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Scavenging of peroxynitrite reduces renal ischemia/reperfusion injury.

Introduction. Nitric oxide (NO) and peroxynitrite (OONO—) are implicated in the pathophysiology of renal ischemia/reperfusion (I/R). The aim of this study was to investigate and compare the efficiency of S-methylisothiourea (SMT), an iNOS inhibitor, and mercaptoethylguanidine (MEG), a scavenger of peroxynitrite, on renal dysfunction and injury induced by I/R of rat kidney. Materials and Methods. Thirty-two male Sprague-Dawley rats were divided into four groups: sham-operated, I/R, I/R+SMT, and I/R+MEG. Rats were given SMT (10 mg/kg ip) or MEG (10 mg/kg ip) 6 h prior to I/R and at the beginning of reperfusion. All rats except sham-operated underwent 60 min of bilateral renal ischemia followed by 6 h of reperfusion. After reperfusion, kidneys and blood were obtained for evaluation. Superoxide dismutase, glutathione peroxidase, malondialdehide, protein carbonyl content, and nitrite/nitrate level (NOx) were determined in the renal tissue. Serum creatinine (SCr), blood urea nitrogen (BUN), and aspartate aminotransferase (AST) were determined in the blood. Additionally, renal sections were used for histological grade of renal injury. Results. SMT and MEG significantly reduced the I/R-induced increases in SCr, BUN, and AST. Both SMT and MEG attenuated the tissue NOx levels, indicating reduced NO production. In addition, SMT and MEG markedly reduced elevated oxidative stress product, restored decreased antioxidant enzymes, and attenuated histological alterations. Interestingly, MEG exerted a greater renoprotective effect than SMT. Conclusions. These data support the finding that iNOS and peroxynitrite are involved in the renal I/R injury, and suggest that a scavenger of peroxynitrite might be more effective than iNOS inhibitors as a therapeutic intervention.

Hyperbaric oxygen therapy reduces the severity of necrotizing enterocolitis in a neonatal rat model

INTRODUCTION Hyperbaric oxygen (HBO) therapy is known to increase oxygen concentration in tissues leading to induction of an adaptive increase in antioxidants, stimulation of angiogenesis, improvement of white blood cell action, and regulation of inflammatory process. Therefore, we tested the potential beneficial effect of HBO in neonatal rat model of necrotizing enterocolitis (NEC). MATERIALS AND METHODS Thirty newborn Sprague-Dawley rats, provided by the Experimental Research Council, Gulhane Military Medical Academy, Ankara,Turkey, were randomly divided into 3 groups as follows: NEC, NEC + HBO, and control. Necrotizing enterocolitis was induced by enteral formula feeding and exposure to hypoxia after cold stress at 4 degrees C and oxygen. The NEC + HBO group received HBO at 2.8 atmosphere absolute (ATA) for 90 minutes daily for 3 days. The pups were killed on the fourth day, and their intestinal tissues were harvested for biochemical and histopathologic analysis. Blood samples were also obtained from the pups. RESULTS The mortality rate was highest in the NEC group (3 pups in the NEC group vs 1 pup in the NEC + HBO group). Malondialdehyde and protein carbonyl content were significantly increased, whereas superoxide dismutase and glutathione peroxidase were significantly decreased in the NEC group. All these changes were similar to control levels in the NEC group by HBO treatment. Nitrate plus nitrite (NO(x)) levels and serum tumor necrosis factor alpha were increased in the NEC group and histopathologic injury score and apoptosis index in the NEC group were significantly higher than in the NEC + HBO group. CONCLUSION Hyperbaric oxygen significantly reduced the severity of NEC in our study.

Effects of Different Doses of Hyperbaric Oxygen on Cisplatin-Induced Nephrotoxicity

Cisplatin, an effective antineoplastic agent, frequently induces acute renal failure in animals and humans. Hyperbaric oxygen (HBO) has been shown to prevent cisplatin-induced nephrotoxicity in rats. This study investigated the effect of two different HBO regimes on renal functions, oxidative stress, and histopathological changes in rat kidneys after cisplatin treatment. Wistar rats were divided into five groups: control, HBO, cisplatin, cisplatin plus once daily HBO, and cisplatin plus twice daily HBO. Cisplatin was given as a single intraperitoneal dose of 6 mg/kg, and HBO was applied for 60 min at 2.5 atm for six days. HBO alone did not alter any biochemical parameters or histopathological findings compared with the control group. Cisplatin increased serum urea and creatinine levels and caused severe histopathological injury. In addition, cisplatin increased lipid peroxidation and impaired superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in kidney tissue. Once daily HBO after cisplatin treatment slightly reduced serum urea and creatinine levels and attenuated histopathological injury. HBO also reduced lipid peroxidation and increased SOD and GSH-Px activities significantly. Although twice daily HBO was determined to be more effective than once daily HBO on oxidative stress parameters, it increased serum creatinine levels and histopathological injury compared with the cisplatin group. It was concluded that HBO alone does not induce nephrotoxicity and oxidative stress in rat kidneys; once daily HBO may prevent cisplatin-induced nephrotoxicity, an effect that is partially mediated by the modification of oxidant/antioxidant systems in the kidneys; and twice daily HBO potentiates cisplatin nephrotoxicity by a ROS-independent mechanism.

