Panduratin A and Pinostrobin Mitigate Aminated Polystyrene Microplastic-Induced Renal Injury: Evidence from In Vitro and In Vivo Studies

Polystyrene microplastics (PS-MPs) are emerging environmental contaminants associated with adverse effects on human health, including renal injury. However, protective strategies against microplastic-induced nephrotoxicity remain limited. This study investigated the nephroprotective potential of panduratin A (PA) and pinostrobin (PIN) against polystyrene microplastic-induced kidney damage using human renal proximal tubular cells (HK-2) and the C57BL/6NJcL mouse model. DLS and zeta potential measurements were used to characterize the three types of particles (plain PS, PS-COOH, and PS-NH2). In deionized water, PS-NH2 had the least negative zeta potential; however, this difference was no longer observed in a medium containing FBS, since PS-NH2 in this case showed the largest increase in polydispersity index (PDI), indicating different aggregation behavior. When HK-2 cells were exposed to the three types of particles at a dose of 50 µg/mL, PS-NH2 showed greater cellular uptake and higher cytotoxicity than either plain PS or PS-COOH, as shown by increased LDH release and greater cellular accumulation. PS-NH2 was therefore selected for further investigation of its ability to produce ROS, induce apoptosis, and to assess the protective effects of PA and PIN. Treatment with either PA or PIN reduced PS-NH2 accumulation, ROS formation, and apoptosis in the HK-2 cells. In the animal study, mice were given PS-NH2 orally at a dose of 0.4 mg/day for 28 days. This exposure caused early proximal tubular injury, as evidenced by mild histopathological changes, despite no significant alterations in body weight, food intake, blood urea nitrogen, or creatinine. Pretreatment with PA (25 mg/kg BW) or PIN (40 mg/kg BW), given once daily one hour before the PS-NH2 exposure, reduced histopathological kidney injury, with PIN more effective than PA. In summary, aminated polystyrene microplastics are nephrotoxic in both in vitro and in vivo models, and panduratin A and pinostrobin reduce these adverse effects, possibly by modulating cellular uptake and intracellular stress pathways.