Polystyrene microplastics exacerbate experimental chronic kidney disease via inflammatory and oxidative pathways involving NF-κB, ERK/p38 MAPK, and sirtuin-1

Human exposure to microplastics (MPs) occurs primarily through ingestion, as they contaminate food and water sources and have been detected in biological samples, including urine. Polystyrene MPs (PSMPs), typically ranging from 80 nm to 2 μm, have been shown to cause renal histological changes including tubular injury; however, their impact on chronic kidney disease (CKD) remains unclear. This study examined the effects of PSMPs on a murine model of adenine-induced CKD. Mice were fed either a normal diet or one containing 0.2 % adenine for 7 days followed by 0.15 % adenine for 4 weeks, and exposed to 2 μm PSMPs (0.2 or 0.4 mg/day, twice weekly) for 4 weeks. In healthy mice, PSMPs reduced creatinine clearance and increased plasma urea, creatinine, and urinary albumin/creatinine ratio. In CKD mice, PSMPs further exacerbated renal dysfunction and enhanced histological evidence of tubular injury, inflammation, and interstitial fibrosis. PSMPs exposure increased renal markers of inflammation, oxidative stress, DNA damage, and apoptosis, particularly in the adenine-induced CKD + PSMP group. Likewise, molecular analyses revealed significant activation of nuclear factor kappa B (NF-κB) and selective stimulation of mitogen-activated protein kinase (MAPK) pathways, specifically ERK and p38, while JNK remained unaffected. These molecular changes were accompanied by a pronounced reduction in sirtuin-1 expression. Collectively, the results indicate that PSMPs exposure exacerbates renal injury in CKD by promoting inflammation, oxidative stress, and fibrosis, in association with activation of NF-κB and ERK/p38 signaling and suppression of sirtuin-1. These findings highlight the potential health risks of microplastic exposure in individuals with kidney disease.