Acute and subacute effects of thymoquinone on acute methanol intoxication: An assessment based on serum TBARS and BDNF levels in rat model

Abstract

Objectives: Previous studies have shown the role of oxidative stress in methanol (MeOH) neurotoxicity. In clinical practice ethanol (EtOH) was used for the treatment of MeOH intoxication. Treatment with EtOH results in depression of the central nervous system, which may occur even at therapeutic doses. It also induces oxidative stress. Antioxidant and neuroprotective effects of thymoquinone (TQ) are known in different models of neurotoxicity. There are no studies investigating the protective effect of TQ against acute MeOH intoxication. We aimed to evaluate the effect of TQ administration on serum thiobarbituric acid reactive substances (TBARS) and Brain-Derived Neurotrophic Factor (BDNF) levels in rats with experimentally-induced MeOH intoxication. Materials and Methods: Six groups were constituted. Methotrexate (Mtx) treatment (0.3 mg/kg/day) intraperitoneally (i.p.) was given for 7 days to slow down the formate metabolism of all rats except controls in order to create a MeOH intoxication similar to that in humans. On the 8th day of the experiment, 3 g/kg MeOH was injected i.p. in MeOH, EtOH and TQ groups. Four hours after MeOH administration, 0.5 g/kg EtOH was injected i.p. in EtOH group and 30 mg/kg TQ was administered i.p. in TQ1 and TQ2 groups. In addition, a total of 5 doses of 30 mg/kg TQ was injected i.p. 24, 48, 72 and 96 hours after the first dose in TQ2 group. Saline solution was given i.p. in the other groups. Blood samples were obtained for evaluating serum TBARS and BDNF levels. Results: The highest TBARS level was found in MeOH+MTx group and this increase was statistically significant as compared to control and Mtx groups (p<0.001) . A statistically significant reduction was detected in serum TBARS levels in MeOH+Mtx+EtOH, MeOH+Mtx+TQ1 and MeOH+Mtx+TQ2 groups (p<0.001). Maximum serum BDNF level elevation was found in MeOH+Mtx group and this increase was statistically significant as compared to control and Mtx groups (p<0.001). Serum BDNF levels were higher in MeOH+Mtx+EtOH, MeOH+Mtx+TQ1 and MeOH+Mtx+TQ2 groups and the difference was statistically significant (p<0.001). Conclusions: Thymoquinone could suppress proinflammation and lipid peroxidation in MeOH intoxication, lead to rapid toxicity adaptation, and play the role of neuroprotection more effectively than EtOH. These results may suggest that TQ could be used as an alternative treatment option in MeOH intoxication.