Cumulative Effects of Paraoxon and Leptin on Oxidative Damages in Rat Tissues: Prophylactic and Therapeutic Roles of N-Acetylcysteine.

Exposure to paraoxon (POX) and leptin (LP) could cause an imbalance between oxidants and antioxidants in an organism, which can be prevented by introduction of exogenous antioxidants such as N-acetylcysteine (NAC). The aim of this study was to evaluate synergic or additive effects of administration of exogenous LP plus POX on the antioxidant status, as well as the prophylactic and therapeutic roles of NAC in various rat tissues. Fifty-four male Wistar rats were divided into nine groups treated with different compounds: Control (no treatment), POX (0.7 mg/kg), NAC (160 mg/kg), LP (1 mg/kg), POX+LP, NAC-POX, POX-NAC, NAC-POX+LP, and POX+LP-NAC. In the last five groups, only the order of administered compounds differed. After 24 h, plasma and tissues were sampled and examined. The results showed that administration of POX plus LP significantly increased biochemical indices in plasma and antioxidant enzymes activities and decreased glutathione content in the liver, erythrocytes, brain, kidney, and heart. In addition, cholinesterase and paraoxonase 1 activities in the POX+LP-treated group were decreased and malondialdehyde level was increased in the liver, erythrocytes, and brain. However, administration of NAC rectified induced changes although not to the same extent. Our study suggests that POX or LP administration engage the oxidative stress system per se; however, their combination did not produce significantly greater effects. Moreover, both prophylactic and therapeutic treatments of rats with NAC supported the antioxidant defense against oxidative damage in tissues, most probably through both its free radical scavenging ability and maintaining intracellular GSH levels. It can therefore be suggested that NAC has particularly protective effects against POX or/and LP toxicity.

Analgesic effects of Terminalia chebula extract are mediated by the suppression of the protein expression of nerve growth factor and nuclear factor-κB in the brain and oxidative markers following neuropathic pain in rats.

BACKGROUND: Due to the complications related to the use of the current pharmacological approach for the alleviation of neuropathic pain, searching for effective compound with fewer complications is a requirement of the present era. It is well known that the pathophysiological mechanism of neuropathic pain is related to excessive inflammation in the nervous system. Hence, the present study focuses on whether the potential analgesic effects of Terminalia chebula (TC) extract are mediated by the changes in the protein expression of nerve growth factor (NGF) and nuclear factor-kappa B (NF-κB) in the brain in a rat model of sciatic nerve chronic constriction injury (CCI). METHOD AND RESULTS: Neuropathic pain was induced by the left sciatic nerve CCI. Male Wistar rats were assigned to three groups: sham, CCI, and CCI + TC (40 mg/kg). Animals received either normal saline (1 mL) or the aqueous-alcoholic extract of TC (40 mg/kg) for 30 days via gavage needles once a day. Cold allodynia and anxiety-like behaviors were examined one day before CCI surgery (day - 1), as well as days 2, 7, 14, and 30 following CCI. We also assessed the effects of the TC extract oxidative stress markers on day 30 following CCI. Moreover, a western blot analysis was performed on day 30 following CCI to evaluate the effects of the TC extract on the protein expression of NGF and NF-κB in the brain. Oral gavage of the TC extract significantly decreased cold allodynia on days 2 and 14 following CCI. Additionally, the CCI model of chronic pain significantly increased the protein expression of NGF and NF-κB in the brain on day 30 following CCI. Furthermore, the TC extract significantly decreased the protein expression of NGF and NF-κB in the brain. The TC extract also significantly increased the brain glutathione (GSH) content and decreased the malondialdehyde (MDA) content. CONCLUSION: It is suggested that the analgesic effects of the TC extract are mediated by the suppression of brain NGF, NF-κB, and by its antioxidant activity in the brain following neuropathic pain in rats.

Evaluation of modulatory effects of saffron (Crocus sativus L.) aqueous extract on oxidative stress in ischemic stroke patients: a randomized clinical trial.

