Comparison of the acute and cumulative dose administrations in doxorubicin-induced hepatotoxicity via evaluation of the histopathological changes and inflammation in rats

Year 2020, Volume: 1 Issue: 3, 73 - 81, 29.12.2020

Ali Akın , Emin Kaymak , Derya Karabulut , Züleyha Doğanyiğit , Tayfun Ceylan , Ayşe Toluk , Saim Özdamar

Abstract

Doxorubicin (DOX) is an anthracycline antibiotic, and it is widely used as an antineoplastic agent in the treatment of many cancer types such as sarcoma, acute lymphoblastic leukemia and as well as breast and liver cancers. However, it 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. For this purpose, thirty male Wistar albino rats were divided into three groups: Group I as Control; Group II: Chronic DOX administered cumulative dose of DOX (2 mg/kg, twice in a week, total 20 mg/kg, i.p); Groups III: Acute DOX group administered single dose DOX (15 mg/kg, i.p) at the 20th day of the experiment. At the end of the 30th day, animals were sacrificed, and liver tissues were extracted for histopathological and immunohistochemical evaluation. Sections were stained with hematoxylin and 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 significant liver damage. However, it was observed that liver damage induced by acute single dose DOX administrations were higher than those cumulative chronic DOX administrations. TNF- and IL-6 immunoreactivity was significantly increased in both Chronic DOX group and Acute DOX group compared to Control group. However, immunoreactivity of TNF- was substantially higher in the Acute DOX group compared to Chronic DOX group. These results demonstrated that acute administrations of DOX relatively induce serious liver damage and inflammatory response when compared to cumulative chronic administrations. In conclusion, it may be advisable to increase studies on the use of acute doses in combination with protective anti-inflammatory agents.

Keywords

doxorubicin, hepatotoxicity, inflammation, liver damage

Project Number

FDK-2018-8165

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