Melatonin prevents oxidative kidney damage in a rat model of thermal injury

Animal models of thermal trauma implicate oxygen radicals as causative agents in local wound response and distant organ injury following burn. This study was designed to determine the effect of melatonin treatment on levels of glutathione (GSH), malondialdehyde (MDA), protein oxidation (PO) and myeloperoxidase (MPO) activity in the kidney tissues of rats with thermal injury. Under ether anaesthesia, shaved dorsum of the rats was exposed to 90 degrees C bath for 10 s to induce burn injury. Rats were decapitated either 3 h or 24 h after burn injury. Melatonin was administered i.p. immediately after burn injury. In the 24-h burn group melatonin injections were repeated for two more occasions. In the sham group the same protocol was applied except that the dorsum was dipped in a 25 degrees C water bath for 10 s. Severe skin scald injury (30% of total body surface area) caused a significant decrease in GSH level, and significant increases in MDA and PO levels, and MPO activity at post-burn 3 and 24 hours. Treatment of rats with melatonin (10 mg/kg) significantly elevated the reduced GSH levels while it decreased MDA and PO levels as well as MPO activity.     

Octreotide improves burn-induced intestinal injury in the rat

The local thermal trauma activates a number of systemic mediator cascades, e.g. a complement activation, cytokine production, resulting in a generalized sequestration and a priming of local and systemic neutrophils and macrophages. We aimed to determine the possible protective effect of octreotide (OCT), a synthetic somatostatin analogue, against burn-induced intestinal tissue damage possibly by inhibiting neutrophil infiltration. Under brief ether anaesthesia, shaved dorsum of the rats was exposed to 90 degrees C bath for 10s to induce burn injury. Rats were decapitated either 3, 24 or 72 h after burn injury. Octreotide (10 microg/kg) or saline was administered subcutaneously (s.c.) immediately after the burn injury. In the 24- and 72-h burn groups, OCT injections were repeated three times daily. In the sham group the same protocol was applied except that the dorsum was dipped in a 25 degrees C water bath for 10 s Malondialdehyde (MDA) and glutathione (GSH) levels and myeloperoxidase (MPO) activity were determined in the intestinal tissue. The results demonstrate that burn injury results in significant neutrophil accumulation, as evidenced by increases in MPO activity. The increase in MDA and the concomitant decrease in GSH levels demonstrate the role of oxidative mechanisms in burn injury. OCT may have some beneficial therapeutic effects by reducing neutrophil-dependent injury and related lipid peroxidation following burn trauma.     

Protective effect of aqueous garlic extract against oxidative organ damage in a rat model of thermal injury

Oxygen free radicals have been implicated in mediating various pathological processes including burn-induced organ damage. This study was designed to determine the possible protective effect of aqueous garlic extract against oxidative organ damage distant from the original burn wound. Under ether anaesthesia, rats were subjected to severe skin scald injury covering 30% of total body surface area. Rats were decapitated either 2 h or 24 h after burn injury. Aqueous garlic extract (1 ml/kg) was administered i.p. immediately after burn injury. In the 24-h burn group injection was repeated once more (at 12 hour) following the burn injury. Liver, intestine and lung tissues were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and protein oxidation (PO). Burn injury caused a significant decrease in GSH level, and significant increases in MDA and PO levels, and MPO activity at post-burn 2 and 24 hours. Since garlic extract reversed these oxidant responses it seems likely that garlic extract protects tissues against oxidative damage.     

