Zingerone effects on arsenic-induced glucose intolerance and hepatotoxicity in mice via suppression of oxidative stress-mediated hepatic inflammation and apoptosis

J Trace Elem Med Biol. 2024 Dec:86:127562. doi: 10.1016/j.jtemb.2024.127562. Epub 2024 Nov 9.

Abstract

Background: Arsenic (As), a poisonous metalloid, is widely distributed in air, water, and soil and has been associated with the occurrence of diabetes and liver toxicity. Zingerone (ZNG), one of the active compounds in ginger, has several pharmacological benefits such as antioxidant and anti-inflammatory characteristics. The objective of this research was to assess the protective role of ZNG against arsenic (As)-induced glucose intolerance (GI) and hepatotoxicity in mice.

Methods: Male NMRI mice were treated with ZNG (25, 50, and 100 mg/kg, oral gavage for 29 days) before As administration (10 mg/kg, oral gavage for 29 days). On the 29th day, fasting blood glucose (FBG) and glucose tolerance test were measured. The animals were euthanized (day 30), and samples from blood and tissue (liver and pancreas) were gathered for further evaluations.

Results: Administration of ZNG inhibited As-induced elevation of FBG and GI. Moreover, hepatic tissue damage and decreased Langerhans islets' diameter caused by As administration were improved by ZNG treatment. Pretreatment with ZNG attenuated the elevation of serum liver enzymes induced by As (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase). Also, the reduction in total thiol content, as well as the decline in antioxidant enzyme activities (catalase, superoxide dismutase, and glutathione peroxidase) and the increase in lipid peroxidation marker (thiobarbituric acid reactive substances) in the liver tissue of As-exposed mice were reversed in ZNG-treated mice. Furthermore, ZNG prevented the increase of hepatic inflammatory markers (nitric oxide and tumor necrosis factor-alpha levels, and protein expression of nuclear factor-kappa B) and apoptosis-related marker (caspase-3 protein expression) in As-treated mice.

Conclusions: This study has provided evidence indicating that ZNG can act as a beneficial agent in preventing As-induced hepatotoxicity and diabetes.

Keywords: Arsenic; Glucose intolerance; Hepatotoxicity; Mice; Zingerone.

MeSH terms

  • Animals
  • Apoptosis* / drug effects
  • Arsenic* / toxicity
  • Chemical and Drug Induced Liver Injury / drug therapy
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / prevention & control
  • Glucose Intolerance* / chemically induced
  • Glucose Intolerance* / drug therapy
  • Guaiacol* / analogs & derivatives
  • Guaiacol* / pharmacology
  • Inflammation* / chemically induced
  • Inflammation* / drug therapy
  • Inflammation* / metabolism
  • Liver* / drug effects
  • Liver* / metabolism
  • Liver* / pathology
  • Male
  • Mice
  • Oxidative Stress* / drug effects

Substances

  • Arsenic
  • zingerone
  • Guaiacol