Small heat shock proteins expression in rat kidneys treated with cyclosporine A alone and combined with melatonin.
Small heat shock proteins (sHSPs) are cytoskeletal chaperones constitutively expressed in the normal kidney but enhanced with beneficial roles during adverse stimuli. Cyclosporine A is an immunosuppressive drug with major adverse side effect such as severe nephrotoxicity. Among possible mechanisms of cyclosporine A-induced renal damage, oxidative stress and cytoskeletal damage have been suggested. Melatonin has been successfully used as antioxidant against many renal diseases. This in vivo study was performed to shed light on the protective effect of melatonin against cyclosporine A-induced renal alterations. We treated rats with cyclosporine A alone, or combined with melatonin, and with melatonin alone (as controls) for 40 days and analysed the renal abundance and distribution of two sHSPs, HSP25 and alpha B-crystallin. These data were correlated with the histopathological effects of the treatments. Cyclosporine A induced insoluble isoforms that moved to soluble fractions after melatonin coadministration as in controls. After cyclosporine A treatment, an intense signal for sHSPs was found within the glomeruli, nucleus and cytoplasm of cortical tubules, collecting ducts and vascular wall. After melatonin supply, the staining was faint, limited to the cytoplasm of cortical tubules, similar to controls. Both fibrosis and tubular alterations significantly decreased after melatonin coadministration. In conclusion, HSP25 and alpha B-crystallin are overexpressed in the rat kidney treated with cyclosporine A but are similar to controls after combined melatonin. This could be a consequence of the cytoprotective effect of melatonin in this nephrotoxic model so that a beneficial sHSPs response is unnecessary.
Stacchiotti
Alessandra
A
Division of Human Anatomy, Department of Biomedical Sciences and Biotechnology, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
Rezzani
Rita
R
Angoscini
Paola
P
Rodella
Luigi
L
Bianchi
Rossella
R
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016572:Cyclosporine / Q000633:toxicity*; D005260:Female; D005355:Fibrosis; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008550:Melatonin / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D038203:alpha-Crystallin B Chain / Q000096:biosynthesis
D000975:Antioxidants; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486114:Hspb1 protein, rat; D009363:Neoplasm Proteins; D038203:alpha-Crystallin B Chain; D016572:Cyclosporine; D008550:Melatonin