Effects of rosmarinic acid and quercetin on methotrexate-induced liver and small intestine damage in rats

Purpose: Rosmarinic acid (RA) is a natural phenolic compound with antioxidant and anti-inflammatory effects. Quercetin (QCT) is a powerful antioxidant that prevents oxidative damage and cell death by clearing oxygen radicals. It also has anti-inflammatory effects. In this study, it was aimed to compare the effects of RA and QCT against liver and small bowel damage that may occur due to methotrexate (MTX) use. Materials and Methods: The study was conducted on a model of MTX-induced liver and small intestine damage in 40 Spraque Dawley male rats. RA and QCT were administered separately and in combination prophylactically (MTX+QCT group, MTX+RA group, MTX+QCT+RA group respectively). At the end of the study, liver and small intestine tissue were removed. Histopathological evaluations were performed using scoring. Malondialdehyde level, superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities were examined in the tissues. Results: In the liver tissue, pathological findings of all prophylaxis groups decreased considerably. When compared to the control group, MDA level increased significantly in the MTX, MTX+RA and MTX+RA+QCT groups The SOD and GPX activities of the MTX group decreased significantly when compared to the control group. It was found that GPX activity increased in the MTX+QCT group and SOD activity increased in the MTX+QCT+RA group when compared to the MTX group. In addition, SOD activity was significantly increased in the MTX+QCT+RA group when compared to the MTX+RA and MTX+QCT groups. In the small intestine tissue, pathological findings decreased significantly in the MTX+QCT group. Pathological findings decreased slightly in MTX+RA, MTX+QCT+RA groups. MDA levels were significantly higher in the MTX and MTX+RA+QCT groups when compared to the control group. The SOD and GPX activities of the MTX group decreased significantly compared to the control group. GPX activity decreased significantly in the MTX+QCT and MTX+RA groups when compared to the control group. SOD activity increased significantly in MTX+RA+QCT group when compared to MTX group, GPX activity increased significantly in MTX+RA+QCT group compared to MTX+QCT group. Conclusion: RA and QCT may be effective in preventing liver damage caused by MTX. It was concluded that QCT may be more effective than RA in preventing small bowel injury caused by MTX.