Burn-induced oxidative injury of the gut is ameliorated by the leukotriene receptor blocker montelukast

There is increasing evidence that oxidative stress has an important role in the development of multiorgan failure after major burn injury. In the present study, we investigated whether the leukotriene receptor blocker montelukast is protective against burn-induced injury of the gut. Under brief ether anaesthesia, shaved dorsum of the rats was exposed to 90 degrees C (burn group) or 25 degrees C (control group) water bath for 10 s. Montelukast (10 mg/kg) or saline was administered intraperitoneally immediately after and at the 12th hour of the burn injury. Rats were decapitated 24 h after burn injury and the skin samples, as well as tissue samples from stomach, ileum and colon, were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Tissues were also examined microscopically. Tumor necrosis factor-alpha (TNF-alpha) and lactate dehydrogenase (LDH) were assayed in serum samples. Severe skin scald injury (30% of total body surface area) caused a significant decrease in GSH level, which was accompanied with significant increases in MDA level, MPO activity and collagen content of tissues. Similarly, serum TNF-alpha and LDH were elevated in the burn group as compared to control group. On the other hand, montelukast treatment reversed all these biochemical indices, as well as histopathological alterations, which were induced by thermal trauma. Findings of the present study suggest that montelukast possesses an anti-inflammatory effect on burn-induced gastrointestinal damage and protects against oxidative injury by a neutrophil-dependent mechanism.     

Melatonin and vitamin C administration ameliorate diazepam-induced oxidative stress and cell proliferation in the liver of rats

Abstract.  Objective : Oxidative stress is a likely molecular mechanism in long-term diazepam administration. The benefits of antioxidants (melatonin and vitamin C) against diazepam-induced cell proliferation, DNA synthesis and oxidative damage were investigated in this study. Materials & methods : Four equal-sized groups of male rats [control, diazepam (3 mg/kg), diazepam plus melatonin (5 mg/kg) and diazepam plus vitamin C (50 mg/kg)] were used. Levels of lipid peroxides (LPO), superoxide dismutase (SOD) activity and glutathione (GSH) concentration were measured in tissue homogenates. Cell proliferation and rate of DNA synthesis were detected by autoradiography. Results : Results documented increased labelling index, ³H-thymidine incorporation (DNA synthesis), LPO plus decrease in GSH levels and SOD activity in livers of diazepam-administered rats versus those of controls. When melatonin and vitamin C were given to diazepam-administered rats, they almost attenuated the increase of labelling index, DNA synthesis and LPO, and restored the levels of GSH and SOD activity. Conclusion : These results suggest long-term hazard in use of drugs such as diazepam; they may be toxic and damage terminates in complex liver damage. Furthermore, melatonin and vitamin C may be useful in combating free radical-induced liver injury resulting from hazard and/or repeated diazepam administration.     

Prophylactic effect of melatonin in reducing lead-induced neurotoxicity in the rat

Oxidative stress is a likely molecular mechanism in lead neurotoxicity. Considering the antioxidant properties of melatonin, this study investigated the neuroprotective potential of melatonin in the hippocampus and corpus striatum of rats treated with lead. Three groups of male rats (control, lead acetate-treated [100 mg/kg], and lead acetate plus melatonin [10 mg/kg] for 21 consecutive days) were used. Levels of products of lipid peroxidation (LPO), glutathione (GSH) and superoxide dismutase (SOD) activity were measured in brain homogenates. Histological changes in the pyramidal cells of the hippocampus and the putamen of the corpus striatum were examined. The results documented increased LPO and decreased GSH and SOD activity in the brain homogenates of lead-treated rats. Histological observations revealed severe damage and a reduction in neuronal density in the hippocampus and corpus striatum. When melatonin was given to lead-treated rats, it almost completely attenuated the increase in LPO products and restored GSH levels and SOD activity. Also, the morphological damage was reduced and neuronal density was restored by melatonin. Considering the ease with which melatonin enters the brain, these results, along with previous observations, suggest that melatonin may be useful in combating free radical-induced neuronal injury that is a result of lead toxicity.     

