Nanofibrous polycaprolactone/gelatin scaffold containing gold nanoparticles: Physicochemical and biological characterization for wound healing.

In this study, gold nanoparticles were loaded into poly (ε-caprolactone) (PCL)/gelatin nanofibrous matrices to fabricate a potential wound dressing. The mats were produced by electrospinning of PCL/gelatin solution supplemented with synthesized gold nanoparticles (200, 400 and 800 ppm). Prepared scaffolds were investigated regarding their chemical properties, morphology, mechanical properties, surface wettability, water-uptake capacity, water vapor permeability, porosity, blood compatibility, microbial penetration test and cellular response. In addition to in vivo study, a full-thickness excisional wound in a rat model was used to evaluate the healing effect of prepared scaffolds. Results showed appropriate mechanical properties and porosity of prepared scaffolds. With L929 cells, the PCL/gelatin scaffold containing 400 ppm gold nanoparticles demonstrated the greatest cell growth. In vivo results validated the favorable wound-healing benefits of the scaffold incorporating gold nanoparticles, which triggered wound healing compared to sterile gauze. Our results showed the capability of nanofibrous matrices containing gold nanoparticles for successful wound treatment.

Erythropoietin improve spatial memory impairment following methamphetamine neurotoxicity by inhibition of apoptosis, oxidative stress and neuroinflammation in CA1 area of hippocampus.

OBJECTIVE: Methamphetamine (METH) is one of the most widely used addictive drugs, and addiction to it is on the rise all over the world. METH abuse has long-term damaging effects that reduce memory and impair cognitive functions. According to studies, the observed effects are strongly related to the nerve cell damage caused by METH, which leads to neurotoxicity. Some of these intra-neuronal events include dopamine oxidation, excitotoxicity, and oxidative stress. Erythropoietin (EPO) is a hormone produced primarily by the kidneys and, in small quantities, by the liver. Studies have shown that EPO exhibits considerable neuroprotective effects. This study aimed to investigate the protective effects of EPO on METH neurotoxicity. METHODS: Initially, 48 male Wistar rats, weighing 250-300 g, were randomly assigned to four groups: control (n = 12), METH (n = 12), and METH+EPO (2500, 5000 IU/kg/IP- n = 12). METH was injected intraperitoneally at a dose of 40 mg per kg of body weight (four injections of 10 mg every two hours) to induce neurotoxicity. EPO was injected at doses of 2500 and 5000 IU/kg seven days after the last METH administration (ip). Morris water maze test was performed following EPO injection (1 day after the last dose) to assess spatial memory. The brains were removed after the behavioral test, biochemical evaluations and immunohistochemistry (caspase-3 and GFAP) was performed. RESULTS: The results showed that EPO treatment significantly improved spatial memory impairment (P < 0.01), compared to the METH group, EPO was a significant reduction in malondialdehyde and TNF-α (P < 0.01), as well as an increase in superoxide dismutase (P < 0.05) and glutathione-PX (P < 0.01). Furthermore, EPO treatment significantly reduced the number of GFAP positive cells (P < 0.01) and caspase 3 (P < 0.001) in the hippocampus (CA1 region). CONCLUSIONS: The study findings suggested that EPO may have great neuroprotective effects on METH neurotoxicity due to its anti-inflammatory, antioxidant, and antiapoptotic properties.

Anti-inflammatory, Antioxidant, and Antiapoptotic Action of Metformin Attenuates Ethanol Neurotoxicity in the Animal Model of Fetal Alcohol Spectrum Disorders.

