Abstract
Cisplatin is a prominent member of the effective broad spectrum antitumor drugs. The clinical usage of cisplatin is, however, restricted due to some adverse side effects including renal toxicity. The present study demonstrates the protective effect of a Zinc-chelate of histidine, [Zn-Hist], against cisplatin induced nephrotoxicity and gastrointestinal toxicity as shown by decreases in BUN, creatinine and lower incidence of diarrhoea. The observed inhibition in cisplatin induced renal and hepatic lipid peroxidation by [Zn-Hist] pretreatment, suggests an importance for Zn in stabilisation of membrane integrity probably through the displacement of the redox-active metals that may be responsible for inducing peroxidative damage at target sites. The findings also suggest that cisplatin may play biochemical role in arginine-metabolism including nitric oxide (NO) production.
MeSH terms
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Animals
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Antineoplastic Agents / antagonists & inhibitors
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Antineoplastic Agents / toxicity*
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Arginine / analogs & derivatives*
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Arginine / metabolism
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Arginine / pharmacology
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Cisplatin / antagonists & inhibitors*
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Cisplatin / toxicity*
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Diarrhea / chemically induced
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Diarrhea / prevention & control
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Digestive System / drug effects
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Digestive System Physiological Phenomena
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Histidine / pharmacology*
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Kidney / drug effects*
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Kidney / metabolism
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Kidney / pathology
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Lipid Peroxidation / drug effects
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Liver / drug effects
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Liver / metabolism
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Male
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NG-Nitroarginine Methyl Ester
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Nitric Oxide / antagonists & inhibitors
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Nitric Oxide / physiology*
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Nitric Oxide Synthase / antagonists & inhibitors
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Nitric Oxide Synthase / metabolism*
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Rats
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Trace Elements / analysis
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Trace Elements / metabolism
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Zinc / pharmacology*
Substances
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Antineoplastic Agents
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Trace Elements
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Nitric Oxide
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Histidine
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Arginine
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Nitric Oxide Synthase
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Zinc
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Cisplatin
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NG-Nitroarginine Methyl Ester