The effect of natural antioxidants, NAO and apocynin, on oxidative stress in the rat heart following LPS challenge

Oxidative damage plays a key role in septic shock induced by lipopolysaccharide (LPS) which is known to enhance the formation of reactive oxygen species (ROS). In this study, biochemical parameters indicative of oxidative stress were tested in the rat heart following LPS challenge, with and without pretreatment with the antioxidants NAO (natural antioxidant) and apocynin. NAO is a natural antioxidant isolated and purified from spinach and its main components are flavonoids and coumaric acid derivatives. Treatment with LPS alone significantly (P<0.05) increased the malondialdehyde (MDA) level in heart, both in cytosolic and mitochondrial fractions by 1.5- and 2.4-fold, respectively, and in plasma (2.66 fold). In the heart homogenate, the level of hydroperoxides also increased significantly (P<0.05). In addition, LPS treatment significantly (P<0.05) increased NADPH oxidase activity in the heart microsomal fraction by approximately 10-fold compared to control. Pretreatment for 7 days with either apocynin or NAO prior to the LPS challenge significantly (P<0.05) improved rat survival, decreased MDA levels in both fractions and decreased microsomal NADPH-oxidase activity, compared to LPS alone. Catalase (CAT) activity slightly increased at 24 h post-LPS injection in LPS group and returned to the control level in the apocynin treated group. No meaningful changes were indicated for glutathione peroxidase activity among all the treatment groups. The activities of cytosolic and mitochondrial superoxide dismutase (SOD) enzymes significantly (P<0.05) increased approximately 20% in the LPS-treated group, compared to control. Apocynin significantly (P<0.05) decreased SOD level in the mitochondrial fraction with no effect on the cytosolic fraction; whereas, NAO had no important effect on SOD level in both fractions. The beneficial pretreatment effects of the antioxidants against oxidative stress in the rat heart presented in this study may suggest a potential chemopreventive effect of this compound in sepsis prevention.     

Effects of Apocynin and Natural Antioxidant from Spinach on Inducible Nitric Oxide Synthase and Cyclooxygenase‐2 Induction in Lipopolysaccharide‐Induced Hepatic Injury in Rat

The immunoreactivity of inducible nitric oxide synthase, and cyclooxygenase‐2 was compared among groups of male Wistar rats comprising those injected with lipopolysaccharide following pretreatment with either natural antioxidant from spinach or the antioxidant apocynin, with lipopolysaccharide without pretreatment with antioxidants, with each of the two antioxidants alone, and untreated controls. The grade of staining of both inducible nitric oxide synthase and cyclooxygenase‐2 increased with the severity of the inflammatory reaction in the lipopolysaccharide‐treated animals, compared to the antioxidant‐treated groups. Interpretation of the results of the immunostained tissues indicated that pretreatment with either antioxidant significantly (P<0.05) attenuated the lipopolysaccharide‐stimulated inducible nitric oxide synthase induction. Analysis of the cycloxygenase‐2‐stained liver samples indicated that the pretreatment with the natural antioxidant NAO significantly (P<0.05) attenuated lipopolysaccharide‐stimulated cycloxygenase‐2 induction; whereas, in animals pretreated with apocynin, there was a trend of reduction in the cyclooxygenase‐2 expression, but not statistically significant (P>0.05). The negative nitrotyrosine immunoreactivity of the lipopolysaccharide‐related hepatic lesions may indicate that there was relatively low interaction between superoxide anions and nitric oxide to form peroxynitrite or that the expression levels of the nitrotyrosine were below the limit of detection. In all treatment groups a positive correlation (P<0.05, r=0.86) found between the inducible nitric oxide synthase and cyclooxygenase‐2 scores suggests a strong relationship between these two parameters. The results indicate the possible therapeutic efficacy of NAO and apocynin in the prevention of liver damage related to clinical endotoxemia known to be associated with oxidative stress.     

