Leukotriene receptor blocker montelukast protects against burn-induced oxidative injury of the skin and remote organs

Thermal injury elicits several systemic consequences, among them the systemic inflammatory response where the generation of reactive oxygen radicals and lipid peroxidation play important roles. In the present study, we investigated whether the leukotriene receptor blocker montelukast is protective against burn-induced remote organ injury. 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 tissue samples from lung, liver, kidney and skin were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Tissues were also examined microscopically. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels and creatinine, urea (BUN) concentrations were determined to assess liver and kidney function, respectively. Tumor necrosis factor-alpha (TNF-alpha) and lactate dehydrogenase (LDH) were also 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 ALT, AST and BUN levels, as well as LDH and TNF-alpha, 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 damage in remote organs and protects against oxidative organ damage by a neutrophil-dependent mechanism.     

Silymarin, the antioxidant component of Silybum marianum, protects against burn-induced oxidative skin injury

BACKGROUND: Despite recent advances, severe burn is one of the most common problems faced in the emergency room. Major thermal injury induces the activation of an inflammatory cascade resulting in local tissue damage, to contribute to the development of subsequent damage of multiple organs distant from the original burn wound. OBJECTIVE: Silymarin, the major component of milk thistle has been shown to have antioxidant properties. In the present study, we investigated the putative antioxidant effect of local or systemic silymarin treatment on burn-induced oxidative tissue injury. METHODS: Wistar albino rats were exposed to 90 degrees C bath for 10 s to induce burn. Silymarin either locally (30 mg/kg) applied on 4 cm(2) area or locally+systemically (50 mg/kg, p.o.) was administered after the burn and repeated twice daily. Rats were decapitated 48 h after injury and blood was collected for tumor necrosis factor-alpha (TNF-alpha) and lactate dehydrogenase (LDH) activity. In skin tissue samples malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and luminol-lucigenin chemiluminescense (CL) were measured in addition to the histological evaluation. RESULTS: Burn caused a significant increase in TNF-alpha and LDH levels. MDA levels were increased and GSH levels were decreased in the skin at 48 h after-burn. Both local and systemic silymarin treatments significantly reversed these parameters. The raised MPO activity and luminol-lucigenin CL were also significantly decreased. CONCLUSION: Results indicate that both systemic and local administration of silymarin was effective against burn-induced oxidative damage and morphological alterations in rat skin. Therefore, silymarin merits consideration as a therapeutic agent in the treatment of burns.     

PPAR-gamma agonist protects podocytes from injury

Podocyte injury and loss contribute to progressive glomerulosclerosis. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a nuclear hormone receptor, which we have found to be increased in podocytes in a variety of kidney diseases. It is not known if PPAR-gamma contributes to renal injury or if it serves as a countermeasure to limit renal injury during disease progression. We tested these possibilities utilizing the puromycin aminonucleoside (PAN) model of renal injury in immortalized mouse podocytes. The cultured podocytes expressed PPAR-gamma mRNA at baseline but this was decreased by PAN. Pioglitazone, a pharmacologic agonist of PPAR-gamma, increased both PPAR-gamma mRNA and activity in injured podocytes, as assessed by a reporter plasmid assay. Further, pioglitazone significantly decreased PAN-induced podocyte apoptosis and necrosis while restoring podocyte differentiation. The PPAR-gamma agonist significantly restored expression of the cyclin-dependent kinase inhibitor p27 and the antiapoptotic molecule Bcl-xL while significantly decreasing proapoptotic caspase-3 activity. Pioglitazone tended to decrease PAN-induced transforming growth factor-beta (TGF-beta) mRNA expression. Our study shows that PPAR-gamma is normally expressed by podocytes and its activation is protective against PAN-induced apoptosis and necrosis. We postulate that this protective effect may be mediated in part by effects on p27 and TGF-beta expression.     

