Showing papers by "University of Ioannina published in 2002"

Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family.

Abstract: Magnesium is an essential ion involved in many biochemical and physiological processes. Homeostasis of magnesium levels is tightly regulated and depends on the balance between intestinal absorption and renal excretion. However, little is known about specific proteins mediating transepithelial magnesium transport. Using a positional candidate gene approach, we identified mutations in TRPM6 (also known as CHAK2), encoding TRPM6, in autosomal-recessive hypomagnesemia with secondary hypocalcemia (HSH, OMIM 602014), previously mapped to chromosome 9q22 (ref. 3). The TRPM6 protein is a new member of the long transient receptor potential channel (TRPM) family and is highly similar to TRPM7 (also known as TRP-PLIK), a bifunctional protein that combines calcium- and magnesium-permeable cation channel properties with protein kinase activity. TRPM6 is expressed in intestinal epithelia and kidney tubules. These findings indicate that TRPM6 is crucial for magnesium homeostasis and implicate a TRPM family member in human disease.

Vanadium in cancer treatment.

Abstract: Vanadium compounds exert preventive effects against chemical carcinogenesis on animals, by modifying, mainly, various xenobiotic enzymes, inhibiting, thus, carcinogen-derived active metabolites. Studies on various cell lines reveal that vanadium exerts its antitumor effects through inhibition of cellular tyrosine phosphatases and/or activation of tyrosine phosphorylases. Both effects activate signal transduction pathways leading either to apoptosis and/or to activation of tumor suppressor genes. Furthermore, vanadium compounds may induce cell-cycle arrest and/or cytotoxic effects through DNA cleavage and fragmentation and plasma membrane lipoperoxidation. Reactive oxygen species generated by Fenton-like reactions and/or during the intracellular reduction of V(V) to V(IV) by, mainly, NADPH, participate to the majority of the vanadium-induced intracellular events. Vanadium may also exert inhibitory effects on cancer cell metastatic potential through modulation of cellular adhesive molecules, and reverse antineoplastic drug resistance. It also possesses low toxicity that, in combination with the synthesis of new, more potent and better tolerated complexes, may establish vanadium as an effective non-platinum, metal antitumor agent.

Long-term risk of mortality and lymphoproliferative disease and predictive classification of primary Sjögren's syndrome.

Abstract: Objective Primary Sjogren's syndrome (SS) may lead to lymphoproliferative disease (LPD) and death in certain patients. We sought to determine the incidence and predictors of adverse long-term outcomes to achieve a rational predictive classification of the syndrome. Methods Predictive modeling was performed in a cohort of 723 consecutive patients with primary SS (587 newly diagnosed [incident] cases and 136 prevalent cases). Results During 4,384 person-years of followup, we recorded 39 deaths (7 due to lymphoma) and 38 diagnoses of LPD. The standardized mortality ratio was 1.15 (95% confidence interval [95% CI] 0.86–1.73) compared with the general population of Greece. In incident cases, the probability of LPD was 2.6% at 5 years and 3.9% at 10 years. Mortality rates were significantly higher in patients with low C4 levels at the first study visit (hazard ratio [HR] 4.39, 95% CI 2.18–8.83). LPD was independently predicted by the presence of parotid enlargement (HR 5.21, 95% CI 1.76–15.4), palpable purpura (HR 4.16, 95% CI 1.65–10.5), and low C4 levels (HR 2.40, 95% CI 0.99–5.83) at the first study visit. All patients who eventually developed lymphoma resulting in death during the followup period had either low C4 levels or palpable purpura at the first study visit. Training-validation split-cohort modeling confirmed the predictive importance of low C4 levels and palpable purpura, both of which were present in 20.9% of patients at their first visit. Conclusions In patients with primary SS, 1 in 5 deaths is attributable to lymphoma. The presence of palpable purpura and low C4 levels at the first visit adequately distinguishes high-risk patients (type I primary SS) from patients with an uncomplicated disease course (type II [low-risk] primary SS).

Coexistence of pregnancy and malignancy.

Abstract: Cancer complicating pregnancy is a rare coexistence. The incidence is approximately 1 in 1,000 pregnancies. The most common cancers are those more frequently seen during the reproductive age of a woman. Breast cancer, cervical cancer, Hodgkin's disease, malignant melanoma, and leukemias are the most frequently diagnosed malignancies during gestation. The diagnostic and therapeutic management of the pregnant patient with cancer is especially difficult because it involves two persons, the mother and the fetus. In this paper we review: A) the therapeutic and diagnostic management of these patients; B) the safety of diagnostic and therapeutic procedures; C) the metastatic pattern of the maternal tumors to the placenta and fetus, and D) the potential recommendations for therapeutic abortion.

