The effect of L-Citrulline on doxorubicin-induced cardiotoxicity using serum oxidative stress biomarkers

Doxorubicin (DOX) is a chemotherapeutic agent widely used against various cancers. However, its usage is linked to cardiotoxicity side effects via production of reactive oxygen species, causing oxidative stress and cardiac myocyte death. L-Citrulline (CIT) is a potent anti-oxidant agent with potential to prevent DOX-induced cardiotoxicity. This study analyzed the effect of CIT against DOX-induced cardiotoxicity using oxidative stress biomarkers. Administration of DOX (intraperitoneal injection) was performed to induce cardiotoxicity in 20 Wistar rats, divided into 4 groups. Two doses (300 and 600 mg/kg of body weight) of CIT were administered via gavage prior to, during, and after DOX injection. Serum levels of glutathione (GSH) and malondialdehyde (MDA) were measured using colorimetric analysis. Both doses of CIT increase slightly the concentration of GSH (P=.063 vs. control). The concentration of MDA was also increased in the low-dose (P=0.103), and high-dose groups (P < 0.001). The observed elevations were dose-dependent. Administration of CIT did not exert a beneficial effect against DOX-induced cardiotoxicity. The increased level of MDA in CIT group indicates increased oxidative stress and lipid peroxidation. Moreover, the elevation of the level of GSH is more likely to be caused by the apoptosis-related GSH efflux mechanism, explained in other literature.