2-Mercaptoethane sulfonate (MESNA) protects against burn-induced renal injury in rats

Animal models of thermal injury implicate oxygen radicals as causative agents in local wound response and distant organ injury following burn. In this study we investigated the putative protective effects of 2-mercaptoethane sulfonate (MESNA) against oxidative kidney damage in rats with thermal injury. Under ether anaesthesia, shaved dorsum of the rats was exposed to 90 degrees C bath for 10s to induce burn injury. Rats were decapitated either 6 or 24h after burn injury. MESNA was administered i.p. immediately after burn injury. MESNA injections were repeated once more 12h after the first injection in the 24h burn group. In the control group the same protocol was applied except that the dorsum was dipped in a 25 degrees C water bath for 10s. Kidney tissues were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, protein oxidation (PO), myeloperoxidase (MPO) activity and collagen contents. Creatinine, urea concentrations (BUN) and lactate dehydrogenase (LDH) in blood were measured for the evaluation of renal functions and tissue damage, respectively. Tissues were also examined microscopically. Severe skin scald injury (30% of total body surface area) caused significant decrease in GSH level, significant increase in MDA level, protein oxidation (PO), MPO activity and collagen content of renal tissue. Serum creatinine was slightly increased at the early phase of thermal trauma but not changed in 24h groups. On the other hand BUN and LDH were significantly elevated by thermal trauma in both 6 and 24h of burn groups. Treatment of rats with MESNA significantly increased the GSH level and decreased the MDA level, PO, MPO activity, collagen contents, BUN and LDH. Since MESNA reversed the oxidant responses seen in burn injury, it seems likely that MESNA could protect against thermal trauma-induced renal damage.     

Dexmedetomidine protects against burn-induced intestinal barrier injury via the MLCK/p-MLC signalling pathway

BackgroundEvidence suggests that sedative dexmedetomidine can prevent intestinal dysfunction. However, the specific mechanisms of its protective effects against burn-induced intestinal barrier injury remain unclear. We aimed to explore the possible positive effects of dexmedetomidine on burn-induced intestinal barrier injury and the effects the myosin light chain kinase (MLCK)/phosphorylated myosin light chain (p-MLC) signalling pathway in an experimental model of burn injury.MethodsIn this study, the plasma concentration of fluorescein isothiocyanate-labelled dextran (FITC-dextran) was measured. Histological changes were evaluated using haematoxylin and eosin (HE) staining. Tight junction proteins were evaluated by western blot and immunofluorescence analyses to assess the structural integrity of intestinal tight junctions. The level of inflammation was detected by enzyme-linked immunosorbent assay (ELISA).ResultsThe results shows that the increase in intestinal permeability caused by burn injury is accompanied by histological damage to the intestine, decreases in the expression of the tight junction proteins Zonula Occludens-1 (ZO-1) and Occludin, increases in inflammatory cytokine levels and elevation of both MLCK protein expression and MLC phosphorylation. After dexmedetomidine treatment, the burn-induced changes were ameliorated.ConclusionsIn conclusion, dexmedetomidine exerted an anti-inflammatory effect and protected tight junction complexes against burn‑induced intestinal barrier damage by inhibiting the MLCK/p-MLC signalling pathways.     

维生素E对人精子冻融氧化应激损伤的保护作用

目的:探讨水溶性维生素E(Trolox)对冻融人精子氧化应激损伤的可能保护作用及机制。方法:选取16份健康生育男性的精液标本,分析精液常规参数及动力学参数后,将每份精液一式4份,1∶1加入冷冻保护液后混匀,不含水溶性维生素E者设为阴性对照组(G0),而G1、G2、G3实验组混合液中分别含有50、100、200μmol/L浓度的水溶性维生素E,冷冻复苏精液常规分析,检测复苏后精液中活性氧(ROS)水平,采用硫巴比妥酸法(TBA)检测精子中脂质过氧化产物丙二醛(MDA)浓度。结果:冻融后各组精子运动参数较新鲜精液参数均明显下降(P0.01),G2组前向运动精子百分率[(53.33±5.63)%]较对照组[(47.85±5.09)%]明显改善(P0.05),精子VCL和VAP高于阴性对照组(P0.05)。G2组与G3组的ROS及MDA均低于阴性对照组(P0.05)。结论:在精液冷冻保护液中添加一定浓度的水溶性维生素E可以减少精子冻融过程中产生的过量ROS,减轻ROS对精子质膜的氧化应激性损伤,从而提高冻融后的精子活力。     

