Molecular hydrogen (dissolved in water) alleviates nephrotoxicity induced by an anti-cancer drug cisplatin (chemotherapy) without compromising anti-tumor activity in mice.
Cisplatin is a widely used anti-cancer drug in the treatment of a wide range of tumors; however, its application is limited by nephrotoxicity, which is affected by oxidative stress ROS. We have reported that molecular hydrogen (H(2)) acts as an efficient selctive antioxidant (Ohsawa et al. in Nat Med 13:688-694, 2007). Here we show that molecular hydrogen efficiently mitigates the side effects of toxic chemotherapeutic cisplatin by reducing oxidative stress.
Mice were administered chemotherapy ( cisplatin) followed by inhaling molecular hydrogen gas (1% H(2) in air). Furthermore, instead of inhaling molecular hydrogen gas, we examined whether drinking water containing hydrogen (hydrogen water; 0.8 mM H(2) dissolved in water) is applicable by examining oxidative stress, mortality, and body-weight loss. Nephrotoxicity was assessed by morphological changes, serum creatinine and blood urea nitrogen (BUN) levels.
Inhalation of molecular hydrogen gas improved mortality and body-weight loss caused by chemotherapy/ cisplatin, and alleviated nephrotoxicity. Molecular hydrogen was detected in blood when molecular hydrogen water was placed in the stomach of a rat. Consuming molecular hydrogen water ad libitum also reduced oxidative stress, mortality, and body-weight loss induced by cisplatin in mice. Molecular hydrogen water improved metamorphosis accompanying decreased apoptosis in the kidney, and nephrotoxicity as assessed by serum creatinine and BUN levels.
Despite molecular hydrogen (water)’s protective effects against cisplatin-induced toxicity, molecular hydrogen water did not impair anti-tumor activity of cisplatin against cancer cell lines in vitro and tumor-bearing mice in vivo.
Molecular hydrogen water has potential for improving the quality of life of patients during chemotherapy by efficiently mitigating the side effects of cisplatin while not compromising antitumor effects.
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Nakashima-Kamimura N, Mori T, Ohsawa I, Asoh S, Ohta S. Molecular hydrogen alleviates nephrotoxicity induced by an anti-cancer drug cisplatin without compromising anti-tumor activity in mice. Cancer Chemother Pharmacol. 2009;64(4):753–61. doi: 10.1007/s00280-008-0924-2.[PubMed] [Cross Ref]