OBJECTIVES: Saffron (Crocus sativus L.) has been widely used in traditional medicine as a treatment of nervous disorders. Saffron as an antioxidant can be considered effective for treatment of oxidative stress in ischemia stroke. Therefore, the aim of the present study was to investigate the role of aqueous extract of saffron in reducing oxidative stress in ischemic strokes patients. METHODS: Forty patients with acute ischemic stroke were randomly divided into two groups including control group and saffron group. During 4 days of experiment, control group received routine stroke care and saffron group received routine care plus capsule of saffron 400 mg/day (200 mg twice per day). Then, two groups were compared using the National Institute of Health Stoke Scale (NIHSS) and serum oxidative stress biomarkers, at the time of hospital admission and 4 days later as well. RESULTS: On the fourth day after ischemic stroke onset, antioxidant enzymes activities and glutathione (GSH) and total antioxidant capacity (TAC) levels were higher in the saffron group compared to the control group, while malondialdehyde (MDA) level was lower. In addition, the severity of stroke, based on the NIHSS scores, was significantly reduced after 4 days in the saffron group. The severity of stroke was negatively correlated with the levels of GSH and TAC and positively correlated with MDA level. CONCLUSIONS: Saffron has modulatory effects on ischemic-induced oxidative stress due to its free radical scavenging and antioxidant properties. Thus, saffron extract can be considered as a potential candidate therapy of the ischemic brain.

Simvastatin and bone marrow-derived mesenchymal stem cells (BMSCs) affects serum IgE and lung cytokines levels in sensitized mice.

INTRODUCTION: The effects of bone marrow-derived mesenchymal stem cells (BMSCs) and simvastatin combination therapy on serum total and specific IgE levels and lung IL-13 and TGF-ß levels in sensitized mouse were examined. MATERIAL AND METHODS: Control (n = 5), Sensitized (S), (n = 5), S + BMSC (n = 6), S + simvastatin (n = 6) and S + BMSC + simvastatin (n = 4) groups of BALB/c mice were studied. Mice were sensitized by ovalbumin. Sensitized mice were treated with a single intravenous injection of BMSCs (1 × 106) or daily intraperitoneal injection of simvastatin (40 mg/kg) or both BMSCs and simvastatin on the last week of challenge. Serum total and ovalbumin specific IgE levels as well as IL-13 and TGF-ß levels in broncho-alveolar lavage (BAL) fluid were evaluated. RESULTS: Serum total and specific IgE levels as well as lung IL-13 and TGF-ß levels were significantly increased in S group compared to control group (P < 0.001 for all cases). Treatment with BMSCs, simvastatin and their combination significantly decreased serum total and specific IgE levels (P < 0.05 to P < 0.01). However, IL-13 and TGF-ß levels were significantly decreased by BMSCs and BMSC + simvastatin combination therapy (P < 0.05 for all cases). The effect of simvastatin and BMSCs combination therapy on serum specific IgE levels as well as lung IL-13 and TGF-ß levels were significantly higher than the effect of BMSCs and simvastatin alone (P < 0.001 for IL-13 and P < 0.01 for other cases). CONCLUSIONS: Simvastatin and BMSCs combination therapy affects serum IgE as well as lung IL-13 and TGFß levels more than BMSC therapy and simvastatin therapy alone which may be due to increased BMSCs migration into the lung tissue.

Modulatory effects of vitamin C on biochemical and oxidative changes induced by acute exposure to diazinon in rat various tissues: Prophylactic and therapeutic roles.

