Poly-ADP-ribose polymerase inhibition provides protection against lung injury in a rat paraquat toxicity model.

OBJECTIVES: Paraquat (PQ) is a widely used herbicide. Exposure to PQ at toxic doses can result in fatal acute lung injury. Inhibition of the poly-(ADP-ribose) polymerase (PARP) enzyme alleviates inflammation and necrosis in various pathologies. Here we aimed to evaluate the effects of PARP inhibition on PQ-induced lung damage in a rat experimental model. METHODS: Female Sprague-Dawley rats (n = 24) were allocated into three groups: sham, PQ and PQ + 3-aminobenzamide (3-AB) that is a PARP inhibitor, groups. Experimental lung injury was induced by administration of 15 mg/kg PQ intraperitoneally in PQ and PQ + 3-AB groups. 3-AB (10 mg/kg twice per day) was administered to the PQ + 3-AB group for four consecutive days. The animals were killed on the fifth day following PQ administration. Lung tissue and blood samples were collected and stored until analysis. RESULTS: Serum lactate dehydrogenase (LDH) and neopterin levels, tissue oxidative stress parameters, transforming growth factor-beta1 (TGF-ß) levels and histological injury scores in the PQ + 3-AB group were significantly lower than in the PQ group (P < 0.05, PQ vs. PQ + 3-AB). Total antioxidant capacity in the PQ + 3-AB group was significantly higher than in the PQ group (P < 0.05, PQ + 3-AB vs. PQ). CONCLUSION: Our results suggested that the use of PARP inhibitors following PQ toxicity might be useful for minimizing lung injury due to paraquat toxicity.

Medical ozone therapy reduces shock wave therapy-induced renal injury.

OBJECTIVES: Extracorporeal shock wave (ESW) lithotripsy is the preferred treatment modality for uncomplicated kidney stones. More recently free oxygen radical production following ESW application has been considered to be crucial in shock wave-induced renal damage. It has been shown that ozone therapy (OT) has ameliorative and preventive effects against various pathological conditions due to increased nitro-oxidative stress. In current study, we aimed to evaluate the efficacy of OT against ESW-induced renal injury. METHODS: Twenty-four male Sprague-Dawley rats were divided into three groups: sham-operated, ESW, and ESW + OT groups. All groups except sham-operated group were subjected to ESW procedure. ESW + OT group received 1 mg/kg/day of oxygen/ozone mixture intraperitoneally at 2 h before ESW, and OT was continued once a day for consecutive three days. The animals were killed at the 4th day, and kidney tissue and blood samples were harvested for biochemical and histopathologic analysis. RESULTS: Serum ALT and AST levels, serum neopterin, tissue nitrite/nitrate levels, and tissue oxidative stress parameters were increased in the ESW group and almost came close to control values in the treatment group (p < 0.05, ESW vs. ESW + OT). Histopathological injury scores were significantly lower in treatment group than the ESW group (p < 0.05, ESW vs. ESW + OT). Immunohistochemical iNOS staining scores in ESW group were higher than those of sham-operated group (p < 0.05, ESW vs. sham-operated), iNOS staining scores in OT group were significantly lower than the ESW group (p < 0.05, ESW + OT vs. ESW). CONCLUSION: OT ameliorates nitro-oxidative stress and reduces the severity of pathological changes in the experimental ESW-induced renal injury of rat model.

Myostatin as a Marker for Doxorubicin Induced Cardiac Damage.

PURPOSE: Doxorubicin (DXR) is an effective chemotherapeutic agent but causes severe cardiac failure over known doses. Thus, early detection and prevention of cardiac damage is important. Various markers have been tested for early detection of cardiac damage. Myostatin is a protein produced in skeletal muscle cells inhibits muscle differentiation and growth during myogenesis. METHODS: We evaluated the role of myostatin as a marker for showing DXR induced cardiac damage and compared with well known cardiac markers like NT-proBNP, hs-TnT and CK in a rat model of chronic DXR cardiotoxicity. RESULTS: Myostatin, NT-proBNP, and hs-TnT but not CK rose significantly during DXR treatment. CONCLUSION: Myostatin can be used as an early marker of DXR induced cardiotoxicity.

Evaluation and comparison of the effect of hypothermia and ozone on ischemia-reperfusion injury of skeletal muscle in rats.