Fetal alcohol exposure has permanent effects on the brain structure, leading to functional deficits in several aspects of behavior, including learning and memory. Alcohol-induced neurocognitive impairment in offsprings is included with activation of oxidative- inflammatory cascade followed with wide apoptotic neurodegeneration in several brain areas, such as the hippocampus. Metformin is the first-line treatment for diabetic patients. It rapidly crosses the blood-brain barrier (BBB) and exerts antioxidant, anti-inflammatory, and neuroprotective effects. In this study, we evaluated the protective effects of metformin on ethanol-related neuroinflammation, as well as neuron apoptosis in the hippocampus of adult male rat in animal model of fetal alcohol spectrum disorders. Treatment with ethanol in milk solution (5.25 and 27.8 g/kg, respectively) was conducted by intragastric intubation at 2-10 days after birth. To examine the antioxidant and anti-inflammatory properties of metformin, an ELISA assay was performed for determining the tumor necrosis factor-α (TNF-α) and antioxidant enzyme concentrations. Immunohistochemical staining was conducted for evaluating the glial fibrillary acidic protein (GFAP) and cleaved caspase-3 expression. Based on the results, metformin caused a significant increase in the superoxide dismutase (SOD) (P < 0.05) and glutathione peroxidase (GSH-Px) (P < 0.01) activities. On the other hand, it reduced the concentrations of TNF-α and malondialdehyde, compared to the ethanol group (P < 0.01). In the metformin group, there was a reduction in cell apoptosis in the hippocampus, as well as GFAP-positive cells (P < 0.01). Overall, apoptotic signaling, regulated by the oxidative inflammatory cascade, can be suppressed by metformin in adult brain rats following animal model of fetal alcohol spectrum disorders.

Bioengineered 3D nanocomposite based on gold nanoparticles and gelatin nanofibers for bone regeneration: in vitro and in vivo study.

The main aim of the present study was to fabricate 3D scaffold based on poly (L-lactic acid) (PLLA)/Polycaprolactone (PCL) matrix polymer containing gelatin nanofibers (GNFs) and gold nanoparticles (AuNPs) as the scaffold for bone tissue engineering application. AuNPs were synthesized via the Turkevich method as the osteogenic factor. GNFs were fabricated by the electrospinning methods and implemented into the scaffold as the extracellular matrix mimicry structure. The prepared AuNPs and Gel nanofibers were composited by PLLA/PCL matrix polymer and converted to a 3D scaffold using thermal-induced phase separation. SEM imaging illustrated the scaffold's porous structure with a porosity range of 80-90% and a pore size range of 80 to 130 µm. The in vitro studies showed that the highest concentration of AuNPs (160 ppm) induced toxicity and 80 ppm AuNPs exhibited the highest cell proliferation. The in vivo studies showed that PCL/PLLA/Gel/80ppmAuNPs induced the highest neo-bone formation, osteocyte in lacuna woven bone formation, and angiogenesis in the defect site. In conclusion, this study showed that the prepared scaffold exhibited suitable properties for bone tissue engineering in terms of porosity, pore size, mechanical properties, biocompatibility, and osteoconduction activities.

Cyanocobalamin improves memory impairment via inhibition of necrosis and apoptosis of hippocampal cell death after transient global ischemia/reperfusion.

OBJECTIVES: Brain ischemia/reperfusion (I/R) causes irreversible damage, particularly in the hippocampus. Cyanocobalamin (CNCbl) is known to be crucial for the proper operation of the nervous system. Vitamin B12 has been demonstrated to exert antioxidant effects via direct and indirect mechanisms. It can also protect cortical neurons against glutamate cytotoxicity. This research was conducted to examine CNCbl protection against neuronal cell death in the rat hippocampal region following transient cerebral ischemia. MATERIALS AND METHODS: In this experiment, 48 male Wistar rats were selected, which were randomly divided into four groups (n=12 in each group): sham, ischemia/reperfusion, ischemia/reperfusion + CNCbl 200 and 400 (µg/kg). By occlusion of both common carotids, ischemia induction was performed within 20 min. CNCbl at the doses of 200 and 400 µg/kg was injected (IP) at the start of the reperfusion, 24 and 48 hr following reperfusion. The spatial memory was assessed 7 days following ischemia through the Morris water maze test. Antioxidant enzymes, apoptosis, and necrosis were measured after behavioral tests. RESULTS: CNCbl significantly improved spatial memory impairments (P<0.05), also CNCbl therapy significantly increased both glutathione (P<0.01) and superoxide dismutase (P<0.05) and reduced malondialdehyde (P<0.01) and TNF-α (P<0.05) in comparison with the ischemia group. In addition, CNCbl significantly decreased both apoptosis and necrosis in the hippocampus CA1 (P<0.01). CONCLUSION: CNCbl improves memory impairment following ischemia injury by decreasing neuronal cell death via its antioxidant properties.