Hyperbaric Oxygen Therapy Attenuates Renal Ischemia/Reperfusion Injury in Rats

Objective: Renal ischemia/reperfusion (I/R) injury occurs in both native and transplanted kidneys. Hyperbaric oxygen (HBO) has been shown to prevent I/R injury in different tissues. The aim of this study was to evaluate the effect of HBO on renal I/R injury in rats. Materials and Methods: Sprague-Dawley rats were randomly assigned to one of three groups. The Control group (n = 6) received right nephrectomy. The I/R (n = 6) and I/R+HBO groups (n = 6) received 30 min left renal ischemia followed by 24 h of reperfusion after right nephrectomy. The I/R+HBO group (n = 6) received additional HBO therapy for 60 min at 2.5 absolute atmospheres starting at the initial 15th minute of reperfusion. Results: In the I/R group, blood urea nitrogen (BUN) and creatinine levels increased significantly compared with the Control and I/R+HBO groups (p < 0.05). BUN and creatinine levels were similar in the Control and I/R+HBO groups. Kidney samples from I/R group rats revealed severe tubular damage and neutrophil infiltration at histopathological examination. The animals treated with HBO showed markedly improved lesions and less neutrophil infiltration compared with the I/R group (p < 0.05). Conclusions: HBO exhibited marked protection against I/R injury in this study as measured using BUN and creatinine levels and renal histopathology. However, further studies are needed to clarify the renoprotective effect of HBO on I/R injury.

Bombesin in Short Bowel Syndrome

Short bowel syndrome comprises the sequel of nutrient, fluid, and weight loss that occurs subsequent to greatly reduced functional surface area of the small intestine. The aim of this study is to investigate the trophic and functional effects of bombesin on remaining gut in rats with experimentally induced short bowel syndrome. Thirty-two rats were allocated randomly and experimental short bowel syndrome was induced by 80% bowel resection in all rats. A regular enteral diet and isocaloric elemental enteral nutrition for 12 days were given in the control group and the elemental nutrition group, respectively. In the bombesin group 10 μg/kg subcutaneous bombesin (tid) for 10 days with regular enteral diet for 12 days was given. In the elemental nutrition and bombesin group the diet consisted of 10 μg/kg subcutaneous bombesin (tid) for 10 days with isocaloric elemental enteral nutrition for 12 days was given. All rats underwent physical, histological, and biochemical evaluation. Reduction in weight loss, bowel diameter, fecal fat content, and glycemia, increase in cellularity, and d-xylose absorption were observed in all treatment groups. These changes were more evident in the bombesin treatment groups. Increases in serum protein and albumin levels were seen with bombesin treatment with or without elemental diet, whereas reductions in villous height and crypt depth were observed only with bombesin treatment without elemental diet. Serum calcium, iron, and vitamin B12levels were not affected with any treatment. It is concluded that bombesin may be a useful trophic agent contributing to increased absorptive capacity and improved biochemical values even in the absence of elemental nutrition.

Effects of wound dressing materials in combination with hyperbaric oxygen on chronic wound healing

Objective: Predominantly circulation problems as well as a number of reasons may cause chronic wounds by impairing wound healing process. In this study, we aimed to investigate the effects of two similar wound dressing materials with and without honey and their combination with hyperbaric oxygen (HBO) therapy on chronic wound healing. Material and Methods: For this purpose, chronic wound model was established on 42 Sprague-Dawley male rats and divided into six groups as follows: Control group without any treatment, HBO treatment group, wound dressing (Dermax®) group, wound dressing with honey (Melmax®) group, Dermax® plus HBO treatment group and Melmax® plus HBO group. HBO treatment was administered two times a day under 2.5 ATA, for 60 minutes. Wound dressing change was performed once in every day. At the eighth day of applications, wound tissues were excised for evaluation under anesthesia. Results: Evaluation of wound surface area, biochemical (malondialdehyde and superoxide dismutase) and histopathological (inflammation, epithelization, collagen synthesis, angiogenesis) parameters showed an apparent healing at all treatment groups when compared with control group. Groups that received combination treatment with wound dressings and HBO were found to have increased wound healing and the difference was statistically significant. Conclusion: In our study, we found that wound dressing applications accelerated the wound healing when compared to control group and HBO treatment combination with wound dressings strengthened the healing process.