The protective effects of Δ9-tetrahydrocannabinol against inflammation and oxidative stress in rat liver with fructose-induced hyperinsulinemia

Abstract

Objectives A large amount of fructose is metabolized in the liver and causes hepatic functional damage. Δ9‐tetrahydrocannabinol (THC) is known as a therapeutic agent for clinical and experimental applications. The study aims to investigate the effects of THC treatment on inflammation, lipid profiles and oxidative stress in rat liver with hyperinsulinemia. Methods Sprague‐Dawley rats were divided into groups: control, fructose (10% fructose in drinking water for 12 weeks), THC (1.5 mg/kg/day for the last 4 weeks, intraperitoneally) and fructose+THC groups. Biochemical parameters were measured spectrophotometrically. ELISA method was used for insulin measurement. Apoptosis and inflammation markers were detected by the streptavidin‐biotin peroxidase method. Key findings The consumptions of food and fluid are inversely proportional to fructose and non‐fructose groups. Insulin levels were the highest in fructose group. The reduced glutathione‐S‐transferase level significantly increased in fructose + THC group compared with fructose group. Total cholesterol level in the fructose + THC group was higher than the fructose group. Caspase‐3 and NF‐κβ immunopositive cell numbers increased in fructose + THC rats compared with fructose group. The number of IL‐6 immunopositive cell decreased in fructose + THC group compared with fructose group. Conclusions According to the result, long‐term and low‐dose THC administration may reduce hyperinsulinemia and inflammation in rats to some extent.

Chlorpyrifos and Δ9 Tetrahydrocannabinol exposure and effects on parameters associated with the endocannabinoid system and risk factors for obesity

“…Δ9- THC had no effects on insulin at 1.5 or 3.0 mg/kg/day across life stages ( Beydogan et al, 2019 , Coskun and Bolkent, 2014 , Gillies et al, 2020 ).…”

“…At 1.5 mg/kg/day Δ9- THC dose, Sprague-Dawley rats treated for 28 days by i.p. in adolescence showed slight but not significant decreases in body weight ( Beydogan et al, 2019 ). Decreased body weights in adolescent male Fischer 344 and Long-Evans rats were seen at higher doses (5.0 mg/kg/day: gavage; 5.6 mg/kg/day: i.p.)…”

Effects of Full-Spectrum Cannabis Oil with a Cannabidiol:Tetrahydrocannabinol 2:1 Ratio on the Mechanisms Involved in Hepatic Steatosis and Oxidative Stress in Rats Fed a Sucrose-Rich Diet

“…Hernandez-Rodas et al [64] demonstrated significantly decreased hepatic NrF2 DNA binding and increased hepatic NF-κB DNA binding in male C57BL/6J mice fed with a high-fat diet for 12 weeks. Beydogan et al [65] showed that the number of NF-ҡB immunopositive cells increased in Sprague-Dawley rats that received 10% fructose in drinking water for 12 weeks. Some molecular effects of cannabinoids depend on NrF2-NF-κB crosstalk.…”

Development and evaluation of novel rodent model of PCOS mimicking clinical phenotype in human disease

“…Metformin, as anticipated, caused a statistically significant decrease in the fasting serum insulin levels in the rats given DHT+f. Concurrent fructose consumption may have led to structural changes in pancreatic cells, resulting in hyperinsulinemia and an inability to control serum blood glucose, which would have indicated insulin resistance [33,34].…”