Research in Pharmaceutical Sciences

ORIGINAL ARTICLE
Year
: 2018  |  Volume : 13  |  Issue : 5  |  Page : 440--449

Atorvastatin mitigates cyclophosphamide-induced hepatotoxicity via suppression of oxidative stress and apoptosis in rat model


Maedeh Hamzeh1, Seyed Jalal Hosseinimehr2, Ali Reza Khalatbary3, Hamid Reza Mohammadi4, Ayat Dashti5, Fereshteh Talebpour Amiri3 
1 Department of Anatomy and Molecular and Cell Biology Research Center; Student Research Committee, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, I.R. Iran
2 Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, I.R. Iran
3 Department of Anatomy and Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, I.R. Iran
4 Department of Toxicology and Pharmacology, Faculty of Pharmacy; Pharmacutical Science Research Center, Mazandaran University of Medical Sciences, Sari, I.R. Iran
5 Student Research Committee, Faculty of Medicine; Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, I.R. Iran

Correspondence Address:
Fereshteh Talebpour Amiri
Department of Anatomy and Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari
I.R. Iran

Cyclophosphamide (CP), as a chemotherapy drug, induces hepatotoxicity through causing oxidative stress. Atorvastatin (ATV) at a low dose has antioxidant and anti-inflammatory properties. The present study was designed to investigate the protective effects of ATV against CP-induced hepatotoxicity in rat. In this experimental study, 32 rats were treated with ATV orally at a dose of 10 mg/kg for 10 consecutive days, 5 days before and 5 days after the administration of a single intraperitoneal injection of CP (150 mg/kg). The hepatoprotective effect of ATV was evaluated by measuring liver function markers, oxidative markers, histological and immunohistochemical assays. The biochemical results showed that administration of CP increased hepatic biomarkers enzymes as aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels. CP increased malondialdehyde (MDA), protein carbonyl (PC) and decreased glutathione (GSH) content in rats. Moreover, administration of CP was associated with periportal leucocyte infiltration, dilation sinusoids, hepatocyte vacuolation, congestion and hemorrhage in livers of rats. CP significantly increased immunoreactivity of caspase-3 as a marker of apoptosis in liver tissue. ATV markedly mitigated liver injury through reduction in oxidative stress biomarkers, histopathological findings and apoptosis. The antioxidant and anti-apoptotic activities of ATV are main proposed mechanisms involved in its hepatoprotective effects against CP-induced hepatic injury.


How to cite this article:
Hamzeh M, Hosseinimehr SJ, Khalatbary AR, Mohammadi HR, Dashti A, Amiri FT. Atorvastatin mitigates cyclophosphamide-induced hepatotoxicity via suppression of oxidative stress and apoptosis in rat model.Res Pharma Sci 2018;13:440-449


How to cite this URL:
Hamzeh M, Hosseinimehr SJ, Khalatbary AR, Mohammadi HR, Dashti A, Amiri FT. Atorvastatin mitigates cyclophosphamide-induced hepatotoxicity via suppression of oxidative stress and apoptosis in rat model. Res Pharma Sci [serial online] 2018 [cited 2022 May 20 ];13:440-449
Available from: https://www.rpsjournal.net/article.asp?issn=1735-5362;year=2018;volume=13;issue=5;spage=440;epage=449;aulast=Hamzeh;type=0