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Toxicology. 2003 Sep 30;191(2-3):143-51.

Carvedilol and trimetazidine attenuates ferric nitrilotriacetate-induced oxidative renal injury in rats.

Author information

1
Pharmacology Division, University Institute of Pharmaceutical Sciences, Punjab University, Chandigarh 160014, India. dr_chopra_k@yahoo.com

Abstract

Intraperitoneal (i.p.) injection of ferric nitrilotriacetate (Fe-NTA) induces acute proximal tubular necrosis as a consequence of lipid peroxidation and oxidative tissue damage, which eventually leads to high incidence of renal adenocarcinoma in rodents. This study was designed to investigate the effect of carvedilol, an antihypertensive and trimetazidine, an antiischemic, both the drugs with additional antioxidative potentials, on Fe-NTA induced nephrotoxicity in rats. One hour after a single i.p. injection of Fe-NTA (8 mg iron per kg), a marked deterioration of renal architecture and renal function as evidenced by a sharp increase in blood urea nitrogen (BUN) and serum creatinine was observed. Fe-NTA induced a significant renal oxidative stress demonstrated by elevated thiobarbituric acid reacting substances (TBARS) and reduction in activities of renal catalase, superoxide dismutase (SOD) and glutathione reductase (GR). Pretreatment of animals with carvedilol (2 mg/kg, i.p.) as well as with trimetazidine (3 mg/kg, i.p.), 30 min before Fe-NTA administration markedly attenuated renal dysfunction, reduced elevated TBARS, restored the depleted renal antioxidant enzymes and normalised the renal morphological alterations. These results clearly demonstrate the role of oxidative stress and its relation to renal dysfunction, and suggest a protective effect of carvedilol and trimetazidine on Fe-NTA-induced nephrotoxicity in rats.

PMID:
12965117
DOI:
10.1016/s0300-483x(03)00259-2
[Indexed for MEDLINE]

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