Effect of bromelain on apoptotic and inflammatory pathways in cyclophosphamide-induced hepatotoxicity

Purpose: Cyclophosphamide (CP) has various adverse effects on the liver in both humans and animals. In the present study, the protective potential of bromelain (BRM), the main proteolytic enzyme derived from pineapple, was evaluated in a CP-induced hepatotoxicity rat model, with a focus on apoptosis and inflammation. Materials and Methods: Twenty-four Wistar albino female rats were distributed to four equal groups (n = 6 per group): Control (received distilled water via oral gavage (o.g.) for 14 days), BRM (received 200 mg/kg BRM via o.g. for 14 days), CP (received 30 mg/kg/day CP intraperitoneally from day 8 until day 14 of the experiment), and CP+BRM. At the end of the study, immunohistochemical staining for caspase-3, tumor necrosis factor-alpha (TNF-α), toll-like receptor-4 (TLR-4), and nuclear factor-κB (NF-κB) was performed on kidney tissues from rats in all groups.Results: In the microscopic evaluation, statistically significant increases in the immunoreactivities of caspase-3; 2.70 (1.80-2.70), TNF-α; 2.70 (1.80-2.70), TLR-4; 2.70 (1.80-2.70), and NF-κB; 1.80 (1.20-2.70) were observed in the CP group compared with the control group. However, in the CP + BRM group, BRM inhibited the CP-induced overexpression of apoptotic and inflammatory markers.Conclusion: The present study provides new insights into the therapeutic potential of BRM against CP hepatotoxicity. BRM at dose 200 mg/kg has the capability to counteract the toxic effects of CP on liver tissue and has beneficial protective effects that is dose-dependent. BRM might represent a novel approach in the therapy of CP hepatotoxicity because of its anti-apoptotic and anti-inflammatory effects.