Therapeutic Effect of Fisetin in Mitigating Methylmercury-Induced Nephrotoxicity During Prenatal Development

Methylmercury (MeHg), a highly toxic mercury compound, presents serious developmental risks, particularly to the kidneys, when exposure occurs during gestation. The present study focuses on investigating the protective effects of fisetin, a bioactive flavonoid, in alleviating MeHg-induced nephrotoxicity in offspring. Pregnant Wistar rats of gestational day 0 (GD 0) were divided into six groups, including control, 20 mg/kg fisetin, 0.5 mg/kg MeHg, 2.5 mg/kg MeHg, 0.5 mg/kg MeHg + 20 mg/kg fisetin, and 2.5 mg/kg MeHg + 20 mg/kg fisetin. The pregnant females were orally dosed on GDs 7, 12, and 17. The study evaluated maternal water intake along with renal function indicators, including serum creatinine and blood urea nitrogen (BUN) levels. Offspring (litters) were assessed for body weight on postnatal day (PND) 7 and PND 21. Additionally, the expression levels of fibrotic markers-MMP-9, SMAD-3, and alpha-SMA-were analyzed using quantitative PCR and Western blot techniques in kidney tissue. Moreover, histopathological analysis of kidney tissues was also conducted to examine potential structural alterations. Results indicated that both the MeHg exposures led to significant nephrotoxicity, evidenced by elevated creatinine and BUN levels, upregulation of fibrotic genes, and pronounced structural damage in the kidneys. However, fisetin administration mitigated these adverse effects, normalizing renal function biomarkers, downregulating fibrotic gene expression, and preserving kidney structure. Our study, therefore, underscores the potential of fisetin as a protective agent against MeHg-induced renal damage during prenatal development, offering insights into its therapeutic role in safeguarding fetal health against environmental toxins.