Involvement of cytokines in the modulation and progression of renal fibrosis induced by unilateral ureteral obstruction in C57BL/6 mice: effects of thalidomide and dexamethasone.

Abstract

This study investigated the kinetics of cytokines that are involved in the development of interstitial fibrosis in mice that were subjected to UUO, the interstitial type I and III collagen deposition, and the effects of Thalido and Dexa treatment on these parameters. Inbred C57BL/6 mice were divided into the groups: Normal (not submitted surgery), Sham (sham surgery), Control (UUO treated with 0.5% carboxymethyl cellulose), Thalido (UUO treated with 5 mg/kg thalidomide), and Dexa (UUO treated with 1 mg/kg dexamethasone). The treatments began the day before surgery and were administered once daily by gavage for 1, 7, or 14 days. At the end of each treatment period, blood samples were collected for the determination of creatinine, urea, cytokines. The Control group exhibited a increase in creatinine concentration compared with the Normal and Sham groups within the first 24 h after UUO, which remained high until days 7 and 14. The urea concentration was higher on days 7 and 14 in the Control group compared with the Sham group. In the Thalido and Dexa groups, a reduction of serum creatinine concentration was seen on day 14. Treatment with Dexa reduced the serum concentration of urea on day 7. The serum concentrations of cytokines (TNF-α, IL-1β, IL-6, IL-10 and IL-17) and chemokines (KC, MIG, bFGF) increased in UUO mice at all of the sampling times. The Dexa and Thalido groups exhibited alterations in the concentrations of these cytokines, suggesting the involvement of anti-inflammatory and immunomodulatory mechanisms that may have modified the fibrosis framework.

• Authors: Luiz Eduardo Bersani-Amado, Jaílson Araujo Dantas, Marcio José Damião, Bruno Ambrósio Rocha, Jean Carlos Fernando Besson, Rafael Lucena Bastos, Letícia Nicoletti Silva, Ciomar Aparecida Bersani-Amado, Roberto Kenji Nakamura Cuman
• Journal: Fundamental & clinical pharmacology (Fundam Clin Pharmacol) Vol. 30 Issue 1 Pg. 35-46 (Feb 2016) ISSN: 1472-8206 [Electronic] England
• PMID: 26501392 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 Société Française de Pharmacologie et de Thérapeutique.

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Thalidomide
• Dexamethasone

Topics

• Animals
• Anti-Inflammatory Agents (administration & dosage, therapeutic use)
• Cytokines (blood)
• Dexamethasone (administration & dosage, therapeutic use)
• Disease Models, Animal
• Disease Progression
• Fibrosis
• Kidney (drug effects, immunology, pathology)
• Kidney Diseases (drug therapy, etiology, immunology, pathology)
• Kidney Function Tests
• Male
• Mice, Inbred C57BL
• Thalidomide (administration & dosage, therapeutic use)
• Ureteral Obstruction (complications, drug therapy, immunology, pathology)