The possible protective effect of simvastatin and pioglitazone separately and in combination on bleomycin-induced changes in mice thin skin.

Abstract

Bleomycin is a chemotherapeutic agent with side effects especially on skin. Simvastatin is a cholesterol-lowering drug with immunomodulatory, anti-inflammatory, and antifibrotic effects. Pioglitazone is a peroxisome proliferator-activated receptor-γ antidiabetic agent with antiproliferative effects on smooth muscle cells (SMCs), and antioxidant and anti-inflammatory actions. The aim of this study was to investigate the anti-inflammatory and antifibrotic efficiencies of simvastatin and pioglitazone separately and in combination against bleomycin-induced changes in mice thin skin using histological, immunohistochemical, and biochemical techniques. In this study, the mice were divided into seven groups, with each group undergoing treatment for 3 weeks: the control group, group 1 was administered 100 μl of bleomycin, group 2 was administered simvastatin (5mg/kg/day), group 3 received pioglitazone (10mg/kg/day), group 4 received simvastatin (5mg/kg/day) 1h before bleomycin, group 5 received pioglitazone (10mg/kg/day) 1h before bleomycin, and group 6 was administered simvastatin (5mg/kg/day) and pioglitazone (10mg/kg/day) 1h before bleomycin. In group 2, dermal thickening, subcutaneous fat atrophy, degeneration of hair follicles, and thickening of cutaneous vessel walls were observed in addition to a significant increase in caspase-3 reaction, transforming growth factor beta 1 (TGF-β1) expression, and hydroxyproline content. A reversal of the previous findings was markedly observed in group 6 compared with groups 4 and 5. We conclude that the concurrent administration of pioglitazone and simvastatin enhanced their beneficial effects in the reversal of bleomycin-induced changes in mice thin skin.