Possible Protective Effects of high- versus low- dose of lutein in combination with irinotecan on Liver of Rats: Role of Oxidative Stress and Apoptosis

Abstract

Objectives: The current study was designed to describe roles of oxidative stress via the measurement
of malondialdehyde and total antioxidant markers, and apoptosis through the measurement of caspase 3
marker, as mechanisms of liver toxicity induced by irinotecan; and to explore the possible protective effects
of high- and low- doses of lutein against irinotecan induced toxicity in the liver of rats.
Methods: Thirty six (36) Sprague-Dawley rats were randomly divided into six groups: Groups ?, rats
received single oral daily dose of dimethyl sulfoxide (4 ml/kg); Group ?? (irinotecan-treated), received
single oral daily dose of dimethyl sulfoxide (4ml/kg) for 25 days by oral gavage and subsequently received
irinotecan (50mg/kg) on days: 5, 10, 15 (total dose=150 mg/kg) by intraperitoneal injection; Groups ???
and ?V, received oral dose of lutein (6mg/kg/day) and (24mg/kg/day), respectively by oral gavage for 25
successive days (lutein-treated); Groups V and V? (lutein+ irinotecan), received oral dose of lutein (6mg/
kg/day) and (24mg /kg/day), respectively by oral gavage for 25 successive days, and subsequently received
irinotecan (50mg /kg body weight) on days: 5, 10, 15 (total dose=150 mg/kg) by intraperitoneal injection.
Results: Orally-administered lutein with total cumulative dose of irinotecan (Groups V and VI), resulted
in significant reduction (P<0.05) of serum aspartate aminotransferase and alanine aminotransferase, and
significant reduction (P<0.05) of malondialdehyde; but, significant elevation (P<0.05) of serum total
antioxidant capacity; and there was significant reduction in caspase 3in liver tissues homogenates compared
to the corresponding levels in the group of rats administered irinotecan (Group II).
Conclusion: Results of the current finding suggested that administration of lutein may be a useful compound
that alleviated irinotecan induced toxicity to the liver