Targeting ERK/COX-2 signaling pathway in permethrin-induced testicular toxicity: a possible modulating effect of matrine

Mol Biol Rep. 2020 Jan;47(1):247-259. doi: 10.1007/s11033-019-05125-7. Epub 2019 Oct 16.

Abstract

Permethrin (PER), the prevalent synthetic pyrethroid, was reported to have genotoxic effects along with male reproductive organs impairment. Matrine, the Chinese herb chief alkaloid constituent, is used extensively owing to its recognized pharmacological properties. The study included 30 rats allocated equally into three groups; Group I: Control group, Group II: PER group and Group III: Matrine treated PER group. All groups were subjected to the measurement of Steroidogenic acute regulatory (StAR) gene expression by PCR technique while testosterone, phosphorylated Extracellular signal-regulated Kinase 1/2 (p-ERK1/2) and Cyclooxygenase 2 (COX-2) levels were assessed by ELISA technique. Malondialdehyde (MDA), total antioxidant capacity (TAC) and glutathione peroxidase (GPx) were also detected spectrophotometrically in addition to assessment of DNA fragmentation. Testicular histological structure as well as sperm count and morphology were studied. Matrine improved testicular toxicity evidenced by significant upregulation of StAR gene expression, elevation of testosterone level and significant decrease of p-ERK1/2 and COX-2 levels. Moreover, enhancements of the antioxidant status together with improvement of the histological findings were observed. These findings could pave the way for matrine to be used as a promising therapeutic agent in treatment of PER toxicity.

Keywords: Cyclooxygenase 2; Matrine; Permethrin; Phosphorylated extracellular signal-regulated kinase; Steroidogenic acute regulatory protein.

MeSH terms

  • Alkaloids / metabolism*
  • Alkaloids / pharmacology
  • Animals
  • Antioxidants / metabolism
  • Cyclooxygenase 2 / metabolism
  • Glutathione Peroxidase / metabolism
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology
  • Male
  • Malondialdehyde / analysis
  • Matrines
  • Permethrin / adverse effects
  • Permethrin / toxicity
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Quinolizines / metabolism*
  • Quinolizines / pharmacology
  • Rats
  • Rats, Wistar
  • Signal Transduction
  • Spermatozoa / cytology
  • Spermatozoa / drug effects
  • Testis / cytology
  • Testis / drug effects*
  • Testis / metabolism
  • Testosterone / analysis

Substances

  • Alkaloids
  • Antioxidants
  • Phosphoproteins
  • Quinolizines
  • steroidogenic acute regulatory protein
  • Testosterone
  • Malondialdehyde
  • Permethrin
  • Glutathione Peroxidase
  • Cyclooxygenase 2
  • Ptgs2 protein, rat
  • Matrines