Published online Jun 20, 2026. doi: 10.5493/wjem.118828
Revised: March 11, 2026
Accepted: May 11, 2026
Published online: June 20, 2026
Processing time: 152 Days and 9.3 Hours
Spinal cord ischemia-reperfusion injury (IRI), which can occur as a result of temporary aortic occlusion during resection of thoracoabdominal aneurysms, can be an unpredictable and devastating complication of aortic surgery. There are no specific medications or guidelines for the prevention and treatment of spinal cord IRI (SCIRI). It is now known that IRI not only exacerbates local tissue damage when blood flow is restored but also affects distant organs, such as the liver, lungs, and brain, through mediators released into the systemic circulation. Studies show that ozone pretreatment reduces oxidative damage by increasing antioxidant capacity, promotes anti-inflammatory signaling, improves blood circulation, and ameliorates IRI. Our study is one of the first to examine the effects of ozone on remote organs (liver, lung, and brain) when administered via different routes (intrathecal, intraperitoneal, rectal) in a spinal cord ischemia-reperfusion model.
To determine whether ozone administered by different routes offers multiorgan protection in SCIRI.
Thirty adult Wistar albino rats were randomly divided into five groups (n = 6, each): A control (C group), an IR group, an IR rectal ozone (IRRO) group, an IR intrathecal ozone (IRITO), and an IR intraperitoneal ozone (IRIPO). In the IR groups, the spinal cord IR models (a 30-minute ischemia period was applied to the infrarenal abdominal aorta using an atraumatic vascular clamp, and then a 120-minute reperfusion period was applied by removing the clamp) were applied. An ozone-oxygen mixture of 1 mg/kg (50 μg/mL) was administered by rectal insufflation to the IRRO group, 0.7 mg/kg (50 μg/mL) via the peritoneum to the IRIPO group, and 20 μL (20 μg/mL) intrathecally to the IRITO group 30 minutes before midline laparotomy. At the end of the reperfusion procedure, histopathological and biochemical analyses of liver, lung, and brain tissues were performed.
Liver tissue malondialdehyde (MDA) levels were significantly lower, and catalase (CAT) enzyme activities were significantly higher in the IRRO, IRITO, and IRIPO groups than in the IR group. Histopathologically, we had favorable results from all three ozone applications compared to the IR group. Lung tissue MDA levels were significantly lower, and CAT enzyme activities were significantly higher in the IRITO and IRIPO groups than in the IR group. We had more positive results in the IRRO group than in the IR group, but the difference was not found to be significant. Histopathologically, we obtained significantly more positive results in the IRITO and IRIPO groups compared with the IR group regarding all the criteria we evaluated. Our results in the IRRO group were also positive. Brain tissue MDA levels were significantly lower and CAT enzyme activities significantly higher in the IRITO and IRIPO groups than in the IR group. We had positive results in the IRRO group compared with the IR group. Histopathologically, we obtained significantly more positive results in the IRITO group regarding all the criteria we evaluated.
We observed histopathologically that single-dose ozone pretreatment administered intrathecally, intraperitoneally, or rectally had positive effects on liver, lung, and brain tissues compared to the IR group in an SCIRI model in rats due to its antioxidant effect. The best histopathological results were obtained with intrathecal, intraperitoneal, and rectally administered ozone, in that order, in all three tissues.
Core Tip: Spinal cord ischemia-reperfusion injury (IRI) is a complex process affecting multiple organs. Current preventive strategies remain insufficient. This study investigated the protective effects of single-dose ozone pretreatment via intrathecal, intraperitoneal, and rectal routes on liver, lung, and brain tissues in a rat spinal cord IRI model. Histopathological results demonstrated that ozone pretreatment through all three routes significantly reduced oxidative damage and improved tissue outcomes compared to the IR group. Medical ozone administration may offer a viable therapeutic option with high efficacy and minimal side effects in preventing IRI-related organ damage.