BACKGROUND: Tourniquet-induced ischemia-reperfusion, which affects local and distant organs, is very common in orthopedic surgery. Hypothermia is used in traumatic tissue during ischemic period commonly. Ozone (O3) has been recommended as a novel therapeutic agent in various medical conditions. The objective of the study was to evaluate and compare the effect of hypothermia (H) and O3 on ischemia-reperfusion injury of skeletal muscle in rats by measuring oxidative parameters and inducible nitric oxide synthase (iNOS) levels. MATERIALS AND METHODS: Eighteen rats (Wistar albino) were separated into five groups randomly (sham, IR, IR + H, IR + O3, IR + H + O3; n = 6). The lower right extremity of all rats was subjected to 2 h of ischemia and 22 h of reperfusion clamping the common iliac artery and using the rubber-band technique at the level of the lesser trochanter under general anesthesia. Two hours of hypothermia were applied during the first 2 h of reperfusion in two groups. O3 was applied in two groups. All rats were sacrificed after the IR period with high dose of anesthesia. The tibialis anterior muscle and blood were saved. Levels of superoxide dismutase, glutathione peroxidase, MDA, NOx, and interleukin-1ß were measured in the muscle. Creatinine kinase, lactate dehydrogenase, aspartate aminotransferase, urea, creatinine, and electrolytes were measured in serum. Immunohistochemical iNOS staining was performed on muscle samples. RESULTS: The levels of MDA, NOx, and interleukin-1ß in muscle were raised in the IR group compared with those in the sham group. The same parameters were lower in the groups of IR + H, IR + O3, and IR + H + O3 compared with those in the IR group. Superoxide dismutase and glutathione peroxidase activities in muscle were lower in the IR group compared with those in the sham group; however, same parameters were higher in the groups of IR + H, IR + O3, and IR + H + O3 compared with those in the IR group. Score and intensity of iNOS staining in skeletal muscle in the IR group was increased compared with that in the sham group and decreased in the groups of IR + H, IR + O3, and IR + H + O3 compared with that in the IR group. Levels of creatinine kinase, aspartate aminotransferase, and K in the three treatment groups decreased compared with those in the IR group. CONCLUSIONS: These findings showed that hypothermia, which has more affect, and O3 decreased the tourniquet-induced IR injury in the rat's muscle-skeletal system by reducing the levels of oxidative and nitrosative stress parameters and enhancing antioxidant enzymes. Hypothermia and O3 had no synergistic effect. Hypothermic reperfusion and O3 preconditioning might be beneficial in skeletal muscle IR injury-associated tourniquet.

PARP inhibition prevents acetaminophen-induced liver injury and increases survival rate in rats.

BACKGROUND/AIM: Acetaminophen (APAP) overdose results in severe liver damage that may develop into acute liver failure. Recent studies have demonstrated that inhibition of poly(ADP-ribose) polymerase (PARP) decreases tissue necrosis and inflammation. We evaluated the efficacy of 3-aminobenzamide (3-AB), a PARP inhibitor, in a rodent model of APAP-induced hepatotoxicity. MATERIALS AND METHODS: Twenty-four Sprague-Dawley rats were divided equally into 3 experimental groups: sham group, APAP group, and APAP + 3-AB group. In the experimental treatment groups APAP was administered orally at 1 g/kg and, in the APAP + 3-AB group, 3-AB was administered intraperitoneally at a dose of 20 mg/kg exactly 1 h after APAP treatment. Surviving animals were euthanized 48 h after initial APAP administration. Blood samples and liver tissues were collected for histopathological and biochemical analysis. RESULTS: A panel of oxidative stress parameters, as well as serum aspartate aminotransferase, alanine aminotransferase, neopterin, and nitrite/nitrate and histological injury scores, were significantly reduced among the APAP + 3-AB treatment group relative to the group treated with APAP alone (P < 0.05, APAP vs. APAP + 3-AB). CONCLUSION: The present study demonstrates that 3-AB inhibited APAP-induced hepatic injury and reduced neopterin levels. Results of the present study indicate that PARP inhibitors may be an effective adjuvant therapy resulting in improved outcomes in APAP-induced hepatotoxicity.

A new utilization area for hyperbaric oxygen? Improving quality of stored blood.

