Comparison of the Acute and Cumulative Dose Administrations in Doxorubicin-induced Hepatotoxicity via Evaluation of the Histopathological Changes and Inflammation in Rats

Abstract

Doxorubicin (DOX) may lead to hepatotoxicity when administered chronically or in a high dose. The aim of this study is to determine dose–dependent effects of DOX in rat liver tissue. Thirty male Wistar albino rats were divided into three groups; group I as control, group II as receiving chronically DOX (2 mg/kg, twice in a week, total 20 mg/kg, intraperitoneally) and group III as receiving an acute–single dose of DOX (15 mg/kg, intraperitoneally, on the 20th day) administered groups. At the end of 30th day, animals were sacrificed, and liver tissues were extracted for histopathological and immunohistochemical evaluation. Sections were stained with hematoxylin & eosin to evaluate the histopathological changes and TNF- and IL-6 expressions were detected by immunohistochemical staining. Both chronic and acute administrations of DOX triggered a significant liver damage. However, it was observed that liver damage induced by acute–single dose DOX administrations were higher than those induced by chronic DOX administrations. TNF- and IL-6 immunoreactivity was significantly increased in both group II and III group compared to control group. However, immunoreactivity of TNF- was substantially higher in the group III compared to control. These results demonstrated that acute administrations of DOX relatively induce serious liver damage and inflammatory response.