Telmisartan prevents the progression of renal injury in daunorubicin rats with the alteration of angiotensin II and endothelin-1 receptor expression associated with its PPAR-γ agonist actions

被引：20

作者：

Arozal, Wawaimuli ^{[1
,2
]}

Watanabe, Kenichi ^{[1
]}

Veeraveedu, Punniyakoti T. ^{[1
]}

Ma, Meilei ^{[1
]}

Thandavarayan, Rajarajan A. ^{[1
]}

Sukumaran, Vijayakumar ^{[1
]}

Suzuki, Kenji ^{[3
]}

Kodama, Makoto ^{[4
]}

Aizawa, Yoshifusa ^{[4
]}

机构：

[1] Niigata Univ Pharm & Appl Life Sci, Dept Clin Pharmacol, Fac Pharmaceut Sci, Akiha Ku, Niigata 9568603, Japan

[2] Univ Indonesia, Fac Med, Dept Pharmacol, Jakarta 10430, Indonesia

[3] Niigata Univ, Grad Sch Med & Dent Sci, Dept Gastroenterol & Hepatol, Niigata 9518510, Japan

[4] Niigata Univ, Grad Sch Med & Dent Sci, Dept Internal Med 1, Niigata 9518510, Japan

来源：

TOXICOLOGY | 2011年 / 279卷 / 1-3期

关键词：

Angiotensin II receptor; Endothelin-1; receptor; Daunorubicin; Telmisartan; PPAR-gamma; Nephrotoxicity; ANTHRACYCLINE-INDUCED CARDIOTOXICITY; DOXORUBICIN-INDUCED CARDIOTOXICITY; OXIDATIVE STRESS; TYPE-1; RECEPTOR; INDUCED CARDIOMYOPATHY; EXOGENOUS MELATONIN; ALDOSTERONE SYSTEM; ACE-INHIBITION; KAPPA-B; FAILURE;

D O I：

10.1016/j.tox.2010.09.013

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Angiotensin II (Ang II) receptor blocker (ARB) suppresses the progression of kidney disease. However, there is limited information regarding the nephroprotective effect of ARB in daunorubicin (DNR)-induced nephrotoxicity in rats. We examined the alteration of the renal Ang II and endothelin-1 (ET-1) receptor expression and the action of telmisartan, an ARB, on DNR-induced nephrotoxicity. Sprague-Dawley rats were treated with a cumulative dose of 9 mg/kg DNR (i.v.). Telmisartan was administered orally every day for 6 weeks. DNR rats showed nephrotoxicity as evidenced by worsening renal function, which was evaluated by measuring protein in urine, levels of urea and creatinine in serum, lipid profiles, malondialdehyde level, and the glutathione peroxidase activity in kidney tissue. These changes were reversed by treatment with telmisartan, which resulted in significant improvement in renal function. Furthermore, telmisartan increased nephrin protein expression, and down-regulated renal expression of Ang II and its receptor Ang II type I. Renal protein expressions of ET-1 and its receptor ET-receptor type A were increased in DNR rats, and treatment with telmisartan attenuated these increased expressions. Telmisartan mediated a further increase in the expression of peroxisome proliferator-activated receptor-gamma (PPAR-gamma). In addition, the expressions of cyclooxygenase-2 and cellular adhesion molecules were increased in DNR rats, which were attenuated by telmisartan. In conclusion, telmisartan has a protective effect on DNR-induced nephrotoxicity through Ang II and ET-1, with the alteration of their receptor expressions, which is associated with its anti-inflammatory and anti-oxidant effects at least in part through PPAR-gamma agonistic actions. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

引用

页码：91 / 99

页数：9

共 74 条

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