Effect of chronomodulated artesunate on some biochemical parameters in methotrexate treated albino mice

Abstract

Methotrexate (MTX) and Artesunate (ART) co-administration is common during chemotherapy with malaria co-infection. Hepatotoxicity from these drugs have been linked to in part, the alterations in essential biochemical processes. Chronomodulation may improve the safety of these drugs even in concurrent use. This study was designed to investigate the effect of time of administration of MTX and ART on some biochemical parameters of the liver in mice. Mice (18-20 g) were treated intraperitoneally with MTX 30 mg/kg and ART 30 mg/kg as either MTX9am, MTX9pm, MTX9pm-ART9am, MTX9pm-ART9pm and corresponding Normal Saline (NSL 10ml/kg) control groups. Relative organ weights (ROW) of the liver and its enzymes (ALT, ALP and AST) were evaluated 24 hours post treatments. Results showed a significant increase (p<0.01) in ROW of the liver with MTX9pm-ART9am compared to MTX9pm. MTX9am showed significantly increased (p<0.01) ALP compared to MTX9pm. There was also significantly increased (p<0.05) ALP in MTX9pm-ART9am compared to MTX9pm. In conclusion, the liver and its enzymes particularly the ALP were severely affected by day time administration of MTX and ART. The safety of these drugs may be improved with evening dosing.

Keywords: Artesunate, Chronomodulation, Liver enzymes, Methotrexate, Safety