BACKGROUND/AIM: Since blood bags have the ability for diffusion of gases, we investigated whether hyperbaric oxygen (HBO) exposure affects several vital parameters of stored blood. MATERIALS AND METHODS: Bloods obtained from the same persons were used as both control and HBO groups and stored in pediatric bags with citrate-phosphate-dextrose solution. HBO administration was performed at 2.5 atm for 90 min, started 1 day after blood collection and repeated every 2 days for a total of 10 times. The study was terminated on the 21st day. Complete blood count, glucose, pH, and osmotic fragility values were measured every week. RESULTS: Glucose and pH levels decreased in stored blood. In the HBO-exposed group, these decreases were less than in the control. In addition, mean corpuscular and platelet volumes tended to increase during storing process, but with HBO, these indexes remained lower, near physiologic levels. Another interesting finding of the study was the relative stable osmotic fragility ratio in the HBO group compared to the control blood. CONCLUSION: HBO exposure has positive effects on pH, stability of erythrocytes, and energy source (glucose) of the medium. Thus, we concluded that HBO may be a useful application for life and quality of stored blood.

Efficacy of poly(adenosine diphosphate-ribose) polymerase inhibition in extracorporeal shock wave-induced renal injury.

OBJECTIVES: Extracorporeal shock wave lithotripsy (ESW) induces renal damage by excessive production of free oxygen radicals. Free Oxygen radicals cause cellular injury by inducing nicks in DNA. The enzyme poly(adenosine diphosphate-ribose) polymerase (PARP) involved in the process of repair of DNA in damaged cells. However, its activation in damaged cells can lead to adenosine triphosphate depletion and death. Thus, we designed a study to evaluate the efficacy of 3-aminobenzamide (3-AB), a PARP inhibitor, against extracorporeal shock wave induced renal injury. METHODS: Twenty-four Sprague-Dawley rats were divided into three groups: control, ESW, ESW + 3-AB groups. All groups except control group were subjected to ESW procedure. ESW + 3-AB group received 20 mg/kg/day 3-aminobenzamide intraperitoneally at 2 h before ESW and continued once a day for consecutive 3 days. The surviving animals were sacrificed at the 4th day and their kidneys were harvested for biochemical and histopathologic analysis. Blood samples from animals were also obtained. RESULTS: Serum ALT and AST levels, serum neopterin and tissue oxidative stress parameters were increased in the ESW group and almost came to control values in the treatment group (p < 0.05, ESW vs. ESW + 3-AB). Histopathological injury score were significantly lower in treatment group than the ESW group (p < 0.05, ESW vs. ESW + 3-AB). CONCLUSION: Our data showed that PARP inhibition protected renal tissue against ESW induced renal injury. These findings suggest that it would be possible to improve the outcome of ESW induced renal injury by using PARP inhibitors as a preventive therapy.

Ozone therapy ameliorates paraquat-induced lung injury in rats.

Paraquat (PQ) overdose can cause acute lung injury and death. Ozone therapy (OT) was previously demonstrated to alleviate inflammation and necrosis in various pathologies. We therefore hypothesized that OT has ameliorative and preventive effects on PQ-induced lung damage due to anti-inflammatory and antioxidants properties. Sprague-Dawley rats (n = 24) were separated into three groups: sham, PQ, and PQ+OT groups. 15 mg/kg PQ was administered intraperitoneally in PQ and PQ+OT groups to induce experimental lung injury. One hour after PQ treatment, PQ+OT group was administered a single dose of ozone-oxygen mixture (1 mg/kg/day) by intraperitoneal route for four consecutive days. The animals were sacrificed on fifth day after PQ administration. Blood samples and lung tissues were collected to evaluate the inflammatory processes, antioxidant defense and pulmonary damage. Serum lactate dehydrogenase (LDH) and neopterin levels, tissue oxidative stress parameters, total TGF-ß1 levels, and histological injury scores in PQ+OT group were significantly lower than PQ group (P<0.05, PQ vs. PQ+OT). Total antioxidant capacity in PQ+OT group was significantly higher than PQ group (P < 0.05, PQ+OT vs. PQ). These findings suggest that outcome in PQ-induced lung injury may be improved by using OT as an adjuvant therapy.

Inhibition of inducible nitric oxide synthase prevents shock wave therapy induced renal injury.