Palmatine ameliorates nephrotoxicity and hepatotoxicity induced by gentamicin in rats.

The aim of this study was to investigate the effects of palmatine on gentamicin toxicity. Rats arranged in four groups: 1- Sham, 2- GM, 3- & 4- GM + palmatine (50 & 100 mg/kg). Gentamicin led to increase in plasma AST, ALT, BUN and creatinine. In addition, fractional excretion of Na and K were increased and urine flow rate and creatinine clearance were decreased in gentamicin group. Liver and renal tissues malondialdehyde were increased, and glutathione was decreased in GM group. TUNEL assay showed induction of apoptosis in liver and kidney in GM group. Palmatine treatment caused reduction in plasma AST, ALT, urine flow rate, creatinine clearance, renal and hapatic malondialdehyde, apoptosis and increase in renal and hapatic glutathione, fractional excretion of Na and K, plasma BUN and creatinine in contrast to GM group. Our data showed palmatine reduced hepatotoxicity and nephrotoxicity by inhibition of oxidative stress and apoptosis.

Bone regeneration in rat using polycaprolactone/gelatin/epinephrine scaffold.

Solid supports like the extracellular matrix network are necessary for bone cell attachment and start healing in the damaged bone. Scaffolds which are made of different materials are widely used as a supportive structure in bone tissue engineering. In the current study, a 3D polycaprolactone/gelatin bone scaffold was developed by blending electrospinning and freeze-drying techniques for bone tissue engineering. To improve the efficiency of the scaffold, different concentrations of epinephrine (EP) due to its effect on bone healing were loaded. Fabricated scaffolds were characterized by different tests such as surface morphology, FTIR, porosity, compressive strength, water contact angle, and degradation rate. The interaction between prepared scaffolds and blood and cells was evaluated by hemolysis, and MTT test, respectively, and bone healing was evaluated by a rat calvaria defect model. Based on the results, the porosity of scaffolds was about 75% and by adding EP, mechanical strength decreased while due to the hydrophilic properties of it, degradation rate increased. In vivo and in vitro studies showed the best cell proliferation and bone healing were in PCL/gelatin/EP1% treated group. These results showed the positive effect of fabricated scaffold on osteogenesis and bone healing and the possibility of using it in clinical trials.

Improving sciatic nerve regeneration by using alginate/chitosan hydrogel containing berberine.

Peripheral nerve injuries are the common results of trauma that lead to pain and handicap in patients. Berberine due to its properties like antibiotic, immunostimulant, antitumor, antimotility, and positive effect on neurological disorders can be used to enhance peripheral nerve injuries. In this study, alginate/chitosan hydrogel containing different concentrations of berberine (0, 0.1, 1, 10% (w/v)) was created, evaluated, and applied as a scaffold for sciatic nerve regeneration. To prepare hydrogel, sodium alginate was dissolved in distilled water and cross-linked with CaCl2, and chitosan was dissolved in acetic acid and cross-linked with ß-glycerol phosphate. The structure, release, swelling, weight loss, cytocompatibility, and hemocompatibility of the prepared hydrogels were assessed. The sciatic nerve crush was created in rats and fabricated hydrogels were injected, and functional analysis was used to evaluate their effectiveness. The results of physical characterization of the hydrogel indicated that the initial average pore size was about 39 µm and about 70% of the main weight of hydrogels was lost after incubation for 21 days and hemocompatibility of hydrogels was also confirmed. The MTT assay showed the cytocompatiblity of hydrogels and also indicated that berberine has dose-dependence effect on cell proliferation. The in vivo results showed the positive effect of berberine especially the hydrogel contained 1% of berberine on regeneration of sciatic nerve. Based on this study, Alg/Chit hydrogel can be applied as a treatment to heal peripheral nerve injuries. Graphical abstract.

