Rutin ameliorates methotrexate induced hepatic injury in rats.

PURPOSE: To investigate the possible protective effect of rutin on methotrexate induced hepatotoxicity in rats. METHODS: Twenty-two rats were divided into three experimental groups; Control-saline, Mtx, Mtx+Rutin. Hepatic tissue was taken for histological assessment and biochemical assays. Oxidative stress parameters malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were investigated. Liver markers aspartate aminotransferase (AST), alanine aminotransferase (ALT) were analyzed in serum. RESULTS: Mtx+Rutin group showed lower histological injury compared to Mtx group, MDA and ALT levels were increased, while SOD and GSH-Px were decreased in Mtx group compared with Control-saline group. MDA and ALT levels were increased, while SOD and GSH-Px were decreased in Mtx group, compared with Mtx +Rutin group. Serum AST levels were similar among the groups. CONCLUSION: Rutin may be a potential adjuvant drug to reduce the hepatic side effects observed during Mtx therapy for various clinical conditions.

Rutin ameliorates methotrexate induced hepatic injury in rats

PURPOSE: To investigate the possible protective effect of rutin on methotrexate induced hepatotoxicity in rats. METHODS: Twenty-two rats were divided into three experimental groups; Control-saline, Mtx, Mtx+Rutin. Hepatic tissue was taken for histological assessment and biochemical assays. Oxidative stress parameters malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were investigated. Liver markers aspartate aminotransferase (AST), alanine aminotransferase (ALT) were analyzed in serum. RESULTS: Mtx+Rutin group showed lower histological injury compared to Mtx group, MDA and ALT levels were increased, while SOD and GSH-Px were decreased in Mtx group compared with Control-saline group. MDA and ALT levels were increased, while SOD and GSH-Px were decreased in Mtx group, compared with Mtx +Rutin group. Serum AST levels were similar among the groups. CONCLUSION: Rutin may be a potential adjuvant drug to reduce the hepatic side effects observed during Mtx therapy for various clinical conditions.

Effects of Hyperbaric Oxygen and Preconditioning on Wound Healing in Colonic Anastomoses.

AIM: The purpose of this study was to evaluate the effects of hyperbaric oxygen (HBO) and HBO preconditioning (pre-HBO) on experimental wound healing and tensile strength in the colonic anastomosis of rats. MATERIALS AND METHODS: A total of 21 Sprague-Dawley rats were divided into three random groups of equal numbers: sham operation, pre-HBO, and HBO. Sham group was given standard left colon resection and end-to-end anastomosis; pre-HBO group received HBO as one dose + colonic resection + anastomosis; HBO group was given colonic resection + anastomosis + HBO. HBO was administrated at 24-hr intervals and relaparatomy was performed on the fifth day. Malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), interleukin (IL)-10, IL-6, tumor necrosis factor-alpha (TNF-α), and hydroxy (OH)-proline levels and anastomotic burst pressure were evaluated. RESULTS: Burst pressure and OH-proline levels markedly increased in the HBO group compared with the sham and pre-HBO groups. When compared with the sham group, MDA and MPO levels were significantly decreased in the HBO and pre-HBO groups. In contrast to these findings, SOD and GSH-Px levels were increased in the HBO group as compared with the sham and pre-HBO groups. TNF-α, IL-6, and IL-10 values were detected at low levels in the HBO group as compared with other groups. CONCLUSIONS: HBO administration accelerated wound healing and strengthened the anastomotic tissue. In the light of these results, the HBO administration has beneficial effects and contributed to wound healing in colonic anastomosis. But, as expected, pre-HBO did not alter the results significantly.

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.

Effectiveness of hyperbaric oxygen and ozone applications in tissue healing in generated soft tissue trauma model in rats: an experimental study.

