167 OBJECTIVE: Ischemia-reperfusion (I/R) leads to reac- tive oxygen species formation and cell death in kidney tissue with injury and organ transplantation. Simvas- tatin (SIM) is an antioxidant, anti-infammatory, and anticoagulant agent. Alterations in I/R-induced acute kidney injury model with SIM treatment were analyzed. STUDY DESIGN: Wistar rats (n = 28) were grouped into Sham, Ischemia, I/R, and I/R + SIM treated. Left rat kidney renal vessels were clamped for 60 minutes for ischemia, and the I/R group had 6 hours of reperfusion. 10 mg/kg SIM was given orally for 28 days. MDA, GSH, and MPO were analyzed. Kidney tissues were paraffn embedded, and primary antibodies TNF-α and caspase-3 were applied for immunohistochemistry. RESULTS: In the I/R group, intense infammatory cell infltration around the vessels and necrosis in the glo- merular structures were observed. In the treated group, proximal and distal tubular cells were found to be close to normal. Immunoexpression of caspase-3 in the ische- mia group was positive in degenerative glomeruli. In the treated group, TNF-α expression was negative in the glomerular structures. MDA and MPO levels were signifcantly increased in ischemia and I/R. CONCLUSION: We suggest that SIM treatment im- proved kidney tissue structure and function in a model of I/R injury. (Anal Quant Cytopathol Histpathol 2021;43:167–173) Keywords: caspase-3; immunohistochemistry; is- chemia/reperfusion; kidney; MPO; simvastatin. Ischemia-reperfusion (I/R) is a situation when the blood supply to an organ is restricted—ischemia— and then reoxygenation of tissues occurs—reper- fusion. Following the reperfusion procedure, when oxygen increases, reactive oxygen species (ROS) generate and cause cell death. 1 Statins, specifc inhi- bitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are used to lower the cho- lesterol level for a long time. 2 Statins have pleiotro- pic effects: antioxidant, inhibiting of thrombogenic responses, and healing of endothelial function. 3 Statins inhibit the formation of proinfammatory cytokines and decrease infammation. 4 Statins used after major abdominal, cardiac, thoracic, and vas- cular surgery decrease the development of acute Analytical and Quantitative Cytopathology and Histopathology ® 0884-6812/21/4304-0167/$18.00/0 © Science Printers and Publishers, Inc. Analytical and Quantitative Cytopathology and Histopathology ® Prolonged Simvastatin Treatment Provided a Decrease in Apoptotic, Infammatory, and Oxidative Stress Markers in Ischemia- Reperfusion–Induced Acute Kidney Injury Model of Rats Alper Kafkasli, M.D., and Ebru Gokalp Ozkorkmaz, Ph.D. From the Urology Clinic, Lutf Kirdar Training and Research Hospital, Istanbul; and the Department of Histology and Embryology, Faculty of Medicine, Dicle University, Diyarbakır, Turkey. Alper Kafkasli is Assistant Professor, Urology Clinic, Lutf Kirdar Training and Research Hospital (Orcid ID: 0000-0002-0362-8165). Ebru Gokalp Ozkorkmaz is Assistant Professor, Department of Histology and Embryology, Faculty of Medicine, Dicle University (Orcid ID: 0000-0002-1967-4844). Address correspondence to: Ebru Gokalp Ozkorkmaz, Ph.D., Department of Histology and Embryology, Faculty of Medicine, Dicle University, 21010 Diyarbakır, Turkey (ebrug76@gmail.com). Financial Disclosure: The authors have no connection to any companies or products mentioned in this article.