Investigation of the protective effect of Chrysin against pemetrexed-induced liver injury in rats

Aim: The aim of our study is to investigate the possible harmful effects of pemetrexed on rat liver and the protective role of chrysin against it. Material and Method: In this study 50 male Spraque-Dawley rats were used. Group I was used a control group. Group II received a p.o. corn oil (chrysin solvent) (5 mg/kg/day for 28 days), group III received an i.p. PMTX (1 mg/kg/week for 4 weeks), group IV received a p.o. chrysin (50 mg/kg/day for 28 days), and group V received an i.p. PMTX (1 mg/kg/week for 4 weeks) + chrysin (50 mg/kg/day). After collecting blood and liver tissues, all rats were slaughtered at the conclusion of the 28th day. Serum samples were used to determine the levels of AST and ALT. The levels of SOD, MDA, TAS, and TOS in liver tissue were measured. Hematoxylin and eosin staining were used histologically, as well as caspase-3 and TNF-alpha immunohistochemistry. Results: AST and ALT levels of the groups, PMTX group were detected significantly increased when compared to other groups (p<0.005). When MDA levels were compared, the PMTX group increased significantly (p<0.005) compared to the control, sham, and CHR groups, whereas SOD enzyme activity was found to be significantly lower in the PMTX group compared to the other groups (p<0.005). TAS levels in liver tissue were examined to be considerably lower in the PMTX group than in the control, sham, and CHR groups (p<0.005). Although TOS levels in the PMTX group were higher than in the other groups, the difference was not statistically significant. There was no histopathologically significant difference between the groups. Pemetrexed treatment was found to enhance caspase-3 and TNF- immunoreactivity, which was statistically significant when compared to other groups (p<0.01). In the PMTX+CHR group, immunoreactivity to caspase-3 and TNF- was significantly reduced (p<0.001). Conclusion: In our study, it was determined that chrysin protects tissues against damage in pemetrexed-induced liver toxicity by acting as an antioxidant. Keywords: pemetrexed, chrysin, liver toxicity, oxidative stress