The Impact of Sex Differences on Renal Protective Effects of Lipopolysaccharide Preconditioning in Septic Shock.

BACKGROUND: Induction of septic shock by lipopolysaccharide (LPS) may lead to acute renal failure. The present study aimed to investigate the impact of sex differences on the effectiveness of low-dose LPS preconditioning (LPS-PC) on LPS-induced acute renal failure in rats. METHODS: This study was conducted at Tehran University of Medical Sciences, in 2017. A total of 48 Wistar rats were equally divided into two groups of male and female rats. The rats in each group were then allocated to three groups (n=8 per group), namely control, septic shock, and LPS-PC group. A high dose of LPS was administered for septic shock induction. LPS-PC was induced by injecting LPS before sepsis induction. The effect of sex differences on renal functional indices, renal oxidative stress markers, plasma tumor necrosis factor-α level, and renal histological changes was evaluated. Data were analyzed using two-way ANOVA followed by Tukey's post hoc test. RESULTS: In the septic shock groups, renal functional parameters (creatinine [Cr] and blood urea nitrogen [BUN]) were increased in both sexes. However, the increase was more significant in male rats (male rats: Cr=2.14±0.13, BUN=81±4.15; female rats: Cr=1.64±0.12, BUN=50±2.7). LPS-PC reduced these indices in both sexes (male rats: Cr=1.24±0.03, BUN=57±4.1; female rats: Cr=0.86±0.02, BUN=30.31±2.25). Renal superoxide dismutase (SOD) activity (male rats: 11.54±1.34, female rats: 24.4±2.04) and catalase (CAT) activity (male rats: 15±1.74, female rats: 25.75±1.97) were significantly higher in the female septic group. LPS-PC significantly increased SOD (male rats: 25.7±2.45, female rats: 42.6±3.31) and CAT (male rats: 37.25±2.34, female rats: 59.21±3.29) activities in renal tissue samples in the LPS-PC group in both sexes compared to the septic groups. In the LPS groups, plasma tumor necrosis factor-α (male rats: 375±25.65, female rats: 285.45±25.94) were significantly higher than in the LPS-PC groups (male rats: 250±21.35, female rats: 121±24.14). CONCLUSION: Male rats were more susceptible to sepsis-induced renal damage. LPS-PC had protective effects on the LPS-induced renal injury, and these effects were most prominent in female rats.

Alginate hydrogel containing hydrogen sulfide as the functional wound dressing material: In vitro and in vivo study.

Functional and bioactive wound dressing materials are revolutionary for wound care and healing applications. In this concept, we fabricated alginate hydrogel (Alg) containing H2S as the wound dressing materials and assessed the morphology, swelling, degradation, and release behavior, as well as the biocompatibility, cytocompatibility, and wound healing activity. The results depicted that the prepared hydrogels have a porous structure with the pore size in the range of 50 to 100 µm. Swelling and degradation studies showed that the hydrogel absorbed water about 179 ± 5% of initial dry weight during 96 h and loos about 80% of the initial dry weight after 7 days. The in vitro assessments illustrated that the optimum concentration of H2S was 0.5% and the higher concentration induced hemolysis and cell toxicity. The in vivo study revealed that the treatment by Alg/H2S 0.5% induced the highest wound closure percent with a value of 98 ± 1.22%. Moreover, the treatment by Alg/H2S 0.5% elicited the formation of sebaceous glands, hair follicles, and complete epithelization without any fibroplasia or inflammation, revealed by the histopathological observations. Accordingly, these results illustrated that the prepared Alg/H2S 0.5% could be applied as the functional and bioactive wound dressing materials.

