Hesperetin alleviates pulmonary injury in a blunt chest trauma-induced pulmonary contusion model in rats serkan kaya1, ihsan karaboğa2*, yasin duran3, elif polat4, fatin rüştü polat5, and zeynep fidanol erboğa4

Abstract Pulmonary contusion (PC), a condition that occurs frequently in severe thoracic injuries, is a significant contributor to mortality in those under the age of 40. Hesperetin, a natural flavonoid derivative of hesperidin, is a substance found in various citrus fruits such as oranges and grapefruits and possesses a variety of biological activities, including antiapoptotic, antioxidant, and anticancer effects. In the current study, we investigated the effect of hesperetin on pulmonary tissue structure, expression of some pro-inflammatory cytokines, and mediators in a PC model induced by blunt chest trauma. In this study, 18 adult male Wistar albino rats (8 – 10 weeks, 250 – 300 g) were used. The rats were divided into three groups: control, PC, and PC + hesperetin. Hesperetin administration (100 mg/kg/day oral) was completed for 7 days following induction of the model. The wet/dry weight ratio of pulmonary tissue was determined. Tumor necrosis factor alpha (TNFα) and malondialdehyde (MDA) in lung tissues, serum interleukin (IL)-6, and IL-1β levels were determined using the enzyme-linked immunosorbent assays. Pulmonary tissue specimens were examined histologically using hematoxylin-eosin and Masson trichrome staining. Inducible nitric oxide synthase (iNOS) activity was determined using immunohistochemical methods. Hesperetin administration reduced TNFα and iNOS activity, serum IL-1β, IL-6, MDA, and wet/dry weight ratio in pulmonary tissue to improve pulmonary function. Our results showed that administration of hesperetin prevents activation of local inflammatory mediators, thereby obstructing the proinflammatory cytokine cascade and tissue injury.