Abstract
Plasticizer di(2-ethylhexyl) phthalate (DEHP) is employed to make polyethylene polymers. Some studies in epidemiology and toxicology have shown that DEHP exposure over an extended period may be hazardous to the body, including nephrotoxicity, and aggravate kidney damage in the context of underlying disease. However, studies on the toxicity of DEHP in diabetes-induced kidney injury have been rarely reported. Using a high-fat diet (HFD) and streptozotocin (STZ, 35 mg/kg)-induced kidney injury in mice exposed to various daily DEHP dosages, we explored the impacts of DEHP on diabetes-induced kidney injury. We discovered that DEHP exposure significantly promoted the renal inflammatory response and oxidative stress in mice, with increased P-p38 and P-p65 protein levels and exacerbated the loss of podocin. The same findings were observed in vitro after stimulation of podocytes with high glucose (30 mmol/L) and exposure to DEHP. Our results suggest that DEHP exacerbates diabetes-induced kidney injury by mediating oxidative stress and activating p38MAPK/NF-κB.