Nephroprotective effect of telmisartan in rats with ischemia/reperfusion renal injury.
We investigated the protective effect of telmisartan, an angiotensin II receptor antagonist, against ischemia/reperfusion renal injury in rats. Bilateral ischemia was induced by clamping both renal vascular pedicles for 45 min followed by reperfusion for 3 h. Untreated rats exposed to ischemia/reperfusion showed significant elevations in blood urea nitrogen and serum creatinine levels, renal tissue levels of malondialdehyde, tumor necrosis factor-alpha and nitric oxide, and caspase-3 activity. This was associated with significant decreases in renal reduced glutathione level, catalase and superoxide dismutase activities. Also, significant increases in serum and renal tissue levels of homocysteine were detected following ischemia/reperfusion. Pre-ischemic treatment with telmisartan (0.3 mg/kg/day, i.p.) for 7 consecutive days significantly attenuated the increases in blood urea nitrogen, serum creatinine, renal malondialdehyde, tumor necrosis factor-alpha, nitric oxide, caspase-3 activity, and serum and renal homocysteine levels, and significantly restored the renal antioxidant defenses. In addition, light and electron microscopic examinations revealed that telmisartan pre-treatment markedly ameliorated ischemia/reperfusion-induced renal tissue damage. It was concluded that telmisartan, through its antioxidant, anti-inflammatory and antiapoptotic effects, can be considered a potential candidate to protect against acute ischemia/reperfusion renal injury.
Fouad
Amr A
AA
Department of Biomedical Sciences, Pharmacology Division, College of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia. amrfouad65@yahoo.com
Qureshi
Habib A
HA
Al-Sultan
Ali Ibrahim
AI
Yacoubi
Mohamed T
MT
Al-Melhim
Walid N
WN
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001806:Blood Urea Nitrogen; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D006710:Homocysteine / Q000097:blood; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D007674:Kidney Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000378:metabolism; D000077333:Telmisartan; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D047228:Angiotensin II Type 1 Receptor Blockers; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D001562:Benzimidazoles; D001565:Benzoates; D014409:Tumor Necrosis Factor-alpha; D006710:Homocysteine; D009569:Nitric Oxide; D008315:Malondialdehyde; D003404:Creatinine; D002374:Catalase; D013482:Superoxide Dismutase; C505410:Casp3 protein, rat; D053148:Caspase 3; D005978:Glutathione; D000077333:Telmisartan