Tags

Type your tag names separated by a space and hit enter

Addition of the antioxidant probucol to angiotensin II type I receptor antagonist arrests progressive mesangioproliferative glomerulonephritis in the rat.
J Am Soc Nephrol. 2006 Mar; 17(3):783-94.JA

Abstract

Angiotensin II (Ang II) and reactive oxidative species (ROS) that are produced by NADPH oxidase have been implicated in the progression of glomerulonephritis (GN). This study examined the effect of simultaneously interrupting Ang II and ROS with an Ang II receptor blocker (ARB), candesartan, and a free radical scavenger, probucol, in a model of progressive mesangioproliferative GN induced by the injection of anti-Thy-1 antibody into uninephrectomized rats. Nephritic rats were divided into four groups and given daily oral doses of the following: Vehicle, 1% probucol diet, 70 mg/L candesartan in drinking water, and probucol plus candesartan. These treatments lasted until day 56. Vehicle-treated nephritic rats developed progressively elevated proteinuria and glomerulosclerosis. Candesartan kept proteinuria significantly lower than vehicle or probucol. The addition of probucol to candesartan normalized urinary protein excretion. Increases in BP in nephritic rats were lowered by these treatments, except with probucol. It is interesting that both glomerular cell number and glomerulosclerosis were significantly decreased by candesartan and normalized by the addition of probucol. Immunohistochemical studies for TGF-beta1, collagen type I, and fibronectin revealed that the combined treatment abolished glomerular fibrotic findings compared with candesartan. In addition, glomerular expression of NADPH oxidase components and superoxide production suggested that the combined treatment completely eliminated NADPH oxidase-associated ROS production. In conclusion, our study provides the first evidence that the antioxidant probucol, when added to an Ang II receptor blockade, fully arrests proteinuria and disease progression in GN. Furthermore, the data suggest that NADPH oxidase-associated ROS production may play a pivotal role in the progression of GN. The combination of probucol and candesartan may represent a novel route of therapy for patients with progressive GN.

Authors+Show Affiliations

Department of Pediatrics, The Institute of Health Bioscience, The University of Tokushima Graduate School, Kuramoto-cho-3-chome, Tokushima 770-8503, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo 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)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16467449

Citation

Kondo, Shuji, et al. "Addition of the Antioxidant Probucol to Angiotensin II Type I Receptor Antagonist Arrests Progressive Mesangioproliferative Glomerulonephritis in the Rat." Journal of the American Society of Nephrology : JASN, vol. 17, no. 3, 2006, pp. 783-94.
Kondo S, Shimizu M, Urushihara M, et al. Addition of the antioxidant probucol to angiotensin II type I receptor antagonist arrests progressive mesangioproliferative glomerulonephritis in the rat. J Am Soc Nephrol. 2006;17(3):783-94.
Kondo, S., Shimizu, M., Urushihara, M., Tsuchiya, K., Yoshizumi, M., Tamaki, T., Nishiyama, A., Kawachi, H., Shimizu, F., Quinn, M. T., Lambeth, D. J., & Kagami, S. (2006). Addition of the antioxidant probucol to angiotensin II type I receptor antagonist arrests progressive mesangioproliferative glomerulonephritis in the rat. Journal of the American Society of Nephrology : JASN, 17(3), 783-94.
Kondo S, et al. Addition of the Antioxidant Probucol to Angiotensin II Type I Receptor Antagonist Arrests Progressive Mesangioproliferative Glomerulonephritis in the Rat. J Am Soc Nephrol. 2006;17(3):783-94. PubMed PMID: 16467449.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Addition of the antioxidant probucol to angiotensin II type I receptor antagonist arrests progressive mesangioproliferative glomerulonephritis in the rat. AU - Kondo,Shuji, AU - Shimizu,Maki, AU - Urushihara,Maki, AU - Tsuchiya,Koichiro, AU - Yoshizumi,Masanori, AU - Tamaki,Toshiaki, AU - Nishiyama,Akira, AU - Kawachi,Hiroshi, AU - Shimizu,Fujio, AU - Quinn,Mark T, AU - Lambeth,David J, AU - Kagami,Shoji, Y1 - 2006/02/08/ PY - 2006/2/10/pubmed PY - 2006/7/28/medline PY - 2006/2/10/entrez SP - 783 EP - 94 JF - Journal of the American Society of Nephrology : JASN JO - J. Am. Soc. Nephrol. VL - 17 IS - 3 N2 - Angiotensin II (Ang II) and reactive oxidative species (ROS) that are produced by NADPH oxidase have been implicated in the progression of glomerulonephritis (GN). This study examined the effect of simultaneously interrupting Ang II and ROS with an Ang II receptor blocker (ARB), candesartan, and a free radical scavenger, probucol, in a model of progressive mesangioproliferative GN induced by the injection of anti-Thy-1 antibody into uninephrectomized rats. Nephritic rats were divided into four groups and given daily oral doses of the following: Vehicle, 1% probucol diet, 70 mg/L candesartan in drinking water, and probucol plus candesartan. These treatments lasted until day 56. Vehicle-treated nephritic rats developed progressively elevated proteinuria and glomerulosclerosis. Candesartan kept proteinuria significantly lower than vehicle or probucol. The addition of probucol to candesartan normalized urinary protein excretion. Increases in BP in nephritic rats were lowered by these treatments, except with probucol. It is interesting that both glomerular cell number and glomerulosclerosis were significantly decreased by candesartan and normalized by the addition of probucol. Immunohistochemical studies for TGF-beta1, collagen type I, and fibronectin revealed that the combined treatment abolished glomerular fibrotic findings compared with candesartan. In addition, glomerular expression of NADPH oxidase components and superoxide production suggested that the combined treatment completely eliminated NADPH oxidase-associated ROS production. In conclusion, our study provides the first evidence that the antioxidant probucol, when added to an Ang II receptor blockade, fully arrests proteinuria and disease progression in GN. Furthermore, the data suggest that NADPH oxidase-associated ROS production may play a pivotal role in the progression of GN. The combination of probucol and candesartan may represent a novel route of therapy for patients with progressive GN. SN - 1046-6673 UR - https://www.unboundmedicine.com/medline/citation/16467449/Addition_of_the_antioxidant_probucol_to_angiotensin_II_type_I_receptor_antagonist_arrests_progressive_mesangioproliferative_glomerulonephritis_in_the_rat_ L2 - http://jasn.asnjournals.org/cgi/pmidlookup?view=long&pmid=16467449 DB - PRIME DP - Unbound Medicine ER -