Quercetin inhibits testicular toxicity induced by the mixture of three commonly used phthalates in rats

J Sci Food Agric. 2023 Feb;103(3):1541-1549. doi: 10.1002/jsfa.12251. Epub 2022 Oct 18.

Abstract

Background: Phthalates (PEs), such as butyl benzyl phthalate, dibutyl phthalate and di(2-ethylhexyl) phthalate, are one of the most widely used plasticizers, and humans are increasingly exposed to them. Phytochemical quercetin (Que) is a typical flavonoid with several biological effects, such as antioxidative and anti-inflammatory. The present study was designed to explore the effect of Que on testicular toxicity caused by the mixture of three commonly used PEs (MPEs), and the underlying mechanism. Forty male Sprague-Dawley rats were randomly and equally divided into five groups (n = 8). Rats in control the group were orally treated with the excipient. Rats in the MPEs group were orally administered with 900 mg kg-1 day-1 MPEs, whereas rats in the MPEs+L-Que, MPEs+M-Que and MPEs+H-Que groups were simultaneously treated with 900 mg kg-1 day-1 MPEs and, respectively, 10, 30 and 90 mg kg-1 day-1 Que for 30 days.

Results: Compared with the control group, the testes weight, epididymides weight, serum testosterone, luteinizing hormone, follicle-stimulating hormone and estradiol levels, and anogenital distance in the MPEs group were significantly decreased (P < 0.05). The testicular tissues were injured with atrophy of seminiferous tubules, hyperplasia of Leydig cells and arrest of spermatogenesis in the MPEs group. Testicular steroidogenic proteins (StAR, P450scc, CYP17A1 and 17β-HSD, P450arom) were up-regulated, whereas P-element-induced wimpy testis proteins (PIWIL1 and PIWIL2) were down-regulated in the MPEs group (P < 0.05). However, the alterations of these parameters were inhibited in the MPEs+M-Que and MPEs+H-Que groups.

Conclusion: MPEs disturbed steroid hormone metabolism and caused testicular injuries. Que could inhibit testicular toxicity of MPEs, which might relate to the improved regulation of steroid hormone metabolism. © 2022 Society of Chemical Industry.

Keywords: PIWI proteins; phthalates; quercetin; steroidogenic proteins; testicular toxicity.

MeSH terms

  • Animals
  • Argonaute Proteins / metabolism
  • Argonaute Proteins / pharmacology
  • Diethylhexyl Phthalate* / metabolism
  • Diethylhexyl Phthalate* / pharmacology
  • Humans
  • Male
  • Quercetin / metabolism
  • Quercetin / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Testis*
  • Testosterone

Substances

  • phthalic acid
  • Quercetin
  • Testosterone
  • Diethylhexyl Phthalate
  • PIWIL1 protein, human
  • Argonaute Proteins
  • PIWIL2 protein, human