Nephroprotective Effect of Bergapten Against Cyclophosphamide-Mediated Renal Stress, Inflammation, and Fibrosis in Wistar Rats: Probable Role of NF-kB and TGF-β1 Signaling Molecules.

Abstract

Cyclophosphamide (CPM) is a well-established antineoplastic drug with marked clinical outcomes in various types of cancers. Despite being a promising drug, its use is associated with significant renal toxicity and often limits its use, leading to compromised clinical outcomes. Therefore, this study explored the renal protective effect of bergapten (BGP), a natural bioactive compound that showed marked antioxidant, anti-inflammatory, anticancer, and neuroprotective effects. Till now, BGP has not been studied for its renal protective effect in an in vivo model. Animals were divided into control, toxic, BGP-3, BGP-10, and BGP Per se. The control group was treated with normal saline for 2 weeks. To the toxic group, CPM 200 mg/kg was given on day 7 as i.p. To BGP-3, 10, and Per se, BGP-3 and 10 mg/kg, ip was given 2 weeks with a single shot of CPM 200 day 7. To the Per se group, only BGP 10 mg/kg, ip was given from day 1 to day 14. After 14 days, animals were sacrificed, and kidneys were removed and studied for the markers of oxidative stress, inflammation, renal injury, renal fibrosis, and renal damage using biochemical, histopathological, and immunohistochemical studies. We found that BGP-10 effectively reversed the damage toward normal, whereas BGP-3 failed to exhibit a significant renal protective effect. We conclude that bergapten could be a potential renal protective drug, and hence, more detailed cellular molecular-based studies are needed to bring this drug from the bench to the bedside.