Telmisartan attenuates oxidative stress and renal fibrosis in streptozotocin induced diabetic mice with the alteration of angiotensin-(1-7) mas receptor expression associated with its PPAR-γ agonist action

Arun Lakshmanan, Kenichi Watanabe, Rajarajan A. Thandavarayan, Flori R. Sari, Meilei Harima, Vijayasree V. Giridharan, Vivian Soetikno, Makoto Kodama, Yoshifusa Aizawa

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

The beneficial effects of telmisartan on Angiotensin (Ang)-II mediated oxidative stress and renal fibrosis in streptozotocin (STZ)-induced diabetic nephropathy (DN) were studied. Thirty mice were divided into normal (NG), STZ-induced diabetic (DG) and telmisartan-treated diabetic (TG) groups. Compared with NG mice, DG mice showed significant up-regulations of AT-1R, TGF-β1, p-p38MAPK, p-MAPKAPK-2, p-Akt, p47phox, p67phox, gp91phox protein and collagen-III and all of these were significantly reversed in TG mice. The down-regulated protein expression of Ang-(1-7) mas receptor, ACE-2, PPAR-γ and PGC-1α were observed in DG mice and a significant up-regulation effect of telmisartan has been seen in the TG mice. Furthermore, TG mice showed reduced expression of fibronectin, production of superoxide radical as well as renal hypertrophy and fibrosis when compared with DG mice. These findings suggest that Ang-II plays a significant role in DN and telmisartan would be beneficial in reducing oxidative stress and fibrosis in STZ-induced DN.

Original languageEnglish
Pages (from-to)575-584
Number of pages10
JournalFree Radical Research
Volume45
Issue number5
DOIs
Publication statusPublished - 1 May 2011
Externally publishedYes

Fingerprint

Peroxisome Proliferator-Activated Receptors
Oxidative stress
Streptozocin
Oxidative Stress
Fibrosis
Kidney
Angiotensin II
Diabetic Nephropathies
Fibronectins
Superoxides
Proteins
Up-Regulation
Collagen
telmisartan
angiotensin I (1-7)
Hypertrophy

Keywords

  • diabetic nephropathy
  • fibrosis
  • oxidative stress
  • Renin-angiotensin-aldosterone system
  • telmisartan

ASJC Scopus subject areas

  • Biochemistry

Cite this

Telmisartan attenuates oxidative stress and renal fibrosis in streptozotocin induced diabetic mice with the alteration of angiotensin-(1-7) mas receptor expression associated with its PPAR-γ agonist action. / Lakshmanan, Arun; Watanabe, Kenichi; Thandavarayan, Rajarajan A.; Sari, Flori R.; Harima, Meilei; Giridharan, Vijayasree V.; Soetikno, Vivian; Kodama, Makoto; Aizawa, Yoshifusa.

In: Free Radical Research, Vol. 45, No. 5, 01.05.2011, p. 575-584.

Research output: Contribution to journalArticle

Lakshmanan, Arun ; Watanabe, Kenichi ; Thandavarayan, Rajarajan A. ; Sari, Flori R. ; Harima, Meilei ; Giridharan, Vijayasree V. ; Soetikno, Vivian ; Kodama, Makoto ; Aizawa, Yoshifusa. / Telmisartan attenuates oxidative stress and renal fibrosis in streptozotocin induced diabetic mice with the alteration of angiotensin-(1-7) mas receptor expression associated with its PPAR-γ agonist action. In: Free Radical Research. 2011 ; Vol. 45, No. 5. pp. 575-584.
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