Positive Effects of Melatonin on Renal Nitric Oxide-Asymmetric Dimethylarginine Metabolism in Fructose-Fed Rats.

Background: The incidence of metabolic syndrome is increasing worldwide and this is mainly attributed to high carbohydrate intake, especially of fructose, and sedentary lifestyles. Nitric oxide (NO), which is synthesized by nitric oxide synthase (NOS) enzymes, is a crucial molecule for endothelial and renal health. Asymmetric dimethylarginine (ADMA) is the most potent inhibitor of NOS and it is degraded by dimethylarginine dimethylaminohydrolase (DDAH). The aim of this study was to investigate the effects of melatonin on renal NO-ADMA metabolism using a metabolic syndrome model achieved by fructose administration. Methods: Thirty-two rats were randomly divided into four groups (n = 8): (1) control group, (2) fructose group, (3) melatonin group, and (4) fructose + melatonin group. Fructose (20%) was given in drinking water. Melatonin [20 mg/(kg·day)] was administered in 0.1% ethanol solution. After 8 weeks, kidney tissues were collected to measure tissue levels of nitrite/nitrate (NOx), ADMA, arginine, symmetric dimethylarginine, DDAH activity, and endothelial NOS (eNOS) and inducible NOS (iNOS) protein levels. Results: Fructose led to low arginine/ADMA ratios (AARs) (P < 0.008). Tissue NOx levels of the fructose + melatonin group were significantly higher than those of the fructose group (P < 0.008). ADMA and arginine were significantly higher in the fructose + melatonin group than the control group (P < 0.008). The DDAH activity of the fructose and fructose + melatonin groups was significantly higher than that of the control group (P < 0.008). eNOS protein levels showed no difference and iNOS protein was not detected in any of the groups. Conclusions: A diminished AAR indicates the toxicity of fructose in the kidneys. Melatonin has beneficial effects on the NO-ADMA pathway as it restores NOx levels and increases DDAH activity, possibly as a result of a compensatory mechanism to metabolize increased ADMA.

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.

The Effectiveness of Raloxifene-Loaded Liposomes and Cochleates in Breast Cancer Therapy.

Liposome (spherical vesicles) and cochleate (multilayer crystalline, spiral structure) formulations containing raloxifene have been developed having dimethyl-ß-cyclodextrin (DM-ß-CD) or sodium taurocholate (NaTC). Raloxifene was approved initially for the treatment of osteoporosis but it is also effective on breast tissue and endometrial cells. Raloxifene inhibits matrix metalloproteinase-2 (MMP-2) enzyme, which is known to be responsible for tumor invasion and the initiation of angiogenesis during the tumor growth. Therefore, raloxifene was selected as a model drug. A series of raloxifene-loaded liposome and cochleate formulations were prepared. In vitro release studies and in vivo tests were performed. Breast cancer cell lines (MCF-7) were also used to find the most effective formulation. Highest antitumor activity was observed, and MMP-2 enzyme was also found to be inhibited with raloxifene-loaded cochleates containing DM-ß-CD. These developed formulations can be helpful for further treatment alternatives and new strategies for cancer therapy.

Beneficial Effect of Etanercept on Hyperoxic Lung Injury Model in Neonatal Rats.

PURPOSE: To determine whether prophylaxis with etanercept, an anti-inflammatory drug, would decrease the severity of lung injury in a neonatal rat model of bronchopulmonary dysplasia (BPD); MATERIALS AND METHODS: Rat pups were divided into three groups: pups exposed to room air (group 1; n = 10), to hyperoxia + placebo (group 2; n = 9), and to hyperoxia + etanercept (group 3; n = 8). Lung morphology was assessed by alveolar surface area percentage, which is a measure of alveolar size. The severities of lung inflammation and antioxidant capacity were assessed by quantifying tumor necrosis factor-α (TNF-α), transforming growth factor-ß (TGF-ß), malondialdehyde (MDA), and superoxide dismutase (SOD) from lung homogenate; RESULTS: The percentage of alveolar surface areas were significantly higher in group 3 compared to group 2 (p = .004) and similar in both group 1 and group 3 (p = .21). The mean level of lung MDA was significantly higher in group 2 compared to group 1 and group 3 (p < .05 for both). Lung homogenate SOD activities in group 3 was significantly higher than group 2 (p < .001). Furthermore, group 3 pups had lower levels of TNF-α and TGF-ß in lung homogenate than that in group 2 (p < .05 for both) but similar in both group 1 and group 3; CONCLUSION: Etanercept has favorable effects on alveolarization as well as inflammation and oxidative stress markers in a neonatal rat model of BPD.

