Evaluation of the Protective Effect of a Well-Characterized n-Hexane Extract of Black Soldier Fly Larvae (Hermetia illucens) Against Acrylamide-Induced Testicular Damage in Male Rats: A Histopathological, Oxidative Stress, Inflammatory, and Molecular Study.

BACKGROUND: Acrylamide (ACR) is a ubiquitous contaminant present in environmental and dietary sources and is formed particularly in starchy foods during high-temperature processing. Prolonged exposure to ACR is associated with testicular dysfunction mediated by oxidative injury, inflammatory responses, and apoptotic cell death. Black soldier fly larvae (BSFL; Hermetia illucens) represent a sustainable source of bioactive lipids, notably lauric acid, which has recognized antioxidant and anti-inflammatory properties. Importantly, BSFL can be cultivated on organic waste, converting low-value materials into lipid-enriched biomass with therapeutic potential, consistent with the principles of the circular economy. OBJECTIVES: This study was designed, for the first time, to investigate the protective potential of a chemically characterized n-hexane extract of BSFL against acrylamide-induced testicular toxicity in a rat model. METHODS: Thirty-five adult male Wistar rats were allocated to five experimental groups (n = 7 per group): vehicle control, ACR (20 mg/kg), ACR plus BSFL180 (180 mg/kg), ACR plus BSFL360 (360 mg/kg), and BSFL360 alone. All treatments were administered orally for 28 consecutive days. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and dihydrotestosterone (DHT) were measured. Testicular specimens were analyzed for oxidative stress markers (malondialdehyde [MDA], superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx], reduced glutathione [GSH]), inflammatory cytokines (TNF-α, IL-6, IL-1β), and apoptosis-related proteins (Nrf2, Bcl-2, Bax). Histological assessment was performed using H&E staining. RESULTS: ACR administration markedly reduced serum FSH, LH, and DHT levels; increased MDA and pro-inflammatory cytokine levels; suppressed antioxidant enzyme activities and GSH content; and induced severe histopathological damage. Co-administration of BSFL extract, particularly at 360 mg/kg, dose-dependently counteracted these detrimental effects. Western blot analysis showed that BSFL extract upregulated Nrf2 and Bcl-2 expression while downregulating Bax, thereby restoring the Bax/Bcl-2 balance. The extract alone produced no adverse effects. CONCLUSIONS: The n-hexane extract of BSFL exerts substantial protective effects against ACR-induced testicular toxicity by restoring hormonal balance, mitigating oxidative stress, suppressing inflammation, and modulating Nrf2 and Bax/Bcl-2 signaling. These findings highlight the therapeutic potential of BSFL as a sustainable, cost-effective natural product within a circular bioeconomy framework and a novel approach to preventing chemically induced testicular injury.