Diallyl disulfide prevention of Cis-diamminedichloroplatinum-induced nephrotoxicity and leukopenia in rats. Potential adjuvant effects

CHIARANDINI FIORE JP; CIGNOLI DE FERREYRA EC; FANELLI SL; CASTRO JA

Washington, D.C.,

Conferencia; Food, Nutrition, Physical activity, and the Prevention of Cancer. A Global Perspective.Launch Conference; 2007

World Cancer Research Fund International. American Institute for Cancer Research.

Cisplatin (cis-diamminedichloroplatinum, CisPt) is one of the most effective chemotherapeutic agents used in the treatment of a wide range of solid tumors. However, CisPt has many side effects that limit its use, including nephrotoxicity and myelotoxicity. Nephrotoxicity is recognized as the main collateral effect and it is the most important limiting factor of its clinical use. There is significant evidence suggesting that in the cytotoxic activity of CisPt the formation of reactive oxygen species (ROS) play an important role. The mechanism of the antitumor action of CisPt involves as the essential event the formation of a variety of platinum adducts with DNA and proteins. In this work we report initial studies on the potential ability of the garlic oil component diallyldisulfide (DADS) to block nephrotoxicity and myelotoxicity without compromising chemotherapy. In these studies, male Sprague-Dawley rats were used (control; DADS; CisPt and CisPt/DADS groups). CisPt was administered subcutaneously as a single dose (10.5 mg/kg) in saline. DADS was administered intragastrically in olive oil as one daily dose during four days (292.5 mg/kg). Controls received saline and olive oil. The animals were sacrificed at the fifth day after CisPt administration. DADS significantly prevented CisPt induced nephrotoxicity as evaluated by serum urea, creatinine, and by histological examination. It also decreased CisPt-induced leukopenia and mortality. DADS increased defenses against CisPt-induced ROS as evidenced by the t-butylhydroperoxide-induced chemiluminiscence test and showed ability to interact with peroxides; hydroperoxides; hydroxyl radicals and with iron. DADS treatment did not significantly change platinum levels in kidney tissue. Since DADS is also known to inhibit cellular replication and to promote apoptosis of tumor cells, our results suggest a potential for DADS to be a coadjuvant of CisPt chemotherapy. Acknowledgement: JPCF has a doctoral fellowship from the National Research Council from Argentina (CONICET).