The effect of
thymoquinone (TQ), the main constituent of the Nigella sativa L. oil, on
ifosfamide (IFO)-induced
Fanconi syndrome (FS) and its antitumor activity were investigated in rats and mice, respectively. In rats, a daily injection of IFO (50 mg/kg per day, i.p.) for 5 days induced a FS characterized by wasting off
glucose,
electrolytes and organic
acids, along with elevated serum
creatinine and
urea, as well as decreased
creatinine clearance rate. Administration of TQ with the
drinking water of rats, (5 mg/kg per day) for 5 days before and during IFO treatment, ameliorated the severity of IFO-induced renal damage. TQ significantly improved IFO-induced
phosphaturia, glucosuria, elevated serum
creatinine and
urea, and significantly normalized
creatinine clearance rate. Moreover, TQ significantly prevented IFO-induced renal
glutathione (GSH) depletion and
lipid peroxide accumulation. In mice bearing Ehrlich
ascites carcinoma (EAC) xenograft, TQ (10 mg/kg per day) administered in
drinking water significantly enhanced the antitumor effect of IFO (50 mg/kg per day, i.p. on days 1-4 and 15-18). Furthermore, mice treated with IFO in combination with TQ showed less
body weight loss and mortality rate compared to IFO single
therapy. These observations demonstrate that TQ may improve the therapeutic efficacy of IFO by decreasing IFO-induced nephrotoxicity and improving its antitumor activity.