Abstract

Background: Doxorubicin is a potent chemotherapeutic drug used for the treatment of various types of cancers. In spite of its high efficacy in the treatment of tumors, its clinical use is highly restricted due to severe adverse effects. Kidney is one of the numerous organs susceptible to doxorubicin toxicity. Several pharmacological benefits have been attributed to lutein, a natural carotenoid found in fruits and vegetables. This study evaluated the protective mechanism of lutein on doxorubicin induced renal toxicity in male Wistar rat.


Methods:Twenty male Wistar rats weighing between 130 -150g were used and they were randomly selected into four groups: Group 1 was administered with distilled water (10ml/kg i.p); Group 2 was induced with doxorubicin (15mg/kg i.p) for three consecutive daysfollowed by vehicle for 25 days; Group 3 was treated with lutein (40mg/kg i.p) for 28 days; and Group 4 was induced with doxorubicin (15mg/kg i.p) for three consecutive days and then treated with lutein (40mg/kg i.p) for 25 days.


Results:Doxorubicin administration resulted in a significant increase in serum creatinine and urea levels and a significant decrease in Na/K ATPase and H/K ATPase pump activities. It also caused a significant increase in sodium ion and a significant decrease in potassium and bicarbonate ions. Renal malondialdehyde and nitrite were increased but there was a significant decrease in GSH level as well as GST, SOD and catalase activities. A significant increase in TNF-α and IL-6 levels was observed. Renal level of caspase-3 level showed significant increase but a significant decrease in Bcl-level. More so, there was a significant increase in beclin-1 and a significant decrease in mTOR expression. The histological examinations revealed disruptions of the normal architectural structure of the kidneys. However, treatment with lutein significantly abated these alterations. Conclusion:These findings demonstrated that lutein might be a therapeutic agent that can be used to treat doxorubicin associated nephrotoxicity. The mechanism of attenuative impact of lutein may be related to suppress oxido- inflammatory burden, inhibition of apoptosis as well as modulation of mTOR/beclin-1 activities