The effect of Myrtus communis L. ethanol extract on the small intestine and lungs in experimental thermal burn injury

Thermal trauma can damage organs away from the skin burn site and lead to multiple organ dysfunction. Following thermal injury, all tissues are exposed to ischemia, and as a result, resuscitation and reperfusion occur during the burning shock. Burn damage starts systemic inflammatory reactions that produce toxins and reactive oxygen radicals that lead to peroxidation. This study aimed to investigate, for the first time, the possible antioxidant effects of Myrtus communis ethanol extract on burn-induced oxidative distant organ injury orally. The thermal trauma was generated under ether anesthesia by exposing the dorsum of rats to 90 ^°C water bath for 10 s. 100 mg/kg/day Mrytus communis ethanol extract was applied orally for two days. Malondialdehyde (MDA) and glutathione (GSH) levels, glutatinone-S-transferase (GST), superoxidedismutase (SOD) and catalase (CAT) activities were determined to detect the possible antioxidant effects of myrtle on small intestine and lung tissues. Burn damage significantly increased MDA levels in lung and small intestine tissues, and significantly decreased GSH levels, CAT and GST activities in the small intestine and lung tissues compared to control group. Mrytus communis ethanol extract decreased MDA level and increased GSH level, SOD, CAT and GST activities significantly in either small intestine or lung tissues. Mrytus communis extract may be an ideal candidate to be used as an antioxidant adjunct to improve oxidative distant organ damage to limit the systemic inflammatory response and decreasing the recovery time after thermal injury.     

Ghrelin improves burn-induced multiple organ injury by depressing neutrophil infiltration and the release of pro-inflammatory cytokines

Mechanisms of burn-induced skin and remote organ injury involve oxidant generation and the release of pro-inflammatory cytokines. In this study the possible antioxidant and anti-inflammatory effects of ghrelin were evaluated in a rat model of thermal trauma. Wistar albino rats were exposed to 90 degrees C bath for 10 s to induce thermal trauma. Ghrelin, was administered subcutaneously (10 ng/kg/day) after the burn injury and repeated twice daily. Rats were decapitated at 6 h and 48 h after burn injury and blood was collected for the analysis of pro-inflammatory cytokines (TNF-alpha and IL-1beta), lactate dehydrogenase (LDH) activity and antioxidant capacity (AOC). In skin, lung and stomach tissue samples malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) and Na(+)-K(+)-ATPase activity were measured in addition to the histological analysis. DNA fragmentation ratio in the gastric mucosa was also evaluated. Burn injury caused significant increase in both cytokine levels, and LDH activity, while plasma AOC was found to be depleted after thermal trauma. On the other hand, in tissue samples the raised MDA levels, MPO activity and reduced GSH levels, Na(+)-K(+)-ATPase activity due to burn injury were found at control levels in ghrelin-treated groups, while DNA fragmentation in the gastric tissue was also reduced. According to the findings of the present study, ghrelin possesses a neutrophil-dependent anti-inflammatory effect that prevents burn-induced damage in skin and remote organs and protects against oxidative organ damage.     

Melatonin ameliorates ionizing radiation-induced oxidative organ damage in rats

This study was designed to study the effects of the potential radioprotective properties of pharmacological doses of melatonin against organ damage induced by whole-body irradiation (IR) in rats. A total of 32 male Sprague-Dawley rats were exposed to irradiation performed with a LINAC producing 6 MV photons at a focus 100 cm distant from the skin. Under ketamine anaesthesia, each rat received a single whole-body dose of 800 cGy. Immediately before and after IR, rats were treated with either saline or melatonin (20 mg/kg and 10 mg/kg, i.p.) and decapitated at 12-h after exposure to irradiation. Another group of rats was followed for 72-h after IR, where melatonin (10 mg/kg, i.p.) injections were repeated once daily. Tissue levels of malondialdehyde (MDA)--an index of lipid peroxidation--, glutathione (GSH)--a key to antioxidant--and myeloperoxidase (MPO) activity--an index of neutrophil infiltration--were estimated in liver, lung, colon and intestinal tissues. The results demonstrate that both 12-h and 72-h following IR, tissue levels of MDA were elevated (p<0.05-0.001), while GSH levels were reduced (p<0.05-0.001) in all organs. On the other hand, melatonin, reduced the levels of MDA and increased the GSH levels significantly, (p<0.05-0.001). MPO activity was increased significantly in the colonic tissue at the both 12-h and 72-h, and in the hepatic tissue at the 72-h following IR, which were reduced by melatonin (p<0.01-0.001). In the lung tissue enzyme activity was decreased at 72nd h of post-irradiation. In conclusion, the increase in MDA levels and MPO activity and the concomitant decrease in GSH levels demonstrate the role of oxidative mechanisms in irradiation-induced tissue damage, and melatonin, by its free radical scavenging and antioxidant properties, ameliorates irradiation-induced organ injury. Thus, supplementing cancer patients with adjuvant therapy of melatonin may have some benefit for successful radiotherapy.     