Antioxidant activities and phenolic composition of extracts from Greek oregano, Greek sage, and summer savory.

Abstract: Oregano vulgare L. ssp. hirtum (Greek oregano), Salvia fruticosa (Greek sage), and Satureja hortensis (summer savory) were examined as potential sources of phenolic antioxidant compounds. The antioxidant capacities (antiradical activity by DPPH* test, phosphatidylcholine liposome oxidation, Rancimat test) and total phenol content were determined in the ethanol and acetone extracts of the dried material obtained from the botanically characterized plants. The ground material was also tested by the Rancimat test for its effect on the stability of sunflower oil. The data indicated that ground material and both ethanol and acetone extracts had antioxidant activity. Chromatographic (TLC, RP-HPLC) and NMR procedures were employed to cross-validate the presence of antioxidants in ethanol and acetone extracts. The major component of all ethanol extracts was rosmarinic acid as determined by RP-HPLC and NMR. Chromatography indicated the presence of other phenolic antioxidants, mainly found in the acetone extracts. The presence of the flavones luteolin and apigenin and the flavonol quercetin was confirmed in the majority of the extracts by the use of a novel (1)H NMR procedure, which is based on the strongly deshielded OH protons in the region of 12-13 ppm without previous chromatographic separation. This deshielding may be attributed to the strong intramolecular six-membered ring hydrogen bond of the OH(5)...CO(4) moiety.

Micelle-mediated extraction as a tool for separation and preconcentration in metal analysis

Abstract: Micelle-based techniques can be utilised for the preconcentration and separation of metal ions, which are either in their native form or in chelates that are produced after reaction under appropriate conditions. In this review, the metal analysis is based on an a priori phase separation in aqueous micellar solutions. In principle, the micelle-mediated extraction technique involves cloud-point extraction, but this review also deals with micellar-enhanced ultrafiltration and reversed micellar phase extraction. The different aspects of surfactant-enhanced, non-classical, metal-extraction schemes are presented and the interactions with the micellar entity are given. The fundamentals of micellar solutions and their solubilization capabilities are highlighted. Also outlined are practical problems when this sort of extraction is implemented in conjunction with different analytical detection systems.

Purchasing motives and profile of the Greek organic consumer: a countrywide survey

Abstract: The present study attempts to offer more insights into the Greek organic market. It examines the organic products as “eco‐products”, suitable for “green” consumers, who are ecologically/environmentally ecology‐aware and who are concerned with health and quality‐of‐life issues. Analysing a countrywide sample, the survey concludes that three consumer types exist in terms of attitude towards, purchase intention and awareness of organic products: the “unaware”, the “aware non‐buyers”, and the “(aware) buyers” (or simply buyers) of organic food products. After developing a detailed profile of the first two, the “aware buyers” type is segmented in terms of five groups of personality and behavioural factors, defined in the international literature as the driving forces of organic purchasing.

A Greedy EM Algorithm for Gaussian Mixture Learning

Abstract: Learning a Gaussian mixture with a local algorithm like EM can be difficult because (i) the true number of mixing components is usually unknown, (ii) there is no generally accepted method for parameter initialization, and (iii) the algorithm can get trapped in one of the many local maxima of the likelihood function. In this paper we propose a greedy algorithm for learning a Gaussian mixture which tries to overcome these limitations. In particular, starting with a single component and adding components sequentially until a maximum number k, the algorithm is capable of achieving solutions superior to EM with k components in terms of the likelihood of a test set. The algorithm is based on recent theoretical results on incremental mixture density estimation, and uses a combination of global and local search each time a new component is added to the mixture.

Enzyme Based Amperometric Biosensors for Food Analysis

Abstract: This review introduces the principles of amperometric detection e.g. oxygen electrodes, hydrogen peroxide electrodes, NADH detection, mediators-aid detection, conductive organic salts and wiring electrodes. A short categorization and description of the materials commonly used for the construction of electrodes, e.g., platinum, glassy carbon, different types of graphite, screen-printed electrodes, rigid carbon-polymer biocomposites, zeolites, clays, and polymeric membranes is given. Approaches to construction of biosensors with respect to various strategies of enzyme immobilization, e.g., physical binding, covalent binding, gel entrapment, electropolymerization, sol-gel techniques and self-assembled architectures are also presented. The requirements and problems for sensing in food industry, examples of enzyme electrodes, published in the literature during the last half-decade, commercial biosensors released into the market along with the current and modern instrumentation, are also presented.