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.

Preservative solution for skeletal muscle biopsy samples.

CONTEXT: Muscle biopsy samples must be frozen with liquid nitrogen immediately after excision and maintained at -80°C until analysis. Because of this requirement for tissue processing, patients with neuromuscular diseases often have to travel to centers with on-site muscle pathology laboratories for muscle biopsy sample excision to ensure that samples are properly preserved. AIM: Here, we developed a preservative solution and examined its protectiveness on striated muscle tissues for a minimum of the length of time that would be required to reach a specific muscle pathology laboratory. MATERIALS AND METHODS: A preservative solution called Kurt-Ozcan (KO) solution was prepared. Eight healthy Sprague-Dawley rats were sacrificed; striated muscle tissue samples were collected and divided into six different groups. Muscle tissue samples were separated into groups for morphological, enzyme histochemical, molecular, and biochemical analysis. STATISTICAL METHOD USED: Chi-square and Kruskal Wallis tests. RESULTS: Samples kept in the KO and University of Wisconsin (UW) solutions exhibited very good morphological scores at 3, 6, and 18 hours, but artificial changes were observed at 24 hours. Similar findings were observed for the evaluated enzyme activities. There were no differences between the control group and the samples kept in the KO or UW solution at 3, 6, and 18 hours for morphological, enzyme histochemical, and biochemical features. The messenger ribonucleic acid (mRNA) of ß-actin gene was protected up to 6 hours in the KO and UW solutions. CONCLUSION: The KO solution protects the morphological, enzyme histochemical, and biochemical features of striated muscle tissue of healthy rats for 18 hours and preserves the mRNA for 6 hours.

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.

Metabolic and Histopathological Effects of Fructose Intake During Pregestation, Gestation and Lactation in Rats and their Offspring.

OBJECTIVE: Studies have demonstrated a significant relationship between maternal fructose intake and metabolic outcome in their offspring. However, there is a paucity of data about the long-term effects of fructose intake on the offspring of fructose-fed dams. Therefore, we planned a study to evaluate the long-term effects of fructose intake on the offspring of dam rats fed a high-fructose diet. METHODS: Sixteen virgin female Sprague-Dawley rats were divided into two groups. Group 1 received a regular diet and Group 2 a high-fructose diet. Both groups received their experimental diets for 8 weeks before conception. They were mated and continued to feed with their experimental diet during mating and during their pregnancy and lactation periods. After weaning, the offspring from each group were divided into two groups. Group 1A received a regular diet, Group 1B - a fructose diet, Group 2A - a regular diet and Group 2B received a fructose diet. After weaning, the offspring were anesthetized and blood samples were collected for biochemical analysis. Liver, kidney and retroperitoneal adipose tissue were harvested for histopathological examination. Primary antibodies against inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were determined as early inflammation markers. RESULTS: After weaning, while daily water consumption was found to be significantly higher in Groups 2B and 1B (p<0.01), daily laboratory chow consumption was significantly lower in Groups 1A and 2A (p<0.01). Body weight was significantly higher in Groups 1B and 2B (p<0.01). Serum glucose, triglyceride, low-density lipoprotein cholesterol and very low-density lipoprotein cholesterol levels were found to be increased and high-density lipoprotein cholesterol levels decreased in Group 2B (p<0.05). The intensities of iNOS staining in the retroperitoneal adipose tissue, COX-2 staining in the liver and both iNOS and COX-2 staining in the kidney were higher in Group 2B (p<0.05). CONCLUSION: Based on our findings, we believe that the offspring of dams which received a high fructose intake during their pregestation, gestation and lactation periods are at risk of developing metabolic syndrome in their later life only if they continue to receive a high intake of fructose. We therefore propose that the risk of developing metabolic syndrome can probably be reduced by modifying the diet of the offspring after weaning.

Effects of hypothermia on skeletal ischemia reperfusion injury in rats.

