Polystyrene nanoplastics exacerbate gentamicin-induced nephrotoxicity in adult rat by activating oxidative stress, inflammation and apoptosis pathways.

Nanoplastics (NPs) and pharmaceutical residues are environmental pollutants that can bioaccumulate in the food chain, thus increasing the risk of harmful effects due to concomitant exposure in both humans and animals. However, the impact of such co-exposure on target tissue toxicity and mechanism remains unclear. In this study, we aimed to investigate the effect of combined exposure to widespread polystyrene NP (Ps-NP) contaminant and a widely used antibiotic, gentamicin (GEN) on nephrotoxicity in adult rat. A total of 40 male Wistar rats were assigned into four groups; control group (C), GEN exposed-group (100 mg/kg/day, i.p.), Ps-NPs exposed-group (2.5 mg/kg/day, orally) and co-exposure-group (100 mg Ps-NPs/kg/day orally + 2.6 mg GEN/kg/day i.p.) for 15 consecutive days. Kidneys were excised at sacrifice on day 15 for the examination of: (i) renal function parameters and renal oxidative stress (oxidant and antioxidant markers); (ii) mRNA expression of key regulators of oxidative stress and inflammation response (NF-κB, TNF-α, IL-6 and NRF-2) and mitochondrial apoptosis pathway (Bax, Bcl-2, caspase-9 and caspase-3); (iii) histopathology. Levels of urea and creatinine in serum of NPs or/and GEN-treated rats were significantly increased with marked histopathological changes in the kidney. Additionally, the oxidative stress markers (MDA, PCO and NO) were increased with a decrease of antioxidant enzyme activities. Furthermore, Ps-NPs or/and GEN-treated rats exhibited increased expression of mRNA related to oxidative stress (NRF-2), inflammation (TNF-α, IL-6) and apoptosis (Bax, Bcl-2, caspase-9 and caspase-3). Our results revealed that co-exposure of adult rats to Ps-NPs and GEN had a synergic-adverse effect on the kidney function. This study highlights a new finding regarding the combined toxicity of NPs and pharmaceutical pollutants on kidney function, suggesting potential synergistic interaction between these substances.