Pharmacological inhibition of endoplasmic reticulum stress ameliorates polystyrene nanoplastic-induced renal injury in female Wistar rats.

Nanoplastics are a relatively new pollutant that has raised growing concern about their deleterious effects on humans. Endoplasmic reticulum (ER) stress is a cellular stress response that helps maintain protein balance in response to internal or external stimuli. The aim of this research was to modulate ER stress in renal tissues by administering 4-PBA to mitigate the nephrotoxicity induced by polystyrene nanoplastics (PSNPs). For this purpose, 24 healthy female Wistar rats were randomly divided into four groups: vehicle control group, PSNPs group, PSNPs + 4-PBA 500 mg/kg group, and PSNPs + 4-PBA 1000 mg/kg group (n = 6). During the experiment, PSNPs (10 mg/kg) were given for 5 weeks, whereas 4-PBA was given for the last two weeks. At the end of the experiment, animals were sacrificed, and tissue samples from the kidney and blood were collected and stored immediately. PSNPs exposure resulted in severe renal dysfunction, including increased serum creatinine, MDA, and nitrite, whereas body weight, kidney weight, and GSH were decreased. Markers related to ER stress, including GRP78, CHOP, and caspase-12, were found to be upregulated, along with distorted renal histopathology in the PSNPs-exposed group. The administration of 4-PBA leads to improvement in histological alterations and biochemical parameters, as well as attenuation of GRP78, CHOP, and caspase-12 expression levels. The results of this study indicate that 4-PBA may serve as a potent intervention to treat PSNP-induced nephrotoxicity. Also, apoptosis through GRP78/CHOP-dependent ER stress signalling plays a significant role in the development of PSNPs-induced nephrotoxicity.