Naringin regulates erectile dysfunction by abolition of apoptosis and inflammation through NOS/cGMP/PKG signalling pathway on exposure to Bisphenol-A in hypertensive rat model

Reprod Toxicol. 2020 Aug:95:123-136. doi: 10.1016/j.reprotox.2020.05.007. Epub 2020 May 16.

Abstract

This study investigated the effect of naringin (NRG) on extracellular metabolism of ATP through the NOS/cGMP/PKG signaling pathway induced by Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) on exposure to Bisphenol-A (BPA) in penis. Fifty-six adult male albino rats were randomly distributed into eight (n = 7) groups. Group I: control animals, Group II was treated with 40 mg/kg L-NAME, Group III was treated with 50 mg/kg BPA, Group IV was treated with 40 mg/kg L-NAME +50 mg/kg BPA. Group V was administered with 40 mg/kg L-NAME +80 mg/kg NRG. Group VI was administered with 50 mg/kg BPA + 80 mg/kg NRG. Group VII was administered with 40 mg/kg L-NAME+50 mg/kg BPA + 80 mg/kg NRG. Lastly, group VIII was treated with 80 mg/kg NRG for 14 days. NRG prevented hypertension and erectile dysfunction by inhibiting the activities of angiotensin-converting enzymes, arginase, and phosphodiesterase-51 (PDE-51) with corresponding down-regulation of inflammatory markers including TNF-α and IL-B. Additionally, hypertensive erectile dysfunction was remarkably prevented by NRG as manifested by the declined activities of AChE, MAO-A and enzymes of ATP hydrolysis (ATPase, ADPase, AMPase and ADA) with resultant increase in NO level. Also, penile expression of antigen presenting cells, CD43 transcript, caspace-9 and tumor suppressor P53 proteins were repressed on treatment with NRG. This study validates the hypothesis that NRG may be a valuable remedy in abrogating penile inflammatory markers, apoptosis and enzymes of ATP-hydrolysis via NOS/cGMP/PKG signaling pathways in hypertensive rat model on exposure to environmental toxicant.

Keywords: Apoptosis; Environmental toxicant; Erectile dysfunction; Hypertension; Inflammation; Naringin; Rat model.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Adenosine Triphosphate / metabolism
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Apoptosis / drug effects
  • Benzhydryl Compounds / toxicity*
  • Cyclic GMP / metabolism
  • Cyclic GMP-Dependent Protein Kinases / metabolism
  • Erectile Dysfunction / blood
  • Erectile Dysfunction / drug therapy*
  • Erectile Dysfunction / metabolism
  • Erectile Dysfunction / pathology
  • Flavanones / pharmacology
  • Flavanones / therapeutic use*
  • Hypertension / blood
  • Hypertension / drug therapy*
  • Hypertension / metabolism
  • Hypertension / pathology
  • Male
  • Malondialdehyde / blood
  • Monoamine Oxidase / metabolism
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide Synthase / metabolism
  • Penis / drug effects
  • Penis / metabolism
  • Penis / pathology
  • Peptidyl-Dipeptidase A / blood
  • Phenols / toxicity*
  • Rats, Wistar

Substances

  • Anti-Inflammatory Agents
  • Benzhydryl Compounds
  • Flavanones
  • Phenols
  • Malondialdehyde
  • Adenosine Triphosphate
  • Nitric Oxide Synthase
  • Monoamine Oxidase
  • Cyclic GMP-Dependent Protein Kinases
  • Acetylcholinesterase
  • Peptidyl-Dipeptidase A
  • Cyclic GMP
  • bisphenol A
  • naringin
  • NG-Nitroarginine Methyl Ester