Background and Objectives: Sepsis and its related complications are associated with high morbidity and mortality, often leading to liver damage. Ozone, a molecule with anti-inflammatory and antioxidant properties, may offer protective effects. This study aimed to evaluate the therapeutic and protective impact of ozone on liver injury in a rat model of sepsis induced by cecal ligation and perforation (CLP). Material and Methods: A total of 36 rats were randomly divided into five groups: control (Group C), ozone (Group O), cecal ligation and perforation (Group CLP), ozone + cecal ligation and perforation (Group O+CLP), and cecal ligation and perforation + ozone (Group CLP+O). In the ozone groups, 4 mL of ozone (20 µ/mL) was injected intraperitoneally. Biochemical and histopathological parameters were evaluated in liver tissue samples obtained at the end of 24 h. Results: Polymorphonuclear leukocyte and monocyte infiltration and the total injury score were significantly reduced in the ozone-treated groups compared to the CLP group (p < 0.001). Tumor necrosis factor and interleukin 10 levels in the rat liver tissue were significantly reduced in the O+CLP and CLP+O groups compared to the CLP group, with the O+CLP group showing a more substantial decrease than the CLP+O group (p < 0.001). Thiobarbituric acid reactive substances and glutathione s-transferase levels were significantly lower in the ozone-treated groups compared to the CLP group (p < 0.001). Catalase activity was significantly elevated in the O+CLP group compared to the CLP group (p < 0.001). Serum aspartate transaminase, alanine transaminase, gamma-glutamyl transferase, and total bilirubin were significantly increased in the CLP group and decreased in the ozone-treated groups (p < 0.001, p < 0.001, p = 0.01, p < 0.001 respectively). Conclusions: Administering ozone to rats one hour before the CLP significantly mitigated liver damage, showing a more pronounced effect compared to administering ozone one hour after CLP. The results indicate that ozone could serve a protective function in managing sepsis-induced liver damage.

Background and Objectives: Lower-extremity ischemia–reperfusion injury can induce distant organ ischemia, and patients with diabetes are particularly susceptible to ischemia–reperfusion injury. Sevoflurane, a widely used halogenated inhalation anesthetic, and fullerenol C60, a potent antioxidant, were investigated for their effects on heart and lung tissues in lower-extremity ischemia–reperfusion injury in streptozotocin (STZ)-induced diabetic mice. Materials and Methods: A total of 41 mice were divided into six groups: control (n = 6), diabetes–control (n = 7), diabetes–ischemia (n = 7), diabetes–ischemia–fullerenol C60 (n = 7), diabetes–ischemia–sevoflurane (n = 7), and diabetes–ischemia–fullerenol C60–sevoflurane (n = 7). Diabetes was induced in mice using a single intraperitoneal dose of 55 mg/kg STZ in all groups except for the control group. Mice in the control and diabetes–control groups underwent midline laparotomy and were sacrificed after 120 min. The DIR group underwent 120 min of lower-extremity ischemia followed by 120 min of reperfusion. In the DIR-F group, mice received 100 μg/kg fullerenol C60 intraperitoneally 30 min before IR. In the DIR-S group, sevoflurane and oxygen were administered during the IR procedure. In the DIR-FS group, fullerenol C60 and sevoflurane were administered. Biochemical and histological evaluations were performed on collected heart and lung tissues. Results: Histological examination of heart tissues showed significantly higher necrosis, polymorphonuclear leukocyte infiltration, edema, and total damage scores in the DIR group compared to controls. These effects were attenuated in fullerenol-treated groups. Lung tissue examination revealed more alveolar wall edema, hemorrhage, vascular congestion, polymorphonuclear leukocyte infiltration, and higher total damage scores in the DIR group compared to controls, with reduced injury parameters in the fullerenol-treated groups. Biochemical analyses indicated significantly higher total oxidative stress, oxidative stress index, and paraoxonase-1 levels in the DIR group compared to the control and diabetic groups. These levels were lower in the fullerenol-treated groups. Conclusions: Distant organ damage in the lung and heart tissues due to lower-extremity ischemia–reperfusion injury can be significantly reduced by fullerenol C60.

