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.
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.
Department of Medicine-Uningá Faculty, Avenida Morangueira, PR 317, 6114, Maringá, Paraná, Brazil.
Luiz Eduardo
LE
Bersani-Amado
Department of Pharmacology and Therapeutic-State University of Maringá, Avenida Colombo, 5790, Maringá, Paraná, Brazil.
Jaílson Araujo
JA
Dantas
Department of Pharmacology and Therapeutic-State University of Maringá, Avenida Colombo, 5790, Maringá, Paraná, Brazil.
Marcio José
MJ
Damião
Department of Pharmacology and Therapeutic-State University of Maringá, Avenida Colombo, 5790, Maringá, Paraná, Brazil.
Bruno Ambrósio
BA
Rocha
Department of Morphological Sciences-State University of Maringá, Avenida Colombo, 5790, Maringá, Paraná, Brazil.
Jean Carlos Fernando
JC
Besson
Fellowship (Medicine), State University of Maringá, Avenida Colombo, 5790, Maringá, Paraná, Brazil.
Rafael Lucena
RL
Bastos
Fellowship (medicine) Evangelical Faculty of Paraná, Rua Padre Anchieta, 2770, Curitiba, Paraná, Brazil.
Letícia Nicoletti
LN
Silva
Department of Pharmacology and Therapeutic-State University of Maringá, Avenida Colombo, 5790, Maringá, Paraná, Brazil.
Ciomar Aparecida
CA
Bersani-Amado
Department of Pharmacology and Therapeutic-State University of Maringá, Avenida Colombo, 5790, Maringá, Paraná, Brazil.
Roberto Kenji Nakamura
RK
Cuman
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood*; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D018450:Disease Progression; D005355:Fibrosis; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D007674:Kidney Diseases / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology / Q000473:pathology; D007677:Kidney Function Tests; D008297:Male; D008810:Mice, Inbred C57BL; D013792:Thalidomide / Q000008:administration & dosage / Q000627:therapeutic use*; D014517:Ureteral Obstruction / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D013792:Thalidomide; D003907:Dexamethasone
cytokines; dexamethasone; renal function; renal interstitial fibrosis; thalidomide