Rhythms in immunoreactive melatonin in the retina and harderian gland of rats: Persistence after pinealectomy

Immunoreactive melatonin levels were measured in the retina and Harderian gland of adult male rats throughout a 24 hour period. The animals were maintained under a light:dark cycle of 14:10 (lights on at 0600h). In intact animals, immunoreactive melatonin values in both organs exhibited a 24h rhythm with peak levels being measured at 0800h, 2 hours after lights on. Pinealectomy significantly increased peak levels at 0800h in both the retina and the Harderian gland. Gonadectomy abolished the peak retinal melatonin levels at 0800h. Likewise, continual light exposure for 1 week depressed the melatonin peak in the retina but not in the Harderian gland.     

Preserving effects of melatonin on the levels of glutathione and malondialdehyde in rats exposed to irradiation

In this study we investigated whether pretreatment with melatonin was protective against the injury of the central nervous system (CNS) in rats receiving LD(50) whole body irradiation. The wistar rats were randomized into four groups: i) the control group (CG), ii) melatonin-administered group (MG; 1 mg/kg body weight), iii) irradiated group (RG; 6.75 Gy, one dose), and iv) melatonin-administered and irradiated group (MRG). Blood samples were drawn from the rats 24 h after the treatment and plasma glutathione levels were assayed. Plasma glutathione level was significantly higher in RG than CG. The melatonin pretreatment prevented GSH increase induced by irradiation. Lipid peroxidation and glutathione levels of rat cerebral cortex were determined in all groups after 24 h. Cortical malondialdehyde (MDA) was significantly higher in the RG. The melatonin pretreatment prevented cortical MDA increase induced by irradiation. Cortical GSH was significantly lower in RG than the CG. The melatonin pretreatment prevented cortical GSH decrease induced by irradiation. Tissue samples were obtained from cerebral cortex and hypothalamus which also were affected by ionizing irradiation in the CNS and were evaluated with electron microscopy. Histopathological findings showed that LD(50) whole body irradiation resulted in damage of the neuronal cells of CNS. The results obtained from this study demonstrated that pretreatment with melatonin prevented the damage that develops in CNS following irradiation. The beneficial effect of melatonin can be related to protection of the CNS from oxidative injury and preventing the decrease in the level of cortical glutathione.     

Neuroprotection by α-Lipoic Acid in Streptozotocin-Induced Diabetes

Glial cells provide structural and metabolic support for neurons, and these cells become reactive to any insult to the central nervous system. The streptozotocin (STZ) rat model was used to study glial reactivity and the prevention of gliosis by alpha-lipoic acid (alpha-LA) administration. The expression of glial fibrillary acidic protein (GFAP), S100B protein, and neuron specific enolase (NSE) was determined as well as lipid peroxidation (LPO) and glutathione (GSH) levels in some brain tissues. Western blot analyses showed GFAP, S100B, and NSE levels significantly increased under STZ-induced diabetes in brain, and LPO level increased as well. Administration of alpha-LA reduced the expression both of glial and neuronal markers. In addition, alpha-LA significantly prevented the increase in LPO levels found in diabetic rats. GSH levels were increased by the administration of alpha-LA. This study suggests that alpha-LA prevents neural injury by inhibiting oxidative stress and suppressing reactive gliosis.     

