家兔内毒素休克时乐及主动脉一氧化碳水平的变化

目的：探讨一氧化碳（ＣＯ）是否作为一种新的内源性介质参与内毒素休克发病机制。结果：血浆以及主动脉ＣＯ和一氧化氮（ＮＯ）水平在内毒素休克时均显著增高，使用血红素氧合酶抑制剂锌原卟咻和恰酶抑制剂糖皮质激素地塞米松均可显著减轻内毒素休克中的血压下降和代谢性酸中毒程度，但是锌原卟咻仅能显著抑制血浆以及主动脉ＣＯ水平的增高，但对ＮＯ２／ＮＯ３水平无显著影响；而使用地塞米松则可显著抑制血浆以及主动脉ＮＯ２／Ｎ     

脂多糖性休克大鼠血浆和主要器官中硫化氢含量的变化和意义

目的：探讨内毒素休克（endotoxic shock，ES）大鼠血浆及肝、肾、心、肺、主动脉等主要器官组织中内源性硫化氢（hydrogen sulfide，H2S）的含量变化及意义。方法：用静脉注射脂多糖（lipopolysaccharide，LPS）法制备LPS攻击大鼠模型，将雄性Wistar大鼠随机分为正常对照组、LPS组、LPS+硫氢化钠（NaHS，H2S供体）组、LPS+炔丙基甘氨酸（PPG，H2S代谢酶抑制剂）组。观察给药后240 min内大鼠平均动脉压（mean arterial pressure，MAP）的变化及测定血浆和以上主要器官中H2S含量，并分析其相关性；光镜观察主要器官的形态学变化。结果：与正常对照组相比，LPS组大鼠血压迅速下降，血浆H2S含量于LPS注射后显著增高，肝、肾、心、肺和主动脉组织中H2S含量亦明显增高（均P<0.05），并出现组织结构损伤；给予PPG能显著抑制血浆以及各组织中H2S含量的增高，并可显著减轻LPS所致的血压下降（均P<0.05）和组织损伤；而给予H2S供体NaHS后，与LPS组相比，大鼠血浆以及各组织中H2S含量显著增高，血压明显下降（均P<0.05），组织损伤加重。LPS攻击大鼠血浆及组织中H2S含量与血压呈高度负相关（均P<0.05）。结论：H2S是一种新的内源性介质，可能参与了ES的一系列病理生理过程。     

赛庚啶对内毒素血症小鼠氧化损伤的对抗作用

目的:研究赛庚啶对内毒素(LPS)血症小鼠氧化损伤的对抗作用。方法:小鼠尾静脉注射LPS,造成内毒素血症模型,观察赛庚啶能否提高小鼠24h存活率,并测定血浆NO的水平,心、肝、肾和脑组织中SOD和GSH-Px活力以及脂质过氧化产物MDA含量。结果:赛庚啶预防给药能够显著提高致死量LPS攻击后小鼠24h的存活率,使血浆NO2-/NO3-的水平显著降低,其中高剂量组SOD和GSH-Px活力增高,MDA含量降低。低剂量组SOD活力增高,但肝和脑组织中MDA含量下降不明显,肝和肾组织GSH-Px活力无明显增高。结论:赛庚啶预防给药能够防治LPS血症,改善小鼠LPS血症时重要脏器氧化性损伤状态,抑制血浆NO水平过度升高。     

内源性舒张因子在失血性休克中的变化

目的探讨内源性舒张因子一氧化氮（NO）与一氧化碳（CO）在失血性休克中的变化。方法按照Wigger’s改良法制作家猪失血性休克模型，失血性休克（H）组经股动脉快速放血使MAP降至40mmHg，然后复苏。对照（C）组处理同H组，但未失血。各组分别在休克前、休克末、复苏末、复苏后30、60、120、240min分别记录平均动脉压（MAP）、心率（HR）、中心静脉压（CVP）、肺动脉压（PAP）、肺动脉楔压（PCWP）、气道压（Peak）的变化，采血测定pH值、BE值、CO、NO及乳酸盐（Lae）水平。结果H组休克后MAP、PAP和CVP降低而HR升高，Peak、PCWP无显著变化。血浆NO水平在休克后逐渐升高，复苏后120min显著高于休克前和c组水平，此后一直维持较高水平，240rain时达到高峰。休克后CO水平逐渐增加，复苏后120min显著高于休克前，并高于c组，此后逐渐下降；Lac在失血后显著升高，休克末达峰值，显著高于休克前和c组，以后逐渐下降。pH值、BE值在休克后逐渐下降，与c组相比有显著差异。结论失血性休克后NO、CO水平增加，可能作为两种内源性保护因子起作用。     