线粒体靶向抗氧化剂Mitoquinone对人精子冻融氧化应激损伤的保护作用

目的:探讨线粒体靶向抗氧化剂Mitoquinone(Mito Q)对冻融人精子的保护作用。方法:选取60份健康生育男性精液标本,每份精液一式6份,不含Mito Q者设为对照组(G0),而G1、G2、G3、G4、G5实验组混合液中分别含有2 nmol/L、20 nmol/L、200 nmol/L、2μmol/L、20μmol/L Mito Q,37℃孵育1 h后检测活性氧(ROS)、丙二醛(MDA)和线粒体膜电位(MMP)变化。选取合适Mito Q浓度B1、B2组用于精子冷冻保存,B0组未添加Mito Q,B1、B2组在精子冷冻保护液中分别含有200 nmol/L和2μmol/L Mito Q,进行冷冻保存,检测冷冻复苏后的ROS水平、MDA含量和MMP改变。结果:新鲜精液添加Mito Q孵育后,G3组和G4组前向运动精子百分率[(30.8±10.2)%和(32.7±13.5)%]和总活动率[(70.6±9.0)%和(70.3±11.9)%]显著高于G0组[(17.6±5.0)%、(54.9±11.5)%](P0.05);随着Mito Q浓度的增加,ROS水平呈下降趋势,G3、G4、G5组(分别为86.5±31.6、93.6±42.0、45.1±15.0)显著低于G0组(160.8±39.7)(P0.05);MDA含量G3、G4组[分别为(0.9±0.5)、(0.9±0.5)μmol/mg]明显低于G0组[(1.9±1.1)μmol/mg](P0.05),而G5组[(1.7±0.7)μmol/mg]不但没有降低,反而显著高于G3、G4组(P0.05);与G0组MMP(1 701±251)相比,G5组(1 156±216)显著降低(P0.05),而G1、G2、G3、G4组(分别为1 810±298、1 995±437、1 950±334、1 582±314)无明显变化。冷冻复苏后各组前向运动精子百分率和总活动率均较新鲜精液明显下降(P0.01),B1组前向运动精子百分率[(3.2±2.3)%]较B0组[(0.8±0.6)%]明显改善(P0.05);B1组精子总活动率[(43.0±9.5)%]较B0组[(26.5±11.4)%]明显改善(P0.05);B1组ROS[(34.6±12.3)]和B2组ROS[(37.0±10.5)]均较B0组[(56.9±14.3)]显著下降(P0.05),B1组MDA[(1.4±0.5)μmol/mg]和B2组MDA[(1.4±0.6)μmol/mg]均较B0组[(2.6±1.0)μmol/mg]显著下降(P0.05),B1组MMP[(1 010.0±131.5)]和B2组MMP[(880.6±128.6)]均显著高于B0组[(721.1±24.8)](P0.05)。结论:在精液冻存液中添加200 nmol/L的Mito Q能有效提高人精子质量,可作为精液冷冻保护添加剂用于精液的冷冻保存。     

Adrenomedullin protects against oxidative stress-induced podocyte injury as an endogenous antioxidant.

BACKGROUND: We previously reported that puromycin aminonucleoside (PAN) increased adrenomedullin (AM) secretion and AM mRNA expression in podocytes, through overproduction of oxidative stress. To clarify the cytoprotective role of AM as antioxidative and antiapoptotic substance in podocytes, we investigated the effect of exogenous AM and AM antagonist on PAN-induced apoptosis in conditionally immortalized murine podocytes. METHODS: The expression of AM, RAMP 2 and RAMP 3 was investigated using real-time PCR, western blotting analysis and immunofluorescence microscopy. Reactive oxygen species (ROS) production was measured by CM-H(2)DCFDA fluorescence intensity method. The percentage of apoptotic cells was measured by Hoechst 33342 staining. RESULTS: PAN (100 microg/ml) significantly (P < 0.01) increased ROS production, associated with an increase in apoptosis; the percentage of apoptotic cells is 5.3% + 0.05% (P < 0.01) with 36 h treatment of PAN compared to 0.24 + 0.16% with no treatment. Several antioxidants could markedly reduce PAN-induced apoptosis in cultured podocytes, suggesting that PAN-induced apoptosis might be attributable to the overproduction of ROS. Accordingly, the administration of exogenous AM (10(-6) M) could significantly reduce not only ROS production via a PKA-dependent pathway, but also the resultant apoptosis induced by PAN. AM antagonists, CGRP8-37, augmented PAN-induced apoptosis, associated with increased ROS production, 2.2- and 2.3-Fold, respectively. RAMP 2 and RAMP 3 could be detected in podocytes and glomeruli. CONCLUSIONS: This suggests that ROS-induced up-regulation of AM with PAN could counteract ROS-induced apoptosis, by the suppression of ROS production. Therefore, AM might have the endogenous antioxidant potential to protect against ROS-induced podocyte injury.     