OBJECTIVE: The aim of this study was to investigate the effect of hypothermia (H) on skeletal ischemia-reperfusion (IR) injury in rats by measuring malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), nitric oxide (NO), and interleukin-1 beta (IL-1ß) in muscle, and measureing immunohistochemical-inducible nitric oxide synthase (iNOS) staining of skeletal muscle. MATERIALS AND METHODS: Eighteen Wistar Albino rats were divided randomly into three groups (sham, IR, hypothermia) (n=6). The sham group had all procedures without the IR period. The lower right extremity of rats in the IR and hypothermia groups was subjected to 2 hours of ischemia and 22 hours of reperfusion by applying a clamp on the common iliac artery and a rubber-band at the level of the lesser trochanter under general anesthesia. Rats in the hypothermia group underwent 4 hours of hypothermia during the first four hours of reperfusion in addition to a 2-hour ischemia and 22-hour reperfusion period. All rats were sacrificed at end of the IR period using a high dose of anesthesia. The tibialis anterior muscles were preserved. Immunohistochemical iNOS staining was performed, and MDA, SOD, GSH-Px, NO, and IL-1ß were measured in the muscle. RESULTS: The level of MDA, NO, and IL-1ß in muscle was increased in the IR group compared with that in the sham group, but these parameters were decreased in the hypothermia group compared with the IR group. The activities of SOD and GSH-Px in muscle were decreased in the IR group; however, these parameters were increased in the hypothermia group. The score and intensity of iNOS staining of skeletal muscle was dens in IR group, mild in hypothermia group, and weak in sham group. CONCLUSION: The present study has shown that hypothermia reduced IR injury in the skeletal muscle by decreasing the levels of MDA, NO, and IL-1ß, and increasing the activities of SOD and GSH-Px. In addition, hypothermia attenuated the score and intensity of iNOS staining.

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.

Glucose: a vital toxin and potential utility of melatonin in protecting against the diabetic state.

The molecular mechanisms including elevated oxidative and nitrosative reactants, activation of pro-inflammatory transcription factors and subsequent inflammation appear as a unified pathway leading to metabolic deterioration resulting from hyperglycemia, dyslipidemia, and insulin resistance. Consistent evidence reveals that chronically-elevated blood glucose initiates a harmful series of processes in which toxic reactive species play crucial roles. As a consequence, the resulting nitro-oxidative stress harms virtually all biomolecules including lipids, proteins and DNA leading to severely compromised metabolic activity. Melatonin is a multifunctional indoleamine which counteracts several pathophysiologic steps and displays significant beneficial effects against hyperglycemia-induced cellular toxicity. Melatonin has the capability of scavenging both oxygen and nitrogen-based reactants and blocking transcriptional factors which induce pro-inflammatory cytokines. These functions contribute to melatonin's antioxidative, anti-inflammatory and possibly epigenetic regulatory properties. Additionally, melatonin restores adipocyte glucose transporter-4 loss and eases the effects of insulin resistance associated with the type 2 diabetic state and may also assist in the regulation of body weight in these patients. Current knowledge suggests the clinical use of this non-toxic indoleamine in conjunction with other treatments for inhibition of the negative consequences of hyperglycemia for reducing insulin resistance and for regulating the diabetic state.

The effect of alpha-lipoic acid in the prevention of peritoneal adhesions.

BACKGROUND/AIMS: Peritoneal adhesions, which occur most frequently after abdominal and pelvic operations, may lead to serious complications such as small intestine obstruction. In various studies, it has been shown that oxidative stress may play a role in the development of peritoneal adhesions, and studies carried out with antioxidants reported positive results. In the present study, the probable preventive role of alpha-lipoic acid, a strong antioxidant, in the development of peritoneal adhesions was investigated. METHODS: Sixteen Sprague-Dawley male rats weighing 200-250 grams were employed. Under ketamine+xylazine anesthesia, on the antimesenteric aspect of the cecum, an adhesion model was formed with an incision, and half of the experimental animals were administered a daily single dose 100 mg/kg alpha-lipoic acid through orogastric gavage, and the other half formed the control group. Abdomens were opened 15 days later, and after adhesions were scored macroscopically, tissue samples were taken for evaluation of biochemical parameters. RESULTS: In both adhesion scoring methods, a statistically significant decrease was found in the alpha-lipoic acid group compared to the control group (p<0.05). The decrease in adhesions was also confirmed by the significantly lower hydroxyproline levels in the alpha-lipoic acid group (p<0.05). In addition, alpha-lipoic acid decreased malondialdehyde levels in the adhesion region and prevented the increase in superoxide dismutase and glutathione peroxidase activities significantly (p<0.05). CONCLUSIONS: It can be concluded from the findings of our study that alpha-lipoic acid decreased the development of adhesions in a peritoneal adhesion model and increased the quality of healing. These findings suggest that alpha-lipoic acid, already long used in various indications, may be tried clinically in patients about to undergo abdominal operations.

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.