Acute and subchronic toxicity of thymoquinone in mice

The effects of acute and subchronic administration of thymoquinone (TQ), the main constituent of the volatile oil of the black seeds Nigella sativa, with significant cytoprotective properties, were studied in male Swiss albino mice. After acute oral administration, the LD50 value (95% CL) was 2.4 g/kg (1.52–3.77). Signs of toxicity at high doses were hypoactivity and difficulty in respiration. Twenty-four hours after TQ (2 and 3 g/kg) administration, a significant reduction in tissue (liver, kidneys, and heart) reduced glutathione (GSH) content was observed. Plasma urea and creatinine concentrations and the enzyme activities of alanine amino transferase (ALT), lactate dehydrogenase (LDH), and creatine phosphokinase (CPK) were significantly increased. In the subchronic study, mice received TQ in drinking water at concentrations of 0.01, 0.02, and 0.03% for 90 days with no resulting mortality or signs of toxicity. The average daily intake of the compound was approximately 30, 60, or 90 mg/kg/day. There were no changes of toxicological significance in body and organ weights, food and water intake, or urine and feces output. Tissue GSH, plasma concentrations of TP, urea, creatinine and triglycerides, and enzyme activities of ALT, LDH, and CPK were also not affected. Histological examination revealed no gross or microscopic tissue damage. TQ, however, produced a significant decrease in fasting plasma glucose level. The results indicate that the acute oral toxicity of TQ in mice is of a low order and it is generally well tolerated when given subchronically at doses previously shown to have cytoprotective activity. Drug Dev. Res. 44:56–61, 1998. © 1998 Wiley-Liss, Inc.