Electrospun cellulose acetate/gelatin nanofibrous wound dressing containing berberine for diabetic foot ulcer healing: in vitro and in vivo studies.

Functional wound dressing with tailored physicochemical and biological properties is vital for diabetic foot ulcer (DFU) treatment. Our main objective in the current study was to fabricate Cellulose Acetate/Gelatin (CA/Gel) electrospun mat loaded with berberine (Beri) as the DFU-specific wound dressing. The wound healing efficacy of the fabricated dressings was evaluated in streptozotocin-induced diabetic rats. The results demonstrated an average nanofiber diameter of 502 ± 150 nm, and the tensile strength, contact angle, porosity, water vapor permeability and water uptake ratio of CA/Gel nanofibers were around 2.83 ± 0.08 MPa, 58.07 ± 2.35°, 78.17 ± 1.04%, 11.23 ± 1.05 mg/cm2/hr, and 12.78 ± 0.32%, respectively, while these values for CA/Gel/Beri nanofibers were 2.69 ± 0.05 MPa, 56.93 ± 1°, 76.17 ± 0.76%, 10.17 ± 0.21 mg/cm2/hr, and 14.37 ± 0.42%, respectively. The antibacterial evaluations demonstrated that the dressings exhibited potent antibacterial activity. The collagen density of 88.8 ± 6.7% and the angiogenesis score of 19.8 ± 3.8 obtained in the animal studies indicate a proper wound healing. These findings implied that the incorporation of berberine did not compromise the physical properties of dressing, while improving the biological activities. In conclusion, our results indicated that the prepared mat is a proper wound dressing for DFU management and treatment.

Sleep Improvement Effect on Sexual Life Quality Among Rotating Female Shift Workers: A Randomized Controlled Trial.

BACKGROUND: Poor sleep quality consequences among shift working nurses are well recognized. AIM: To investigate the impact of sleep improvement on sexual quality of life. METHODS: The study was a parallel randomized controlled trial, conducted among 120 female nurses in 2 educational hospitals in the Northeast of Iran, Shahroud. Using random blocks of four, 120 eligible participants were randomly assigned to study groups. Data collecting tools included a demographic data questionnaire, Pittsburgh Sleep Quality Index to assess sleep quality, and the survey of sexual quality of life-female and Sexual Self-Efficacy Questionnaire to evaluate level of sexual quality of life and sexual self-efficacy, respectively. The intervention consisted of 3 weekly sleep intervention sessions that lasted from 90 to 120 minutes. OUTCOMES: The study's primary and secondary outcomes were sleep quality, and the level of sexual self-efficacy and sexual quality of life, respectively. RESULTS: By 3-month follow-up, the loss to follow-up rate was 5.9%. The mean sleep quality score was 7.61 ± 2.26 in the recruited participants. Following the intervention, the sleep quality score showed statistically significant differences compared to the control group [mean difference (CI 99.98%), -1.89 (-2.40, -1.38)]. Participants in the intervention group showed modest increases in both measures; sexual self-efficacy [mean difference (CI 99.98%), 8.82 (6.83, 10.81)] and sexual quality of life [mean difference (CI 99.98%), 19.64 (18.08, 21.20)]. CLINICAL IMPLICATIONS: These findings suggest that sleep improvement could promote the sexual quality of life among shift working nurses. STRENGTHS & LIMITATIONS: Strengths of this study include the use of a validated outcome measure. Focusing the study on female nurses and the small size of the study population are the limitations. CONCLUSION: Improved sleep showed an impact on sexual quality of life among rotating female shift workers. Khastar H, Mirrezaie SM, Chashmi NA, et al. Sleep Improvement Effect on Sexual Life Quality Among Rotating Female Shift Workers: A Randomized Controlled Trial. J Sex Med 2020;17:1467-1475.