Diazinon (DZN) as an organophosphate pesticide may cause oxidative stress in different tissues. Antioxidants increase tissue protection from oxidative stress. The aim of the present study was to investigate prophylactic and therapeutic effects of vitamin C against oxidative stress caused by DZN in various tissues of male Wistar rats. Thirty rats were divided into five groups: control group received corn oil as DZN solvent, DZN group received 100 mg/kg of DZN, C group received 200 mg/kg of vitamin C, C-DZN and DZN-C groups received vitamin C before and after DZN injection. Plasma and various tissues were prepared and evaluated for measurement of the biochemical parameters and oxidative stress biomarkers. Results showed that acute administration of DZN significantly increased superoxide dismutase and glutathione-S-transferase activities and malondialdehyde level in all tissues, catalase (CAT) activity in liver, kidney and heart and some plasma biochemical indices, while it decreased cholinesterase and lactate dehydrogenase activities and glutathione content in all tissues. CAT activity in erythrocytes, brain and spleen was decreased in DZN-exposed rats compared with the control group. Administration of vitamins C in both prophylactic and therapeutic groups ameliorated in these parameters, although all these tests in tissues did not return to the normal level. These data suggest that oxidative stress is an essential mechanism involved in DZN-induced adversity effect, as evidenced by the altered activity of antioxidant enzymes, depleted GSH content and the enhanced membrane lipid peroxidation. Both the prophylactic and therapeutic treatments of rats to vitamin C have beneficial effects against oxidative stress and cholinergic hyperactivity induced by DZN in tissues especially in the brain tissue through free radical scavenging.

Antidiabetic, antioxidant, and antilipid peroxidative activities of Dracocephalum polychaetum shoot extract in streptozotocin-induced diabetic rats: In vivo and in vitro studies.

CONTEXT: Dracocephalum polychaetum Bornm. (Lamiaceae) is used in folk medicine and contains antioxidant agents. OBJECTIVES: The objective of this study is to investigate the antidiabetic, antioxidant, and antilipid peroxidative properties of methanol extract of D. polychaetum aerial parts. MATERIALS AND METHODS: The effect of extract (200, 300, and 400 mg/kg, b.w.) on oral glucose tolerance test (OGTT) was investigated. Also, extract (300 mg/kg) administered orally in diabetic rats for 14 d then, serum levels of some biochemical factors were evaluated. Pancreas samples were used for the determination of malondealdehyde (MDA) level, glutathione (GSH) content, superoxide dismutase, and catalase enzyme activities. Red blood cells (RBCs) and plasma were used for MDA estimation. Pancreatic α-amylase inhibition, DPPH (1,1-diphenyl-2-picrylhydrazyl), and FRAP (ferric reducing antioxidant power) assays were done. The total flavonoid content of the extract was determined by spectrophotometry. RESULTS: Extract (300 mg/kg) decreased serum glucose level (27.1%) significantly at 120 min in OGTT. Serum levels of creatinine, triglycerides, cholesterol, alanine amino transferase and MDA levels in plasma, RBCs, and pancreas significantly decreased in treated (300 mg/kg) diabetic rats, while pancreatic GSH content, superoxide dismutase, and catalase enzymatic activities increased (p < 0.05). The IC50 values for the extract and butyl hydroxyanisole were 5.6 and 1.15 mg/mL in DPPH and 0.155 and 0.062 mg/mL in the FRAP methods, respectively. The extract had no inhibitory effect on α-amylase activity. The total amount of flavonoids of the extract was estimated to be 1.8% (g/g) on the basis of quercetin content. CONCLUSION: Dracocephalum polychaetum shoot extract has antioxidant, antihyperlipidemic, and antilipid peroxidative properties.

Multipotent bone marrow stromal cell therapy promotes endogenous cell proliferation following ischemic stroke.

Despite extensive research over the years, there still exists some debate as to what constitutes the optimal therapeutic strategy to promote recovery following stroke. Due to the complexity of injured brain pathophysiology, treatment approaches should ideally address numerous factors, ultimately aiming to promote tissue protection, axonal regrowth and functional recovery. This study extends the understanding of the effects of bone marrow stromal cell (BMSC) treatment following experimentally induced ischemic stroke in rats. Focal ischemic brain injury was experimentally induced in rats by placing a preformed clot into the middle cerebral artery. Animals were injected intravenously with BMSCs at 24 h after stroke and were killed 7 days post injury. When administered BMSCs following stroke, the neurological outcome was significantly improved relative to controls. There was an increase in the number of BMSCs labelled with BrdU present in the injured hemisphere of the brain compared to the non-injured side. Furthermore, administration of BMSCs also led to increases in astrocytosis, vascularization and endogenous proliferation. These findings provide insight into the mechanisms of action of BMSC treatment and further argue for the therapeutic potential of BMSCs as an effective treatment following cerebral stroke.

