Oxidative Stress and Liver Morphology in Experimental Cyclosporine A-Induced Hepatotoxicity.
Cyclosporine A is an immunosuppressive drug used after organ's transplantation. The adverse effects on such organs as kidney or liver may limit its use. Oxidative stress is proposed as one of the mechanisms of organs injury. The study was designed to elucidate CsA-induced changes in liver function, morphology, oxidative stress parameters, and mitochondria in rat's hepatocytes. Male Wistar rats were used: group A (control) receiving physiological saline, group B cyclosporine A in a dose of 15 mg/kg/day subcutaneously, and group C the CsA-vehicle (olive oil). On the 28th day rats were anesthetized. The following biochemical changes were observed in CsA-treated animals: increased levels of ALT, AST, and bilirubin in the serum, statistically significant changes in oxidative stress parameters, and lipid peroxidation products in the liver supernatants: MDA+4HAE, GSH, GSSG, caspase 3 activity, and ADP/ATP, NAD(+)/NADH, and NADP(+)/NADPH ratios. Microscopy of the liver revealed congestion, sinusoidal dilatation, and focal hepatocytes necrosis with mononuclear cell infiltration. Electron microscope revealed marked mitochondrial damage. Biochemical studies indicated that CsA treatment impairs liver function and triggers oxidative stress and redox imbalance in rats hepatocytes. Changes of oxidative stress markers parallel with mitochondrial damage suggest that these mechanisms play a crucial role in the course of CsA hepatotoxicity.
Department of Clinical Pathomorphology, Medical University, Jaczewskiego 8, 20-950 Lublin, Poland.
Agnieszka
0000-0003-1016-2735
A
Korolczuk
Department of Clinical Pathomorphology, Medical University, Jaczewskiego 8, 20-950 Lublin, Poland.
Kinga
0000-0001-7767-2401
K
Caban
Department of Clinical Pathomorphology, Medical University, Jaczewskiego 8, 20-950 Lublin, Poland.
Magdalena
0000-0002-2718-8213
M
Amarowicz
Department of Gastroenterology with Endoscopic Unit, Medical University, Jaczewskiego 8, 20-950 Lublin, Poland.
Grażyna
G
Czechowska
Department of Clinical Pathomorphology, Medical University, Jaczewskiego 8, 20-950 Lublin, Poland.
Joanna
J
Irla-Miduch
D000818:Animals; D016572:Cyclosporine / Q000009:adverse effects* / Q000627:therapeutic use; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D017093:Liver Failure / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D014180:Transplantation / Q000009:adverse effects*
D016572:Cyclosporine