BACKGROUND: Soft tissue trauma is a type of acute traumatic ischemia. We investigated in this study whether the edema, inflammation and ischemia caused by the trauma could be affected positively by hyperbaric oxygen (HBO) and ozone therapy. METHODS: Soft tissue trauma was generated in a total of 63 adult male Sprague-Dawley rats. Subsequently, rats were divided into three groups. The first group was treated with ozone, the second group with HBO, and the third group served as controls. Tissue and blood samples were taken at the end of the procedures. Tissue lipid peroxidation (LPO), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), inducible nitric oxide synthase (iNOS), heme oxygenase (HO)-1, and hypoxia-inducible factor (HIF)-1 levels were detected. Hematoxylin-eosin staining was used to determine the inflammation and edema histopathologically. RESULTS: We also detected HIF-1 activity, which decreases when the oxygen concentration increases, HO-1 activity, which has anti-inflammatory effects, and iNOS activity, which releases in any type of acute case. We determined a statistically significant reduction in iNOS and LPO levels in both the HBO and Ozone groups. A significant decrease in inflammation was detected in both the Ozone and HBO groups compared with the Control group, and a significant decrease in edema was detected in all three groups. CONCLUSION: We think that HBO and Ozone therapy have beneficial effects on biochemical and histopathological findings. Related clinical trials will be helpful in clarifying the effects.

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.

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.

Inhibition of iNOS reduces the therapeutic effects of ozone in acute necrotizing pancreatitis: an in vivo animal study.

OBJECTIVE: Previously, it was shown that ozone and S-methylthiourea (SMT) treatments had ameliorative effects on experimental models of acute necrotizing pancreatitis (ANP). It is possible that the combination of ozone and SMT may be more effective than either therapy. Therefore, we investigated the efficacy of combination therapy with ozone and SMT in an experimental rat model of ANP. MATERIAL AND METHODS: Sprague-Dawley rats were divided into five experimental groups. Groups were designed as Sham-operated, ANP, ANP + Ozone, ANP + SMT and ANP + Ozone + SMT. A model of ANP was induced by injection of sodium taurocholate into the common biliopancreatic duct. Four days after induction, blood and tissue samples were obtained for biochemical, microbiological and histopathological analysis. RESULTS: Survival rates, serum amylase, lipase and neopterin levels, tissue oxidative stress parameters, bacterial translocation and tissue injury scores were better in the ozone and SMT groups than in the ANP group. There was no bacterial translocation in the ozone-treated groups. Tissue injury scores in the ozone group were better compared to all ANP induced groups. Ozone and SMT treatment in combination did not have better biochemical, microbiological and histological data compared to ozone or SMT treatments separately in experimental ANP. CONCLUSIONS: The combination of ozone and SMT did not provide any therapeutic advantage in ANP possibly because SMT inhibited nitric oxide synthesis which was needed for ozone action.

Long-term exposure to repetitive hyperbaric oxygen results in cumulative oxidative stress in rat lung tissue.

CONTEXT: Despite its known benefits, hyperbaric oxygen (HBO) is also reported to enhance the production of reactive oxygen species and can cause oxidative stress in several tissues. Previous studies had shown that HBO-induced oxidative stress is directly proportional to both its exposure pressure and duration. Nevertheless, these studies were usually performed with single-session HBO exposure but its clinical use commonly depends on long-term exposure periods. OBJECTIVE: To clarify the oxidative effect of long-term repetitive HBO in the lung tissue of rats. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into six study groups exposed to consecutive HBO sessions (2.8 atm/90 min) for 5, 10, 15, 20, 30, and 40 days. Animals were sacrificed 24 h after the last HBO session. An additional control group was set to obtain normal data. Lung malondialdehyde (MDA) and carbonylated protein (PCC) levels were determined as measures of oxidative stress along with the activities of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase. RESULTS: None of the measured parameters showed any changes among the groups exposed to 5-15 HBO sessions. However, MDA, PCC, and SOD were found to be significantly increased in the 20 to 40 session groups. DISCUSSION AND CONCLUSION: These results indicate that repetitive treatment with HBO may cause oxidative stress in critical tissues including the lung. Although HBO-mediated free radicals are accepted to be responsible for the benefits of this therapeutic modality, especially in cases with prolonged exposure, possible injurious effects of supranormal values of bio-oxidative products need to be considered.

Ozone therapy and hyperbaric oxygen treatment in lung injury in septic rats.

