Effects of delta 9-tetrahydrocannabinol on colon tissue in rats fed with high-carbohydrate diet

The detrimental effect of a high-carbohydrate diet on energy balance leads to the development and progression of metabolic diseases. Dysfunctional insulin secretion induces a metabolic disorder known as hyperinsulinemia (HI). Researchers have reported that delta 9– tetrahydrocannabinol (THC) can be used as a therapeutic agent in metabolic disorders. The aim of this study was to elucidate the molecular mechanisms of high-carbohydrate diet-associated oxidative stress, inflammation, apoptosis death pathway and cannabinoid receptors in THCtreated Sprague-Dawley rat colon tissue. A total of 28 male rats were divided into (7 rats in each group) control (C), HI, THC-treated C (THC) and THC-treated HI (HI+THC) groups. The HI rat model was established by adding 10% fructose to the drinking water for 12 weeks. During the last four weeks of the experiment, rats in the HI+THC and THC groups were administered 1.5 mg/kg/day THC intraperitoneally. The findings obtained from biochemical analyses showed that glutathione level significantly increased in the HI+THC group compared to the HI group, but no significant changes were found in other reactive oxygen species such as malondialdehyde, protein carbonyl, catalase, glutathione-S-transferase. When qRT-PCR method was applied to detect cannabinoid receptors, inflammation and apoptosis markers, G protein-coupled receptor 55 (Gpr55), tumor necrosis factor-α, nuclear factor-κB, caspase-3, caspase-8 and caspase-9 gene expressions were significantly increased in HI+THC group compared to HI. In conclusion, we can say that THC acts through the GPR55 receptor, as well as its antioxidant, inflammatory and apoptotic properties, in the colon tissue of rats fed highcarbohydrate diet.