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【Cancer research】氢气可对抗化疗药物引起的肾毒
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Cancer Chemother Pharmacol. 2009 Jan 16. [Epub ahead of print] Links
Molecular hydrogen alleviates nephrotoxicity induced by an anti-cancer drug cisplatin without compromising anti-tumor activity in mice.Nakashima-Kamimura N, Mori T, Ohsawa I, Asoh S, Ohta S.
Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Nippon Medical School, Kawasaki, Kanagawa, 211-8533, Japan.
PURPOSE: 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. We have reported that molecular hydrogen (H(2)) acts as an efficient antioxidant (Ohsawa et al. in Nat Med 13:688-694, 2007). Here we show that hydrogen efficiently mitigates the side effects of cisplatin by reducing oxidative stress. METHODS: Mice were administered cisplatin followed by inhaling hydrogen gas (1% H(2) in air). Furthermore, instead of inhaling hydrogen gas, we examined whether drinking water containing hydrogen (hydrogen water; 0.8 mM H(2) 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. RESULTS: Inhalation of hydrogen gas improved mortality and body-weight loss caused by cisplatin, and alleviated nephrotoxicity. Hydrogen was detected in blood when hydrogen water was placed in the stomach of a rat. Consuming hydrogen water ad libitum also reduced oxidative stress, mortality, and body-weight loss induced by cisplatin in mice. Hydrogen water improved metamorphosis accompanying decreased apoptosis in the kidney, and nephrotoxicity as assessed by serum creatinine and BUN levels. Despite its protective effects against cisplatin-induced toxicity, hydrogen did not impair anti-tumor activity of cisplatin against cancer cell lines in vitro and tumor-bearing mice in vivo. CONCLUSION: Hydrogen has potential for improving the quality of life of patients during chemotherapy by efficiently mitigating the side effects of cisplatin.
Introduction
The development of chemotherapeutic drugs exhibiting
weak side eVects is desired; at the same time, overcoming
side eVects is essential for the clinical use of anti-cancer
drugs. Cisplatin (cis-diamminedichloroplatinum II) is currently
one of the most eVective chemotherapeutic agents in
the treatment of a variety of tumors, including those of the
head, neck, testis, ovary and breast [1]. Higher doses of cisplatin
are more eYcacious; however, high-dose therapy is
limited by nephrotoxic side eVects [2]. Cisplatin causes the
accumulation of reactive oxygen species (ROS), such as
superoxide anions and hydroxyl radicals, by suppressing
antioxidant activity through decreasing the reduced form ofglutathione [3–7]. Oxidative stress seems to play a critical
role in cisplatin-induced nephrotoxicity [8–11]. So far, antioxidants
that improve nephrotoxic side eVects have been
extensively explored; however, although some antioxidants
exhibited protective eVects in model animals, the eVects
were not satisfactory or the dosage of antioxidants was
extremely high for clinical use [11–13]. In addition,
concerns about possible interference with the anti-tumor
activity of cisplatin limit its use to clinical trials [11].
We have reported that molecular hydrogen is a mild but
eYcient antioxidant by gaseous rapid diVusion into tissues
and cells [14]. Moreover, we have recently shown that consumption
of water dissolving molecular hydrogen at a saturated
level (hydrogen water) prevents stress-induced
cognitive declines in mice [15].
Here we show that inhalation of hydrogen gas and drinking
hydrogen water ad libitum mitigate cisplatin-induced
nephrotoxicity in mice. Drinking hydrogen water may be
more convenient for consumption of hydrogen rather than
hydrogen gas. Consuming hydrogen water ad libitum was
eYcacious for renal failure caused by cisplatin without
compromising anti-tumor activity in mice. Thus, we propose
that hydrogen consumption, whether hydrogen gas or
hydrogen water, is applicable to alleviate nephrotoxic side
eVects induced by an anti-cancer drug. [标签:content1][标签:content2]
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作者:admin@医学,生命科学 2011-04-29 14:38
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