A single exposure of rats to water-immersion restraint stress induces oxidative stress more severely in the thymus than in the spleen

Abstract

Objectives

We examined whether a single exposure of rats to water-immersion restraint stress (WIRS) induces oxidative stress in the thymus and spleen.

Methods

Vitamin E, ascorbic acid, reduced glutathione (GSH), and lipid peroxide (LPO) were assayed in the thymus and spleen of rats with and without 6 hours of WIRS.

Results

In unstressed rats, vitamin E, ascorbic acid, GSH, and LPO levels were higher in the thymus than in the spleen. Thymic ascorbic acid level was lower in stressed rats than in unstressed rats. Splenic ascorbic acid level was similar in both groups. Thymic and splenic GSH levels were lower in stressed rats than in unstressed rats but the reduced amount of GSH was lower in the spleen than in the thymus. Thymic vitamin E level was lower in stressed than in unstressed rats. Splenic vitamin E level was higher in stressed rats than in unstressed rats. Thymic and splenic LPO levels were higher in stressed rats than in unstressed rats but the increased amount of LPO was higher in the thymus than in the spleen.

Conclusion

It is indicated that a single expose of rats to WIRS induces oxidative stress more severely in the thymus than in the spleen.     

Melatonin treatment protects against sepsis-induced functional and biochemical changes in rat ileum and urinary bladder

Sepsis is commonly associated with enhanced generation of reactive oxygen metabolites, which lead to multiple organ dysfunction. The aim of this study was to examine the role of melatonin, a potent antioxidant, in protecting the intestinal and bladder tissues against damage in a rat model of sepsis. Sepsis was induced by cecal ligation and perforation (CLP) in Wistar Albino rats. Sham operated (control) and CLP group received saline or melatonin (10 mg/kg, ip) 30 minutes prior to and 6 hours after the operation. Sixteen hours after the surgery, rats were decapitated and the intestinal and urinary bladder tissues were used for contractility studies, or stored for the measurement of malondialdehyde (MDA) content -an index of lipid peroxidation-, glutathione (GSH) levels -a key antioxidant- and myeloperoxidase (MPO) activity- an index of neutrophil infiltration-. Ileal and bladder MDA levels in the CLP group were significantly increased (p < 0.001) with concomitant decreases in GSH levels (p < 0.01 - p < 0.001) when compared to the control group. Similarly, MPO activity was significantly increased (p < 0.001) in both ileum and bladder tissues. On the other hand, melatonin treatment significantly reversed (p < 0.001) the elevations in MDA and MPO levels, while reduced GSH levels were increased back to the control levels (p < 0.01 - p < 0.001). In the CLP group, the contractility of the ileal and bladder tissues decreased significantly compared with controls. Melatonin treatment of the CLP group restored these responses. In this study, CLP induced dysfunction of the ileal and bladder tissue of rats was reversed by melatonin treatment. Moreover, melatonin, as an antioxidant, abolished the elevation in lipid peroxidation products and myeloperoxidase activity, and reduction in the endogenous antioxidant glutathione and thus protected the tissues against sepsis-induced oxidative damage.     

Effect of Zinc and Melatonin on Oxidative Stress and Serum Inhibin-B Levels in a Rat Testicular Torsion–Detorsion Model

