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.

Lycopene regulates the mitochondrial unfolded protein response to prevent DEHP-induced cardiac mitochondrial damage in mice

“…79 A previous study has demonstrated that the exposure of DEHP will cause mitochondrial dysfunction and accumulation of oxygen radicals. 80,81 The accumulation of oxygen free radicals results in the activation of the Nrf2 system. Meanwhile, the accumulation of oxygen radicals results in the activation of HSPs to refold or degrade misfolded proteins.…”

Role of Toll-like Receptor/MyD88 Signaling in Lycopene Alleviated Di-2-ethylhexyl Phthalate (DEHP)-Induced Inflammatory Response

“…Lycopene (Lyc) is a carotenoid that is widely found in fruits and vegetables. , It belongs to the carotenoid family of lipid-soluble antioxidants and displays strong singlet oxygen quenching ability. − Lyc has many biological functions, including anti-inflammatory activities. Moreover, Lyc plays the potential role of modulating several cellular processes, and it can act on target cells in many ways. − In previous studies, it was observed that Lyc could promote apoptosis and autophagy and inhibit cell proliferation. , Other important functions of Lyc include the inhibition of oxidative damage and the stimulation of the activity of phase II enzymes . The inflammatory response is related to many pathological conditions.…”

IL-6/STAT3/Foxo1 axis as a target of lycopene ameliorates the atrazine-induced thymic mitophagy and pyroptosis cross-talk

“…ATZ represented its toxic effects on the target organs by ROS generation and accumulation. 18,37,38 Interestingly, it was observed that the levels of DHE and 3′NT in the thymus were unchanged with ATZ exposure (Fig. 2).…”