P-004 Silymarin attenuates BPA-induced testicular endocrine and spermatogenesis disruption by inhibiting testicular iron accumulation and amyloidosis via the modulation of Nrf2/HO-1 and TLR4/NF-kB signaling

Abstract Study question Will silymarin alleviate BPA-induced testicular endocrine and spermatogenesis disruption? Summary answer Silymarin abrogated BPA-induced testicular endocrine and spermatogenesis disruption by modulating Nrf2/HO-1 and TLR4/NF-kB signaling What is known already Bisphenol A (BPA) is a synthetic chemical used in producing polycarbonate plastics and epoxy resins and is commonly found in everyday items like water bottles and food containers. Despite its usefulness, it has been reported to induce testicular toxicity and impair steroidogenesis and spermatogenesis via an Nrf2/NF-kB-dependent mechanism. On the contrary, silymarin, a natural polyphenolic compound, upregulates Nf2/HO-1 and downregulates TLR4/NF-kB. However, whether or not silymarin protects against BPA-induced testicular toxicity is not known. Study design, size, duration This is a prospective experimental study that used an animal model. Forty sexually mature littermate male Wistar rats of comparable weight were used for the study. The study lasted 8 weeks. Participants/materials, setting, methods Thirty-two animals were acclimatized for two weeks and then randomly assigned to four groups (n = 8). The control were vehicle-treated, silymarin-treated had 100 mg/kg/day of silymarin, BPA-treated received 50 mg/kg/day of BPA, and the BPA+silymarin-treated received BPA and silymarin as those in the BPA and silymarin groups respectively. Treatments were via gavage for 8 weeks. The doses of drugs used were as earlier reported. Main results and the role of chance BPA led to a significant decline in total and daily spermatid production, sperm concentration, motility, and viability and a rise in abnormal sperm morphology. In addition, BPA markedly reduced the serum levels of GnRH, FSH, LH, and testosterone as well as testicular 3β-HSD and 17β-HSD activities. These findings were associated with increased iron and amyloid accumulation (histological studies), as well as MDA, TNF-α, IL-1β, IL-6, TLR4, and NF-kB and reduced GSH, GPx4, SOD, catalase, Nrf2, and HO-1 (biochemical studies) in the testicular tissues. Nonetheless, silymarin treatment significantly attenuated BPA-induced perturbation in these histopathological and biochemical markers. Limitations, reasons for caution This was a rat model study, and the findings should be extrapolated to humans with caution. Clinical trials are suggested to validate these findings. Wider implications of the findings This study revealed that silymarin protected against BPA-induced testicular oxidative injury and endocrine and spermatogenesis perturbation via the modulation of Nrf2/HO-1 and TLR4/NF-kB signaling. These observations provide convincing evidence of the protective activity of silymarin in BPA-induced testicular dysfunction. Trial registration number No