Lycopene Ameliorates Di(2-ethylhexyl) Phthalate-Induced Pyroptosis in Spleen via Suppression of Classic Caspase-1/NLRP3 Pathway

J Agric Food Chem. 2021 Feb 3;69(4):1291-1299. doi: 10.1021/acs.jafc.0c06534. Epub 2021 Jan 21.

Abstract

Lycopene (Lyc) as a natural antioxidant has attracted widespread attention. Di(2-ethylhexyl) phthalate (DEHP) can cause serious spleen injury in animals via the environment and food chain. For investigation of whether Lyc could alleviate DEHP-exerted pyroptosis in spleen through inhibiting the Caspase-1/NLRP3 pathway activation, 140 male mice were randomly divided into 7 groups: control group, vehicle control group, Lyc group (5 mg/kg BW/day), DEHP-exposed group (500 or 1000 mg/kg BW/day, respectively), and DEHP + Lyc groups by daily administration for 28 days. Pathological results showed that the supplementation of Lyc alleviated DEHP-induced inflammatory infiltration. Moreover, the addition of Lyc inhibited DEHP-induced Caspase-1, NLRP3, ASC, NF-κB, IL-1β, and IL-18 overexpression and GSDMD down-expression. These results indicate that Lyc could inhibit DEHP-induced Caspase-1-dependent pyroptosis and the inflammatory response. Taken together, the study provided new evidence that Lyc may be a strategy to mitigate spleen injury induced by DEHP.

Keywords: Caspase-1/NLRP3 pathway; di(2-ethylhexyl) phthalate; inflammatory response; lycopene; pyroptosis.

MeSH terms

  • Animals
  • Caspase 1 / genetics
  • Caspase 1 / metabolism*
  • Diethylhexyl Phthalate / toxicity*
  • Lycopene / administration & dosage*
  • Male
  • Mice
  • Mice, Inbred ICR
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Pyroptosis / drug effects*
  • Spleen / drug effects*
  • Spleen / metabolism

Substances

  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Diethylhexyl Phthalate
  • Caspase 1
  • Lycopene