Abstract
Ischemia-reperfusion (IR) injury is a multifaceted pathological process characterized by excessive oxidative stress and inflammatory responses upon restoration of blood flow. Bromelain, a proteolytic enzyme complex derived from pineapple, exhibits robust antioxidant and anti-inflammatory activities. This study aimed to evaluate the protective effects and underlying mechanisms of bromelain on oxidative stress and inflammation in an experimental rat model of lower limb ischemia-reperfusion injury. Twenty-four male Wistar Albino rats were randomly allocated into four groups: Sham-operated control (SHAM), Bromelain-only (BR), Ischemia-Reperfusion (IR), and Ischemia-Reperfusion with Bromelain treatment (IR + BR). Bromelain (40 mg/kg) was administered intraperitoneally before ischemia induction. The IR model involved 45 min of infrarenal abdominal aorta occlusion followed by 120 min of reperfusion. Oxidative biomarkers (total antioxidant status [TAS], total oxidant status [TOS], oxidative stress index [OSI]) and histopathological parameters (muscle atrophy, degeneration, leukocyte infiltration, internalization of nuclei, fragmentation, and hyalinization) were analyzed. Significant increases in muscle degeneration, leukocyte infiltration, nuclear internalization, fragmentation, and elevated oxidative stress biomarkers (increased TOS and OSI, decreased TAS) were observed in the IR group compared to controls. Bromelain treatment (IR + BR) significantly ameliorated these effects, reducing muscle tissue damage, inflammation, and oxidative imbalance compared to the untreated IR group. Bromelain effectively mitigates lower limb ischemia-reperfusion injury by reducing oxidative stress, restoring antioxidant capacity, and suppressing inflammatory responses. These protective effects suggest that bromelain holds potential as a therapeutic agent for managing oxidative and inflammatory damages associated with IR conditions, warranting further clinical investigation.