多系统器官衰竭家兔前列腺素E2的释放与内毒素血症的研究

本文采用家兔多系统器官衰竭(MSOF)的实验模型,初步观察了血浆PGE_2的改变与内毒素血症的关系及其对MSOF发生、发展的影响。结果表明:(1)伤后24小时血浆PGE_2水平迅速升高,其中发生MSOF者上升的幅度显著高于未发生MSOF者;(2)休克24小时后血浆内毒素值与PGE_2水平的变化趋势相平行;(3)休克1小时即出现内毒素血症,此时PGE_2水平无明显异常。提示严重失血性休克后内毒素血症发生甚早,它对血浆PGE_2水平有明显影响,而PGE_2的大量产生与释放可能是导致机体免疫功能抑制、诱发脓毒症及MSOF的免疫学基础之一。     

人参二醇组皂苷对内毒素休克大鼠脑皮质TLR4 mRNA表达的影响

目的：通过观察内毒素休克大鼠脑皮质中NOS活性、NO含量和TLR4 mRNA的表达及人参二醇组皂苷（PDS）对其的影响，探讨内毒素引起脑组织损伤的分子机制。 方法： 大鼠随机分为实验对照（control）组、内毒素休克（LPS）组、地塞米松（LPS+Dex）组和人参二醇组皂苷（LPS+PDS）组。大鼠静脉注射内毒素（4 mg/kg）4 h后测定脑组织中NOS活性、NO含量及TLR4 mRNA的表达。 结果： LPS+Dex组和LPS+PDS组NOS活性、NO2-/NO3-含量显著低于LPS组（P＜0.05），TLR4 mRNA表达亦明显低于LPS组。 结论： PDS能够下调脑组织中TLR4 mRNA的表达，降低NOS活性、NO含量，对中枢神经系统具有保护作用。     

肝移植围术期血浆一氧化氮和一氧化氮合酶活性的变化及意义

目的：动态观察肝移植围术期血浆一氧化氮（NO）水平和一氧化氮合酶（NOS）活性的变化，并探讨其意义。 方法： 30例终末期肝病患者接受原位肝移植术。用放免法、比色法分别测定肝移植围术期5个时点血浆NO2-/NO3-水平和NOS活性，观察其动态变化。同步抽取桡动脉和肺动脉血做血气分析，记录不同时期的PO2、PCO2、SO2、Hb，根据肺内分流标准模型公式计算(Qs/Qt)。并监测围术期心输出量（CO）、心率（HR）、中心静脉压（CVP）、平均动脉压（MABP）、体循环阻力（SVR）。 结果： (1) 无肝前10 min NO2-/NO3-水平明显高于麻醉后术前。无肝期30 min NO2-/NO3-显著低于无肝前10 min。新肝期30 min NO2-/NO3-显著高于麻醉后术前、无肝期30 min。（2）TNOS活性各时点无显著差异。无肝前10 min、新肝30 min时iNOS活性明显高于麻醉后术前。与无肝30 min值比较，新肝期30 min iNOS活性显著升高。（3）MABP在开放下腔静脉后1 min明显下降，CO和CVP在无肝期下降，新肝期增高。SVR在无肝期增高，新肝期明显下降。（4）Qs/Qt在无肝期下降，新肝期30 min升高。 结论： 在肝移植围术期各个时段，NO水平及iNOS活性各不相同。高NO水平可能是新肝期低阻力、肺内分流增加的原因。     

过敏性哮喘豚鼠肺泡灌洗液一氧化氮的变化

采用镉还原柱层析和比色法测定了过敏性哮喘豚鼠模型血浆及支气管肺泡灌洗液中亚硝酸／硝酸根离子（NO2-／NO3－）水平,以及CGMP和循环内皮细胞（CEC）水平。以探讨一氧化氮（NO）在过敏性哮喘发病机理中的作用。结果：（1）过敏性哮喘豚鼠血浆NO2－／NO3－水平无明显变化,而支气管肺泡灌洗液中水平显著升高（P＜0．01）;（2）哮喘组血浆及支气管肺泡灌洗液中cGMP均明显升高（P分别＜0．05、＜0．01）,循环血中CEC水平亦升高显著（P＜0．05）;（3）糖皮质激素可降低cGMP及CEC水平,减轻哮喘发作.提示：支气管肺泡灌洗液水平与过敏性哮喘密切相关,NO参与了哮喘的病理生理变化,糖皮质激素具有明显的治疗作用．     