Effects of apocynin and natural antioxidant from spinach on inducible nitric oxide synthase and cyclooxygenase-2 induction in lipopolysaccharide-induced hepatic injury in rat

The immunoreactivity of inducible nitric oxide synthase, and cyclooxygenase-2 was compared among groups of male Wistar rats comprising those injected with lipopolysaccharide following pretreatment with either natural antioxidant from spinach or the antioxidant apocynin, with lipopolysaccharide without pretreatment with antioxidants, with each of the two antioxidants alone, and untreated controls. The grade of staining of both inducible nitric oxide synthase and cyclooxygenase-2 increased with the severity of the inflammatory reaction in the lipopolysaccharide-treated animals, compared to the antioxidant-treated groups. Interpretation of the results of the immunostained tissues indicated that pretreatment with either antioxidant significantly (P<0.05) attenuated the lipopolysaccharide-stimulated inducible nitric oxide synthase induction. Analysis of the cycloxygenase-2-stained liver samples indicated that the pretreatment with the natural antioxidant NAO significantly (P<0.05) attenuated lipopolysaccharide-stimulated cycloxygenase-2 induction; whereas, in animals pretreated with apocynin, there was a trend of reduction in the cyclooxygenase-2 expression, but not statistically significant (P>0.05). The negative nitrotyrosine immunoreactivity of the lipopolysaccharide-related hepatic lesions may indicate that there was relatively low interaction between superoxide anions and nitric oxide to form peroxynitrite or that the expression levels of the nitrotyrosine were below the limit of detection. In all treatment groups a positive correlation (P<0.05, r=0.86) found between the inducible nitric oxide synthase and cyclooxygenase-2 scores suggests a strong relationship between these two parameters. The results indicate the possible therapeutic efficacy of NAO and apocynin in the prevention of liver damage related to clinical endotoxemia known to be associated with oxidative stress.     

Effects of water-soluble antioxidant from spinach, NAO, on doxorubicin-induced heart injury.

Doxorubicin (DOX) produces clinically restorative responses in numerous human cancers, but its cardiotoxicity has limited its usefulness. Because reactive oxygen species may affect DOX-induced antitumor activity and cardiotoxicity, we evaluated the prophylactic effect of spinach natural antioxidant (NAO) on DOX-induced cardiotoxicity and oxidative stress in female Balb/c mice using histological, electron microscopical and biochemical parameters. Mice were treated with NAO for 7 days prior to and/or for 6 days after DOX administration. Pretreatment with NAO (cumulative dose: 130 mg/kg) did not hinder the effectiveness of DOX. Light and electron microscopy of DOX-treated heart revealed myocardial degeneration. When administered combined before and after DOX, NAO conferred the most significant cardiac protection. The effects of NAO on the lipid peroxidation product, malondialdehyde, and on H2O2/ hydroperoxides were examined on day 6 following DOX administration; levels of both were elevated in DOX-treated mice, compared to control. Pretreatment with NAO prevented these changes. Pretreatment with NAO before DOX administration decreased catalase and increased superoxide dismutase activities compared to the DOX group. Our results suggest usage of NAO in combination with DOX as a prophylactic strategy to protect heart muscle from DOX-induced cellular damage.     

Protective effects of apocynin nitrone on acute lung injury induced by lipopolysaccharide in rats

Acute lung injury (ALI) is a major cause of mortality and morbidity worldwide. In a previous study we reported the synthesis of a series of apocynin derivatives. Although the anti-inflammatory activity of them contributes to these cytoprotective effects. However, the mechanisms and effects of improving LPS-induced ALI in vivo remain unknown, so the purpose of our investigation was designed to reveal the effect of apocynin derivatives on LPS-induced acute lung injury in rats. The present study showed that apocynin derivatives reduces overall protein levels and tumor necrosis factor α (TNF-α) level, inhibits the activation of NADPH oxidase, and increases the levels of superoxide dismutase (SOD). Especially, compound 11 significantly reduces pulmonary vascular permeability, white blood cell content and protein expressions of p67^phox and p47^phox. These results suggest that compound 11 can ameliorate ALI induced by LPS through inhibition of NADPH oxidase.     

Apocynin ameliorates endotoxin-induced acute lung injury in rats

Acute lung injury (ALI) is a serious clinical syndrome with a high rate of mortality. In this study, the effects of apocynin, a NADPH-oxidase (NOX) inhibitor on lipopolysaccharide (LPS)-induced ALI in rats were investigated. Male Sprague–Dawley rats were treated with apocynin (10 mg/kg) intraperitoneally (i.p.) 1 h before LPS injection (10 mg/kg, i.p.). The results revealed that apocynin attenuated LPS-induced ALI as it decreased total protein content, lactate dehydrogenase (LDH) activity and the accumulation of the inflammatory cells in the bronchoalveolar lavage fluid (BALF), In addition, apocynin significantly increased superoxide dismutase (SOD) and reduced glutathione (GSH) activities with significant decrease in the lung malondialdehyde (MDA) content as compared to LPS group in lung tissue and decreased pulmonary artery contraction induced by LPS. It also upregulated mRNA expression of inhibitory protein kappaB-alpha (NFκBia) and downregulated mRNA expression of Toll-Like receptor 4 (TLR4) and decreased inflammation observed in lung tissues.Collectively, these results demonstrate the protective effects of apocynin against the LPS-induced ALI in rats through its antioxidant and antiinflammatory effect that may be attributed to the decrease in mRNA expression of TLR4 and increasing that of NFκBia.     

