Lycopene alleviates di(2-ethylhexyl) phthalate-induced splenic injury by activating P62-Keap1-NRF2 signaling

• Published in: Food and chemical toxicology Vol. 168; p. 113324
• Main Authors: Dai, Xue-Yan, Zhu, Shi-Yong, Chen, Jian, Li, Mu-Zi, Zhao, Yi, Talukder, Milton, Li, Jin-Long
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01-10-2022
• Subjects: Di(2-ethylhexyl) phthalate; Lycopene; P62-Keap1-NRF2 pathway; Spleen; Di(2-ethylhexyl) phthalate; Spleen; P62-Keap1-NRF2 pathway; Lycopene
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2022.113324

Di(2-ethylhexyl) phthalate (DEHP) is an omnipresent environmental pollutant. It has been determined that DEHP is involved in multiple health disorders. Lycopene (Lyc) is a natural carotenoid pigment, with anti-inflammatory and antioxidant properties. However, it is not clear whether Lyc can protect the spleen from DEHP-induced oxidative damage. A total of 140 mice were randomly divided into seven groups (n = 20) and continuously gavaged with corn oil, distilled water, DEHP (500 or 1000 mg/kg BW/day) and/or Lyc (5 mg/kg BW/day) for 28 days. Histopathological and ultrastructural results showed a DEHP-induced inflammatory response and mitochondrial injuries. Moreover, DEHP exposure induced redox imbalance, which resulted in the up-regulation of ROS activity and MDA content, and the down-regulation of T-AOC, T-SOD and CAT in the DEHP groups. Simultaneously, our results also demonstrated that DEHP-induced kelch-like ECH-associated protein 1 (Keap1) expression was downregulated, and the expression levels of P62, nuclear factor erythroid 2-related factor (NRF2) and their downstream target genes were up-regulated. However, the supplementary Lyc reverted these changes to normal levels. Together, Lyc prevented DEHP-induced splenic injuries by regulating the P62-Keap1-NRF2 signaling pathway. Hence, the protective effects of Lyc might be a therapeutic strategy to ameliorate DEHP-induced splenic damage.
Exposure to persistent environmental pollutants such as di(2-ethylhexyl) phthalate (DEHP) has been involved in multiple health disorders, including splenic diseases. In this study, we clarified the potential protective effect of lycopene on DEHP-induced splenic injury. The results showed that Lyc inhibited DEHP induced oxidative damage by regulating the P62-Keap1-NRF2 signaling pathway, indicating that Lyc could alleviate the toxic effects of DEHP and may be helpful in reducing spleen injury. [Display omitted]
•Lyc alleviated DEHP exposure-induced splenic injury.•Lyc alleviated the DEHP exposure-induced redox imbalance.•Lyc mitigated the inhibition of P62-Keap1-NRF2 pathway induced by DEHP exposure.•Lyc alleviated the splenic cell mitochondrial injuries induced by DEHP exposure.