The present study was aimed to examine the effects of 3-week zinc and melatonin administration on testicular tissue injury and serum Inhibin-B levels caused by unilateral testicular torsion–detorsion in rats. The study was performed on 60 Wistar Albino-type adult male rats. The animals were allocated to 6 groups in equal numbers. 1. Control; 2. Sham; 3. Ischemia–reperfusion; 4. Zinc + ischemia–reperfusion; 5. Melatonin + ischemia–reperfusion; 6. Zinc + melatonin + ischemia–reperfusion. Zinc and melatonin were administered before ischemia–reperfusion at doses of 5 and 3 mg/kg respectively, by intraperitoneal route for a period of 3 weeks. Testicular torsion–detorsion procedures consisted of ischemia for 1 h and then reperfusion for another hour of the left testis. Blood and testicular tissue samples were collected to analyze erythrocyte and tissue GSH and plasma and tissue MDA, Inhibin-B levels. The highest erythrocyte and testis GSH values were found in zinc, melatonin, and zinc + melatonin groups (p < 0.001). Torsion–detorsion group has significantly lower erythrocyte GSH levels and higher plasma MDA values (p < 0.001). Serum inhibin-B and spermatogenic activity levels in the torsion–detorsion group were also significantly lower than those in the other groups (p < 0.001). However, zinc-, melatonin-, and melatonin + zinc-supplemented groups have higher inhibin-B and spermatogenetic activity (p < 0.001). The results of the study show that zinc, melatonin, and melatonin + zinc administration partially restores the increased oxidative stress, as well as the reduced inhibin-B and spermatogenic activity levels in testes ischemia–reperfusion in rats. Suppressed inhibin-B levels in the testicular tissue may be a marker of oxidative stress.     

Vitamin D and melatonin protect the cell’s viability and ameliorate the CCl4 induced cytotoxicity in HepG2 and Hep3B hepatoma cell lines

Carbon tetrachloride (CCl₄) is widely used to induce liver toxicity in in vitro/in vivo models. Lipid peroxidation (LPO) begins with toxicity and affects cell viability. Recently, the beneficial effects of melatonin and Vitamin D on cell proliferation in human normal and cancer cells were found. This study was planned to evaluate antioxidant and cytoprotective activity of melatonin and Vitamin D in CCl₄ induced cytotoxicity in HepG2 and Hep3B hepatoma cell lines. Based on the cytotoxicity assay, melatonin and Vitamin D were evaluated for cytotoprotective potential against CCl₄ induced toxicity in HepG2 and Hep3B liver cell lines by monitoring cell viability, LPO and glutathione (GSH) level. Different dosages of CCl₄ (0.1, 0.2, 0.3 and 0.4 % v/v) were applied to HepG2 and Hep3B cells in order to determine the most toxic dosage of it in a time dependent manner. The same experiments were repeated with exogenously applied melatonin (MEL) and Vitamin D to groups treated with/without CCL₄. Cell viability was determined with MTT measurements at the 2nd, 24th and 48th h. GSH content and Malondialdehyde levels were measured from the cell lysates. As a result, both melatonin and Vitamin D administration during CCl₄ exposure protected liver cells from CCl₄ induced cell damage. Increase in LPO and decrease in GSH were found in the CCl₄ groups of both cells. Contrary to these results administration of MEL and Vitamin D on cells exhibited results similar to the control groups. Therefore, melatonin and Vitamin D might be a promising therapeutic agent in several toxic hepatic diseases.     

Melatonin and schistosomal antigens ameliorate the anti-oxidative and biochemical response to Schistosoma mansoni infection in hamster

The present study was designed to investigate the potential protective effect of melatonin as an antioxidant separately or in combination with antigens (cercarial; CAP or soluble worm; SWAP) against Schistosoma mansoni infection in hamsters. Each hamster was sensitized with an initial immunization of 0.6 ml of the extracted antigen (30 μg protein/mL). After four days,a second injection of 0.4 mL was given (20 μg protein/mL). Then,each hamster was exposed to 260±20 S.mansoni cercariae followed with melatonin...     