Various therapeutic protocols were used for the management of sepsis including hyperbaric oxygen (HBO) therapy. It has been shown that ozone therapy (OT) reduced inflammation in several entities and exhibits some similarity with HBO in regard to mechanisms of action. We designed a study to evaluate the efficacy of OT in an experimental rat model of sepsis to compare with HBO. Male Wistar rats were divided into sham, sepsis+cefepime, sepsis+cefepime+HBO, and sepsis+cefepime+OT groups. Sepsis was induced by an intraperitoneal injection of Escherichia coli; HBO was administered twice daily; OT was set as intraperitoneal injections once a day. The treatments were continued for 5 days after the induction of sepsis. At the end of experiment, the lung tissues and blood samples were harvested for biochemical and histological analysis. Myeloperoxidase activities and oxidative stress parameters, and serum proinflammatory cytokine levels, IL-1ß and TNF-α, were found to be ameliorated by the adjuvant use of HBO and OT in the lung tissue when compared with the antibiotherapy only group. Histologic evaluation of the lung tissue samples confirmed the biochemical outcome. Our data presented that both HBO and OT reduced inflammation and injury in the septic rats' lungs; a greater benefit was obtained for OT. The current study demonstrated that the administration of OT as well as HBO as adjuvant therapy may support antibiotherapy in protecting the lung against septic injury. HBO and OT reduced tissue oxidative stress, regulated the systemic inflammatory response, and abated cellular infiltration to the lung demonstrated by findings of MPO activity and histopathologic examination. These findings indicated that OT tended to be more effective than HBO, in particular regarding serum IL-1ß, lung GSH-Px and histologic outcome.

Effect of preconditioned hyperbaric oxygen and ozone on ischemia-reperfusion induced tourniquet in skeletal bone of rats.

BACKGROUND: The aim of the study was to investigate effect of I/R injury on bone tissue and protective role of hyperbaric oxygen precondition (HBO-PC) and ozone precondition (O(3)-PC) on I/R injury by using biochemical analysis. MATERIALS AND METHODS: Thirty-two rats were included in study. The animals were divided into four equal groups: sham operation, I/R, I/R+HBO and I/R+O(3). One session of 60 min, 3 ATA, 3-4 L/min, 100% oxygenation was defined as one dose of HBO. First dose of HBO was administrated 72 h before ischemia. Subsequent, one-dose of HBO administrated per 12 hours until ischemia time (total seven doses); 0.7 mg/kg ozone/oxygen mixture intraperitoneally was defined as one dose of ozone. First dose of O(3) was administered 72 h before ischemia (total four doses). I/R model was induced in anesthetized rats by unilateral (right) femoral artery clipping for 2 h followed by 22 h of reperfusion. The right tibia and were harvested. Tissue was assayed for levels of malondialdehyde (MDA) and protein carbonyl (PCO), activities of superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). RESULTS: MDA and PCO levels were increased in I/R group. SOD activity was increased; GSH-Px activity was decreased in I/R group. MDA and PCO levels were decreased, SOD and GSH-Px activities were increased in both HBO+I/R and O(3)+I/R groups. CONCLUSION: It has been shown that levels of MDA and PCO in bone were increased followed by 2 h of ischemia and 22 h of reperfusion period. Ozone-PC and HBO-PC has protective effect against skeletal bone I/R injury by decreasing levels of MDA and PCO, increasing activities of SOD and GSH-Px in rats.

The efficacy of ozone therapy in experimental caustic esophageal burn.

INTRODUCTION: Ozone has been proposed as an antioxidant enzyme activator, immunomodulator and cellular metabolic activator. This study was designed to investigate the efficacy of ozone therapy in the prevention of esophageal damage and stricture formation developed after esophageal caustic injuries in the rat. MATERIALS AND METHODS: Forty-five rats were allocated into three groups; sham-operated, un-treatment and treatment groups. Caustic esophageal burn was created by instilling 15% NaOH in the distal esophagus. The rats were left untreated or treated with 1 mg/kg/day ozone intraperitoneally. All rats were sacrificed at 28 days. Efficacy of the treatment was assessed by measuring the stenosis index (SI) and histopathologic damage score, and biochemically by determining tissue hydroxyproline content (HP), superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA) and protein carbonyl content (PCC) in esophageal homogenates. RESULTS: Whereas seven (47%) rats died in the un-treatment group, all rats in the sham-operated and the treatment group survived during the study. SI, the histopathologic damage score, was significantly lower in the ozone-therapy group than the un-treatment group. HP levels were significantly higher in the un-treatment group than the group treated with ozone. Caustic esophageal burn increased MDA and PCC levels and also decreased SOD and GPx enzyme activities. In contrast, ozone therapy decreased the elevated MDA and PCC levels and also increased the reduced SOD and GPx enzyme activities. CONCLUSION: Ozone has a preventive effect in the development of fibrosis by decreasing tissue damage and increasing the antioxidant enzyme activity in an experimental model of corrosive esophageal injury.

