Sex difference in response to a carcinostatic agent aristolochic acid

ABSTRACT

Toxicity and tumor studies were done with a local medicinal plant alkaloid, aristolochic acid against Ehrlich Ascites Carcinoma in mice. A striking and consistent sex difference in response, both in toxicity and antitumor activity was observed. There was at least a dual effect on males and females as regards toxicity, depending on whether the drug was given in acute single doses or in short or long-term chronic regimens. With acute doses, males were found more susceptible to the drug. Conversely, the females were more affected by chronically administered drug. The cause/s of death in either case may not be the sameAt dose levels below the ED50 (1.15 mg/kg), it showed higher antitumor activity in males compared to the females. At higher doses beyong the ED50, the reverse is true, females more than malesThe possible role of sex hormones in regulating membrane permeability, which is believed to be altered in carcinogenesis is emphasized. The significant relationship of biochemical structure, that is lipids, proteins and carbohydrate residues, to membrane permeability, is also discussed. Investigations, both at the gross and biochemical level confirm its antineoplastic activity. Marked renal and hepatotoxicity, however, are risks one has to contend with should it be used in clinical cancer chemotherapy. (Summary)