Pretreatment with bilirubin protects islet against oxidative injury during isolation and purification

Background

A high yield of pure, viable islets is one of the most important prerequisites for successful islet transplantation. However, during isolation and purification, many factors may cause oxidative stress, impacting islet viability. Accumulating evidence indicates that bilirubin (BR) not only has antioxidative but also has cytoprotective activities. In this study, we investigated whether pretreatment with bilirubin would protect islets against oxidative damage during isolation and purification.

Methods

Wistar rats were randomly divided into control and BR groups. The latter rats received an injection of BR 2 hours before islet isolation, whereas the controls received vehicle. Islet purity was determined using a dithizone stain. Survival rate and viability were determined using acridine orange and propidium iodide staining and the Cell Counting Kit-8 Kit. Islet function was quantified by testing glucose-stimulated insulin secretion. Islet damage caused by oxidative stress was quantified by measuring the malondialdehyde (MDA) in freshly isolated islets.

Results

Pretreatment with bilirubin did not enhance the purity, but significantly enhanced the survival rate and viability of the islets. Islet function in the BR group was significantly better than that in the control cohort. The MDA level was 0.62 ± 0.23 nmol/L/μg protein in the BR group, which was significantly lower (P < .05) than that in controls (1.31 ± 0.34 nmol/L/μg protein).

Conclusions

We concluded that oxidative stress during islet isolation and purification can be mitigated by BR pretreatment. BR exerts antioxidant and cytoprotective properties by reducing lipid peroxidation (MDA) and enhancing islet viability and function. Pretreatment with BR may become a simple, clinical applicable means to improve human islet isolation and transplantation outcomes.     

Mesna protects splanchnic organs from oxidative stress induced by pneumoperitoneum

Background  We investigated the potential beneficial effect of the antioxidant 2-mercaptoethane-sulfonate (mesna) against oxidative stress induced by pneumoperitoneum in splanchnic organs. Methods  Wistar rats were subjected to either (a) CO₂ pneumoperitoneum (15 mmHg for 60 min) (group P), (b) pretreatment with mesna (400 mg/kg, p.o.) followed by pneumoperitoneum with a 180 min interval (group MP), (c) sham operation (group S), or (d) administration of mesna only (group M). Forty-five minutes after desufflation (groups P and MP), 60 + 45 min after the induction of anesthesia (group S), or 180 min after mesna administration (group M), tissue specimens were excised from liver, kidneys, jejunum and stomach. Tissue oxidative state was assessed on the basis of glutathione-to-glutathione disulfide ratio, malondialdehyde concentration , and superoxide dismutase activity. Results  Pneumoperitoneum deteriorated all the oxidative stress markers in the organs studied. Mesna prevented the occurrence of oxidative stress following pneumoperitoneum in all the organs studied. In the absence of pneumoperitoneum, the administration of mesna caused mild enhancement of the oxidative state of liver, stomach, and kidneys compared to sham controls. Conclusions  Prophylaxis with mesna prevents oxidative stress induced by pneumoperitoneum in splanchnic organs.     

Paeonol protects against testicular ischaemia-reperfusion injury in rats through inhibition of oxidative stress and inflammation

Ischaemia-reperfusion (IR) is the most common form of testicular injury that results in oxidative damage and inflammation ending by subinfertility. Paeonol, a natural phenolic compound, exhibits antioxidant and anti-inflammatory effects. Thus, the present study investigated the role of paeonol in rat testicular IR injury. Thirty adult Wistar rats were randomly divided into five groups; sham, sham treated with paeonol, IR injury, and IR pre-treated with paeonol at low and high doses. Serum testosterone and testicular levels of malondialdehyde and reduced glutathione (GSH) besides superoxide dismutase (SOD) activity were determined. Gene quantifications for tumour necrosis factor-α (TNF-α), hypoxia-inducible factor-1α (HIF-1α) and heat shock protein 70 (HSP70) were also assessed. Histopathological pictures and the immunohistochemical expression of testicular nuclear factor erythroid 2-related factor 2 (Nrf2), interleukin-1β (IL-1β) and interleukin-6 (IL-6) were shown. Pre-treatment with paeonol prevented the drop in serum testosterone, alongside with improvement of testicular malondialdehyde and GSH levels plus SOD activity. Paeonol regained the normal spermatogenesis with prevention of IR-induced increase in TNF-α, HIF-1α and HSP70 gene expression besides IL-1β and IL-6 immunostaining and reduction in Nrf2 protein expression. Paeonol exerted a dose-dependent beneficial effect on testicular IR injury. This effect was achieved by its antioxidant and anti-inflammatory effects.     

