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.

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.