Serum Heme Oxygenase-1 Research Articles

Low HO-1 and high KEAP1 serum levels in children with attention deficit hyperactivity disorder : the first clinical study

Objective: The purpose of this study was therefore to evaluate serum heme oxygenase-1 (HO-1), kelch-like ECH-associated protein 1 (KEAP1), and nuclear factor erythroid 2 related factor 2 (NRF2) levels in children with attention deficit hyperactivity disorder (ADHD) and to reveal their association with the severity of ADHD. Methods: The patient group consisted of 41 children aged 6–12 years, first diagnosed with ADHD and the control group consisted of 34 age- and gender- matched children. ADHD was diagnosed by child psychiatrists during clinical interviews based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). The parents of the children in the ADHD group were also given the Turgay DSM-IV-based Disruptive Behavior Disorders Child and Adolescent Rating and Screening Scale (T-DSM-IV-S). Serum HO-1, KEAP1, and NRF2 levels were determined in the biochemistry laboratory using the ELISA technique. Results: HO-1 levels in the patient group were significantly lower than in the control group, while KEAP1 levels were significantly higher, but no significant difference was observed between the groups in terms of NRF2 (p=0.041, p

Changes of serum vascular endothelial growth factor, apelin and heme oxygenase-1 levels in patients with type 2 diabetes mellitus and their relationship with diabetic retinopathy

Objective To observe the serum vascular endothelial growth factor (VEGF), apelin and heme oxygenase-1 (HO-1) levels in patients with type 2 diabetes mellitus (T2DM) and to explore their their relationship with diabetic retinopathy (DR). Methods A total of 208 patients with T2DM and 50 healthy subjects (control group) from the Central Hospital of Western Hainan during January 2014 and December 2017 were selected in this study. Vision, slit lamp microscope, indirect ophthalmoscope and FFA examinations were performed on all the subjects. According to the results of the examinations combined with the DR clinical staging criteria, the patients were divided into non-DR (NDR) group, non-proliferative DR (NPDR) group, and proliferative DR (PDR) group, with 72, 76 and 60 patients in each, respectively. The clinical data of each group were recorded, and the levels of fasting blood glucose (FPG), HbA1c, total cholesterol (TC), three acylglycerol (TG), high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), VEGF, apelin and HO-1 were detected in each group. The receiver operating characteristic curve (ROC) were used to analyze the value of VEGF, apelin and HO-1 in predicting the occurrence of PDR. Correlation analysis of serum VEGF, Apelin and HO-1 with clinical parameters in PDR patients by Pearson correlation analysis. Results The level of VEGF (56.82±10.16 vs 91.74±22.83, 140.15±36.40, 195.28±42.26 pg/ml) and apelin (2.95±0.53 vs 4.68±0.74, 7.25±1.13, 10.16±1.35 ng/ml) in PDR group were significantly higher than those in NPDR, NDR and control groups (F=17.306, 21.814; P<0.05). The level of HO-1 (50.37±10.14 vs 43.58±8.16, 30.25±6.28, 22.60±4.72 mmol/L) in PDR group was significantly lower than those in NPDR, NDR and control groups (F=15.827, P<0.05). The ROC curve analysis showed that the best cut-off values of serum VEGF, apelin and HO-1 were 162.50 pg/ml, 8.30 ng/ml, 27.13 mmol/L, and the three combined to predict PDR of AUC (95%CI) was 0.906 (0.849−0.962), and their sensitivity (90.3%) and specificity (83%) were better. The correlation analysis showed that the VEGF, apelin and HO-1 of PDR patients were correlated with the course of diabetes (r=0.382, 0.416, −0.36; P<0.05), FPG (r=0.438, 0.460, −0.397; P<0.05) and HbAlc (r=0.375, 0.478, −0.405; P<0.05), and the serum VEGF were correlated with apelin and HO-1 (r=0.793, −0.594; P<0.01). Conclusion Elevated serum VEGF and apelin levels and reduced HO-1 levels are associated with the progression of DR, and the three combination helps predict the occurrence of PDR. Key words: Diabetic retinopathy/etiology; Diabetes mellitus, type 2; Vascular endothelial growth factors; Receptors, angiotensin; Heme oxygenase-1

Serum Inflammatory Cytokines Comparison in Gastric Cancer Therapy.