异丙酚预处理对脑缺血再灌注损伤的保护作用

目的观察不同时间异丙酚预处理对沙土鼠脑缺血再灌注损伤的保护作用.方法沙土鼠42只,随机分为对照组、缺血损伤组、异丙酚预处理组(脑缺血前48h、24h、12h、6h、1h各组分别以异丙酚100mg@kg-1.腹腔注射)等7组,观察指标为脑组织内皮素(ET)、降钙素基因相关肽(CGRP)、丙二醛(MDA)含量以及超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-px)活性的改变并制作电镜标本行透射电镜观察.结果异丙酚预处理各组ET含量、ET/CGRP含量的比值及MDA含量明显低于缺血损伤组(P＜0.05),而CGRP含量和SOD、GSH-px活性明显高于缺血损伤组(P＜0.05),其中尤以异丙酚预处理24h组的ET及ET/CGRP值降低更明显,而CGRP值明显高于其余异丙酚预处理组(P＜0.05);电镜结果也显示异丙酚预处理24h组脑组织的超微结构改变最小、损伤最轻.结论缺血前48h至缺血前1h各时点异丙酚预处理对沙土鼠缺血性脑损伤均有不同程度的保护作用,尤以缺血前24h给药对沙土鼠脑缺血再灌注损伤的保护作用优于其它各时点异丙酚预处理组.     

Thermotolerance protects against endotoxin-mediated microvascular injury

An early event in endotoxin-induced tissue injury is adhesion and migration of leukocytes through the endothelium. This is a three-stage process, initially low-grade selectin-mediated adhesion, seen as a decrease in rolling velocity, followed by integrin-mediated adhesion and transmigration. Thermotolerance has been shown to reduce tissue injury and mortality induced by endotoxin. The aim of this study was to investigate the effect of thermotolerance on leukocyte-endothelial interactions. Intravital video microscopy was used to examine hemodynamic parameters, leukocyte rolling, adhesion, and migration in rat mesenteric postcapillary venules. Sprague-Dawley rats were randomized into control, lipopolysaccharide (LPS), and thermotolerance + LPS groups. Thermotolerance was induced 18 h prior to administration of LPS by elevating core body temperature to 41 + 0.5 degrees C for 15 min. LPS (055:B5 15 mg/kg) was administered via the jugular vein after baseline recording. Leukocyte rolling velocity and the number of adherent and migrated leukocytes were measured by intravital microscopy at baseline 0 min and 10, 30, 60, and 90 min after LPS administration. Heat shock protein 72 (HSP72) expression in tissues was determined by Western immunoblotting. The results indicated that LPS administration significantly decreased leukocyte rolling velocity during endotoxemia and increased leukocyte adhesion (10.3 +/- 1.67, 13.2 +/- 1.40, and 10.0 +/- 1.57/100 microm) and migration (5.7 +/- 1.02 and 8.3 +/- 1.76/field) at 30, 60, and 90 min after LPS injection (P < 0.01 vs baseline and control group). Thermotolerance maintained leukocyte rolling velocity and significantly reduced leukocyte adhesion (5.7 +/- 0.88 and 4.0 +/- 0.68/100 microm) and migration (2.8 +/- 0.32 and 3.0 +/- 0.68/field) at 30 and 60 min after LPS administration (P < 0.01 and 0.05 vs LPS group). Expression of HSP72 was induced in mesentery, gut, and lung by thermotolerance. This study indicates that thermotolerance attenuated LPS-induced microvascular injury by decreasing leukocyte-endothelial adhesion and migration.     

