4-Hexylresorcinol Attenuates Ethanol-Induced Hepatic and Pancreatic Injury by Modulating Metabolic Dysfunction and...

Area of Science:

• Biochemistry
• Toxicology
• Cell Biology

Background:

• Chronic ethanol consumption causes significant metabolic dysfunction and multi-organ injury, particularly affecting the liver and pancreas.
• Oxidative stress and endoplasmic reticulum (ER) stress are identified as key mechanisms underlying alcohol-induced hepato-pancreatic damage.

Purpose of the Study:

• To evaluate the protective efficacy of 4-hexylresorcinol (4HR) against chronic ethanol (EtOH)-induced injury in the liver and pancreas.
• To investigate the impact of 4HR on metabolic parameters, oxidative stress markers, and ER stress indicators in EtOH-exposed mice.

Main Methods:

• Male C57BL/6J mice were administered a liquid ethanol diet for 5 weeks, with co-administration of 4HR at 5 mg/kg or 10 mg/kg.
• Assessment included glucose homeostasis tests, serum insulin analysis, and histological, biochemical, and molecular analyses of liver and pancreas tissues.
• Key markers evaluated were hepatic inflammation, ALT levels, glycogen deposition, pancreatic lipid peroxidation, and GADD153 (CHOP) expression.

Main Results:

• Chronic ethanol exposure led to impaired glucose homeostasis, increased hepatic inflammation and ALT, depleted hepatic glycogen, elevated pancreatic lipid peroxidation, and upregulated GADD153 expression.
• 4HR treatment, especially at 10 mg/kg, significantly attenuated hepatic inflammation, reduced pancreatic malondialdehyde levels, and suppressed GADD153 expression in both organs.
• While a trend towards increased hepatic glycogen was observed, quantitative analysis did not confirm significant restoration of EtOH-induced depletion by 4HR.

Conclusions:

• 4-hexylresorcinol demonstrates protective effects against alcohol-induced hepatic inflammation, pancreatic lipid peroxidation, and ER stress, as indicated by reduced GADD153 expression.
• The compound shows potential as a multi-organ protective agent against alcohol-induced inflammatory, oxidative, and ER stress.
• 4HR's efficacy in restoring EtOH-induced hepatic glycogen depletion was limited under the experimental conditions.