In vitro study of the insulin-mimetic behaviour of vanadium(IV, V) coordination compounds

Abstract: A representative set of vanadium(IV and V) compounds in varying coordination environments has been tested in the concentration range 1 to 10–6 mM, using transformed mice fibroblasts (cell line SV 3T3), with respect to their short-term cell toxicity (up to 36 hours) and their ability to stimulate glucose uptake by cells. These insulin-mimetic tests have also been carried out with non-transformed human fibroblasts (cell line F26). The compounds under investigation comprise established insulin-mimetic species such as vanadate ([H2VO4]–), [VO(acetylacetonate)2], [VO2(dipicolinate)]– and [VO(maltolate)2], and new systems and coordination compounds containing OO, ON, OS, NS and ONS donor atom sets. A vitality test assay, measuring the reduction equivalents released in the mitochondrial respiratory chain by intracellular glucose degradation, is introduced and the results are counter-checked with 3H-labelled glucose. Most compounds are toxic at the 1 mM concentration level, and most compounds are essentially non-toxic and about as effective as or more potent than insulin at concentrations of 0.01 mM and below. VV compounds tend to be less toxic than VIV compounds, and complexes containing thio functional ligands are somewhat more toxic than others. Generally, ON ligation is superior in insulin-mimetic efficacy to OO or O/NS coordination, irrespective of the vanadium oxidation state. There is, however, no striking correlation between the nature of the ligand systems and the insulin-mimetic potency in these cell culture tests, encompassing 41 vanadium compounds, the results on 22 of which are reported in detail here. The syntheses and characteristics of various new compounds are provided together with selected speciation results. The crystal and molecular structures of {[VO(naph-tris)]2} [where naph-tris is the Schiff base formed between o-hydroxynaphthaldehyde and tris(hydroxymethyl)amine] are reported. Electronic supplementary material to this paper can be obtained by using the Springer Link server located at http://dx.doi.org/10.1007/s00775-001-0311-5

Organic product avoidance: Reasons for rejection and potential buyers’ identification in a countrywide survey

Abstract: The present study attempts to offer more insights into the Greek organic market. It examines the organic products as “eco‐products”, suitable for “green” consumers, conscious in matters of ecology‐environment, who follow a wider health and quality‐sensitive stance of life. Analyzing a countrywide sample, the survey concludes that three consumer types exist in terms of attitude towards, purchase intention and awareness of organic products: the “unaware”, the “aware non‐users”, and the “aware users” (or simply users) of organic food products. After developing a detailed profile of the other two, the “aware non‐users” type is segmented in terms of five groups of personality and behavioral factors defined in the international literature as the driving forces of organic purchase. Then, organic products’ rejection reasons and potential organic buyer segments are revealed and their profile is fully described.

Role of the Fcgamma receptor IIa polymorphism in susceptibility to systemic lupus erythematosus and lupus nephritis: a meta-analysis.

Abstract: Objective To assess the impact of the Fcγ receptor type IIa (FcγRIIa)–R/H131 polymorphism on the risk for systemic lupus erythematosus (SLE) and development of lupus nephritis. Methods A meta-analysis was performed based on the Medline and Embase databases (last retrieval August 2001), assessment of bibliographies of pertinent articles, and additional data gathered after contact with primary investigators. Results A total of 25 comparisons from 17 studies involving R/H131 genotyping of 1,405 patients with lupus nephritis, 1,709 SLE patients without nephritis, and 2,580 non-SLE controls were included. No association between RR genotype and risk of lupus nephritis relative to both other genotypes (odds ratio [OR] 1.05, 95% confidence interval [95% CI] 0.88–1.27) was demonstrated in the total meta-analysis or in any racial subgroup. The RR genotype was more frequent in SLE patients as a whole (OR 1.30, 95% CI 1.10–1.52) and in SLE patients without nephritis (OR 1.27, 95% CI 1.04–1.55) compared with disease-free controls. A potential dose–response relation between the R131 allele and the risk of SLE was also identified, with an OR of 1.23 for RR versus RH (95% CI 1.03–1.46). The OR was 1.55 for RR versus HH (95% CI 1.21–1.98). There was no significant heterogeneity between racial subgroups. The population-attributable fractions of SLE cases due to the FcγRIIa-R131 allele were 13%, 40%, and 24% in subjects of European, African, and Asian descent, respectively. Conclusion The FcγRIIa-R/H131 polymorphism represents a significant risk factor for SLE but has no clear effect on susceptibility for lupus nephritis.

