Orally administered zingerone does not mitigate alcohol-induced hepatic oxidative stress in growing Sprague Dawley rat pups

Drug Chem Toxicol. 2023 Nov;46(4):736-745. doi: 10.1080/01480545.2022.2085740. Epub 2022 Jun 23.

Abstract

Neonatal alcohol exposure (NAE) can induce oxidative stress. We determined whether zingerone (ZO), a phytochemical with anti-oxidant activity, can mitigate the negative impact of neonatal alcohol-induced oxidative stress. Seventy ten-day-old Sprague-Dawley rat pups (35 male, 35 female) were randomly assigned and administered the following treatment regimens daily from postnatal day (PND) 12-21: group 1 - nutritive milk (NM), group 2 - NM +1 g/kg ethanol (Eth), group 3 - NM + 40 mg/kg ZO, group 4 - NM + Eth + ZO. Growth performance, blood glucose and plasma triglycerides (TGs), total cholesterol, HDL-cholesterol, leptin and insulin concentration were determined. Cytochrome p450E21(CYP2E1) and thiobarbituric acid (TBARS); markers of hepatic oxidative stress and catalase, superoxide dismutase (SOD) and total glutathione (GSH), anti-oxidant markers of the pups were determined. Oral administration of ethanol (NM + Eth), zingerone (NM + ZO) and combined ethanol and zingerone (NM + Eth + ZO) did not affect the growth performance and insulin and leptin concentration of the rats (p > 0.05). Ethanol significantly reduced plasma TGs concentration of female rats (p = 0.04 vs control). However, ethanol and/or its combination with zingerone decreased hepatic GSH (p = 0.02 vs control) and increased CYP2E1 (p = 0.0002 vs control) activity in male rat pups. Zingerone had no effect (p > 0.05 vs control) on the rats' CYP2E1, GSH, SOD and catalase activities. Neonatal alcohol administration elicited hepatic oxidative stress in male rat pups only, showing sexual dimorphism. Zingerone (NM + ZO) prevented an increase in CYP2E1 activity and a decrease in GSH concentration but did not prevent the alcohol-induced hepatic oxidative stress in the male rat pups.

Keywords: Zingerone; alcohol; oxidative stress; rat pups.

MeSH terms

  • Animals
  • Antioxidants* / pharmacology
  • Catalase / metabolism
  • Cytochrome P-450 CYP2E1
  • Ethanol / toxicity
  • Female
  • Glutathione / metabolism
  • Insulins* / pharmacology
  • Leptin / pharmacology
  • Male
  • Oxidative Stress
  • Rats
  • Rats, Sprague-Dawley
  • Superoxide Dismutase / metabolism

Substances

  • Antioxidants
  • Catalase
  • Leptin
  • zingerone
  • Cytochrome P-450 CYP2E1
  • Ethanol
  • Glutathione
  • Superoxide Dismutase
  • Insulins