To compare serum inflammatory cytokines between laparoscopic-assisted and open radical gastrectomy in the perioperative period, 80 cases of advanced gastric cancer were chosen for the study. They were divided into laparoscopy group (40 cases) and abdominal open surgery group (40 cases), performed laparoscopic-assisted radical gastrostomy and conventional open radical gastrectomy, respectively. Serum Heme oxygenase-1 (HO-1), TNF-α, IL-6 and CRP were measured by ELISA on preoperative day 1, post-operative day 1 and post-operative day3. Serum HO-1, TNF-α, IL-6 and CRP had no significant difference between the laparoscopy group and the open group on pre-operative day 1. Serum HO-1, IL-6 and CRP of the laparoscopy group were significantly lower than that of the open group on post-operative day 1 and day 3 except for Serum TNF-α which had no significant difference. Laparoscopic-assisted radical gastrectomy was minimally invasive compared with conventional open radical gastrectomy in advanced gastric cancer patients.

HO-1 concentrations 24 hours after cardiac surgery are associated with the incidence of acute kidney injury: a prospective cohort study.

BackgroundAcute kidney injury (AKI) is a serious complication after cardiac surgery that is associated with increased mortality and morbidity. Heme oxygenase-1 (HO-1) is an enzyme synthesized in renal tubular cells as one of the most intense responses to oxidant stress linked with protective, anti-inflammatory properties. Yet, it is unknown if serum HO-1 induction following cardiac surgical procedure involving cardiopulmonary bypass (CPB) is associated with incidence and severity of AKI.Patients and methodsIn the present study, we used data from a prospective cohort study of 150 adult cardiac surgical patients. HO-1 measurements were performed before, immediately after and 24 hours post-CPB. In univariate and multivariate analyses, the association between HO-1 and AKI was investigated.ResultsAKI with an incidence of 23.3% (35 patients) was not associated with an early elevation of HO-1 after CPB in all patients (P=0.88), whereas patients suffering from AKI developed a second burst of HO-1 24 hours after CBP. In patients without AKI, the HO-1 concentrations dropped to baseline values (P=0.031). Furthermore, early HO-1 induction was associated with CPB time (P=0.046), while the ones 24 hours later lost this association (P=0.219).ConclusionThe association of the second HO-1 burst 24 hours after CBP might help to distinguish between the causality of AKI in patients undergoing CBP, thus helping to adapt patient stratification and management.

Clinical Significance of Serum Hemeoxygenase-1 as a New Biomarker for the Patients with Interstitial Pneumonia.

Background Serum hemeoxygenase-1 (HO-1) has been proposed to be a biomarker of lung disease activity and prognosis. The present study aimed at evaluating whether HO-1 could be a useful marker for evaluating disease activity and predicting prognosis in patients with interstitial pneumonia (IP). Materials and Methods Serum HO-1 levels of newly diagnosed or untreated patients with IP were measured at hospitalization. We evaluated the relationships between serum HO-1 and other serum biomarkers, high resolution CT (HRCT) findings, and hospital mortality. Results Twenty-eight patients with IP, including 14 having an acute exacerbation (AE) and 14 not having an AE, were evaluated. The patients having an AE had significantly higher HO-1 levels than those not having an AE (53.5 ng/mL vs. 24.1 ng/mL; p < 0.001), and the best cut-off level to discriminate between having an AE or not having an AE was 41.6 ng/mL. Serum HO-1 levels were positively correlated with serum levels of surfactant protein-D (r=0.66, p < 0.001) and the ground glass opacity score (calculated from HRCT; r=0.40, p=0.036). Patients who subsequently died in hospital had presented with significantly higher HO-1 levels than those who did not die in hospital (64.8 ng/mL vs. 32.0 ng/mL; p=0.009). Conclusion Serum HO-1 may serve as a useful biomarker for detecting AE or predicting hospital mortality in patients with IP.

The relationship between the changes of serum NGF, HO-1, IL-1 beta and cognitive function in patients with severe OSAHS after comprehensive treatment

Objective:To explore the relationship between the levels of serum nerve growth factor(NGF), hemeoxygenase 1(HO-1),interleukin-1 beta (IL-1β) and cognitive function in OSAHS patients. Method:the levels of serum NGF, HO-1 and IL-1β concentrations in 60 severe OSAHS patients were measured before and after treatment, and the Montreal cognitive score (MoCA), AHI and the LSaO₂ were also recorded. Result:①OSAHS patients have serum NGF decreased and serum HO-1, IL-1β increased.②In severe OSAHS patients the AHI was negatively correlated with NGF (r=－0.648), positively correlated with HO-1 (r=0.695), and positively correlated with IL-1β(r=0.616).③The MoCA value was positively correlated with NGF (r=0.663), negatively correlated with HO-1 (r=－0.614), and negatively correlated with IL-1β(r=－0.346).④After half a year of follow-up, the AHI and Serum HO-1 and IL-1β were significantly decreased, while the MoCA values and serum NGF were significantly increased after treatment. Conclusion:①Severe OSAHS patients have cognitive impairment.②The changes of serum NGF, HO-1 and IL-1β may be related to the changes of cognitive function in OSAHS patients. ③Comprehensive treatment can improve the patient's LSaO₂,reduce AHI, and improve the cognitive function.④Regular monitoring the concentration of serum NGF, HO-1, and IL-1β may be helpful to assess the patient's condition and recovery.