Protective effects of ascorbic acid, Dl-α-tocopherol acetate, and sodium selenate on ethanol-induced gastric mucosal injury of rats

In this study, the effect of ascorbic acid (vitamin C), Dl-α-tocopherol acetate (vitamin E), and sodium selenate (selenium) on ethanol-induced gastric mucosal injury in rats was investigated morphologically and biochemically. The gastric mucosal injury was produced by administration of 1 mL of absolute ethanol to each rat. Animals received vitamin C (250 mg/kg), vitamin E (250 mg/kg), and selenium (0.5 mg/kg) for 3 d 1 h prior to the administration of absolute ethanol. In gastric mucosa of rats given ethanol according to control groups, neuronal nitric oxide expression decreased. This immunoreactivity was much lower in the group given ethanol+vitamin C+vitamin E+selenium than the control group and the ethanol-induced group. Scanning electron microscopic evaluation of the ethanol-induced group, when compared to control groups, revealed degenerative changes in gastric mucosa, whereas a good arrangement in surface topography of gastric mucosa in the group given ethanol + vitamin C+vitamin E + selenium was observed. In the group administered ethanol, a reduction of the stomach glutathione (GSH) and serum total protein levels and increases in serum sialic acid, triglycerides, and stomach lipid peroxidation (LPO) levels were observed. Vitamin C+vitamin E+Se administration to alcohol-treated rats significantly increased the serum total protein, triglyceride levels, and stomach GSH levels and significantly lowered the levels of serum sialic acid and stomach LPO compared to untreated alcohol-supplemented rats. As a result of these findings, we can say that the combination of vitamin C, vitamin E, and selenium has a protective effect on ethanol-induced gastric mucosal injury of rats.     

Leptin ameliorates burn-induced multiple organ damage and modulates postburn immune response in rats

The present study was designed to determine whether exogenous leptin reduces remote organ injury in the rats with thermal burn trauma. Leptin (10 microg/kg) or saline was administered intraperitoneally after burn injury, and the rats were decapitated at either 6 or 24 h. Plasma samples of 24-h burn group were assayed for the determination of monocyte and neutrophil apoptosis. Thermal injury increased tissue-associated myeloperoxidase (MPO) activity and microscopic damage scores in the lung, liver, stomach, colon and kidney of both 6- and 24-h burn groups. In the 6-h burn group, leptin reduced microscopic damage score in the liver and kidney only, while damage scores in the 24-h burn group were reduced in all the tissues except the lung. Also, in both burn groups, leptin reduced elevated MPO activity in all tissues except the lung. The percentage of mononuclear cells was significantly reduced at the 24 h of burn injury, while the granulocyte percentage was increased. Leptin treatment, however, had no significant effect on burn-induced reversal of white blood cell ratios. On the other hand, burn-induced increase in the death of mononuclear cells and granulocytes was significantly reduced in leptin-treated rats. The results of the present study suggest that leptin may provide a therapeutic benefit in diminishing burn-induced inflammation and associated multiple organ failure.     

Blood oxidative stress generation after intraperitoneal administration of functionalized single-walled carbon nanotubes in rats

Single-walled carbon nanotubes (SWCNTs) have been proposed for various medical applications. However, their safety for human administration has not been yet fully demonstrated. In vitro studies have pointed oxidative stress as a mechanism involved in their cytotoxic effects. In the present study we have evaluated the capacity of DNA functionalized SWCNTs to induce oxidative stress in blood after intraperitoneal (ip) administration in rats. The presence of SWCNTs in blood was confirmed by Raman spectroscopy 30 minutes after their ip administration. Oxidative stress parameters (malondialdehyde - MDA, protein carbonyls - PC, antioxidant capacity measured as hydrogen donating capacity - HD, sulfhydryl groups - SH, glutathione - GSH and nitrites - NO) were assessed in blood at 3, 6, 24, respectively, and 48 hours after ip injection. MDA, PC and NO exhibited a significant increase at 3-6 hours interval from exposure, followed by a recovery trend. The levels of HD reached a bottom level at 6 hours after administration, while SH strongly decreased at 3 hours interval and increased slightly up to 48 hours without attending the initial values. GSH level recorded an increasing tendency at the 3rd hour, an incomplete recovery process at 24 hours followed by a secondary significant increase following a 48-hour interval. Significant inverse correlations were obtained between the PC and SH levels and between the NO and HD values. In conclusion, the ip administration of DNA functionalized SWCNT in rats results in oxidative stress generation in plasma, with a transient pattern of evolution.