Calcium modulation of toxicities due to cisplatin

Abstract

Cisplatin (CDDP) is a potent anti-neoplastic agent with associated toxicities, especially gastrointestinal and nephrotoxicity that are its dose-limiting factors in clinical oncology. In an attempt to elucidate its mechanism(s) of action, liver and kidney tissues from normal and CDDP treated (1.8 mg/kg) dogs were evaluated for changes in various dehydrogenases [MDH, SDH, β-HBDH, IDH and G-6-PDH] and nonspecific lipase enzymes. CDDP treatment induced an inhibition of all the enzymes studied except G-6-PDH and nonspecific lipases, where there was a significant increase. Supplemental pretreatments with calcium 2.50 mg (150,000 USP units) ergocalciferol plus 1000 mg of elemental calcium as Tums 500 (EffeCal; calcium carbonate)/day seemed to retain enzyme levels close to normal with no apparent toxic side effects observed after CDDP. Calcium supplements post-CDDP treatment did not have any protective effect.