Impacts of n-acetyl cysteine on gibberellic acid-induced testicular dysfunction through regulation of inflammatory cytokines, steroid and antioxidant activity

Andrologia. 2021 Jun;53(5):e14036. doi: 10.1111/and.14036. Epub 2021 Mar 16.

Abstract

In agriculture, gibberellic acid (GA3) is commonly used with extreme dangers for public health. The current research evaluates the improving effects of n-acetyl cysteine (NAC, 150 mg/kg bw) co-administered with GA3 (55 mg/kg bw) mediated testicular injury. Twenty-four male albino rats were split into 4 groups: Negative control (CNT), NAC group, positive GA3 group and protective group, co-administered NAC plus GA3. On day 21, rats were anesthetised then euthanised by decapitation. Blood samples were collected; testicular samples were taken for semen analysis, serum chemistry, RNA extraction, histological and antioxidants markers examination. Our results revealed a significant decline p < .05 of catalase level and total antioxidant capacity. There was a substantial rise of MDA concentration in GA3-treated rats along with a considerable decrease of the antioxidant markers (SOD, GSH) and serum male reproductive hormones. In GA3-treated rats, an overexpression of the inflammatory cytokines (TNF-α, IL-1β) and anti-inflammatory cytokine IL-10 with boost mRNA expression of nuclear factor-kappa (NFk B) were confirmed. There was downregulation of steroidogenesis genes and decrease in sperm quality and concentration with an increase in sperm abnormalities, all were reported in GA3-treated rats. NAC treatment significantly increased the antioxidant state, testicular function beside structural germ cell and seminiferous tubules histology accompanied by upsurge of steroidogenic mRNA expressions (P450scc and 3β-HSD) and downregulated the pro-inflammatory cytokines mRNA expression (TNF-α, IL-1β). These results confirm the antioxidant capability of NAC and afford robust evidence about the ameliorative effect of the NAC to attenuate the testicular injury induced by GA3 through modulation of the antioxidant defence system, steroidogenic and pro-inflammatory cytokines mRNA expression.

Keywords: NAC protection; gene expression analysis; gibberellic acid; testis toxicity.

MeSH terms

  • Acetylcysteine* / pharmacology
  • Animals
  • Antioxidants* / metabolism
  • Antioxidants* / pharmacology
  • Cytokines / genetics
  • Cytokines / metabolism
  • Gibberellins
  • Male
  • Oxidative Stress
  • Rats
  • Steroids / metabolism
  • Testis / metabolism

Substances

  • Antioxidants
  • Cytokines
  • Gibberellins
  • Steroids
  • gibberellic acid
  • Acetylcysteine

Associated data

  • RefSeq/M22615.1
  • RefSeq/NM_001007719.3
  • RefSeq/AF079314
  • RefSeq/NM_031144