Oleuropein attenuates cardiac and lung injury induced by 5-fluorouracil via modulating oxidative stress and TNF-α/IL-6 signaling pathway

Abstract

The cardiac and lung damage are considered a serious risk associated with the administration of chemotherapy agents like 5-fluorouracil (5-FU). Oleuropein (OLE) is valuable medicinal plant that has diverse pharmacological properties with remarkable antioxidant activities. This research aimed to evaluate the impact of OLE on cardiac and pulmonary toxicity induced by 5-FU. 24 adult rats were randomly assigned to four groups (N = 6), which included a control group, a group receiving 5-FU at a dosage of 100 mg/kg, a group administered OLE at 200 mg/kg, and a group treated with both 5-FU and OLE (5-FU + OLE). Following the treatment, blood samples were obtained for the assessment of biochemical parameters, and the cardiac and pulmonary tissues were removed for the measurement of oxidative stress and inflammatory cytokines and histological alterations. 5-FU elevated lipid profiles (triglyceride, low-density lipoprotein (LDL), and cholesterol), glucose serum levels, and myocardial injury markers (CK-MB and LDH), malondialdehyde (MDA), interleukin‐6 (IL-6) and tumor necrosis factor alpha (TNF-α) expression. Additionally, the histopathological analysis of 5-FU revealed dystrophic calcification (DC) in the cardiac tissues and neutrophil infiltration in the lung tissues. However, the administration of OLE reduced lipid profiles, glucose, lactate dehydrogenase (LDH), creatine kinase-myocardial band (CK-MB) levels and inflammation, improved antioxidant capacity, and pathological alterations. It seems that OLE exerts cardio-pulmonary protective effects against 5-FU toxicity through the decrease of oxidative stress and inflammatory cytokines.