The role of apoptosis in the cellular response of liver and spleen of BALB/c mice in cutaneous leishmaniasis.

BACKGROUND: Cutaneous leishmaniasis is a common parasitic disease in Iran being mainly caused by Leishmania (L.) major. The aim of this study was to investigate the occurrence of apoptosis in the spleen and liver of female mice infected with L. major. METHODS: BALB/c mice were randomly assigned into the control and experimental groups (ten mice per group). The experimental groups were subcutaneously inoculated with promastigotes of L. major at stationary phase. The animals were sacrificed after 20, 40, 60, 90, and 120 days of injection. The liver and spleen were analyzed for various parameters of apoptosis. RESULTS: Activities of superoxide dismutase and caspase-3, levels of superoxide anion production and malondialdehyde, and the percent of DNA fragmentation were increased in the liver and spleen of the infected mice. Catalase activity in the liver was increased, while glutathione level in both tissues was decreased after 90 and 120 days of infection. The numbers of apoptotic nuclei in the spleen were higher than the liver at 90 and 120 days post-infection using the TUNEL method. CONCLUSION: L. major infection induces a time-dependent increase in apoptosis in the liver and spleen as evidenced by the production of ROS, increasing activation of caspase-3, elevated DNA fragmentation, and increasing lipid peroxidation. Induction of oxidative stress was observed in the liver and spleen after 90 and 120 days of initiation of the infection. However, the spleen tissue appears to be more sensitive to the infection to L. major on oxidative stress and apoptosis induction compared with the liver tissue.

Electrochemical study of the effect of radiofrequency on glutamate oxidase activity using a glutamate oxidase-based biosensor.

A biosensor based on glutamate oxidase (GluOx) was developed to measure glutamate concentration. The main function of this type of biosensor is related to the structure and catalytic activity of GluOx. Since radiofrequency, as the widest spectrum of electromagnetic fields, can affect the catalytic activity and structure of GluOx, in this study, the effect of these fields on the analytical parameters of the fabricated biosensor was investigated. To build the biosensor a sol-gel solution of chitosan and native GluOx were prepared and then immobilized on the surface of the platinum electrode. Similarly, to investigate the effect of radiofrequency fields on the analytical parameters of the biosensor, instead of the native GluOx, irradiated GluOx was used to build the biosensor. To evaluate the biosensor responses, cyclic voltammetry experiments were performed and voltammograms were considered as biosensor responses. To determine the analytical parameters including detection limit, linear range, and saturation region of the responses, calibration curves were drawn for each of the biosensors. Also the long-term stability and selectivity of the fabricated biosensor were evaluated. Thereafter, the optimum pH and temperature for each of these two biosensors were examined. The results showed that radiofrequency waves harmed the detection and response of biosensors in the saturation region, while they had little effect on the linear region. Such results could be due to the effect of radiofrequency waves on the structure and function of glutamate oxidase. In general, the results indicate that when a glutamate oxidase-based biosensor is used to measure glutamate in radiofrequency fields, corrective coefficients for this type of biosensor should be considered to accurately measure glutamate concentration.

The role of oxidative stress in diazinon-induced tissues toxicity in Wistar and Norway rats.

