Telmisartan inhibits both oxidative stress and renal fibrosis after unilateral ureteral obstruction in acatalasemic mice
| Autor: | Mizuho Kobayashi, Noriyoshi Masuoka, Yasushi Yamasaki, Da Hong Wang, Hitoshi Sugiyama, Shohei Kira, Reiko Sunami, Yohei Maeshima, Hirofumi Makino |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Male
medicine.medical_specialty Kidney Benzoates Superoxide dismutase Acatalasia Mice Internal medicine In Situ Nick-End Labeling medicine Renal fibrosis Animals Telmisartan chemistry.chemical_classification Mice Inbred C3H Transplantation Angiotensin II receptor type 1 NADPH oxidase biology business.industry Glutathione peroxidase NADPH Oxidases Fibrosis Immunohistochemistry Angiotensin II Mice Mutant Strains Disease Models Animal Oxidative Stress Treatment Outcome medicine.anatomical_structure Endocrinology chemistry Nephrology biology.protein Benzimidazoles Kidney Diseases Lipid Peroxidation business Angiotensin II Type 1 Receptor Blockers Ureteral Obstruction medicine.drug |
| Zdroj: | Nephrology Dialysis Transplantation. 20:2670-2680 |
| ISSN: | 1460-2385 0931-0509 |
| DOI: | 10.1093/ndt/gfi045 |
| Popis: | Background. Reactive oxygen species are involved in many of the angiotensin II signalling pathways. We have thus investigated whether the angiotensin II type 1 (AT1) receptor antagonist, telmisartan, can inhibit the accelerated renal fibrosis and excess oxidative stress, which occurs after unilateral ureteral obstruction (UUO) in acatalasemic mice. Methods. The effect of daily intraperitoneal injection of telmisartan (0.1–0.3 mg/kg body weight) on the renal tubulointerstitial injury induced by UUO has been studied in homozygous acatalasemic mutant mice (C3H/AnLCs b Cs b ) and wild-type mice (C3H/ AnLCs a Cs a ). We evaluated the systemic blood pressure of the mice on the seventh day. In addition, the tubulointerstitial expression of collagens type I and type IV, the p22-, p47- and p67-phox subunits of NADPH oxidase, 4-hydroxy-2-nonenal, and 4-hydroxy-2-hexenal lipid peroxidation products were assessed by immunohistochemistry. The level of apoptosis was determined by terminal deoxynucleotidyl transferase nick end-labelling analysis, while the mRNA level of the p22-, p47- and p67-phox subunits was quantified by real-time PCR. The renal content of each of the antioxidant enzymes catalase, glutathione peroxidase and superoxide dismutase was determined by specific assay. Results. Obstructed kidneys from acatalasemic mice exhibited increased tubulointerstitial deposition in dilated tubules of collagens type I and IV, lipid peroxidation products, and the p22/p47/p67-phox subunits of NADPH oxidase. The level of the p22/ p47/p67-phox subunit mRNA, and of apoptosis in tubular epithelial cells, was also increased compared with those from wild-type kidneys. Treatment with telmisartan attenuated all of the changes and prevented renal fibrosis in a dose-dependent manner; despite the low dose (0.1 mg/kg). The treatment did not lower the systemic blood pressure. The catalase activity remained low in acatalasemic obstructed kidneys without compensatory upregulation of glutathione peroxidase or superoxide dismutase activity; the level of neither anti-oxidant enzymes in obstructed kidneys was affected by telmisartan. Conclusions. The AT1 receptor antagonist telmisartan ameliorated renal fibrosis after UUO by inhibition of oxidative stress, even under acatalasemic conditions. |
| Databáze: | OpenAIRE |
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