OBJECTIVES: Shock wave lithotripsy treatment (SWT) is not completely free from side effects; one of the accused mechanisms for renal injury during SWT is oxygen- and nitrogen-derived free radical productions. Therefore, we aimed to evaluate the effect of inhibition of nitric oxide (NO) production by N-[3(aminomethyl) benzyl) acetamidine] (1400W), highly selective inducible nitric oxide synthase (iNOS) inhibitor, at SWT-induced kidney damage. MATERIALS AND METHODS: Twenty-four rats those underwent right nephrectomy procedure were divided equally into three groups as control, SWT, and SWT + 1400W. 1400W was administered at a dose of 10 mg/kg at 2 h prior to SWT procedure and at the beginning of SWT procedure via intraperitoneal route and continued daily for consecutive 3 days. At the end of the fourth day, animals were killed via decapitation and trunk blood and the left kidneys were taken for biochemical and histopathologic evaluation. RESULTS: SWT caused renal tubular damage and increased lipid peroxidation and antioxidant enzyme activities and SWT also significantly increased nitro-oxidative products. Inhibition of iNOS via administration of 1400W ameliorated renal injury and decreased tissue lipid peroxidation (malondialdehyde), superoxide dismutase, glutathione peroxidase and nitrite/nitrate levels (NOx). In addition, it was seen that histolopathological changes were attenuated in the SWT + 1400W group when compared to SWT group. CONCLUSION: SWT-induced renal injury might be due to excessive production of oxygen free radicals and NO production. Inhibition of iNOS attenuates renal injury following SWT treatment. It can be concluded that iNOS inhibitors or peroxynitrite scavengers might be used to protect the kidneys against SWT-induced morphological and functional injuries.

Beneficial effects of Etanercept on experimental necrotizing enterocolitis.

PURPOSE: Tissue damage in necrotizing enterocolitis (NEC) of infants occurs as a result of an uncontrolled inflammatory response. The aim of this study was to investigate any potential anti-inflammatory effects that Etanercept may have on the inflammatory response in an experimental NEC model in newborn rats. METHODS: Newborn pups were randomized into three groups immediately after birth (Control, NEC + Placebo and NEC + Etanercept). Pups in the NEC + Placebo and NEC + Etanercept groups were subjected to an NEC-inducing protocol (hypercarbia, hypothermia and hyperoxia) twice a day for 3 days. Pups in the NEC + Etanercept group were given an intraperitoneal injection of Etanercept. Rats were harvested for biochemical and histopathological examinations. RESULTS: The histopathological injury score of rats in the NEC + Placebo group was significantly higher compared to the NEC + Etanercept and Control groups (p < 0.05 for both comparisons). Tissue levels of tumor necrosis factor-α, interleukin-1ß, and malondialdehyde were higher in the placebo group compared to the Etanercept group. CONCLUSION: Our results suggest that Etanercept attenuates intestinal tissue damage in NEC by reducing inflammation and blocking the production of free-oxygen radicals, while also reducing tissue levels of tumor necrosis factor-α and interleukin-1ß.

Ozonated olive oils and the troubles.

One of the commonly used methods for ozone therapy is ozonated oils. Most prominent type of used oils is extra virgin olive oil. But still, each type of unsaturated oils may be used for ozonation. There are a lot of wrong knowledge on the internet about ozonated oils and its use as well. Just like other ozone therapy studies, also the studies about ozone oils are inadequate to avoid incorrect knowledge. Current data about ozone oil and its benefits are produced by supplier who oversees financial interests and make misinformation. Despite the rapidly increasing ozone oil sales through the internet, its quality and efficacy is still controversial. Dozens of companies and web sites may be easily found to buy ozonated oil. But, very few of these products are reliable, and contain sufficiently ozonated oil. This article aimed to introduce the troubles about ozonated oils and so to inform ozonated oil users.

The protective effect of melatonin and S-methylisothiourea treatments in nitrogen mustard induced lung toxicity in rats.