NADPH氧化酶对自发性高血压大鼠体内氧化应激的影响

目的考察NADPH氧化酶对自发性高血压大鼠体内氧化应激的影响。方法22wk龄自发性高血压大鼠(SHR)和正常血压WKY大鼠,采用尾套法测定血压,Greiss反应测定血清一氧化氮分泌量,ABTS和FRAP法进行血清总抗氧化能力测定,血管环舒缩测定来评价超氧阴离子清除剂超氧化物歧化酶(SOD)和NADPH氧化酶抑制剂夹竹桃麻素(Apo)对大鼠腹主动脉内皮依赖性舒张反应;采用RT-PCR考察内皮型一氧化氮合酶(eNOS)、NADPH氧化酶亚基p22phox以及NADPH氧化酶亚基gp91phox类似物nox4mRNA表达。结果与WKY大鼠相比,SHR血压升高,而血清总抗氧化水平及NO分泌量均降低。PCR显示SHR胸主动脉中eNOS及p22phoxmRNA表达与WKY大鼠相比差异无显著性,而nox4表达则升高。SHR腹主动脉内皮依赖性舒张反应与WKY相比降低,SOD或Apo均能明显逆转该变化。结论结果提示SHR体内氧化应激状态与NADPH氧化酶gp91phox类似物nox4mRNA过表达有关;NADPH氧化酶依赖性的氧化应激参与了SHR内皮功能障碍的发生发展;药理调节NADPH氧化酶功能或应用抗氧化治疗可明显改善SHR内皮依赖性舒张反应。     

Melatonin attenuates lipopolysaccharide (LPS)-induced apoptotic liver damage in D-galactosamine-sensitized mice

D-Galactosamine (GalN) depletes UTP primarily in liver, resulting in decreased RNA synthesis in hepatocytes. When given together with a sublethal dose of lipopolysaccharide (LPS), GalN highly sensitizes animals to produce apoptotic liver injury with severe hepatic congestion, resulting in rapid death. Melatonin is a cytokine modulator, antioxidant and anti-apoptotic agent. In the present study, we investigated the effect of melatonin on LPS-induced apoptotic liver damage in GalN-sensitized mice. Female CD-1 mice were intraperitoneally (i.p.) injected with melatonin (5.0mg/kg) 30min before GalN/LPS (700mg10microg/kg, i.p.), another two doses of melatonin (2.5mg/kg, i.p.) being administered 1 and 2h after GalN/LPS. Results showed that serum alanine aminotransferase (ALT) activities were markedly increased 8h after GalN/LPS treatment, massive hemorrhage being observed in histological sections of liver from GalN/LPS-treated mice. Melatonin significantly attenuated GalN/LPS-induced elevation of serum ALT. In parallel, melatonin distinctly improved GalN/LPS-induced congestion. Additional experiment showed that melatonin significantly attenuated GalN/LPS-induced hepatic apoptosis, measured by inhibition of caspase-3 activities and attenuation of DNA laddering. Furthermore, melatonin markedly increased hepatic Se-dependent glutathione peroxidase (GSH-Px) and glutathione reductase (GSH-Rd) activities and attenuated hepatic glutathione (GSH) depletion in GalN/LPS-treated mice. Increases in serum tumor necrosis factor alpha (TNF-alpha), which were observed in GalN/LPS-treated mice, were significantly reduced by melatonin. However, melatonin had no effect on LPS-evoked nitric oxide production in GalN-sensitized mice. Taken together, these results indicate that melatonin protected against LPS-induced liver damage in GalN-sensitized mice through its strong ROS-scavenging, antiinflammatory and antiapoptotic effects.     

