Evaluation of Endoplasmic Reticulum Stress in an Experimental Intestinal Ischemia–Reperfusion Model in Rats: The Role of Ozone Therapy and Trimetazidine

Abstract

Aim: The objective of the study was to assess the impact of ozone (O3) and trimetazidine on the intestines following ischemia–reperfusion (I/R) injury through the investigation of endoplasmic reticulum stress. Methods: Forty Sprague Dawley rats were separated into five groups. The groups were named as follows: control, O3, I/R, I/R + trimetazidine (TMZ), and I/R + O3. The control group had laparotomy and exploration of the superior mesenteric artery (SMA) only. Furthermore, alongside laparotomy and SMA exploration, an intraperitoneal (i.p.) administration of a 0.7 mg/kg ozone–oxygen (O3-O2) combination was given to the O3 group. In the experimental groups, the SMA was blocked with the silk suture ligation technique for a duration of 1 h and then restored to normal blood flow for another hour. In the I/R + O3 group, ozone was delivered i.p. at a dosage of 0.7 mg/kg, 30 min after ischemia. In the I/R + TMZ group, a dose of 20 mg/kg/day of trimetazidine was administered orally via gavage for a duration of 7 days, beginning 1 week prior to the induction of ischemia. Intestinal tissues were taken to assess indicators of intestinal mucosal injury and oxidative stress. Results: The level of the lipid peroxidation marker malondialdehyde (MDA) was significantly reduced in the experimental groups as compared to the I/R group (p < 0.05). The experimental groups had considerably greater levels of glutathione (GSH), which reflects antioxidant capacity, compared to the I/R group (p < 0.05). Nevertheless, the concentration of GSH was observed to be increased in the I/R + O3 group in comparison to the I/R + TMZ group (p < 0.05). The histopathological damage score showed a substantial decrease in the experimental groups as compared to the I/R group (p < 0.05). The I/R + O3 group had the lowest injury score. The experimental groups exhibited significantly reduced positivity of the endoplasmic reticulum (ER) stress markers C/EBP homologous protein (CHOP) and glucose-regulated protein (GRP)-78 compared to the I/R group (p < 0.05). Conclusions: The findings provide evidence for the potential advantages of utilizing ozone therapy in the treatment of intestinal ischemia–reperfusion injury. Additionally, they propose that ozone should be assessed in more extensive clinical trials in the future as a therapeutic agent that can disrupt endoplasmic reticulum stress.