Diazinon (DZN) is an organophosphate pesticide widely used in agricultural to control insects and in veterinary medicine to control ectoparasites. This study investigated the induction of oxidative stress in the brain, heart, and spleen of Wistar and Norway rats treated with acute doses of DZN. Female Wistar and Norway rats were treated with 25, 50, 100, and 200 mg/kg of DZN by intraperitoneal injection. The animals were sacrificed 24 h after treatment, and tissues were isolated and analyzed. The result of this study shows that DZN at higher doses increased the level of malondialdehyde, superoxide dismutase and glutathione S-transferase activities and decreased glutathione (GSH) level, lactate dehydrogenase, and cholinesterase activities in the brain, heart, and spleen of both rat strains. At these concentrations, DZN toxicity also lead to a significant decrease in catalase (CAT) activity in all tissues of Wistar rat and brain of Norway rat, while it increased heart CAT activity in Norway rat. However, the alteration of these parameters was observed at lower doses of DZN in Wistar rat. These results suggest that DZN at higher doses induces the production of free radicals and oxidative stress in rat tissues and strains by alteration of antioxidant enzyme activity, depletion of GSH, and increasing lipid peroxidation. Induction of oxidative stress in DZN-treated rats is in the order of brain > heart > spleen. Wistar rats appear to be more sensitive to the effects of DZN on oxidative stress induction compared to Norway rat.

GERD related micro-aspiration in chronic mustard-induced pulmonary disorder.

BACKGROUND AND AIM: Bronchiolitis obliterans (BO) is the main pulmonary involvement resulting from sulfur mustard (SM) gas exposure that was used against Iranian civilians and military forces during the Iran-Iraq war. The present study aimed to investigate the prevalence of gastro-esophageal reflux (GER) and gastric micro-aspiration in SM gas injured patients with chronic pulmonary diseases and recurrent episodes of exacerbations. MATERIALS AND METHODS: This cross-sectional study was done at Baqiyatallah University of Medical Sciences, Tehran, Iran. Gastric micro-aspiration and GER were assessed in the enrolled patients by assessing bile acids, pepsin and trypsin in their bronchoalveolar lavage fluid. RESULTS: Our result showed that bile acids were found to be high in 21.4% patients, and low in 53.6% of patients. Only in 16% patients, no bile was detected in the BALF. Trypsin and pepsin were detected in BAL fluid of all patients. CONCLUSION: Most of BO patients after exposure to SM suffer GER, while none the etiologic factors of GER in post lung transplant BO are present. It would be hypothesized that GER per se could be considered as an aggregative factor for exacerbations in patients. Further studies will provide more advances to better understanding of pathophysiological mechanism regarding GER and BO and treatment.

Tissues toxicity attenuation by vitamin E on oxidative damage induced by diazinon.

Organophosphorus insecticides such as diazinon (DZN) are used worldwide in industry, veterinary practice, and agriculture. They may induce oxidative stress in different tissues. The use of antioxidants can protect tissues against oxidative stress. The aim of this study was to investigate the prophylactic and therapeutic roles of vitamin E against DZN-induced oxidative damage and biochemical alterations in various tissues of male Wistar rats. Thirty rats were divided into five groups: Control group received only corn oil as DZN solvent, DZN group received 100 mg/kg of DZN, E group received 150 mg/kg of vitamin E, E-DZN group received vitamin E and then dosed with DZN and DZN-E group received DZN and then dosed with vitamin E. All injections were carried out intraperitoneally. Plasma and various tissues were prepared and evaluated. Results showed that acute administration of DZN caused a significant induction of oxidative damage in the tested tissues via increased malondialdehyde level and some plasma biochemical indices, depletion of glutathione (GSH), reduced cholinesterase activity and change in the activities of superoxide dismutase, catalase and glutathione-S transferase. Treatment of rats with vitamin E resulted in an elevation in the level of GSH, normalizing the antioxidant enzymes activities and decreasing lipid peroxidation, although all these tests did not return to the normal level in certain tissues. The findings of this study suggest that both prophylactic and therapeutic treatments of rats with vitamin E provide a protective role against DZN-induced oxidative stress and cholinergic hyperactivity through free radicals scavenging and membrane stabilizing.

Comparison of ameliorative effects of Taraxacum syriacum and N-acetylcysteine against acetaminophen-induced oxidative stress in rat liver and kidney.