Sophisticated polycaprolactone/gelatin nanofibrous nerve guided conduit containing platelet-rich plasma and citicoline for peripheral nerve regeneration: In vitro and in vivo study.

Peripheral nerve injury (PNI) is a devastating condition that may result in loss of sensory function, motor function, or both. In the present study, we construct an electrospun nerve guide conduit (NGC) based on polycaprolactone (PCL) and gelatin filled with citicoline bearing platelet-rich plasma (PRP) gel as a treatment for PNI. The NGCs fabricated from PCL/Gel polymeric blend using the electrospinning technique. The characterizations demonstrated that the fabricated nanofibers were straight with the diameter of 708 ±â€¯476 nm, the water contact angle of 78.30 ±â€¯2.52°, the weight loss of 41.60 ±â€¯6.94% during 60 days, the tensile strength of 5.31 ±â€¯0.97 MPa, and the young's modulus of 3.47 ±â€¯0.10 GPa. The in vitro studies revealed that the PCL/Gel/PRP/Citi NGC was biocompatible and hemocompatible. The in vivo studies conducted on sciatic nerve injury in rats showed that the implantation of PCL/Gel/PRP/Citi NGC induced regeneration of nerve tissue, demonstrated with histopathological assessments. Moreover, the sciatic function index (SFI) value of -30.3 ±â€¯3.5 and hot plate latency time of 6.10 ±â€¯1.10 s revealed that the PCL/Gel/PRP/Citi NGCs recovered motor and sensory functions. Our findings implied that the fabricated NGC exhibited promising physicochemical and biological activates favorable for PNI treatment.

Sulfur dioxide reduces hippocampal cell death and improves learning and memory deficits in a rat model of transient global ischemia/reperfusion.

OBJECTIVES: According to recent the findings, sulfur dioxide (SO2) is produced by the cardiovascular system, influencing some major biological processes. Based on previous research, SO2 exhibits antioxidant effects and inhibits apoptosis following cardiac ischemia/reperfusion. Therefore, the objective of the current study was to examine the neuroprotective impact of SO2 following global cerebral ischemia/reperfusion (I/R). MATERIALS AND METHODS: Forty-eight male Wistar rats that weighed 260-300 g, were randomly allocated into 4 groups: sham group (n=12), I/R group (n=12), and I/R+SO2 groups (NaHSO3 and Na2SO3; 1:3 ratio; 5 and 10 µg/kg, respectively; for 3 days, n=12). Cerebral ischemia model was prepared by occlusion of both common carotid arteries for 20 min. Saline as a vehicle and SO2 donor at doses 5 µg/kg (intraperitoneally) were injected for 3 days after reperfusion. Four days after ischemia, the passive avoidance memory test was carried out in four groups, and after behavioral assessment, necrosis, apoptosis, and antioxidant enzyme analysis were carried out. RESULTS: O2 treatment could significantly improve memory impairments in rats with cerebral ischemia/reperfusion (I/R) (P<0.05). An increase in both superoxide dismutase and glutathione and a reduction in malondialdehyde were reported in the SO2 group versus the ischemic group (P<0.05). Moreover, SO2 could significantly decrease necrotic and apoptotic cells in the CA1 region (P<0.01). CONCLUSION: According to the findings, SO2 exerts significant neuroprotective effects on cerebral I/R due to its antioxidant activity.

Protective effects of hydroxytyrosol on gentamicin induced nephrotoxicity in mice.