Association of Polymorphisms of the Estrogen Receptor α Gene With Bone Mineral Density and Fracture Risk in Women: A Meta‐Analysis

Abstract: The contribution of genetic polymorphisms to bone mineral density (BMD) and fracture risk in women is a controversial topic We evaluated the effect of the XbaI and PvuII polymorphisms of the estrogen receptor a to BMD and fracture risk in a meta-analysis, including published data and additional information from investigators Five thousand eight hundred thirty-four women from 30 study groups were analyzed with fixed and random effects models The PvuII polymorphism was not associated with BMD at any skeletal site examined and 95% CIs exclude effects over 0015 g/cm2 for both the femoral neck and the lumbar spine Conversely, XX homozygotes (women carrying two copies of the gene variant without an XbaI restriction site) consistently had higher BMD than other subjects The magnitude of the effect was similar in the femoral neck and lumbar spine (0014 g/cm2 [95% CI, 0003-0025] and 0015 g/cm2 [95% CI, 0000-0030], respectively; no between-study heterogeneity for either) Total body BMD was also significantly higher in XX homozygotes (by 0039 g/cm2 and 0029 g/cm2 compared with Xx and xx, respectively) Available data on fractures suggested a protective effect for XX (odds ratio [OR], 066 [95% CI, 047-093] among 1591 women), but not PP (OR, 093 [95% CI, 072-118] among 2,229 women) In summary, we have found that XX homozygotes may have higher BMD and also a decreased risk of fractures when compared with carriers of the x allele, whereas the PvuII polymorphism is not associated with either BMD or fracture risk

The genetic basis of polycystic ovary syndrome.

Abstract: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. The disorder is characterized by clinical features of hyperandrogenism, menstrual irregularities and often central obesity and hyperinsulinaemia. PCOS may increase the risk for infertility, type 2 diabetes mellitus, dyslipidaemia, cardiovascular disease and endometrial cancer, emphasizing the need for early diagnosis of the syndrome. The genetic basis of PCOS is unknown. There is a strong familial component but the mode of inheritance is uncertain and several candidate genes have been proposed to contribute to susceptibility. Not only genes involved in steroid hormone biosynthesis have been studied but also genes associated with the regulation of insulin secretion and action since hyperinsulinaemia is a characteristic of PCOS. So far there is evidence that INS VNTR (insulin variable number of tandem repeats) or CYP11alpha (cholesterol side chain cleavage) genes are associated with this syndrome. PCOS appears, however, to be an oligogenic disorder and more studies are necessary to define the genetic basis.

The role of oxidative stress in mechanisms of metal-induced carcinogenesis

Abstract: Metals are necessary for the normal functioning of cells and the survival of organisms. However, exposure to higher than the physiological levels of several metals may lead to tumor development. Although the exact molecular mechanism(s) of metal-induced carcinogenesis is not clear, a vast body of evidence indicates that metal-induced generation of reactive oxygen species (ROS) may play a central role in this process. Two main pathways of ROS-induced effects are discussed in this chapter: (i) increased DNA damage induced either directly or indirectly by impeding DNA repair, and (ii) modulation of nuclear transcriptional factor activities, such as NF-kappaB and AP-1, through mitogen-activated protein kinases signal transduction mechanisms.

The hyponatremic patient: a systematic approach to laboratory diagnosis

Abstract: HYPONATREMIA (SERUM SODIUM LEVEL LESS THAN 134 MMOL/L) is a common electrolyte disturbance. Its high prevalence and potential neurologic sequelae make a logical and rigorous differential diagnosis mandatory before any therapeutic intervention. A history of concurrent illness and medication use as well as the assessment of extracellular volume status on physical examination may provide useful clues as to the pathogenesis of hyponatremia. Measurement of the effective serum tonicity (serum osmolality less serum urea level) is the first step in the laboratory evaluation. In patients with normal or elevated effective serum osmolality (280 mOsm/kg or greater), pseudohyponatremia should be excluded. In the hypo-osmolar state (serum osmolality less than 280 mOsm/kg), urine osmolality is used to determine whether water excretion is normal or impaired. A urine osmolality value of less than 100 mOsm/kg indicates complete and appropriate suppression of antidiuretic hormone secretion. A urine sodium level less than 20 mmol/L is indicative of hypovolemia, whereas a level greater than 40 mmol/L is suggestive of the syndrome of inappropriate antidiuretic hormone secretion. Levels of hormones (thyroid-stimulating hormone and cortisol) and arterial blood gases should be determined in difficult cases of hyponatremia.