OBJECTIVES: Mustard is highly toxic to the lung. Its toxic effects are associated with inflammatory cell accumulation and increased pro-inflammatory cytokines as well as reactive oxygen and nitrogen species. In this study, we aimed to investigate the efficiency of melatonin (MEL) and S-methylisothiourea (SMT) on mechlorethamine (MEC) induced lung toxicity. METHODS: Thirty-six male rats were randomly divided into four groups: control, MEC, MEC+MEL, and MEC+SMT. Control group was given saline only via transdermal route. Other groups were exposured to a single dose of MEC (3.5 mg/kg) via transdermal route. MEL (100 mg/kg) was administered intraperitoneally 30 min after the application of MEC, and after the same dose of MEL was given every 12 h for a total of six doses. SMT (50 mg/kg) was also given intraperitoneally 30 min after the application of MEC. RESULTS: MEC injection resulted in alveolar epithelial injury, hemorrhage, inflammation, edema and interalveolar septal thickening in the lung tissues. The tissue TNF-α, IL-1ß, and nitrate/nitrite (NOx) levels were found significantly different for all groups (p<0.001). TNF-α and IL-1ß levels increased significantly with MEC exposure, and MEL and SMT ameliorated these increases in lung tissues. MEC also elevated NOx levels in lung tissue. Melatonin showed meaningful protection against lung injury. But protection of SMT was weaker. CONCLUSION: Inflammation plays an important role in the MEC induced lung toxicity as well as oxidative and nitrosative stress. Melatonin has also anti-inflammatory properties similar to SMT, as well as anti-oxidant properties. But melatonin treatment was found more efficient than SMT treatment.

All-trans-retinoic acid attenuates intestinal injury in a neonatal rat model of necrotizing enterocolitis.

BACKGROUND: Ischemia/reperfusion-induced intestinal injury is mediated by reactive oxygen species and inflammatory mediators. OBJECTIVES: This study was designed to evaluate whether all-trans-retinoic acid (ATRA) administration can attenuate intestinal injury and to analyze the antioxidant and anti-inflammatory effects of ATRA in a neonatal rat model of necrotizing enterocolitis (NEC). METHODS: Twenty-nine Wistar albino rat pups were randomly divided into 3 groups: group 1 = control, group 2 = NEC and saline, and group 3 = NEC and ATRA treatment. NEC was induced by hyperosmolar enteral formula feeding and exposure to hypoxia after cold stress at +4°C and oxygen. Pups in group 3 were injected intraperitoneally with ATRA (0.5 mg/kg body weight) once a day prior to each NEC procedure, beginning on postnatal day 1 and daily through postnatal day 4. The pups were killed on the 4th day and their intestinal tissues were harvested for biochemical and histopathological analysis. RESULTS: Mucosal injury scores and intestinal malondialdehyde levels in group 2 were found to be significantly higher than other groups (p < 0.05). Intestinal superoxide dismutase and glutathione peroxidase activities in group 3 were significantly higher than group 2 (p = 0.04 and p = 0.04, respectively). Intestinal tissue tumor necrosis factor-α levels were significantly reduced with ATRA treatment in group 3 compared to group 2 (p < 0.001). CONCLUSIONS: It is likely that oxidative stress and inflammatory mediators contributed to the pathogenesis of NEC and that ATRA had a protective effect on intestinal injury through its anti-inflammatory and antioxidant properties.

Protective effects of colchicine in an experimental model of necrotizing enterocolitis in neonatal rats.

BACKGROUND: The pathophysiology of necrotizing enterocolitis (NEC) includes the massive production of endogenous cytokines with exaggerated activation of inflammatory pathways. Colchicine has been used as an anti-inflammatory agent. The aim of this study was to investigate the possible beneficial effects of colchicine in a neonatal rat model of NEC. MATERIALS AND METHODS: We randomly divided rat pups into three groups: a control group, a saline-treated NEC group, and a colchicine-treated NEC group. We induced NEC by hyperosmolar enteral formula feeding and exposure to hypoxia/reoxygenation after cold stress. Intestinal samples were harvested for biochemical and histopathologic analyses. RESULTS: The grade of intestinal injury of pups in the saline-treated NEC group was significantly higher than in the control and colchicine-treated groups (P < 0.001 and 0.003, respectively). The median level of intestinal malondialdehyde was significantly higher in the saline-treated NEC group compared with the control group (P = 0.006) or the colchicine-treated NEC group (P = 0.015). We observed significantly higher activity levels of intestinal superoxide dismutase and glutathione peroxidase in the colchicine-treated NEC group compared with the saline-treated NEC group (P = 0.033 and 0.030, respectively). The tissue levels of tumor necrosis factor-α and interleukin-1ß were significantly higher in the saline-treated NEC group compared with the colchicine-treated NEC group (P < 0.001 and 0.003, respectively). CONCLUSIONS: We observed that in this model of NEC, colchicine had favorable effects on intestinal histologic and biochemical changes.

