in a dose dependent manner- progressive deterioration in all measured parameters with regard to control group. Treatment with thymoquinone, commenced 7 days before insult, ameliorated these abnormalities with greater protection induced by higher thymoquinone dosing. These current results demonstrated thymoquinone as a potential cardioprotective agent against Naja nubiae acute cardiac toxicity which represents novel promising approach to the fight against snake envenomation by elucidating new mechanisms involved in establishing such effect. |