Caffeic acid phenethyl ester (CAPE) prevents methotrexate-induced hepatorenal oxidative injury in rats

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This study aimed to investigate the antioxidant and anti-inflammatory effects of caffeic acid phenethyl ester (CAPE) on the methotrexate (MTX)-induced hepatorenal oxidative damage in rats.


Following a single dose of methotrexate (20 mg/kg), either vehicle (MTX group) or CAPE (10 μmol/kg, MTX + CAPE group) was administered for five days. In other rats, vehicle (control group) or CAPE was injected for five days, following a single dose of saline injection. After decapitation of the rats, trunk blood was obtained, and the liver and kidney tissues were removed for histological examination and for the measurement of malondialdehyde (MDA) and glutathione (GSH) levels and myeloperoxidase (MPO) and sodium potassium-adenosine triphosphatase (Na+/K+-ATPase) activity. TNF-α and IL-1β levels were measured in the blood.

Key findings

Methotrexate administration increased the tissue MDA levels, MPO activity and decreased GSH levels and Na+/K+-ATPase activity, while these alterations were reversed in the CAPE-treated MTX group. Elevated TNF-α and IL-1β levels were also reduced with CAPE treatment.


The results of this study revealed that CAPE, through its anti-inflammatory and antioxidant actions, alleviates methotrexate-induced oxidative damage, which suggests that CAPE may be of therapeutic benefit when used with methotrexate.

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