Silymarin attenuates post-weaning bisphenol A-induced renal injury by suppressing ferroptosis and amyloidosis through Kim-1/Nrf2/HO-1 signaling modulation in male Wistar rats

Abstract

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. Although its usefulness cannot be overemphasized, the major challenge is its toxicity, including renal toxicity. BPA has been reported to induce ferroptosis and amyloidosis via the modulation of Nrf2/HO-1 signaling. On the other hand, silymarin activates the Nrf2/HO-1 pathway, thus providing cellular defense. However, the effect of silymarin on BPA-induced renal toxicity is yet to be reported. This study investigated the potential impact of silymarin on renal structure and function following post-weaning BPA exposure. Twenty-four male Wistar rats were randomly assigned into four equal groups. The control was vehicle-treated, while the silymarin-treated received 100 mg/kg/day of silymarin and BPA-treated rats received 50 mg/kg/day of BPA. The BPA + silymarin-treated rats received treatments as BPA-treated and silymarin-treated. Silymarin diminished BPA-induced rise in serum urea, creatinine, BUN, and plasma kim-1 levels. Also, silymarin improved BPA-induced dyslipidemia. More so, silymarin abrogated toxic amyloid formation and improved renal histoarchitecture in BPA-exposed rats. These events were associated with the suppression of BPA-induced rise in renal iron, MDA, TNF-α, IL-1β, and cytochrome c levels, and myeloperoxidase and caspase 3 activities by silymarin therapy. Furthermore, silymarin attenuated BPA-induced downregulation of Nrf2 and GSH levels, and HO-1, GPX4, SOD, catalase, GST, and GR activities. In conclusion, silymarin mitigated post-weaning BPA-induced renal toxicity by suppressing ferroptosis and amyloidosis through Kim-1/Nrf2/HO-1 modulation.