BACKGROUND: Gentamicin (GM) is an effective and common antibiotic against severe gram-negative infections. However, its nephrotoxic action has limited the extent of its use. The aim of this study was to investigate the protective effects of hydroxytyrosol (HT) on gentamicin induced nephrotoxicity in mice. METHODS: Male mice (n = 27) were randomly assigned to three groups: (1) Sham, (2) GM (100 mg/kg for 7 days) (3) GM + HT (2 mg/kg BW; gastric gavages, for 7 days). 24-h urine samples were collected on day 8 and then animal were anesthetized. The blood and kidney tissue samples were collected. RESULTS: Gentamicin led to increase in plasma BUN and creatinine, fractional excretion of sodium and potassium and decrease in creatinine clearance and urine flow rate. SOD and GSH levels were reduced and MDA was increased in the GM group compared with the sham group. In GM + HT group, plasma BUN and creatinine, fractional excretion of Na, creatinine clearance and urine flow rate were decreased in contrast to GM group. Increase in SOD and GSH activity and decrease in MDA compared to GM group were seen. CONCLUSIONS: Findings suggest that HT partly protected the kidneys from gentamicin induced nephrotoxicity and it is partly due to antioxidant effect of HT.

Protective effects of vitamin E against liver damage caused by renal ischemia reperfusion.

Recent studies have reported that remote organs are affected by renal ischemia reperfusion (IR). The present study investigates the role of vitamin E on the liver damage after renal IR. First, male mice were subjected to three groups (n = 9): 1) sham-operated, (2) renal IR (45 min ischemia), (3) renal IR + Vitamin E (150 mg/kg trough feeding tube for 28 d). After 24 h of reperfusion, animal were anesthetized for sample collections. Liver tissues malondialdehyde (MDA) increased and total glutathione (GSH) concentration decreased in the IR group compared to the sham group. Vitamin E consumption diminished the IR-induced increase in plasma AST and ALT. In addition, Vitamin E inhibited the IR-induced decrease in GSH activity and diminished IR-induced increase in MDA concentration. These findings showed that vitamin E consumption partly inhibited the IR-induced liver damage.

Leukocyte involvement in renal reperfusion-induced liver damage.

BACKGROUNDS/AIMS: Renal ischemia-reperfusion (IR) induces organ damage in remote organs. The aim of this study was to assess the role of leukocytes in the induction of liver damage after renal IR injury. METHODS: Inbred mice were subjected to either sham operation or bilateral renal IR injury (60 min ischemia followed by 3 h reperfusion). Mice were then anesthetized for collection of leukocytes by heart puncture. Isolated leukocytes were transferred to two other groups: intact recipient mice that received leukocytes from IR mice and intact recipient mice that received leukocytes from sham-operated control mice. After 24 h, recipient mice were anesthetized and samples were collected. RESULTS: Alanine aminotransferase, aspartate aminotransferase, and hepatic malondialdehyde increased significantly, and hepatic glutathione decreased significantly in intact recipient mice that received leukocytes from IR mice in comparison with intact recipient mice that received leukocytes from sham-operated control mice. Loss of normal liver architecture, cytoplasmic vacuolization, and focal infiltration of leukocytes were seen. CONCLUSION: These results suggest that leukocytes are one of the possible factors that contribute to liver damage after renal IR injury and this damage is partly due to the induction of oxidative stress.

Liver Oxidative Stress after Renal Ischemia-Reperfusion Injury is Leukocyte Dependent in Inbred Mice.

OBJECTIVES: There are some reports in recent years indicating that renal ischemia - reperfusion (IR) induces deleterious changes in remote organs such as liver. The aim of this study was to investigate whether leukocytes have a role on the induction of oxidative stress in liver after renal IR. MATERIALS AND METHODS: Inbred mice in IR donor group were subjected to renal IR injury. In sham donor group the procedure was almost the same except that ischemia was not induced. Then, mice were anesthetized and blood was collected. Leukocytes were isolated from donor groups and were then transferred to intact recipient mice (from IR donor mice to IR recipient mice and from sham donor mice to sham recipient mice). RESULTS: After 24 hr, hepatic superoxide dismutase (SOD) and catalase (CAT) activities decreased significantly in recipient mice that received leukocytes from IR donor mice in comparison to recipient mice received leukocytes from sham donor mice. CONCLUSION: These findings indicate that leukocytes are one of the mediators that induce hepatic oxidative stress after renal IR.