Three-dimensional echocardiography in the diagnosis of myocardial infarction and its correlation with the expressions of serum HIF-1α, HO-1 and VEGF.

To investigate the correlation between three-dimensional echocardiography and the expressions of hypoxia-inducible factor-1 alpha (HIF-1α), heme oxygenase 1 (HO-1) and vascular endothelial growth factor (VEGF) in patients with myocardial infarction. A total of 40 patients with acute myocardial infarction treated with three-dimensional echocardiography and 40 patients receiving normal physical examination were selected. According to whether the disease occurred, they were divided into the myocardial infarction group and the normal group. Relevant indexes of two-dimensional and three-dimensional echocardiography and the expressions of HO-1, HIF-1α and VEGF in the myocardial infarction group and the normal group were compared. Besides, the correlation of the left ventricular ejection fraction (LVEF) measured by three-dimensional echocardiography with HIF-1α area, HO-1 area and VEGF area was analyzed. The left ventricular end-diastolic diameter (LVEDD) in the myocardial infarction group was significantly larger than that in the normal group (p<0.05), while the left ventricular inferior wall thickness (LVIWT) and LVEF in the myocardial infarction group were significantly smaller than those in the normal group (p<0.05). The global end-diastolic volume (GEDV) and global end-systolic volume (GESV) measured by three-dimensional echocardiography in the myocardial infarction group were significantly higher than those in the normal group (p<0.05), while the level of GEF in the myocardial infarction group was lower than that in the normal group; the levels of HIF-1α, HO-1 and VEGF in the myocardial infarction group were significantly higher than those in normal group (p<0.05). LVEF measured by three-dimensional echocardiography was negatively correlated with HIF-1α area, HO-1 area and VEGF area (p<0.05). Three-dimensional echocardiography significantly improves the diagnostic value of patients with myocardial infarction, and its index, LVEF, is negatively correlated with the expressions of serum HIF-1α, HO-1 and VEGF, which can be used for evaluating cardiac functions and predicting the prognosis of patients.

ELISA Development for Serum Hemeoxygenase-1 and Its Application to Patients with Acute Respiratory Distress Syndrome.

Background Hemeoxygenase-1 (HO-1) is an essential enzyme in heme catabolism and has been proposed as a biomarker of lung disease prognosis. We modified a commercial HO-1 enzyme-linked immunosorbent assay (ELISA) kit to achieve higher sensitivity and evaluated if serum HO-1 could be a biomarker to predict the prognosis of acute respiratory distress syndrome (ARDS) patients. Methods Serum samples were collected from 15 healthy volunteers to validate the modified ELISA. In the 22 patients with ARDS who were enrolled, serum HO-1 was measured upon diagnosis (D0) and at 7 days after diagnosis (D7). Results The serum HO-1 concentration could be measured in all healthy volunteers. The intra- and interassay tests and the percentage recovery test were acceptable. Compared with normal control subjects, patients with ARDS had significantly higher D0 HO-1 concentrations (75.4 ng/mL versus 31.7 ng/mL, P < 0.001). The 28-day survival was significantly better in patients with low D0 HO-1 (<75.8 ng/mL) than in those with high D0 HO-1 (≥75.8 ng/mL) (mortality rate: 18% versus 73%, P=0.016). Nonsurvivors had significantly higher D0 and D7 HO-1 concentrations than survivors (P < 0.05). Conclusion Serum HO-1 may be a useful biomarker to predict the prognosis of patients with ARDS.

QUERCETIN AND ELLAGIC ACID IN GASTRIC ULCER PREVENTION: AN INTEGRATED SCHEME OF THE POTENTIAL MECHANISMS OF ACTION FROM IN VIVO STUDY

