Methyl palmitate reversed estradiol benzoate-induced endometrial hyperplasia in female rats

Toxicol Mech Methods. 2021 Jan;31(1):43-52. doi: 10.1080/15376516.2020.1827329. Epub 2020 Oct 6.

Abstract

Early detection and treatment of endometrial hyperplasia (EH) is mandatory for endometrial cancer prevention. Several bioactive agents of plant origin have been shown to elicit their chemotherapeutic effect against tumors and cancer via induction of mitochondrial permeability transition(mPT) pore opening. This research was therefore aimed at evaluating the potential chemopreventive effect of methyl palmitate (MP), on estradiol benzoate(EB)-induced EH, looking at the mitochondrial-mediated pathway and other possible mechanisms of action. Mitochondria were isolated using differential centrifugation. The mPT pore, mitochondrial ATPase (mATPase) activity, lipid peroxidation and cytochrome c release were determined by standard methods using spectrophotometer. Uterine interleukin 1b, MDA levels and SOD, GSH activities, were determined using commercially available kits. The uterine histological and immunohistochemical assessment of estrogen receptor (ERα), IL-1b and caspas-3 were carried out. The fibroblast cell count density was determined using histomorphometry. At all the concentrations of MP used, there was no significant induction of mPT pore opening, neither any enhancement of mATPase activity nor release of cytochrome c when compared to the control. Similar pattern of results were recorded for the in vivo study. However, there was marked increase in the uterine MDA and interleukin 1b levels, with concurrent decrease in SOD and GSH activities, in the EB-treated group, which was significantly reversed by MP co-administration. Endometrial Hyperplasia observed in the EB-treated group was ameliorated by MP co-administration. The immunoexpression of ERα and IL-1b in the EB-treated group was reversed by MP co-administration. This study suggests anti-inflammatory, antioxidant and anti-proliferative potential of MP against EB-induced EH.

Keywords: Methyl palmitate; apoptosis; endometrial hyperplasia; estradiol benzoate; mitochondrial permeability transition pore.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Cell Proliferation / drug effects*
  • Cytochromes c / metabolism
  • Endometrial Hyperplasia / chemically induced
  • Endometrial Hyperplasia / metabolism
  • Endometrial Hyperplasia / pathology
  • Endometrial Hyperplasia / prevention & control*
  • Endometrium / drug effects*
  • Endometrium / metabolism
  • Endometrium / pathology
  • Estradiol / analogs & derivatives*
  • Estradiol / toxicity
  • Estrogen Receptor alpha / metabolism
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Interleukin-1beta / metabolism
  • Lipid Peroxidation / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Mitochondrial Proton-Translocating ATPases / metabolism
  • Oxidative Stress / drug effects
  • Palmitates / pharmacology*
  • Rats, Wistar
  • Signal Transduction

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Estrogen Receptor alpha
  • IL1B protein, rat
  • Interleukin-1beta
  • Palmitates
  • estradiol 3-benzoate
  • Estradiol
  • Cytochromes c
  • methyl palmitate
  • Mitochondrial Proton-Translocating ATPases