血红素氧合酶-内源性一氧化碳系统对感染性休克大鼠低血压形成的影响

目的：探讨血红素氧合酶-内源性一氧化碳系统是否参与了感染性休克大鼠低血压的形成。 方法： 将Sprague-Dawley大鼠随机分为对照（C）组、感染性休克（SS）组、感染性休克+ZnPP-IX(SZ)组、ZnPP-IX（Z）组。连续监测MAP；并检测血中COHb的浓度，主动脉和股动脉血管组织内HO-1 mRNA、HO-2 mRNA及HO-1、HO-2蛋白水平。 结果： ①SZ组大鼠其MAP水平均高于SS组(P<0.05)；②SS组大鼠主动脉和股动脉组织内HO-1 mRNA 及HO-1蛋白水平明显高于SZ组(P<0.05)，而两组主动脉和股动脉组织内HO-2 mRNA 及HO-2蛋白水平相比无显著差异(P>0.05)；③SS组大鼠血中COHb水平明显高于SZ组(P<0.05)。 结论： 感染性休克大鼠严重低血压形成的部分原因是由于HO-1蛋白水平的上调及随后的CO浓度升高所致。     

抗炎药能抑制内毒素休克大鼠血浆CGRP浓度的升高

我们在以前的工作中证明休克时血浆中的降钙素基因相关肽(CGRP)浓度升高,地塞米松可减轻休克并抑制血浆GRPC浓度为升高。本实验观察消炎痛、布洛芬、纳洛酮和吗啡对清醒大鼠注射内毒素5mg/hg 3h血浆CGRP浓度的影响,以期认识炎症与休克时CGRP释放的关系。结果显示动物(n=10)注射内毒素后     

Effect of inhaled nitric oxide on endotoxin-induced hypoxaemia in rabbits

In five mechanically ventilated rabbits, we studied the property of inhaled nitric oxide in helping to treat hypoxaemia which was induced by intravenous endotoxin (Escherichiacoli-derived lipopolysaccharide, serotype 0111: B4). We used measurements of arterial partial pressure of oxygen to check a therapeutic nitric oxide benefit. Pulmonary artery pressure was continuously monitored. Furthermore, we determined the single-breath diffusing capacity for nitric oxide. Measurements of plasma nitrite/nitrate concentration served as an indicator of endogenous nitric oxide output. The first infusion of endotoxin led to a transient pulmonary vasoconstriction, whereas arterial partial pressure of oxygen was permanently reduced by 30 ± 10 mmHg (mean ± SD), attaining minimal values of 48 ± 3.4 mmHg due to additional endotoxin. Single-breath diffusing capacity for nitric oxide declined by 20 ± 5.5% of baseline values until the experiments were concluded. Endotoxin induced an increase in plasma nitrite/nitrate concentration in the five rabbits as well as in the control animals (four rabbits) without exogenous nitric oxide supply. During the 25 inhalations of nitric oxide (3–50 ppm), arterial oxygenation did not change significantly. Thus endotoxin permanently impaired pulmonary gas exchange without inducing pulmonary hypertension. Inhaled nitric oxide did not improve arterial oxygenation during endotoxaemia.     

Relationship between systemic nitric oxide metabolites and cyclic GMP in healthy male volunteers

Aim: Nitric oxide (NO) is an endogenous mediator of many physiological processes, many of which are mediated by cyclic guanosine 3′,5′‐monophosphate (cGMP). Much effort has been made to validate clinical markers of NO production or bioavailability. While the measurement of plasma nitrate, nitrite, and cGMP concentrations have been suggested to reflect endogenous production of NO, there is no study showing whether there is correlation between these three markers. In the present study, we investigate whether there is correlation between the plasma concentrations of nitrate, nitrite, and cGMP in a relatively homogeneous group of 141 healthy subjects. Methods: Venous blood samples were collected from healthy male subjects and plasma aliquots were then immediately removed and stored at ?70 °C until analysed in duplicate for their nitrite and nitrate content using ozone‐based chemiluminescence assays. Plasma cGMP levels were determined by using a commercial enzyme immunoassay. Results: While we found no significant correlation between plasma nitrite and nitrate concentrations (P = 0.747), or between plasma nitrate and cGMP concentrations (P = 0.221), a significant positive correlation was found between plasma cGMP and nitrite concentrations (P = 0.017, r_s = 0.270). Conclusions: The significant correlation we found between plasma nitrite and cGMP concentrations is consistent with the notion that nitrite or cGMP concentrations in plasma may be useful clinical markers of NO formation in healthy subjects.     

