The Protective Effects of Ramelteon on Acute Intestinal Injury Caused by Experimentally Induced Endoplasmic Reticulum...

Intestinal circulatory disturbances have been shown to cause increase endoplasmic reticulum (ER) stress.

Forty-eight male Sprague Dawley rats were divided into six groups. The control group received saline solution alone. In the mesenteric artery ischemia (MAI) group, the mesenteric artery was occluded, and intestinal ischemia was induced for 1 h, and then terminated. The MAI + Ramelteon (Ram) group received 10 mg/kg Ram for 7 d. The final dose of Ram was administered half an hour prior to exposure to MAI on day 7. The MAI and reperfusion (MAI/R) group underwent 1 h of ischemia followed by 1 h of induced ischemia-reperfusion injury, respectively. The MAI/R + Ram group received 10 mg/kg Ram for 7 d before reperfusion induction. The final dose of Ram on day 7 was applied in the second half hour following ischemia induction. The Sham + Ram 10 mg/kg group received Ram for 7 d. Malondialdehyde, glutathione, tumor necrosis factor alpha, interleukin-10, caspase-3, 8-hydroxy-2'-deoxyguanosine, CAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), and glucose-regulated protein 78 levels were then examined.

Oxidative stress and inflammation induced by MAI and MAI/R activated the ER stress cascade. Through its protective effects, Ram significantly attenuated the elevated CHOP expression levels observed (P = 0.003 for MAI + Ram compared to MAI and P = 0.001 for MAI/R + Ram compared to MAI/R). Conversely, a significant increase in levels of the anti-inflammatory cytokine interleukin-10 was detected (P < 0.05).

Ram appears to possess the potential ability to ameliorate experimentally induced small bowel damage by suppressing ER stress.