TY - JOUR
T1 - 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
AU - Arozal, Wawaimuli
AU - Watanabe, Kenichi
AU - Veeraveedu, Punniyakoti T.
AU - Ma, Meilei
AU - Thandavarayan, Rajarajan A.
AU - Sukumaran, Vijayakumar
AU - Suzuki, Kenji
AU - Kodama, Makoto
AU - Aizawa, Yoshifusa
N1 - Funding Information:
This research was supported by a Yujin Memorial Grant, Ministry of Education, Culture, Sports and Technology of Japan and by a grant from the Promotion and Mutual Aid Corporation for Private Schools, Japan. We thank Flori Ratna Sari, Hiroko Shimazaki, Sayaka Mito, and Yoshiyasu Kobayashi for their assistance in this research work.
PY - 2011/1/11
Y1 - 2011/1/11
N2 - 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-γ (PPAR-γ). 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-γ agonistic actions.
AB - 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-γ (PPAR-γ). 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-γ agonistic actions.
KW - Angiotensin II receptor
KW - Daunorubicin
KW - Endothelin-1 receptor
KW - Nephrotoxicity
KW - PPAR-γ
KW - Telmisartan
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U2 - 10.1016/j.tox.2010.09.013
DO - 10.1016/j.tox.2010.09.013
M3 - Article
C2 - 20888384
AN - SCOPUS:78650030818
SN - 0300-483X
VL - 279
SP - 91
EP - 99
JO - Toxicology
JF - Toxicology
IS - 1-3
ER -