Taraxacum syriacum (TS) with natural antioxidant and pharmacological activities may be considered for treatment of oxidative stress induced by acetaminophen (APAP). The aim of this study was to evaluate the ameliorative effects of the ethanol extract of TS root against hepatorenal toxicity induced by APAP in comparison to N-acetylcysteine (NAC) as a standard drug. Thirty male Wistar rats were randomly divided into five groups. Control group; APAP (1 g/kg) group; APAP-NAC (160 mg/kg) group and APAP-TS100 and APAP-TS200 groups: APAP plus 100 and 200 mg/kg of TS extract, respectively. After 7 days treatment, serum and liver and kidney tissues were prepared and evaluated. TS extract ameliorated the increased lipid peroxidation level and decreased antioxidant enzymes activities and glutathione level in liver and kidney of APAP-treated rats. Moreover, treatment with the TS extract caused significant reduction in the histopathological damages and high levels of serum biochemical markers of hepatic and renal functions after APAP treatment. This study suggests that the extract of TS roots has dose-dependent ameliorative effect against APAP-induced oxidative damage in liver and kidney due to its free radical scavenging and antioxidant properties. The overall efficacy of the extract at 200 mg/kg dose is comparable with NAC.

Glutathione and malondialdehyde levels in late pulmonary complications of sulfur mustard intoxication.

It has been hypothesized that antioxidant and oxidant capacities may be related to the severity of obstructive lung impairment in patients with sulfur mustard (SM)-induced lung injuries. Our study was designed to measure the level of glutathione (GSH) and malondialdehyde (MDA) activities in patients intoxicated with SM and to evaluate the relationship between their activity and the severity of pulmonary dysfunction. A total of 250 patients with a history of exposure to a single high dose of SM gas and also 60 healthy nonsmoking individuals with no history of exposure to SM were selected. All patients underwent spirometry; based on its indices they were divided into two groups: mild (n = 140) and moderate-to-severe (n = 110) pulmonary dysfunction. Also, serum GSH and MDA concentration measurements were performed for all patients and controls. The mean GSH level in controls was 29.85 +/- 3.26 micromol/ml, which was significantly higher than in patients with mild and moderate-to-severe pulmonary dysfunction (19.02 +/- 2.36 and 17.89 +/- 2.16 micromol/ml, respectively). Also, the mean MDA level in controls was 0.69 +/- 0.09 micromol/ml, which was significantly lower than in patients with mild and moderate-to-severe pulmonary dysfunction (0.74 +/- 0.05 and 0.75 +/- 0.05 micromol/ml, respectively). There was a weak linear correlation between GSH level and some of the pulmonary function indices. On the other hand, there was no significant relationship between the MDA level and pulmonary indices. Our study confirmed important alterations in the oxidative-antioxidative system in patients suffering from SM-induced lung injuries, as shown by a decreased serum level of GSH and an increased level of MDA. Individuals with moderate-to-severe SM-induced lung injuries show a greater tendency for a decreased level of GSH and an increased level of MDA than those with mild injuries; however, there is only minimal association between pulmonary function parameters and the serum level of MDA and GSH. These findings encourage us to examine therapeutic measures to correct such imbalances in future studies.

Pretreatment with oxygen protects rat kidney from cisplatin nephrotoxicity.

Cisplatin (CP) nephrotoxicity is mainly due to reactive oxygen species. Oxygen pre-exposure as a mild oxidative stress may enhance some endogenous defense mechanisms, so its effect on cisplatin-induced acute renal failure was investigated in present study. Twenty-four rats were divided into four groups. The O(2)+ CP and Air + CP groups were were subjected to i.p. injection of 5 mg/kg cisplatin, and in the Air + Saline and O(2) + Saline groups, saline was injected instead of cisplatin. O(2)+ CP and O(2)+ Saline groups were pretreated with oxygen (3h/d for two days), and the other two groups were pretreated with room air. Cisplatin was administered 24 h after last pretreatment session. Three days after cisplatin injection, plasma samples were obtained, and parts of kidney tissue were frozen for biochemical analysis or fixed in formalin for histological assessments. Preconditioning with oxygen prior to cisplatin administration led to reduced tubular necrosis and luminal cast formation and improvement of renal function, as was evidenced by significant reduction in plasma creatinine and urea levels. Oxygen pretreatment also significantly reversed cisplatin-induced reduction in renal catalase activity and glutathione level. It could be concluded that oxygen pretreatment could have a delayed protective effect against cisplatin nephrotoxicity, and that increased renal catalase activity may be involved in this protective effect of hyperoxia.

