Lycopene Preventing DEHP-Induced Renal Cell Damage Is Targeted by Aryl Hydrocarbon Receptor.

Abstract

Di (2-ethylhexyl) phthalate (DEHP) is an environmentally persistent and bioaccumulative plasticizer. Accumulation of DEHP in the body can eventually cause kidney damage. As a type of natural carotenoid, lycopene (LYC) has a potential protective effect on renal cells, but the protective mechanism has not yet been elucidated. The major goal of this study was to see how effective LYC was at treating DEHP-induced nephrotoxicity in mice. ICR mice were treated with DEHP (500 mg/kg BW/day or 1000 mg/kg BW/day) or LYC (5 mg/kg BW/day) for 28 days. Through histopathology and ultrastructure, we found that LYC attenuated DEHP-induced renal tubular cell and glomerular damage. LYC relieved DEHP-induced kidney injury evidenced by lower levels of blood urea nitrogen (Bun), creatinine (Cre), and uric acid (Uric). Meanwhile, the reduced expression of kidney injury molecule-1 (Kim-1) also supported it. Notably, LYC can alleviate the activity or content of cytochrome P450 system (CYP450s) interfered with by DEHP. In addition, LYC treatment reduced nuclear accumulation of DEHP-induced aromatic hydrocarbon receptor (AhR) and AhR nuclear transporter (Arnt), and its downstream target genes such as cytochrome P450-dependent monooxygenase (CYP) 1A1, 1A2, and 1B1 expression significantly decreased to normal in the LYC treatment group. In summary, LYC can mediate the AhR/Arnt signaling system to prevent kidney toxicity in mice caused by DEHP exposure.