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Renoprotective properties of pirfenidone in subtotally nephrectomized rats.
Eur J Pharmacol. 2010 Mar 10; 629(1-3):118-24.EJ

Abstract

Renal fibrosis is the final common pathway of chronic kidney disease, and its progression predicts the degree of renal dysfunction. We investigated the renoprotective properties of pirfenidone in a remnant kidney model of chronic renal failure to determine its pharmacological potency compared to enalapril. Five-sixths nephrectomized rats were fed diet containing pirfenidone (approximately 700mg/kg/day) for 8weeks. Pirfenidone steadily inhibited the progression of proteinuria, but not to a significant degree. Pirfenidone prevented the elevation of plasma creatinine and blood urea nitrogen. At the end of the experiment, pirfenidone had reduced systolic blood pressure by means of its renoprotective effect. In a histological study, pirfenidone improved interstitial fibrosis in the renal cortex. These effects were supported by the suppression of the expression of TGF-beta and fibronectin in the mRNA of the kidney. In contrast, pirfenidone had little effect on the expression of alpha-smooth muscle actin, which is one of the proteins responsible for epithelial-mesenchymal transition. This property was confirmed by the TGF-beta-induced transdifferentiation observed in cultured normal rat kidney tubular epithelial NRK52E cells. These results suggest that pirfenidone improves the progression of chronic renal failure via its antifibrotic action, although pirfenidone has less effective TGF-beta-induced epithelial to mesenchymal transdifferentiation.

Authors+Show Affiliations

Pharmacology Research Lab., Drug Discovery Research, Astellas Pharma Inc. 21, Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. koji.takakura@jp.astellas.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20006961

Citation

Takakuta, Koji, et al. "Renoprotective Properties of Pirfenidone in Subtotally Nephrectomized Rats." European Journal of Pharmacology, vol. 629, no. 1-3, 2010, pp. 118-24.
Takakuta K, Fujimori A, Chikanishi T, et al. Renoprotective properties of pirfenidone in subtotally nephrectomized rats. Eur J Pharmacol. 2010;629(1-3):118-24.
Takakuta, K., Fujimori, A., Chikanishi, T., Tanokura, A., Iwatsuki, Y., Yamamoto, M., Nakajima, H., Okada, M., & Itoh, H. (2010). Renoprotective properties of pirfenidone in subtotally nephrectomized rats. European Journal of Pharmacology, 629(1-3), 118-24. https://doi.org/10.1016/j.ejphar.2009.12.011
Takakuta K, et al. Renoprotective Properties of Pirfenidone in Subtotally Nephrectomized Rats. Eur J Pharmacol. 2010 Mar 10;629(1-3):118-24. PubMed PMID: 20006961.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Renoprotective properties of pirfenidone in subtotally nephrectomized rats. AU - Takakuta,Koji, AU - Fujimori,Akira, AU - Chikanishi,Toshihiro, AU - Tanokura,Akira, AU - Iwatsuki,Yoshiyuki, AU - Yamamoto,Masanori, AU - Nakajima,Hidenori, AU - Okada,Masamichi, AU - Itoh,Hiroyuki, Y1 - 2009/12/13/ PY - 2009/04/08/received PY - 2009/11/20/revised PY - 2009/12/07/accepted PY - 2009/12/17/entrez PY - 2009/12/17/pubmed PY - 2010/3/31/medline SP - 118 EP - 24 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 629 IS - 1-3 N2 - Renal fibrosis is the final common pathway of chronic kidney disease, and its progression predicts the degree of renal dysfunction. We investigated the renoprotective properties of pirfenidone in a remnant kidney model of chronic renal failure to determine its pharmacological potency compared to enalapril. Five-sixths nephrectomized rats were fed diet containing pirfenidone (approximately 700mg/kg/day) for 8weeks. Pirfenidone steadily inhibited the progression of proteinuria, but not to a significant degree. Pirfenidone prevented the elevation of plasma creatinine and blood urea nitrogen. At the end of the experiment, pirfenidone had reduced systolic blood pressure by means of its renoprotective effect. In a histological study, pirfenidone improved interstitial fibrosis in the renal cortex. These effects were supported by the suppression of the expression of TGF-beta and fibronectin in the mRNA of the kidney. In contrast, pirfenidone had little effect on the expression of alpha-smooth muscle actin, which is one of the proteins responsible for epithelial-mesenchymal transition. This property was confirmed by the TGF-beta-induced transdifferentiation observed in cultured normal rat kidney tubular epithelial NRK52E cells. These results suggest that pirfenidone improves the progression of chronic renal failure via its antifibrotic action, although pirfenidone has less effective TGF-beta-induced epithelial to mesenchymal transdifferentiation. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/20006961/Renoprotective_properties_of_pirfenidone_in_subtotally_nephrectomized_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(09)01132-7 DB - PRIME DP - Unbound Medicine ER -