title: 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.
authors.affiliation: Histology Department, Faculty of Medicine, Tanta University, Tanta, Egypt. Electronic address: sskandeel@hotmail.com.
authors.forename: Samah
authors.initials: S
authors.lastname: Kandeel
authors.affiliation: Pharmacology Department, Faculty of Medicine, Tanta University, Tanta, Egypt. Electronic address: m_balaha@hotmail.com.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Balaha
mesh_terms: D000818:Animals; D001761:Bleomycin / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism; D000077205:Pioglitazone; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D001761:Bleomycin; D019821:Simvastatin; D000077205:Pioglitazone
keywords: Bleomycin; Histology; Immunohistochemistry; Pioglitazone; Simvastatin; Skin