Cisplatin-induced changes in the gastric smooth muscle and its calcium modulation

Cisplatin (cis-Dichlorodiammineplatinum II; CDDP) a potent broad spectrum anti-cancer drug produces severe toxic side effects including kidney damage, nausea and vomiting, loss of hearing, peripheral neuropathy, hypomagnesemia and hypocalcemia. Our studies using rat as the model system show that these toxicities are related to calcium homeostasis and can be controlled through the exogenous administration of calcium before CDDP treatment. Cytochemical and ultrastructural studies in Wistar rats [Crl:(WI)BR] show that CDDP in its hydrolyzed state under low chloride ion concentrations, within the cell, causes uncoupling of oxidative phosphorylation, calcium efflux from the mitochondria, inhibits ATP synthesis, lowers membrane-associated calcium and various membrane transport enzymes. It also induces an increase in the number of lysosomes. CDDP causes a drop in the blood calcium levels with a corresponding increase in the dark cells of the parathyroid gland. In rats CDDP causes hypercontraction of the uterine smooth muscle and an undue distension of the stomach through the noncontractility of its smooth muscle thus inhibiting gastric motility, leading to the development of ulcers.