N-acetylcysteine attenuates lipopolysaccharide-induced apoptotic liver damage in D-galactosamine-sensitized mice

Aim： To investigate the effects of N-acetylcysteine on D-galactosamine （GAIN）/ lipopolysaccharide （LPS）-induced apoptotic liver injury in mice. Methods： When given together with a low dose of LPS, GaIN highly sensitizes animals to produce apoptotic liver injury with severe hepatic congestion, resulting in rapid death. In the GalN/LPS model, TNF-α is the major mediator leading to apoptotic liver injury. Reactive oxygen species （ROS） are involved in GaiN-induced sensitization to TNF-α-evoked hepatocyte apoptosis. N-acetylcysteine （NAC） is an antioxidant and a glutathione （GSH） precursor. In this study, we investigated the effects of NAC on LPS-induced apoptotic liver injury in GaiN-sensitized mice. Results： Pretreatment with NAC significantly reduced GalN/LPS-induced elevation of serum alanine aminotransferase levels. In parallel, GalN/LPS-induced hepatic necrosis and congestion were obviously improved by NAC. Furthermore, NAC pretreatment significantly alleviated GalN/LPS-induced hepatic apoptosis, measured by the inhibition of hepatic caspase-3 activity and attenuation of DNA laddering. NAC pretreatment had no effect on LPS-evoked nitric oxide production in GaiN-sensitized mice. Increases in serum TNF-α concentration, which were observed in GalN/LPS-treated mice, were not significantly reduced by NAC. Although NAC pretreatment significantly alleviated LPS-induced hepatic GSH depletion, DL-buthionine-（SR）-sulfoximine, an inhibitor of GSH synthesis, did not influence the protective effect of NAC on GalN/LPS-induced apoptotic liver injury. Conclusion： NAC attenuates GalN/LPS-induced apoptotic liver injury via its strong ROS scavenging and anti-apoptotic effects.     

Inhibitory effect of apocynin on methylglyoxal‐mediated glycation in osteoblastic MC3T3‐E1 cells

Methylglyoxal (MG), a highly reactive metabolite of hyperglycemia, can enhance protein glycation, oxidative stress or inflammation. The present study investigated the effects of apocynin on the mechanisms associated with MG toxicity in osteoblastic MC3T3‐E1 cells. Pretreatment of MC3T3‐E1 cells with apocynin prevented the MG‐induced protein glycation and formation of intracellular reactive oxygen species and mitochondrial superoxide in MC3T3‐E1 cells. In addition, apocynin increased glutathione levels and restored the activity of glyoxalase I inhibited by MG. These findings suggest that apocynin provide a protective action against MG‐induced cell damage by reducing oxidative stress and by increasing the MG detoxification system. Apocynin treatment decreased the levels of proinflammatory cytokines such as tumor necrosis factor‐α and interleukin‐6 induced by MG. Additionally, the nitric oxide level reduced by MG was significantly increased by apocynin. These findings indicate that apocynin might exert its therapeutic effects via upregulation of glyoxalase system and antioxidant activity. Taken together, apocynin may prove to be an effective treatment for diabetic osteopathy. Copyright © 2014 John Wiley & Sons, Ltd.     

胡黄连苷元（香荚兰乙酮）对失血性休克及内毒素诱导“两次打击”损伤的保护作用

目的:评价胡黄连苷元对大鼠“两次打击”损伤的保护作用.方法:采用大鼠“两次打击”损伤模型(失血性休克40 mmHg 45 min后iv细菌内毒素LPS 150 μg/kg).大鼠随机分为七组:对照组,内毒素组,失血组,失血/内毒素组和失血/内毒素 胡黄连苷元(2.5,5.0,10.0 mg/kg)组.胡黄连苷元溶于复苏液(生理盐水,NS)中并在2 h内经静脉给药。在LPS或NS注射后,观察大鼠8,16,24及48 h存活率;检测肺组织(iv LPS后3 h及6 h)及血清(失血前,失血后及iv LPS/NS后0,0.5,1,2,4,6 h)丙二醛含量;检测肺及肝组织(iv LPS/NS后 3 h及 6 h)髓过氧化物酶活性.结果:与对照组比较,“两次打击”损伤大鼠8 h(64.3％,P<0.05),16 h(35.7％,P<0.01),24 h(28.6％,P<0.01),48 h(14.3％,P<0.01)存活率显著降低;血清及肺组织丙二醛含量显著增多,肺、肝组织髓过氧化物酶活力显著升高.胡黄连苷元剂量依赖性升高失血性休克大鼠平均动脉压(P<0.05),提高大鼠存活率,降低血清及组织丙二醛含量,下调肺及肝组织髓过氧化物酶活力.结论:胡黄连苷元可保护由失血性休克及细菌内毒素诱导的大鼠“两次打击”损伤.     

