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Published on: July 3, 2013
Effects of prochlorperazine on experimental nephrotoxicity
Cancer Chemotherapy and Pharmacology
|December 1, 1982
Summary
Prochlorperazine, an antiemetic, demonstrated protective effects against kidney damage caused by the chemotherapy drug methyl-CCNU and mercury in rodent models. This finding suggests a potential role for prochlorperazine in mitigating drug-induced nephrotoxicity.
Area of Science:
- Nephrology
- Pharmacology
- Toxicology
Background:
- The antitumor drug methyl-CCNU (1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea) was predicted to be nephrotoxic in humans based on early animal studies.
- Clinical confirmation of methyl-CCNU-induced nephrotoxicity in cancer patients lagged significantly behind initial animal model predictions.
- The antiemetic prochlorperazine's potential to influence the development of drug-induced nephrotoxicity was investigated.
Purpose of the Study:
- To evaluate the protective effect of prochlorperazine against methyl-CCNU-induced nephrotoxicity in mice.
- To assess prochlorperazine's impact on mercuric chloride (HgCl2)-induced nephrotoxicity in rats.
- To investigate the potential of prochlorperazine in mitigating acute kidney injury from nephrotoxic agents.
Main Methods:
- Mice received varying doses of prochlorperazine followed by nephrotoxic doses of methyl-CCNU; plasma urea nitrogen and renal lesions were assessed.
- Rats were treated with prochlorperazine and mercuric chloride (HgCl2); urinary enzyme excretion and histopathological renal damage were evaluated.
- Dose-response relationships and histopathological severity scores were used to quantify the effects of prochlorperazine.
Main Results:
- Prochlorperazine administration significantly reduced plasma urea nitrogen levels and the severity of renal lesions in methyl-CCNU-treated mice in a dose-dependent manner.
- In rats, prochlorperazine inhibited the HgCl2-induced urinary excretion of N-acetylglucosaminidase and leucine aminopeptidase, biomarkers of tubular damage.
- Histopathological examination revealed significantly reduced renal lesions in rats co-treated with prochlorperazine and HgCl2 compared to HgCl2 alone.
Conclusions:
- Prochlorperazine exhibits protective activity against acute nephrotoxicity induced by both methyl-CCNU and mercuric chloride in rodent models.
- The findings suggest that prochlorperazine may play a role in ameliorating drug-induced kidney injury.
- Further research is warranted to elucidate the pharmacological mechanisms underlying prochlorperazine's nephroprotective effects.
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