Objective: Lower extremity ischemia-reperfusion injury (IRI) may occur with trauma-related vascular injury and various vascular diseases, during the use of a tourniquet, in temporary clamping of the aorta in aortic surgery, or following acute or bilateral acute femoral artery occlusion. Mitochondrial dysfunction and increased basal oxidative stress in diabetes may cause an increase in the effects of increased reactive oxygen species (ROS) and mitochondrial dysfunction due to IRI. It is of great importance to examine therapeutic approaches that can minimize the effects of IRI, especially for patient groups under chronic oxidative stress such as DM. Cerium oxide (CeO₂) nanoparticles mimic antioxidant enzymes and act as a catalyst that scavenges ROS. In this study, it was aimed to investigate whether CeO₂ has protective effects on skeletal muscles in lower extremity IRI in mice with streptozocin-induced diabetes. Methods: A total of 38 Swiss albino mice were divided into six groups as follows: control group (group C, n = 6), diabetes group (group D, n = 8), diabetes–CeO₂ (group DCO, n = 8), diabetes–ischemia/reperfusion (group DIR, n = 8), and diabetes–ischemia/reperfusion–CeO₂ (group DIRCO, n = 8). The DCO and DIRCO groups were given doses of CeO₂ of 0.5 mg/kg intraperitoneally 30 min before the IR procedure. A 120 min ischemia–120 min reperfusion period with 100% O₂ was performed. At the end of the reperfusion period, muscle tissues were removed for histopathological and biochemical examinations. Results: Total antioxidant status (TAS) levels were found to be significantly lower in group DIR compared with group D (p = 0.047 and p = 0.022, respectively). In group DIRCO, total oxidant status (TOS) levels were found to be significantly higher than in group DIR (p < 0.001). The oxidative stress index (OSI) was found to be significantly lower in group DIR compared with group DCO (p < 0.001). Paraoxanase (PON) enzyme activity was found to be significantly increased in group DIR compared with group DCO (p < 0.001). The disorganization and degeneration score for muscle cells, inflammatory cell infiltration score, and total injury score in group DIRCO were found to be significantly lower than in group DIR (p = 0.002, p = 0.034, and p = 0.001, respectively). Conclusions: Our results confirm that CeO₂, with its antioxidative properties, reduces skeletal muscle damage in lower extremity IRI in diabetic mice.

Objective: Lower extremity ischemia-reperfusion injury (IRI) may occur with trauma-related vascular injury and various vascular diseases, during the use of a tourniquet, temporary clamping of the aorta in aortic surgery, and acute or bilateral acute femoral artery occlusion. Mitochondrial dysfunction and increased basal oxidative stress in diabetes may cause an increase in the effects of increased reactive oxygen species (ROS) and mitochondrial dysfunction due to IRI. It is of great importance to examine therapeutic approaches that can minimize the effects of IRI, especially for patient groups under chronic oxidative stress. Cerium oxide (CeO2) nanoparticles mimic the antioxidant enzymes and act as a catalyst that scavenges ROS. In this study, it was aimed to investigate whether CeO2 has protective effects on skeletal muscles in lower extremity IRI in mice with streptozocin-induced diabetes. Methods: A total of 38 Swiss albino mice were divided into six groups as follows: control group (group C, n=6), diabetes group (group D, n=8), diabetes-CeO2 (group DCO, n=8), diabetes-ischemia/reperfusion (group DIR, n=8), and diabetes-ischemia/reperfusion-CeO2 (group DIRCO, n=8). DCO and DIRCO groups were given doses of CeO2 0.5mg/kg intraperitoneally 30 minutes before the IR procedure. A 120-minute ischemia-120-minute reperfusion period with 100% O2 was performed. At the end of the reperfusion period, muscle tissues were removed for histopathological and biochemical examinations. Results: Total antioxidant status (TAS) levels were found to be significantly lower in group DIR compared with group D (p=0.047 and p=0.022, respectively). In group DIRCO and total oxidant status (TOS) levels were found to be significantly higher than in group DIR (p

Topiramate (TPM), a carbonic anhydrase (CA) inhibitor, is known for its anti-obesity effect. Even though, nonalcoholic fatty liver disease (NAFLD) is present in 80% of obese patients, TPM's effects on oxidant-antioxidant parameters and CA activity on fatty liver is not known. 24 Wistar albino rats were divided into four groups: control, TPM, diet, and diet + TPM. Diet groups fed with high-fat diet while control and TPM groups received standard chow for six weeks. Than 100 mg/kg/day TPM (po) was added to TPM groups for 21 days. Rats' weight and blood glucose levels were monitored weekly, and at the end of the study liver removed for biochemical and histological analysis. TPM eliminated the increases in weight and blood glucose levels caused by high-fat diet. TPM decreased CA activity in all groups. MDA levels increased significantly in TPM and DT groups (p = 0.004; p = 0.008). GSH levels were decreased in the TPM, D and DT groups (p = 0.004; p = 0.015; p = 0.003). Similarly, GPx activity levels were significantly decreased in all groups. Histological evaluation revealed notable infiltration, eosinophilia and cytoplasmic vacuolization in the TPM group. Steatosis and NAFLD activity score (NAS) were higher in the diet group. Ballooning, infiltration and NAS were higher in the diet + TPM group compared to control. CA activity negatively correlated with MDA (p < 0.001), and positively correlated with GSH (p < 0.001). TPM caused oxidant stress and liver damage, which are exacerbated in NAFLD induced rats. Therefore, use of TPM in patients with liver disease should be considered very carefully.