Nanoplastics exacerbated renal injury amid hypertension: Rethinking health hazards in disease and implication of renal senescence and EMT associated with Sirt1 downregulation.

Hypertensive nephropathy is a chronic disease posing a remarkable health risk to the pre-existing hypertensive population. Nanoplastics could elicit potential harm to multiple organs, including the kidneys. To identify the hazards of aged polystyrene nanoplastics (aPS-NPs) in the context of hypertension and investigate the underlying toxicological mechanisms, spontaneously hypertensive rats (SHRs) were treated with aPS-NPs (75 mg/kg/day) by gavage for 35 days. We observed exacerbated renal injury with increased collagen deposition and elevated expression of fibrosis-related proteins (FN, COL1A1, and α-SMA) in SHRs exposed to aPS-NPs. Our results showed increased oxidative stress and inflammation in the aPS-NPs group, and renal Sirt1 expression significantly decreased. We also revealed that aPS-NPs exacerbated renal senescence and epithelial-mesenchymal transition (EMT) in the kidneys. Moreover, we found that resveratrol, a compound that can activate Sirt1, alleviated renal injury exacerbation induced by aPS-NPs in SHRs, manifested in decreased collagen deposition and fibrosis-related protein expressions, as well as inhibition of renal senescence and EMT. Our findings demonstrated that aPS-NPs exacerbated renal injury in hypertension. The key mechanisms of renal senescence and EMT, and the pivotal role of Sirt1, were suggested, shedding light on strategies to prevent exacerbation of renal injury in the hypertensive model at high risk of exposure to micro- and nanoplastics (MNPs).