Differential induction of nitric oxide synthase in various organs of the mouse during endotoxaemia: role of TNF-alpha and IL-1-beta.

BALB/c mice injected intraperitoneally with bacterial lipopolysaccharide (LPS) developed lethal septic shock. This was accompanied by significantly elevated concentrations of nitrite and nitrate in the plasma and expression of high levels of nitric oxide (NO) synthase activity in the lungs, heart, spleen and peritoneal macrophages. Mice pretreated with anti-tumour necrosis factor-alpha (TNF-alpha) monoclonal antibody or anti-interleukin-1 beta (IL-1 beta) polyclonal antibody were protected, in a dose-dependent manner, from endotoxin-induced mortality. This effect was accompanied by a significant reduction in plasma levels of nitrite and nitrate. Antibody treatment also reduced the level of NO synthase activity in peritoneal macrophages, spleen and heart but had no effect on enzyme expression in the lung. These results demonstrate that TNF-alpha and IL-1 beta play an important role in the induction of NO following administration of LPS and in the development of endotoxin-induced shock. In addition, NO synthase activity is differentially expressed in various organs and this may not always require TNF-alpha and IL-1 beta.     

Pathophysiology of blood pressure variability in patients with chronic renal failure under maintenance hemodialysis

The rise of blood pressure is negatively related with the glomerullar filtration rate(GFR) in patients with terminal renal failure. Hypertension may be a mechanism to maintain renal blood flow and GFR constant by the increased driving force of blood to the kidney. Elevated levels of a so-called third factor, now designated as endogenous digitalis, are found in those patients. The most likely candidate of the endogenous digitalis is ouabain, which causes hypertension with chronic administration. On the other hand, extreme hypotension often occurs during maintenance hemodialysis, and since hemodynamic alterations closely resemble endotoxin shock, the involvement of nitric oxide(NO) over-production has been suggested. When we measured nitrate anion as the final metabolite of NO, the concentration was significantly higher in patients with marked hypotension during hemodialysis than those without hypotension. Since reflex tachycardia was not observed during hypotension, we speculated that those patients had autonomic disturbances, and assessed autonomic function by heart rate spectral analysis. Although the high frequency spectral power, regarded as the vagal tone, was not significantly different between the groups, low/high frequency spectral power ratio, which was thought to be a sympathetic component, was significantly lower in patients with hypotension during hemodialysis than that in patients without hypotension. We speculated that NO synthase may be induced by the stimuli to monocytes by tubes and dialyser membrane made of synthetic materials leading to the over production of NO during and after regular hemodialysis. Thus, cytokines may be the mediator of the induction of NO synthase. Dilated capacitance vessels decrease the venous return to the heart, which may be the direct cause of dialysis-induced hypotension.     

