S-Adenosyl-L-methionine increases serum BUN and creatinine in cisplatin-treated mice

Cisplatin is an effective antineoplastic agent in the treatment of various solid tumors, although its full clinical utility is limited because of its renal toxicity. Several measures to protect the kidneys from cisplatin toxicity have been investigated and implemented in clinical trials; however, none of these were completely effective or without secondary effects. The aim of this study was to investigate S-adenosyl-L-methionine (SAM) as an agent that protects against cisplatin nephrotoxicity without affecting the antineoplastic activity of cisplatin. The cytotoxic effect was evaluated in cultured HeLa cells treated with cisplatin, SAM, and the combination cisplatin + SAM. No modification of the cytotoxic effect of cisplatin was induced by SAM. Similarly, SAM did not influence the antitumoral activity of cisplatin observed in HeLa cells implanted in nude mice. However, a significant increase in renal dysfunction was induced by SAM in animals treated with cisplatin. To our knowledge, this is the first report of a potential severe adverse effect of SAM administration, which should be considered for further evaluation due to the wide use of SAM as a nutritional supplement in humans.