Effects of nitric oxide on gentamicin toxicity in isolated perfused rat kidneys.

BACKGROUND: There have been many studies in recent years concerning the role of nitric oxide (NO) in acute renal failure (ARF). In this study, the effects of the inhibition or the induction of NO synthase (NOS) on gentamicin-induced ARF was investigated in isolated perfused rat kidneys. METHODS: Kidneys from male Sprague-Dawley rats were perfused in situ for 90 min. Perfusion was conducted in the presence of inulin (60 mg/dL in perfusion buffer) as a glomerular filtration rate (GFR) marker. Six groups (total: 42 rats) were studied: group 1, controls with no treatment; group 2, L-arginine (2 mM in perfusate); group 3, L-nitro-arginine-methyl ester (L-NAME, 0.1 mM in perfusate); group 4, gentamicin (GM, 0.5 mg/mL in perfusate); group 5, GM + L-arginine (same dose as groups 2 and 4) and; group 6, GM + L-NAME (same dose as groups 3 and 4). Cell injury was assessed by measuring N-acetyl-beta-D-glucosaminidase (NAG), lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) activity in urine. RESULTS: L-arginine prevented, whereas L-NAME enhanced, GM-induced enzyme release and GFR reduction. Histological studies showed that GM-treated kidneys had clear signs of tubular damage and this damage was increased by simultaneous L-NAME and GM administration. CONCLUSION: This study suggests that NO formation could prevent the GM-induced nephrotoxicity in this ARF model.

Effects of co-supplementation of vitamins E and C on gentamicin-induced nephrotoxicity in rat.

Gentamicin (GM) is an effective antibiotic against severe gram-negative infections. However it can produce nephrotoxicity in human. Reactive oxygen species (ROS) have been proposed as the causative factors of the renal side effects the drug. This study was performed to investigate the protective role of antioxidant vitamins against GM-mediated nephropathy in an in situ model of isolated rat kidney. Male Sprague-Dawley rats were randomly assigned to one of the following groups of seven rats: group 1 (Control) was perfused with Tyrode solution; group 2 (GM), 200 microg ml(-1) GM was added to the perfusate; group 3 (GM + Vit C), as group 2 with vitamin C added to the drinking water for 3 days (200 mg l(-1)) and to the perfusate (100 mg l(-1)); group 4 (GM + Vit E), as group 2 with vitamin E (100 mg (100 g body weight)(-1), i.m.) injected 12 h before the start of the experiment; group 5 (GM + Vit C + Vit E) as group 2 with vitamin E and C co-administered (concentrations and conditions as in groups 3 and 4). To compare the groups, urinary lactate dehydrogenase (LDH), N-acetyle-beta-D-glucosaminidase (NAG) and alkaline phosphatase (ALP) activities, inulin clearance (glomerular filtration rate, GFR) and renal tissue glutathione (GSH) content were measured. GM caused a significant nephrotoxicity demonstrated by an increase in urinary LDH, NAG and ALP activities. Reduction in GSH content and a marked decrease in GFR were observed compared to controls. Vitamin C inhibited the GM-induced increase in urinary enzyme activities but did not show a significant effect on the GSH content or GFR. Vitamin E prevented the GM-induced reduction in GSH level without a significant improvement in GFR. Co-administration of vitamins C and E significantly prevented the GM-induced nephrotoxicity demonstrating by preservation of GFR and GSH levels and prevention of increase in urinary enzyme activities. We conclude that co-administration of moderate doses of vitamins C and E has beneficial effects on renal preservation in GM-induced nephrotoxicity.