Evaluation of the effects of different intensities of forced running wheel exercise on oxidative stress biomarkers in muscle, liver and serum of untrained rats.

Exercise induces different effects on antioxidant status depending on its intensity. The forced running wheel (FRW) model maintains a constant intensity and volume during exercise. The aim of the present study was to investigate the effects of FRW exercise at different running speeds on several serum biochemical parameters of liver and muscle functions and on oxidative stress biomarkers in skeletal muscle, liver and serum in the rat. Thirty-six male Wistar rats were randomly divided into six groups. Five groups participated in constant power tests at intensities of 10, 13, 14.5, 16, and 17.5 m/min, and a non-exercise group was chosen as the control. Serum, muscle and liver tissues were collected after the tests and analyzed. At speeds >16 m/min, exercise on an FRW significantly increased several serum biochemical parameters, malondialdehyde level and superoxide dismutase activity in all tissues of exercise rats compared with control rats; FRW exercise also increased catalase activity in the liver and glutathione S-transferase activity in muscle, whereas it decreased glutathione level in all tissues and catalase activity in muscle and serum. These data suggest that FRW exercise in rats activates an adaptation of the antioxidant system response in skeletal muscle at speeds <16 m/min, whereas it induces oxidative stress at higher speeds in muscle, liver and serum. In addition, we observed a correlation between the systematic and local oxidative stress status in rats after exercise on FRW.

Hyperoxia-induced protection against rat's renal ischemic damage: relation to oxygen exposure time.

BACKGROUND: Pre-exposure to hyperoxic gas (>or= 95%) has been shown to protect the heart and central nervous system from ischemia-reperfusion injury. In the present study, we investigated whether oxygen pretreatment induces delayed renal protection in rats. The possible role of some renal antioxidant agents was also investigated. MATERIALS AND METHODS: Adult male Wistar rats were kept in a hyperoxic (HO) (>or= 95% O(2)) environment for 0.5 h, 1 h, 2 h, 3 h, 6 h, and 2 h/day for three consecutive days and 4 h/day for six consecutive days, and control group (IR) animals were kept in the cage with no HO, one day before subjecting their kidney to 40 minutes of ischemia and 24h of reperfusion. Renal function was assessed by comparing plasma creatinine (Cr), blood urea nitrogen (BUN), creatinine clearance (CLCr), and fractional excretion of sodium (FENa%). Histopathological injury score was also determined according to the Jablonski method. To examine the antioxidant system induction by hyperoxia, we measured renal catalase and superoxide dismutase activity, and renal glutathione and malondialdehyde content. RESULTS: Our data demonstrated that only in 4 h/day HO for six consecutive days, the renal function tests (Cr, CLCr, BUN, and FENa%) and Jablonski histological injury were better than control group (p < 0.05). The beneficial effect of oxygen pretreatment in this group was associated with increased renal catalase activity compared with those obtained from control group (p < 0.05). CONCLUSION: The present study demonstrates that repeated exposure to hyperoxic (>or= 95% O(2)) environment can reduce subsequent rat's renal ischemia-reperfusion damage. Induction of endogenous antioxidant system may partially explain this beneficial effect of hyperoxic preconditioning.

Activity and function in lung injuries due to sulphur mustard.