Effects of maternal smoking on fetal organs.

BACKGROUND: Unfavorable effects of in-utero smoke exposure have been shown in several studies. OBJECTIVES: In this experimental study, the authors aimed at showing detrimental effects of cigarette smoke on fetal tissues by assessing apoptosis that is detected by performing TUNEL staining. MATERIAL AND METHODS: Designed groups were smoke exposed rats before and during pregnancy and control groups. Rat offsprings were sacrificed when they were 12 days old. RESULTS: Lung, kidney, adrenal and gonad tissues were harvested for histopathologic analysis and assessed by TUNEL (Terminal dUTP Nick End Labeling) staining. CONCLUSIONS: Smoke exposure caused increased apoptotic activity in lung parenchyma of study groups.

Antioxidant effects of N-acetylcysteine in a neonatal rat model of necrotizing enterocolitis.

BACKGROUND/PURPOSE: Hypoxia and ischemia appear to play an important role in the pathogenesis of necrotizing enterocolitis (NEC), which may be related to oxygen-derived free radical formation. This study was designed to evaluate the role of oxidative stress and potentially beneficial effects of N-acetylcysteine (NAC) in a neonatal rat model of NEC. METHODS: Thirty Wistar albino rat pups were randomly divided into 3 groups: group 1, control; group 2, NEC and saline; and group 3, NEC and NAC treatment. Necrotizing enterocolitis was induced by hyperosmolar enteral formula feeding and exposure to hypoxia after cold stress at 4°C and oxygen. The pups were killed on the fourth day, and their intestinal tissues were harvested for biochemical and histopathologic analysis. RESULTS: Mucosal injury scores and intestinal malondialdehyde levels in group 2 were found to be significantly higher than that in other groups (P ≤ .05). Intestinal superoxide dismutase activities in group 3 were significantly higher than that in group 2 (P = .018). Intestinal tissue tumor necrosis factor α levels were significantly reduced with NAC treatment in group 3 compared with group 2 (P < .003). CONCLUSIONS: It is likely that oxidative stress and inflammatory mediators contribute to the pathogenesis of NEC and that NAC has a protective effect on intestinal injury through its antiinflammatory and antioxidant properties.

Colchicine protects against hyperoxic lung injury in neonatal rats.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is characterized by inflammation, fibrosis and mucosal necrosis, which leads to emphysematous coalescence of alveoli. OBJECTIVE: We tested whether prophylaxis with colchicine , an anti-inflammatory, antioxidant and antifibrotic drug, would decrease the severity of lung injury in an animal model of BPD. METHODS: Twenty-five rat pups were divided into three groups: control (n = 8), hyperoxia (n = 7), and hyperoxia + colchicine (n = 10). The hyperoxia groups were exposed to >95% oxygen from day 1 to 10 of life. On day 10, the animals were sacrificed and the lungs were processed for histology and biochemical analysis. Lung morphology was assessed by the mean linear intercept (MLI), a measure of alveolar size. The degree of lung inflammation and antioxidant capacity were assessed by quantifying lung homogenate tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels. RESULTS: Colchicine significantly decreased lung damage as determined by the MLI in the hyperoxia groups (p < 0.01). The median level of lung MDA was significantly higher in the hyperoxia group compared with the control group (p < 0.05) and the colchicine-treated group (p < 0.05). Lung homogenate SOD and GSH-Px activities in the colchicine-treated group were significantly higher than in the hyperoxia group (p < 0.05). Furthermore, colchicine-treated pups had lower lung homogenate TNF-α and IL-1ß levels compared with the hyperoxia group (p < 0.05). CONCLUSIONS: Colchicine has favorable effects on alveolarization as well as inflammation and oxidative stress markers in an animal model of BPD.

Medical ozone therapy decreases postoperative uterine adhesion formation in rats.