Neutrinoless double beta decay from a modern perspective

Abstract: Neutrinoless double beta decay is a very important process both from the particle and nuclear physics point of view. From the elementary particle point of view it pops up in almost every model. giving rise, among others, to the following mechanisms: a) The traditional contributions like the light neutrino mass mechanism . b) The exotic R-parity violating supersymmetric (SUSY) contributions. Similar considerations apply to its sister lepton and muon number violating muon to positron conversion. The observation of neutrinoless double beta decay will signal that the neutrinos are massive Majorana particles. For nuclear physics it is challenging, because: 1) The nuclei, which can undergo double beta decay, have complicated structure. 2) The energetically allowed transitions are suppressed. 3) One must cope with the short distance behavior of the transition operators. Thus novel effects (decay of pions in flight between nucleons etc) have to be considered. 4) One has to take into account possible momentum dependent terms of the nucleon current. For light neutrinos such modifications of the nucleon current reduce the nuclear matrix elements by about 25 per cent. In the case of heavy neutrino the effect is much larger and model dependent. With the above effects the nuclear matrix elements for all interesting nuclei A = 76, 82, 96, 100, 116, 128, 130, 136 and 150 are discussed. Some have been obtained in the shell model but most in QRPA. Thus we have extracted new limits on the various lepton violating parameters. We find an average neutrino mass of about 0.5eV and, for reasonable choices of the parameters of SUSY models, we get a stringent limit on the R-parity violating parameter less than 0.00068.

Transcription factor E2F-1 acts as a growth-promoting factor and is associated with adverse prognosis in non-small cell lung carcinomas.

Abstract: Numerous upstream stimulatory and inhibitory signals converge to the pRb/E2F pathway, which governs cell-cycle progression, but the information concerning alterations of E2F-1 in primary malignancies is very limited. Several in vitro studies report that E2F-1 can act either as an oncoprotein or as a tumour suppressor protein. In view of this dichotomy in its functions and its critical role in cell cycle control, this study examined the following four aspects of E2F-1 in a panel of 87 non-small cell lung carcinomas (NSCLCs), previously analysed for defects in the pRb-p53-MDM2 network: firstly, the status of E2F-1 at the protein, mRNA and DNA levels; secondly, its relationship with the kinetic parameters and genomic instability of the tumours; thirdly, its association with the status of its transcriptional co-activator CBP, downstream target PCNA and main cell cycle regulatory and E2F-1-interacting molecules pRb, p53 and MDM2; and fourthly, its impact on clinical outcome. The protein levels of E2F-1 and its co-activator CBP were significantly higher in the tumour area than in the corresponding normal epithelium (p Asp) and one carrying a polymorphism at codon 393 (Gly-->Ser). Carcinomas with increased E2F-1 positivity demonstrated a significant increase in their growth indexes (r=0.402, p=0.001) and were associated with adverse prognosis (p=0.033 by Cox regression analysis). The main determinant of the positive association with growth was the parallel increase between E2F-1 staining and proliferation (r=0.746, p<0.001), whereas apoptosis was not influenced by the status of E2F-1. Moreover, correlation with the status of the pRb-p53-MDM2 network showed that the cases with aberrant pRb expression displayed significantly higher E2F-1 indexes (p=0.033), while a similar association was noticed in the group of carcinomas with deregulation of the p53-MDM2 feedback loop. In conclusion, the results suggest that E2F-1 overexpression may contribute to the development of NSCLCs by promoting proliferation and provide evidence that this role is further enhanced in a genetic background with deregulated pRb-p53-MDM2 circuitry.

Effects of fibrates on serum metabolic parameters.