AIM: Pulmonary complications are known to occur in over half the patients exposed to sulphur mustard. Many studies have focused on the clinical complications, often ignoring the pathogenesis of sulphur mustard. Also, the reasons for the variable severity of lung injuries caused by sulphur mustard are unclear. Hence, the current study was performed to evaluate the correlation between superoxide dismutase (SOD) and catalase (CAT) activity and pulmonary function in patients exposed to sulphur mustard. METHODS: Our study was a comparative cross-sectional survey. Two hundred and fifty incident survivors were selected from the Sardasht population who were exposed to sulphur mustard in 1987. A control group from non-exposed civilians was also selected. We used a pulmonary function test, and SOD and CAT activity was measured in these groups. RESULTS: The mean SOD activity in the healthy control group (70.5+/-10.8 U ml(-1)) was higher than in the moderate-to-severe group (67.0+/-6.1 U ml(-1)) (p <0.001, one-tail ANOVA, least significant difference (LSD) post hoc). The mean activity in the mild group (72.5+/-6.9 U ml(-1)) was no higher than in the healthy control group (70.5+/-10.8 U ml(-1)) (p=0.095 one-tail ANOVA, LSD post hoc). The mean CAT activity in the healthy control group (4.9+/-1.5 U ml(-1)) was lower than in the moderate-to-severe group (8.0+/-1.8 U ml(-1)) (p <0.001, one-tail ANOVA, LSD post hoc) and in the mild group (7.5+/-1.5 U ml(-1)) (p=0.012 one-tail ANOVA, LSD post hoc). CONCLUSION: According to our findings, it is reasonable to hypothesize that re-establishment of the activation-inactivation or oxidant-antioxidant balance in favour of the activation and antioxidant balances would be useful as a therapeutic strategy to suppress pathological mechanisms underlying lung injuries.

Ameliorative effect of sixteen weeks endurance training on biochemical and oxidative damage in high fat diet induced obese rats

Obesity is mainly caused by consumption of high fat diet (HFD) and a lack of physical activity. Physical activity is an efficient strategy to delay development of obesity. In this studyv we tried to evaluate attenuating properties of 16 weeks endurance training on plasma oxidative stress and some biochemical parameters in HFD induced obese rats. Twenty-four male Wistar rats were randomly divided into four groups: standard diet group (SD), standard diet with endurance training group (ESD), HFD group and HFD with endurance training group (EHFD). After sixteen weeks, plasma was prepared and evaluated for measurement of different parameters. The results showed that HFD significantly decreased the activities of superoxide dismutase (33.58%), catalase (26.51%) and glutathione S-transferase (22.77%), while endurance training increased these enzymes activities. However, exercise ameliorated the increased malondialdehyde level and depletion of glutathione. In addition, it significantly reduced the increased levels of liver enzymes activities and lipid profiles. These findings suggest that endurance training has found to have beneficial effects against HFD-induced oxidative damage through increasing reduced antioxidants levels and inhibition of lipid peroxidation due to its antioxidant property. Thus, it can be considered an interesting strategy for the management of obesity related diseases.

Dose- and time-dependent effects of sulfur mustard on antioxidant system in liver and brain of rat.

This study investigates the dose- and time-dependent effects of sulfur mustard (SM) on antioxidant system and lipid peroxidation in liver and brain of rats. For this purpose, male Wistar rats were randomly divided into eight groups and treated as follows: group 1 as control and groups 2-8 as experimental groups that received SM (1-80 mg/kg) through intraperitoneal injection. Rats were killed after 2, 7 and 14 days of exposure. SM dose-dependently decreased body weight. Superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST) activities in liver were significantly increased at SM doses lower than 10 mg/kg after 2 and 7 days of exposure. However, the recovery of these parameters was observed after 14 days. At these concentrations, no significant change in glutathione (GSH) and malondialdehyde (MDA) levels were observed. At doses higher than 10 mg/kg, SM significantly decreased SOD, CAT, glutathione peroxidase (GPX), and GST activities in liver and brain and decreased glutathione reductase (GR) activity in liver, which was associated with a depletion of GSH and increased MDA level. Present data indicate that the effect of SM is dose- and time-dependent and at higher doses (>10 mg/kg) induces an oxidative stress response by depleting the antioxidant defense systems and increasing lipid peroxidation in liver and brain of rats.