Chronic administration of delta9-tetrahydrocannabinol protects hyperinsulinemic gastric tissue in rats

Abstract

Hyperinsulinemia (HI) can result from some reasons such as an increase in basal/fasting circulating insulin and/or potentiation of postprandial insulin production. Diabetes mellitus (DM) is indirectly related to HI since it both causes and results from insulin resistance. Understanding the causes of HI and treating this is crucial for preventing DM. Previous research has shown that delta9-tetrahydrocannabinol (THC) has medicinal benefits. In light of this, the relationship between THC and oxidative stress, DNA repair mechanism, apoptosis, and its regulatory impact on appetite hormones in the gastric tissue of hyperinsulinemic rats has been investigated for the first time. Male rats (Spraque-Dawley, total = 32) were used, and they were randomly divided into the following groups (n = 8 in each group): control (CTRL), HI, THC administered control (THC, 1.5 mg/kg/day, during 4 weeks), and THC administered HI (HI + THC) groups. The number of poly (ADP-ribose) polymerase-1 and proliferating cell nuclear antigen (PCNA) and caspase-3 immunopositive cells in the HI group was significantly reduced compared to the CTRL group. The number of PCNA and caspase-9 immunopositive cells was significantly increased in the HI + THC group compared to the HI group. Obestatin immunopositive cell numbers in the HI + THC group were higher than in the HI and CTRL groups. The results show that THC administration may affect the regulation of appetite hormones and regeneration in the fundus of rats with HI. Glutathione (GSH) levels were higher in the HI + THC group than in the HI group. Both immunohistochemical and biochemical analyses revealed that THC promotes regeneration and regulates appetite hormones in hyperinsulinemic gastric tissues. Hyperinsulinemia (HI) can result from dysregulation in the circulation and production of insulin. Since HI is indirectly associated with diabetes mellitus (DM), understanding the causes of HI and treating HI is crucial to prevent DM. This study was conducted to investigate the damage caused by HI in the stomach and to develop an alternative perspective on the treatment of this damage. The demonstration of the therapeutic effects of delta9-tetrahydrocannabinol (THC) by different studies and the legalization of its use for medical purposes attract the attention of researchers. In light of this knowledge, the regulatory effect of THC on gastric tissue of hyperinsulinemic rats was evaluated by considering oxidative stress, DNA repair mechanism, apoptosis, and appetite hormones. The findings obtained from this study show that THC promotes regeneration in gastric tissue of hyperinsulinemic rats. This study is a pioneering study designed to evaluate the possible efficacy of THC in the treatment of gastric damage caused by HI.