Nrf2/BAX/Bcl2 Signaling Crosstalk and Histopathological Correlates of Renoprotection by Black Soldier Fly Larval Oil Against Aflatoxin B1-Induced Oxidative and Inflammatory Kidney Injury in Rats

Abstract

Background Aflatoxin B1 (AFB1) is a highly hazardous mycotoxin commonly detected in contaminated food supplies and poses serious health risks to both humans and animals. Although its hepatotoxic effects are well established, the kidney, a principal organ for toxin elimination, remains highly susceptible to AFB1-induced injury through mechanisms involving oxidative stress, inflammatory responses, and apoptotic cell death. Black soldier fly larvae (BSFL) oil, characterized by a high content of medium-chain fatty acids and other bioactive lipids, represents a sustainable and promising source of naturally derived antioxidant and anti-inflammatory agents. Objectives This study aimed to evaluate the renoprotective potential of the n-hexane BSFL extract against AFB1-induced nephrotoxicity in a rat model, with particular emphasis on elucidating the involvement of Nrf2-driven antioxidant pathways and BAX/Bcl2-regulated apoptotic signaling. Methods Thirty-five male Wistar rats were allocated to five experimental groups: control, AFB1 (75 µg/kg), BSFL (360 mg/kg), AFB1 + BSFL180, and AFB1 + BSFL360. After a 28-day treatment period, renal function indicators (BUN, creatinine, uric acid), oxidative stress markers (MDA, SOD, CAT, GSH), inflammatory cytokines (TNF-α, IL-6, NF-κB), and apoptosis-related proteins (Nrf2, BAX, Bcl2) were evaluated. Histopathological assessments were also performed to examine tubular necrosis, glomerular damage, and inflammatory infiltration. Results AFB1 exposure resulted in marked increases in BUN, creatinine, uric acid, MDA, TNF-α, IL-6, NF-κB, and BAX levels, along with significant decreases in SOD, CAT, GSH, Nrf2, and Bcl2 (P < 0.001). Co-administration of BSFL extract, particularly at the higher dose (360 mg/kg), effectively reversed these alterations and restored the BAX/Bcl2 ratio toward normal values. Histological examination corroborated these biochemical improvements by showing reduced tubular necrosis, glomerular injury, and inflammatory cell infiltration in the extract-treated groups. Conclusions These findings indicate that BSFL extract confers substantial renoprotection against AFB1-induced kidney injury through the coordinated regulation of Nrf2-mediated antioxidant defense and BAX/Bcl2-dependent apoptotic pathways. The absence of intrinsic toxicity, together with the sustainable and eco-friendly production of BSFL oil, underscores its potential as a promising natural therapeutic candidate for mitigating mycotoxin-associated nephrotoxicity.