Safeguarding Spermatogenesis: Garcinia kola Extract and Kolaviron Effectively Ameliorate Testicular Toxicity in Rats Treated With Bleomycin, Etoposide, and Cisplatin Combination Therapy

Abstract

Background: Emerging evidence indicates that certain chemotherapeutic agents, particularly the bleomycin, etoposide, and cisplatin (BEP) regimen, exert deleterious effects on male reproductive function, including impaired spermatogenesis. Previous studies have demonstrated that Garcinia kola (GK) seed extract and its bioactive biflavonoid constituent, kolaviron (KV), exhibit beneficial properties in reproductive physiology. However, their potential protective effects against BEP-induced testicular toxicity remain underexplored. This study evaluated the chemopreventive efficacy of GK extract (GKE) and KV in attenuating BEP-mediated testicular damage in a preclinical rodent model. Methods: Adult male Wistar rats (n = 8 per group) were subjected to three 21-day cycles of BEP chemotherapy (0.5 mg/kg bleomycin, 5 mg/kg etoposide, and 1 mg/kg cisplatin, administered intraperitoneally). Concurrently, treatment groups received oral supplementation with GKE (100 mg/kg), KV (100 mg/kg), silymarin (SLM; 10 mg/kg), or prednisolone (PRED; 5 mg/kg), with dosages determined via prior dose–response optimization. Post-treatment assessments included: sperm functional analysis (count, motility, morphology), serum reproductive hormone profiling [testosterone (TST), luteinizing hormone (LH), follicle stimulating hormone (FSH)], oxidative stress markers [glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST)], lipid peroxidation indicators [malondialdehyde (MDA), nitric oxide (NO)], inflammatory cytokines (TNF-α, IL-6), and apoptotic markers [caspase-3 (CAS-3) and caspase-9 (CAS-9)]. Results: BEP administration significantly impaired spermatogenic output, which was ameliorated by GKE, KV, SLM, and PRED co-treatment. Notably, TST levels remained stable in GKE- and KV-supplemented groups. All test compounds enhanced antioxidant capacity, suppressing lipid peroxidation (reduced MDA and NO). Furthermore, GKE and KV significantly attenuated BEP-induced elevations in pro-inflammatory cytokines (TNF-α, IL-6) and apoptotic mediators (CAS-3, CAS-9). Conclusion: GKE and KV conferred substantial protection against BEP-induced testicular toxicity, primarily through mechanisms involving oxidative stress mitigation, anti-inflammatory action, and apoptosis suppression. Their efficacy paralleled that of established agents (SLM, PRED), suggesting potential utility as adjunctive therapies to preserve male fertility during chemotherapy. These findings warrant further clinical investigation to assess translational applicability.