白芍总苷对卡介苗加脂多糖引起的小鼠免疫性肝损伤的保护作用

目的　研究白芍总苷对小鼠免疫性肝损伤的保护作用。方法　在建立BCG +LPS诱导免疫性肝损伤小鼠模型的基础上 ,分光光度法检测血清中ALT、AST、NO水平和肝匀浆MDA、GSH Px、SOD含量 ;放免法检测TNF α的生物学活性 ;细胞增殖法测定脾淋巴增殖反应。结果　白芍总苷 (6 0、12 0、2 4 0mg·kg-1)ig给药可明显降低免疫性肝损伤小鼠增高的血清ALT、AST活性 ,同时能减少肝匀浆MDA含量 ,使降低的肝匀浆GSH Px、SOD活性升高 ,进一步研究发现白芍总苷可明显抑制免疫性肝损伤小鼠血清NO和TNF α的产生。白芍总苷还可抑制小鼠腹腔巨噬细胞TNF α的产生 ,对ConA诱导的脾淋巴增殖反应具有恢复作用 ,而对LPS诱导的脾淋巴增殖反应无明显影响。结论　白芍总苷对免疫性肝损伤具有保护作用。     

The role of Kupffer cells and TNF-alpha in monocrotaline and bacterial lipopolysaccharide-induced liver injury.

Coexposure to small, noninjurious doses of the pyrrolizidine alkaloid phytotoxin monocrotaline (MCT) and bacterial lipopolysaccharide (LPS) results in synergistic hepatotoxicity. Both centrilobular and midzonal liver lesions occur and are similar to those seen from large, toxic doses of MCT and LPS, respectively. The nature of the lesions in vivo and results from studies in vitro suggest that injury is mediated indirectly rather than from a simple interaction of MCT and LPS with hepatic parenchymal cells. Accordingly, the role of inflammatory factors, such as Kupffer cells and TNF-alpha, in the development of MCT/LPS-induced liver injury was investigated. In Sprague-Dawley rats, MCT (100 mg/kg, i.p.) was administered 4 h before LPS (7.4 x 10(6) EU/kg, i.v.). Pretreatment of these animals with gadolinium chloride, an inhibitor of Kupffer cell function, attenuated liver injury 18 h after MCT administration. An increase in plasma TNF-alpha preceded the onset of hepatic parenchymal cell injury, raising the possibility that this inflammatory cytokine contributes to toxicity. Either pentoxifylline, an inhibitor of cellular TNF-alpha synthesis, or anti-TNF-alpha serum coadministered to MCT/LPS-treated animals significantly attenuated liver injury. These results suggest that Kupffer cells and TNF-alpha are important mediators in the synergistic hepatotoxicity resulting from MCT and LPS coexposure.     

Dexamethasone improves vascular hyporeactivity induced by LPS in vivo by modulating ATP-sensitive potassium channels activity

(1) Septic shock represents an important risk factor for patients critically ill. This pathology has been largely demonstrated to be a result of a myriad of events. Glucocorticoids represent the main pharmacological therapy used in this pathology. (2) Previously we showed that ATP-sensitive potassium (KATP) channels are involved in delayed vascular hyporeactivity in rats (24 h after Escherichia coli lipopolysaccharide (LPS) injection). In LPS-treated rats, we observed a significant hyporeactivity to phenylephrine (PE) that was reverted by glybenclamide (GLB), and a significant increase in cromakalim (CRK)-induced hypotension. (3) We evaluated the effect of dexamethasone (DEX 8 mg kg-1 i.p.) whether on hyporeactivity to PE or on hyperreactivity to CRK administration, in vivo, in a model of LPS (8 x 106 U kg-1 i.p.)-induced endotoxemia in urethane-anaesthetised rats. (4) DEX treatment significantly reduced, in a time-dependent manner, the increased hypotensive effect induced by CRK in LPS-treated rats. This effect was significantly (P<0.05) reverted by the glucocorticoid receptor antagonist RU38486 (6.6 mg kg-1 i.p.). (5) GLB-induced hypertension (40 mg kg-1 i.p.), in LPS-treated rats, was significantly inhibited by DEX if administered at the same time of LPS. (6) Simultaneous administration of DEX and LPS to rats completely abolished the hyporeactivity to PE observed after 24 h from LPS injection. (7) In conclusion, our results suggest that the beneficial effect of DEX in endotoxemia could be ascribed, at least in part, to its ability to interfere with KATP channel activation induced by LPS. This interaction may explain the improvement of vascular reactivity to PE, mediated by DEX, in LPS-treated rats, highlighting a new pharmacological activity to the well-known anti-inflammatory properties of glucocorticoids.     