Blockade of CD40-CD40 ligand protects against renal injury in chronic proteinuric renal disease

BACKGROUND: Interaction between CD40 and CD40 ligand (CD40L) is involved in both cognate and innate immune responses. Blockade of CD40-CD40L interactions reduces severity of renal injury in murine lupus nephritis and membranous nephropathy. We hypothesized that CD40-CD40L could contribute to renal injury in models that are not antibody-dependent, and that anti-CD40L could diminish inflammation and fibrosis in murine adriamycin nephropathy. METHODS: Male BALB/c mice were divided into three groups (N = 6 per group): (1). saline-treated, age-matched control; (2). adriamycin only; and (3). MR1 + adriamycin. In group 3, mice were treated with intraperitoneal injections of anti-CD40L antibody (clone MR1, 0.4 mg per mouse) after the onset of proteinuria at days 5, 7, 9, and 11 after adriamycin treatment. Animal subgroups were compared at 14 and 42 days after induction of adriamycin nephropathy. Functional and pathologic markers of disease severity, cellular components of interstitial inflammation, and the degree of CD40 expression were assessed. Relative cortical RNA expression of the chemokine monocyte-chemoattractant protein-1 (MCP-1) and regulated on activation normal T cell expressed and secreted (RANTES) was also compared between animal groups. RESULTS: CD40 was weakly expressed in tubules of normal mice but was expressed in tubules, interstitium, and glomeruli of mice with adriamycin nephropathy in a time-dependent manner. MR1 treatment resulted in a significant attenuation of the severity of adriamycin nephropathy at day 42 [e.g., glomerular sclerosis (%), group 3, 20.1 +/- 4.7 vs. group 2, 30.2 +/- 7.2, P < 0.001]. CD40L blockade significantly reduced tubulointerstitial injury as well [tubular diameter microm), group 3, 42.5 +/- 6.9 vs. group 2, 66.3 +/- 13.7, P < 0.001; and group 1, 37.3 +/- 5.7, P < 0.01; tubular cell height microm), group 3, 16.3 +/- 1.7 vs. group 2, 11 +/- 1.8, P < 0.01; and group 1, 18.2 +/- 1.9, P < 0.01; interstitial volume (%), group 3, 13.9 +/- 5.1 vs. group 2, 26.2 +/- 4.9, P < 0.001; and group 1, 1.3 +/- 0.7, P < 0.001; proteinuria (mg/24 hours), group 3, 1.8 +/- 0.6 vs. group 2, 4.3 +/- 0.8, P < 0.001; and group 1, 0.7 +/- 0.2, P < 0.05; and creatinine clearance microL/min), group 3, 75 +/- 4 vs. group 2, 35 +/- 2, P < 0.001; and group 1, 82 +/- 4, P < 0.01] were also improved by MR1. MR1 treatment also resulted in a significant reduction in the number of cortical macrophages at both 14 and 42 days after adriamycin (P < 0.01). Cortical expression of MCP-1 and RANTES was significantly reduced by MR1 treatment at 42 days after adriamycin (P < 0.01 and P < 0.05, respectively). CONCLUSION: Blockade of CD40-CD40L interaction protects against renal structural and functional injury in this murine model of chronic proteinuric renal disease.     

S-nitroso-n-acetylcysteine protects skeletal muscle against reperfusion injury

The effects of a nitric oxide (NO) donor on microcirculation and contractile function of reperfused skeletal muscle were studied. Rat cremaster muscles underwent 5 hours of ischemia and 90 minutes of reperfusion and were divided into two groups systemically infused with S-nitroso-N-acetylcysteine (SNAC, 100 nmol/ min) and phosphate-buffered saline (PBS), respectively. The results showed that the vessels in the SNAC group had more rapid and complete recovery than that in controls. A significant difference was found from 10 to 40 minutes and at 90 minutes in 10–20-μm arterioles, from 10 to 90 minutes in 20–40-μm arterioles, and at 10 and 90 minutes in 40–70-μm arteries. When compared to controls, SNAC-treated muscles showed larger fluorescein filling areas at 15, 30, 60, and 90 minutes and greater isometric tetanic contractile forces in response to stimulation frequencies of 40, 70, 100, and 120 Hz. The data indicate that supplementation of exogenous NO could effectively improve microcirculation and contractile function of skeletal muscle during early reperfusion. © 1998 Wiley-Liss, Inc. MICROSURGERY 18:299–305, 1998