Lutein protection against doxorubicin-induced liver damage in rats is associated with inhibition of oxido-inflammatory stress and modulation of Beclin-1/mTOR activities

Abstract

A wide range of clinical applications are reported for doxorubicin (DOX), yet both people and research animals experience substantial tissue damage. However, the protective mechanism of lutein, a natural carotenoid against doxorubicin associated liver toxicity has not been fully studied. Therefore, the aim of this study is to investigate the protective mechanism of lutein in doxorubicin-induced liver damage. Twenty male Wistar rats were randomly assigned to four groups and treated as follows: group 1 was administered 10-ml/kg body weight of normal saline intraperitoneally for a duration of 28 days. Group 2 was administered doxorubicin (15-mg/kg body weight) intraperitoneally for 3 days in a row. Group 3 was administered intraperitoneal injections of lutein (40-mg/kg body weight) daily for 28 days, and group 4 was administered intraperitoneal injections of lutein (40-mg/kg body weight) daily for 28 days with last 3 days in a row (days 26, 27, and 28) of doxorubicin injection (15-mg/kg body weight). Our results showed that lutein reduced levels of AST, ALT, ALP, LDH, MDA, nitrite, beclin-1, caspase-3, IL-6 as well as TNF-α against the increase caused by doxorubicin. GSH, SOD, GST, catalase, mTOR as well as Bcl-2 were markedly increased by lutein against the harmful effect of doxorubicin. Moreso, lutein restored normal histoarchitecture as well as reduced fibrosis. In conclusion, lutein protection against doxorubicin-induced liver damage in male Wistar rat is associated with inhibition of oxidative stress, pro-inflammatory reactions, and modulation of Beclin-1/mTOR activities.

Keywords: Antioxidants; Apoptosis; Autophagy; Doxorubicin; Inflammation; Liver; Lutein.