Role of superoxide and hydrogen peroxide in hypertension induced by an antagonist of adenosine receptors

Treatment of Wistar rats for 7 days with 1,3-dipropyl-8-sulfophenylxanthine (DPSPX), an antagonist of adenosine receptors, induces long-lasting hypertension associated with marked changes in vascular structure and reactivity and renin-angiotensin system activation. This study aimed at evaluating the role of oxidative stress in the development of DPSPX-induced hypertension and also at identifying the relative contribution of superoxide radical (O2.-) vs hydrogen peroxide (H2O2). Vascular and systemic prooxidant/antioxidant status was evaluated in sham (saline, i.p., 7 days) and DPSPX (90 microg/kg/h, i.p., 7 days)-treated rats. Systolic blood pressure was determined by invasive and non-invasive methods. The activity of vascular NADPH oxidase, superoxide dismutase (SOD), catalase and glutathione peroxidase was assayed by fluorometric/spectrophotometric methods. H2O2 levels were measured using an Amplex Red Hydrogen Peroxide kit. Plasma thiobarbituric acid reactive substances and plasma antioxidant capacity were also measured. In addition we tested the effects of antioxidants or inhibitors of reactive oxygen species generation on blood pressure, vascular hyperplasia and oxidative stress parameters. DPSPX-hypertensive rats showed increased activity of vascular NADPH oxidase, SOD, catalase and glutathione peroxidase, as well as increased H2O2 generation. DPSPX-hypertensive rats also had increased plasma lipid peroxidation and decreased plasma antioxidant capacity. Treatment with apocynin (1.5 mmol/l, per os, 14 days), or with polyethylene glycol (PEG)-catalase (10,000 U/kg/day, i.p., 8 days), prevented the DPSPX-induced effects on blood pressure, vascular structure and H2O2 levels. Tempol (3 mmol/l, per os, 14 days) failed to inhibit these changes, unless PEG-catalase was co-administered. It is concluded that O2.- generation with subsequent formation of H2O2 plays a major role in the development of DPSPX-induced hypertension.     

Thaliporphine increases survival rate and attenuates multiple organ injury in LPS-induced endotoxaemia

This study addressed the question of whether thaliporphine, a phenolic aporphine alkaloid obtained from Chinese herbs and possessing antioxidant and -1 adrenoceptor antagonistic activity, has protective effects in endotoxaemic rats and we attempted to elucidate the mechanisms contributing to such protective effects. Injection of rats with endotoxin (E. coli lipopolysaccharide, LPS) induced severe hypotension and tachycardia as well as vascular hyporeactivity to noradrenaline. Pretreatment of LPS-treated rats with thaliporphine attenuated the delayed hypotension significantly whilst only a higher dose (1 mg/kg) of thaliporphine decreased LPS-induced tachycardia. LPS significantly increased nitric oxide (NO·) and superoxide anion (O₂·^–) levels, a response that was reduced by pretreatment with 1 mg/kg thaliporphine. Endotoxaemia for 240 min resulted in a bell-shaped time course for the change of serum tumour necrosis factor- (TNF-) level with a peak at 60 min. Pretreatment of LPS-treated rats with 1 mg/kg thaliporphine significantly reduced the serum TNF- level at 60 min. In addition, LPS caused a biphasic change in blood glucose and thaliporphine attenuated the late-phase decrease in blood glucose. Endotoxaemia induced multiple organ injury in the liver, kidney and heart, as indicated by increases of aspartate aminotransferase (GOT), alanine aminotransferase (GPT), creatinine (CRE), lactate dehydrogenase (LDH) and creatine phosphate kinase muscle-brain (CKMB) levels in serum. These increases of biochemical markers and inflammatory cell infiltration into injured tissues were reduced significantly by treatment with thaliporphine. In addition, thaliporphine increased the survival rate of LPS-treated mice dose-dependently. In conclusion, our results suggest that thaliporphine could be a novel agent for attenuating endotoxin-induced circulatory failure and multiple organ injury and may increase the survival rate. These beneficial effects of thaliporphine may be attributed to the suppression of TNF-, NO· and O₂·^– production.