3-硝基酪氨酸在细菌内毒素诱导大鼠血管低反应性中的介导作用

目的：观察3-硝基酪氨酸（3-NT）对感染性休克大鼠血管低反应性的介导作用及抗氧化剂对此的治疗效果。 方法： 40只雄性SD大鼠随机分成空白对照组(n=10); LPS休克组（LPS 15 mg·kg-1 iv, n=10）; 尿酸(UA)治疗组（注射LPS 1 h后200 mg·kg-1 ip, n=10）; N-乙酰-5-甲氧基色胺（melatonin）治疗组（注射LPS 1 h后10 mg·kg-1 ip, n=10）。空白对照组及注射LPS 6 h后各组动物，静注去氧肾上腺素（PE, 0.5-2.5 μg·kg-1）,记录注药后MAP的增加百分比。所有in vivo实验结束后取大鼠胸主动脉环作张力实验,，建立PE的剂量-反应曲线并计算相应的Emax、EC50值。注射LPS 6 h后检测各组动物血浆丙二醛（MDA）、硝酸盐/亚硝酸盐（nitrate/nitrite）与3-NT的含量。 结果： 静脉注射PE后，休克组动物MAP的平均增长率与对照组相比显著降低至54.60%（P<0.01）；而UA组、melatonin组MAP对PE反应的增长率较之休克组分别增高了37.70%、40.03%(P<0.05)。休克组大鼠胸主动脉环对PE的反应［(Emax，35.30%±9.80%； EC50， (15.70±4.50)nmol/L］与对照组相比有显著差异［（Emax，100%； EC50， (4.71±2.04) nmol/L, P<0.05］，经UA、melatonin治疗后血管反应性有显著改善(P<0.05)。尿酸、N-乙酰-5-甲氧基色胺治疗组的血浆MDA、硝酸盐/亚硝酸盐和3-NT的浓度也明显低于休克组(P<0.05)。 结论： 3-NT是感染性休克血管低反应的重要介导因子，抗氧化剂通过清除氧自由基，减少脂质过氧化物的形成、抑制体内NO的过量合成及有效清除3-NT，从而改善α-肾上腺素能受体介导的血管低反应性，对临床感染性休克病人的治疗可能有积极作用。     

Adenosine infusion attenuates soluble RAGE in endotoxin‐induced inflammation in human volunteers

Aim: To evaluate possible anti‐inflammatory effects of pre‐treatment with adenosine in a human experimental inflammatory model. Methods: The study design was double‐blind, crossover, placebo‐controlled and randomized. In the Intensive Care Unit of a university hospital, 16 healthy male volunteers were treated for 5.5 h with infusions of adenosine 40 μg kg^?1 min^?1 or placebo. Thirty minutes after the start of adenosine or placebo, 2 ng kg^?1E‐Coli endotoxin was administered. Heart rate, body temperature, blood pressure, plasma cytokines (TNF‐α, IL‐6 and IL‐10), soluble RAGE and resistin, exhaled nitric oxide and nitrite/nitrate in urine were determined. Results: Endotoxin elicited the expected clinical signs of an inflammatory reaction (tachycardia, fever) and led to prominent release of the cytokines studied (P < 0.001). Resistin in plasma increased after endotoxin (P < 0.001). After placebo treatment, soluble RAGE (sRAGE) in plasma increased 5 h after the endotoxin challenge (P < 0.001) but not after adenosine. After placebo, orally exhaled NO increased with a peak at 4 h (P < 0.001), although there was no statistically significant difference between the two treatments. Nitrite/nitrate in urine (n = 11) did not differ between adenosine and placebo treatments. Conclusion: In conclusion, adenosine infusion starting before endotoxin challenge in humans attenuated sRAGE significantly but otherwise had no clear anti‐inflammatory effect. Adenosine as a potential anti‐inflammatory treatment in humans needs further study, including use of higher doses. The mechanism underlying the effect of adenosines on sRAGE remains unknown.     

Brain dysfunction associated with an induction of nitric oxide synthase following an intracerebral injection of lipopolysaccharide in rats

We investigated the pathophysiological role of nitric oxide synthesized by inducible nitric oxide synthase in the brain, by injecting lipopolysaccharide directly into the rat cerebral cortex/hippocampus. The levels of nitric oxide metabolites, nitrite and nitrate, began to increase in a dose-dependent manner with a 3-h lag, and reached approximately seven-fold the basal levels 8 h after the direct injection of lipopolysaccharide (5 microg). The lipopolysaccharide-induced increase in nitrite and nitrate levels was inhibited by treatment with the specific inducible nitric oxide synthase inhibitor aminoguanidine. The protein synthesis inhibitor cycloheximide delayed the onset of the increase in nitric oxide metabolite levels, and reduced the peak levels. Lipopolysaccharide increased Ca2+-independent, but not Ca2+-dependent, nitric oxide synthase activity in the brain. Intense nicotinamide adenine dinucleotide phosphate-diaphorase activity was observed in round cells in the vicinity of the site of injection of lipopolysaccharide 8 h after the injection. Neuronal death was observed seven days after the injection of lipopolysaccharide. Spatial memory, as assessed by performance in a water maze task and spontaneous alternation behavior in a Y-maze, was significantly impaired in rats which had had previous bilateral injections of lipopolysaccharide into the hippocampus. The lipopolysaccharide-induced neuronal death and spatial memory impairments were prevented by aminoguanidine. These results suggest that direct injection of lipopolysaccharide into the brain causes an induction of inducible nitric oxide synthase in vivo. Furthermore, it is suggested that nitric oxide produced by inducible nitric oxide synthase is responsible for the lipopolysaccharide-induced brain dysfunction.     