PURPOSE: Various studies have been performed to find out novel treatment strategies to prevent postoperative adhesion formation. Ozone therapy (OT) is shown to reduce inflammation in several pathological conditions. Therefore, we aimed to evaluate the efficacy of OT in a rat model of experimental uterine adhesion (EUA). METHODS: Thirty female Wistar rats (200-250 g) were divided into three groups: sham, EUA and EUA+OT. EUA and EUA+OT groups were subjected to the postoperative adhesion procedure by bipolar coagulation on the uterine horns and corresponding pelvic sidewall parietal peritoneum. EUA+OT group received 0.7 mg/kg daily single dose for 3 days of ozone/oxygen mixture intraperitoneally after adhesion induction. All animals were killed on the 7th day and uterine adhesions were scored. Uterine tissues and peritoneal washing fluid were harvested for all analyses. RESULTS: Uterine malondialdehyde levels in the EUA group were significantly higher compared to the other groups. However, in the EUA group, uterine superoxide dismutase and glutathione peroxidase activities were lower than in other groups. Peritoneal fluid TNF-α levels were found to be significantly different for all groups (p < 0.001). Macroscopic total adhesion score was significantly higher in the EUA group compared to the other groups (p < 0.001). But, total score in the EUA+OT group was lower than in the EUA group (p = 0.006). CONCLUSIONS: Medical OT prevents postoperative uterine adhesions by modulating TNF-α levels and oxidative/antioxidative status in an experimental uterine adhesion model.

The effects of medical ozone therapy on renal ischemia/reperfusion injury.

INTRODUCTION: This study was designed to investigate the possible beneficial effects of medical ozone therapy (OT), known as an immunomodulator and antioxidant, on the renal function, morphology, and biochemical parameters of oxidative stress in kidneys subjected to ischemia/reperfusion injury (IRI). MATERIALS AND METHODS: Thirty male Sprague-Dawley rats were classified into three groups: control, renal IRI, and renal IRI + OT. The IRI group was induced by bilateral renal ischemia for 60 min, followed by reperfusion for 6 h. After reperfusion, the kidneys and blood of rats were obtained for histopathologic and biochemical evaluation. RESULTS: Renal IRI increased the tissue oxidative stress parameters (lipid peroxidation, protein oxidation, and nitrite plus nitrate) and decreased the antioxidant enzyme activities (superoxide dismutase and glutathione peroxidase). The serum neopterin levels showed correlation with oxidative stress parameters. All these parameters were brought to control values in the treatment group. Histopathologically, the kidney injury in the treatment group was significantly lesser than in the renal IRI group. CONCLUSIONS: Our results clearly showed that OT has beneficial effect to protect kidney against IRI. The serum neopterin levels might be used as a marker to detect the degree of renal IRI.

The protective effects of ozone therapy in a rat model of acetaminophen-induced liver injury.

OBJECTIVES: Acetaminophen (APAP) overdose may cause acute liver injury. Ozone therapy (OT) is shown to reduce inflammation and necrosis in several entities. Thus, we have designed this study to evaluate the efficacy of OT in a rat model of APAP-induced liver injury. METHODS: Twenty-seven Sprague-Dawley rats were divided into three groups: sham, APAP and APAP+OT groups. In the APAP and the APAP+OT groups, liver injury was induced by oral administration of 1 g/kg APAP. The APAP+OT group received a single dose ozone/oxygen mixture (0.7 mg/kg) intraperitoneally 1h after APAP administration. All animals were killed at 24 hour after APAP administration. Blood samples and liver tissues were harvested to determine liver injury and oxidative stress parameters. Liver tissues and blood samples were obtained for biochemical and histopathological analyses. RESULTS: APAP administration caused necrosis in the liver after 24h. The degrees of liver necrosis of the APAP group were higher than the other groups (in both p<0.05, respectively). In the APAP+OT group, liver antioxidant enzymes activities were significantly higher than the APAP group (p<0.05), but were lower than the sham group (p<0.05). In the sham group, serum neopterin, a marker of cell-mediated immunity, concentrations (4.8±1.2 nmol/L) were lower than the APAP (14.7±1.4 nmol/L) and APAP+OT groups (7.5±2.4 nmol/L) (in both p<0.05, respectively). CONCLUSION: Our results showed that OT prevented liver necrosis in rats and reduced neopterin levels. These findings suggest that the use of OT as an adjuvant therapy which might improve the outcome in APAP induced liver injury.