Abstract: Fibric acid derivatives are a class of hypolipidaemic drugs used in the treatment of patients with hypertriglyceridaemia, mixed hyperlipidaemia and diabetic dyslipidaemia. Fibrate therapy results in a significant decrease in serum triglycerides and an increase in high-density lipoprotein (HDL) cholesterol levels. The latest drugs of this class are also effective in lowering low-density (LDL) cholesterol levels and can change the distribution of LDL towards higher and larger particles. The effects of fibrates on lipid metabolism are mostly mediated through the activation of peroxisome proliferator-activated receptors (PPARalpha). A number of angiographic and clinical trials have confirmed that fibrates can slow the progression of atherosclerotic disease and decrease cardiovascular morbidity and mortality. Recently published data suggest that the ability of fibrates to prevent atherosclerosis is not related only to their hypolipidaemic effects but also to other 'pleiotropic effects', such as their anti-inflammatory, antioxidant and antithrombotic effects, as well as their ability to improve endothelial function. Interestingly, fibrates may favourably influence the thrombotic/fibrinolytic system. In fact, most of these drugs can significantly decrease plasma fibrinogen levels and inhibit tissue factor expression and activity in human monocytes and macrophages. Some studies have shown that fibrates can improve carbohydrate metabolism in patients with dyslipidaemia, including diabetic patients. Among fibrates only fenofibrate can significantly decrease serum uric acid levels by increasing renal urate excretion. Fibrates, with the possible exception of gemfibrozil, can significantly increase serum creatinine and homocysteine levels. Finally, a reduction in serum alkaline phosphatase and gamma glutamyltranspeptidase (gammaGT) activity is a well-documented effect of therapy with fibrates. The fibrates are generally well-tolerated drugs with few side-effects. The most important side-effect is myositis, which is observed in patients with impaired renal function or when statins are given concomitantly.

Atorvastatin Preferentially Reduces LDL-Associated Platelet-Activating Factor Acetylhydrolase Activity in Dyslipidemias of Type IIA and Type IIB

Abstract: Human plasma platelet-activating factor acetylhydrolase (PAF-AH) is a phospholipase A(2) that is primarily associated with low density lipoprotein (LDL). PAF-AH activity has also been found in high density lipoprotein (HDL), although it has recently been indicated that there is no PAF-AH protein in HDL. Plasma paraoxonase 1 (PON1) is an HDL-associated esterase, which also exhibits PAF-AH-like activity. The effect of atorvastatin (20 mg per day for 4 months) on PAF-AH and PON1 activities in patients with dyslipidemia of type IIA (n=55) or type IIB (n=21) was studied. In both patient groups, atorvastatin significantly reduced plasma PAF-AH activity because of the decrease in LDL plasma levels and the preferential decrease in PAF-AH activity on dense LDL subfractions (LDL-4 and LDL-5). Drug therapy did not affect HDL-associated PAF-AH activity or serum PON1 activities toward paraoxon and phenylacetate in either patient group. However, because of the reduction in LDL cholesterol levels, the ratios of HDL-associated PAF-AH and serum PON1 activities to LDL cholesterol levels were significantly increased after drug administration. The reduction of the LDL-associated PAF-AH activity and the elevation in the ratios of HDL-associated PAF-AH and PON1 activities to LDL plasma levels may represent a new dimension in the antiatherogenic effect of atorvastatin.

Luteolin reduces lipopolysaccharide-induced lethal toxicity and expression of proinflammatory molecules in mice.

Abstract: Luteolin is a flavonoid that has been shown to reduce proinflammatory molecule expression in vitro. In the present study, we have tested the ability of luteolin to inhibit lipopolysaccharide (LPS)- induced lethal toxicity and proinflammatory molecule expression in vivo. Mice receiving LPS (Salmonella enteriditis LPS, 32 mg/kg, intraperitoneally) exhibited high mortality with only 4.1% of the animals surviving seven days after the LPS challenge. On the contrary, mice that had received luteolin (0.2 mg/kg, intraperitoneally) before LPS showed an increased survival rate with 48% remaining alive on Day 7. To investigate the mechanism by which luteolin affords protection against LPS toxicity we measured intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor-alpha (TNF-alpha) production in response to LPS in the presence or absence of luteolin pretreatment. Treatment of animals with LPS increased serum TNF-alpha levels in a time-dependent manner. The increase in peak serum TNF-alpha levels was sensitive to luteolin pretreatment. Luteolin pretreatment also reduced LPS-stimulated ICAM-1 expression in the liver and abolished leukocyte infiltration in the liver and lung. We conclude that luteolin protects against LPS-induced lethal toxicity, possibly by inhibiting proinflammatory molecule (TNF-alpha, ICAM-1) expression in vivo and reducing leukocyte infiltration in tissues.