Carvedilol protects against the renal mitochondrial toxicity induced by cisplatin in rats.
The clinical use of cisplatin is highly limited by its nephrotoxicity, which has been associated with mitochondrial dysfunction. We investigated the protective effect of carvedilol, an antihypertensive with strong antioxidant properties, against the nephrotoxicity induced by cisplatin in rats. Carvedilol was able to counteract the renal damage by preventing the mitochondrial dysfunction induced by cisplatin. The mitochondrial eletrochemical potential, calcium uptake, respiration and the phosphorylative capacity were preserved by the co-administration of carvedilol. The mechanism of protection probably does not involve alterations in the cellular and sub-cellular distribution of cisplatin. The study suggests that carvedilol is a potential drug for the adjuvant nephroprotective therapy during cisplatin chemotherapy.
Rodrigues
M A Carvalho
MA
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto-USP, Av. do Café s/n, 14040-903 Ribeirão Preto, SP, Brazil.
Rodrigues
J L
JL
Martins
N M
NM
Barbosa
F
F
Curti
C
C
Santos
N A G
NA
Santos
A C
AC
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002227:Carbazoles / Q000008:administration & dosage / Q000494:pharmacology*; D000077261:Carvedilol; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D011412:Propanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000959:Antihypertensive Agents; D000970:Antineoplastic Agents; D000975:Antioxidants; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D002945:Cisplatin; D002118:Calcium