Misoprostol decreases oxidative stress and liver injury in bacterial lipopolysaccharide-induced endotoxemia in mice

The effect of misoprostol, a synthetic prostaglandin E1 analog, on the development of oxidative stress induced in mice with lipopolysaccharide (LPS) endotoxin was investigated. Misoprostol was administered by intraperitoneal route (i.p.) at doses of 10, 100, or 1,000 μg/kg at the time of LPS injection (200 μg/kg, i.p.). Mice were euthanized 4 h later. Lipid peroxidation (malondialdehyde; MDA), reduced glutathione (GSH), nitric oxide (nitrite/nitrate) levels as well as paraoxonase activity were measured in brain and liver. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities as well as DNA fragmentation were determined in the liver. The administration of LPS increased oxidative stress both in the brain and liver tissue. There were significantly increased MDA and nitrite and decreased GSH and PON1 activity in the brain and liver, respectively. In addition, LPS was associated with markedly elevated plasma ALT and AST level as well as increased liver DNA fragmentation. The administration of misoprostol at 100 or 1,000 μg/kg decreased brain MDA by 17.6 and 30 %, increased GSH by 29.8 and 33.3 %, and decreased nitric oxide by 21.74 and 42.5 %, respectively, compared with the lipopolysaccharide control group. Liver MDA decreased by 27 %, GSH increased by 47.7 %, and nitric oxide decreased by 37.2 % with misoprostol at 1,000 μg/kg. Paraoxonase activity increased in both the brain and liver by misoprostol administration. The increase in liver AST and ALT and DNA fragmentation after endotoxin administration was normalized by misoprostol. These results indicate that misoprostol can alleviate oxidative stress in the presence of a mild systemic inflammatory illness, indicating a new and potentially important therapeutic application for the drug.     

Nitric oxide in postmenopausal women taking three different HRT regimens

OBJECTIVE: To search and compare the effects of three different HRT regimens on nitric oxide levels of postmenopausal women. METHODS: Four groups of postmenopausal women were included in this prospective, randomised, placebo controlled study. 34 women used 0.625 mg conjugated estrogen continuously combined with 5 mg medroxyprogesterone acetate, 32 women used 2.5 mg tibolone, 26 women used 50 mcg transdermal estrogen alone continuously and 32 women used placebo for 12 months. Before the treatment and after 1 year, serum NO (nitrate/nitrite) and some other biochemical parameters were evaluated. RESULTS: All HRT using groups had increased serum nitric oxide levels significantly compared to placebo group and also there was not any difference among three HRT using groups concerning to increases in nitric oxide levels. CONCLUSION: Both conjugated estrogen combined with continuous progestin and transdermal estrogen alone and also tibolone increases serum nitric oxide levels of postmenopausal women equally for 12-months of treatment.     

Ozone oxidative preconditioning reduces nitrite levels in blood serum in LPS: induced endotoxic shock in mice

Objective and design  Reactive oxygen species, and also reactive species of nitrogen such as nitric oxide, play an important role in the pathogenesis of peritonitis and septic shock. Ozone oxidative preconditioning (OOP) has shown protective effects in various experimental models of peritonitis in rats and endotoxic shock in mice. Currently, strong evidence is available that this protective effect of OOP is due to its action on the balance between endogenous antioxidants and pro-oxidants, which is favorable for anti-oxidant defense. The aim of this research was to elucidate whether or not OOP is able to reduce nitrite levels in blood serum of mice treated with lipopolysaccharide (LPS). We used an experimental model of endotoxic shock induced by LPS in mice in which the animals were pre-treated with ozone/oxygen mixture for 5 days (once daily), with injection of LPS 24 h thereafter to induce endotoxic shock. Results  Mice pretreated with OOP showed a significant decrease in nitrite levels with all three doses tested [0.2 mg/kg (50.91%), 0.4 mg/kg (47.3%) and 1.2 mg/kg (34.6%)]. Conclusions  Ozone oxidative preconditioning significantly reduced nitrite levels in blood serum of mice with endotoxic shock induced by LPS. We propose that OOP merits further testing in studies as a potential alternative treatment to reduce nitrite levels in patients with sepsis syndrome and septic shock.