Establishing the use of melatonin as an adjuvant therapeutic against paraquat-induced lung toxicity in rats.

It is well known that the intake of paraquat (PQ) causes severe tissue injury leading to numerous fatalities. Considering that the main target for PQ toxicity is the lung and involves the production of reactive oxygen and nitrogen species, transcription factors and inflammatory cytokines, it may be hypothesized that the combination of a potent antiinflammatory and antioxidant agent may counteract more of PQ's effects than an antiinflammatory agent alone. For this purpose, combination of dexamethasone (Dex) and melatonin (Mel) was compared with Dex alone. A total of 40 male Wistar albino rats were divided into four groups as control, PQ, Dex only, and Dex plus Mel. The animals were given intraperitoneally a toxic dose of 19 mg/kg PQ dissolved in 1 ml saline. Control animals were injected with the same amount of saline only. A dose of 1 mg/kg Dex was administered 2 hrs after PQ administration. In the combination treatment group, 20 mg/kg Mel was given with Dex. All drugs were given every 12 hrs for a total of six doses. Five animals in PQ group and three animals in Dex only group died by the end of the study. No deaths occurred in the Dex+Mel group. Dex exerted improvements in several oxidative and antioxidative parameters. However, combination treatment provided beneficial effects against PQ toxicity far greater than Dex alone. This difference was also apparent when tissues were histologically compared. In conclusion, Mel exhibited strong additive beneficial effects with Dex and can be considered as a safe treatment modality against PQ toxicity.

Effects of hyperbaric oxygen on energy production and xanthine oxidase levels in striated muscle tissue of healthy rats.

We investigated the effects of hyperbaric oxygen (HBO) treatment on striated muscle tissue in healthy rats. The treatment group of rats (n=16) was given HBO daily on weekdays for 2 h over a 4-week period while a control group (n=8) was not treated. Tissue samples were taken from the left and right vastus lateralis before and after the HBO treatment period, respectively, for all rats in both groups. Levels of adenosine monophosphate (AMP), adenosine diphosphate, andenosine triphosphate (ATP) and xanthine oxidase in the muscle tissue were determined. HBO treatment caused a statistically significant increase in ATP (p=0.001) and decrease in AMP (p=0.02) in the HBO-treated group, while there were no significant differences in metabolites in the control group. These results suggest that HBO treatment induces an increase in the ATP levels of muscle tissue with normal mitochondria. Thus, HBO might have some beneficial effects in the treatment of heteroplasmic mitochondrial disease, where normal and defective mitochondria coexist.

Hyperbaric oxygen treatment augments the efficacy of cilazapril and simvastatin regimens in an experimental nephrotic syndrome model.

BACKGROUND: Oxidative stress plays a role in the mechanism of chronic kidney disease (CKD), and antioxidant regimes are regarded as promising treatment modalities. We compared the effects of cilazapril, simvastatin, and hyperbaric oxygen (HBO) treatment on proteinuria and on oxidative stress in adriamycine (ADR)-induced proteinuria. METHODS: Seventy male Sprague-Dawley rats were housed, and 60 were injected with ADR to induce nephrosis. After the stabilization of proteinuria, rats were treated for 6 weeks with simvastatin (n = 10, 4 mg/kg/day), cilazapril (n = 10, 10 mg/kg/day), HBO (n = 10, 2.8 athmosphere absolute, 90 min/daily), HBO + cilazapril (n = 10), HBO + simvastatin (n = 10), and vehicle (n = 10). After euthanization at 12 weeks, protein carbonyl (PCO), superoxide dismutase (SOD), and glutathion peroxidase (GPx) levels were analyzed from tissues. The histological alterations in the kidneys were determined by semiquantitative scoring. RESULTS: Protein carbonyl (PCO) levels were higher (p < 0.001), and the GPx and SOD levels were lower (p < 0.001 for all) in the nephrotic rats. Proteinuria was correlated to PCO (r = 0.483), GPx (r = -0.686), or SOD (r = -0.620) (p < 0.001 for all). Superoxide dismutase (SOD) (beta = -0.381, p = 0.02) and GPx (beta = -0.509, p < 0.001) were independently related to proteinuria levels. Both cilazapril and simvastatin significantly improved GPx, SOD, PCO, and proteinuria. When HBO was combined with either drug, the above markers further improved (p < 0.001). Both regimens caused distinct histological features, while the combination of HBO made much significant histological improvement. CONCLUSION: Both cilazapril and simvastatin regimens improve oxidative stress and proteinuria, while the effects significantly increase with the combination of HBO treatment. HBO seems to be a candidate antioxidant strategy in glomerular diseases.

