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

Food Chem Toxicol. 2022 Oct:168:113324. doi: 10.1016/j.fct.2022.113324. Epub 2022 Jul 31.

Abstract

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.

Keywords: Di(2-ethylhexyl) phthalate; Lycopene; P62-Keap1-NRF2 pathway; Spleen.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Corn Oil / pharmacology
  • Diethylhexyl Phthalate* / toxicity
  • Environmental Pollutants* / pharmacology
  • Kelch-Like ECH-Associated Protein 1 / metabolism
  • Lycopene / pharmacology
  • Mice
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Phthalic Acids
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Spleen / metabolism
  • Superoxide Dismutase / metabolism
  • Water

Substances

  • Antioxidants
  • Environmental Pollutants
  • Keap1 protein, mouse
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • Phthalic Acids
  • Reactive Oxygen Species
  • Water
  • phthalic acid
  • Corn Oil
  • Diethylhexyl Phthalate
  • Superoxide Dismutase
  • Lycopene