Mitigation of PFAS toxicity through sorbent treatment in Sprague-Dawley rats during prenatal and postnatal exposure

Abstract

PFAS (per- and polyfluoroalkyl substances) are prevalent and persistent environmental pollutants with significant toxicity, especially during critical windows of exposure such as pregnancy and lactation. This study investigated the prenatal and postnatal effects of PFAS exposure on the serum and liver of Sprague-Dawley rats, and the mitigating efficacy of orally administered sorbents. Animal groups included vehicle control, PFAS (0.95 mg/kg-bw/day), and PFAS co-treated with calcium montmorillonite (CM), CM-carnitine, CM-choline, activated carbon (AC), or acid processed montmorillonite (APM). Oral administration of PFAS resulted in accumulation in serum and liver by postnatal day (PND) 21, especially for PFOS. PFAS exposure also reduced body weight gain by 24 % in females and 35 % in males via reduced food and water conversion rates, impaired liver histopathological structure, caused hepatocellular hypertrophy, disrupted serum biochemistry, and reduced vitamins A and B2 in both sexes. Additionally, PFAS exposure increased oxidative stress and liver damage as evidenced by reduced antioxidants (GSH, SOD, GST), induced ALT, AST and pro-inflammatory cytokines (TGF-β and TNF-α), and suppressed CRP. Importantly, CM-carnitine and CM-choline were the most effective mitigating sorbents, significantly reducing PFAS bioavailability in the liver and serum and restoring biochemical parameters such as cholesterol, total protein, and glucose in serum. All sorbent treatments alleviated oxidative stress, normalized inflammatory markers, and improved nutrient levels in both serum and liver. Furthermore, the study revealed sex-specific responses, with females showing greater susceptibility to PFAS-induced metabolic changes and a more prominent response to sorbent mitigation. This study highlights the toxic effect of PFAS exposure in serum and liver during vulnerable windows of exposure such as pregnancy and lactation, and establishes the proof of concept for the oral administration of sorbents, particularly CM-carnitine, CM-choline, and a mixture of sorbents, as preventive mitigation strategies.