Exposure time related oxidative action of hyperbaric oxygen in rat brain.

Hyperbaric oxygen (HBO) is known to cause oxidative stress in several organs and tissues. Due to its high rate of blood flow and oxygen consumption, the brain is one of the most sensitive organs to this effect. The present study was performed to elucidate the relation of HBO exposure time to its oxidative effects in rats' brain cortex tissue. For this purpose, 49 rats were randomly divided into five groups. Except the control group, study groups were subjected to three atmospheres HBO for 30, 60, 90, and 120 min. Their cerebral cortex layer was taken immediately after exposure and used for analysis. Thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and nitrate-nitrite (NOX) levels were determined. TBARS and SOD levels were found to increase in a time-dependent manner. GSH-Px activity reflected an inconsistent course. NOX levels were found to be increased only in the 120 min exposed group. The results of this study suggests that HBO induced oxidative effects are strongly related with exposure time.

Oxidative stress levels in rats following exposure to oxygen at 3 atm for 0-120 min.

BACKGROUND: Hyperbaric oxygen (HBO) is known to cause oxidative stress in several organs and tissues. We previously defined the pressure-related oxidative effects of HBO in several tissues of rats. This study was performed to elucidate the relationship of HBO exposure time to its oxidative effects. METHODS: A total of 49 rats were randomly divided into 5 groups. Study groups were subjected to 3 atm HBO for 30, 60, 90, and 120 min except the control group. Their blood and lungs were removed immediately after exposure and used for analysis. Thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels were determined to reflect oxidant and antioxidant status. RESULTS: TBARS levels were found to increase in a time-dependent manner in both erythrocytes [median (min-max); from 0.65 (0.39-0.84) with 30 min HBO exposure up to 1.26 (1.00-1.44) nmol x g(-1) hemoglobin after 120 min] and lung tissue [from 2140 (1550-2510) up to 5465 (5090-5950) nmol x g(-1) protein]. Similarly, SOD activity also presented a dose-dependent course from 0.06 (0.05-0.10) to 0.18 (0.14-0.26) U x g(-1) hemoglobin in erythrocytes and from 16,660 (3479-25,994) to 52,522.5 (41,362-65,799) U x g(-1) protein in lung tissue. In contrast, GSH-Px activity reflected an irregular trend; its levels were mostly found to be increased, but they were decreased at one stage (in the erythrocytes of 30-min exposed rats). CONCLUSIONS: The results of this study exhibited a clear relationship of HBO-induced oxidative action to exposure time. This action was most pronounced from 90 to 120 min of exposure.

Time-dependent course of hyperbaric oxygen-induced oxidative effects in rat lung and erythrocytes.

1. The oxygen toxicity of hyperbaric oxygen (HBO) treatment has long been of interest. There is an extensive amount of information regarding the role oxidative stress plays after HBO exposure in different tissues, but the question of the persistence of this oxidative effect has not been thoroughly elucidated. 2. The present study was performed to elucidate the persistence of the oxidative effects of HBO on rat lungs and erythrocytes after they had been subjected to 100% oxygen exposure. 3. Rats were divided into five groups. All animals, except those in the control group, were subjected to 100% oxygen for 2 h at 3 ATA ( identical with 300 kPa). Rats were killed at 30, 60, 90 or 120 min after exposure and thiobarbituric acid-reactive substances (TBARS) levels and the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were determined. 4. Thiobarbituric acid-reactive substances levels and SOD and GPx levels were found to be significantly increased in lung tissue up to 60 min after exposure. Superoxide dismutase activity persisted at significantly high values for 90 min after exposure in erythrocytes and the lung. The TBARS levels in erythrocytes were also significantly higher for 60 min, whereas increased GPx activity was observed to persist for only 30 min. 5. The oxidative effect of HBO exposure declines to physiological levels within 90 min at most for erythrocytes and in lung tissue in rats. Further studies should focus on the molecular mechanisms that can be activated during this time interval.