Objective: The present study was initiated to describe the gastroprotective role of quercetin (Qu) and ellagic acid (EA) on aspirin-induced gastric ulcer (GU) in rats.Methods: Forty adult female albino rats of Wistar strain were distributed into: Control group, GU group, Omeprazole group, Qu group, and EA group. Gross examination, biochemical analyses including serum adrenocorticotropic hormone (ACTH), serotonin (ST), ferritin, heme oxygenase-1 (HO-1), interleukin-2 (IL-2), advanced glycosylation end products (AGEs), and fibronectin (FN) levels were estimated. Moreover, histopathological and histochemical examinations of stomach tissue samples were carried out.Results: Gross examination of gastric mucosa of rats in GU group revealed hyperemia of the stomach mucosa. Furthermore, rats in GU group experienced a significant rise in serum ACTH, ferritin, HO-1, IL-2 and AGEs levels accompanied with significant drop in serum ST and FN levels versus control counterparts. Pre-treatment of GU group with Omeprazole, Qu or EA caused marked improvement in the measured biochemical parameters. Histopathological and histochemical examinations of stomach tissue samples documented the protective action of Omeprazole, Qu and EA with different degrees against GU caused by aspirin.Conclusion: As a conclusion to this study, we can state that both Qu and EA have gastroprotective effect against aspirin-induced GU in rat model. Of note, Qu showed superior impact than EA as an antiulcer agent in this study. The corresponding mechanisms are speculated to be associated with inhibiting stress-induced gastric lesion, attenuating the oxidative stress, iron chelation and blunting ferritin level, modulating inflammatory cascade, and promoting the healing process.

QUERCETIN AND ELLAGIC ACID IN GASTRIC ULCER PREVENTION: AN INTEGRATED SCHEME OF THE POTENTIAL MECHANISMS OF ACTION FROM IN VIVO STUDY

Objective: The present study was initiated to describe the gastroprotective role of quercetin (Qu) and ellagic acid (EA) on aspirin-induced gastric ulcer (GU) in rats.Methods: Forty adult female albino rats of Wistar strain were distributed into: Control group, GU group, Omeprazole group, Qu group, and EA group. Gross examination, biochemical analyses including serum adrenocorticotropic hormone (ACTH), serotonin (ST), ferritin, heme oxygenase-1 (HO-1), interleukin-2 (IL-2), advanced glycosylation end products (AGEs), and fibronectin (FN) levels were estimated. Moreover, histopathological and histochemical examinations of stomach tissue samples were carried out.Results: Gross examination of gastric mucosa of rats in GU group revealed hyperemia of the stomach mucosa. Furthermore, rats in GU group experienced a significant rise in serum ACTH, ferritin, HO-1, IL-2 and AGEs levels accompanied with significant drop in serum ST and FN levels versus control counterparts. Pre-treatment of GU group with Omeprazole, Qu or EA caused marked improvement in the measured biochemical parameters. Histopathological and histochemical examinations of stomach tissue samples documented the protective action of Omeprazole, Qu and EA with different degrees against GU caused by aspirin.Conclusion: As a conclusion to this study, we can state that both Qu and EA have gastroprotective effect against aspirin-induced GU in rat model. Of note, Qu showed superior impact than EA as an antiulcer agent in this study. The corresponding mechanisms are speculated to be associated with inhibiting stress-induced gastric lesion, attenuating the oxidative stress, iron chelation and blunting ferritin level, modulating inflammatory cascade, and promoting the healing process.

Fetal Microsatellite in the Heme Oxygenase 1 Promoter Is Associated With Severe and Early-Onset Preeclampsia.

Preeclampsia is a vascular pregnancy disorder that often involves impaired placental development. HO-1 (heme oxygenase 1, encoded by HMOX1) is a stress response enzyme crucial for endothelial and placental function. Long version of the guanine-thymine (GTn) microsatellite in the HMOX1 promoter decreases HO-1 expression, and the long maternal repeat is associated with late-onset preeclampsia. Our aim was to study whether the length of fetal repeat is associated with mother's preeclampsia, whether the length of fetal and maternal repeats affect HO-1 levels in placenta and maternal serum, and whether HO-1 levels are altered in preeclampsia. We genotyped the repeat in the cord blood of 609 preeclamptic and 745 nonpreeclamptic neonates. HO-1 levels were measured in 36 placental samples, and in the first (222 cases/243 controls) and third (176 cases/53 controls) pregnancy trimester serum samples using enzyme-linked immunosorbent assay. The long fetal GTn repeat was associated with preeclampsia and its severe and early-onset subtypes. Interaction analysis suggested the maternal and fetal effects to be independent. Placental or serum HO-1 levels were not altered in preeclamptics, possibly reflecting heterogeneity of preeclampsia. Carriers of the long fetal and maternal repeats had lower placental and serum HO-1 levels, respectively, providing functional evidence for the association. We conclude that the long fetal GTn repeat may increase mother's risk for especially severe and early-onset preeclampsia. The fetal and maternal risk alleles likely predispose to different disease subtypes.

The study of using salvianolate treat acute lung injury in rats induced by paraquat

Objective: To establish to paraquat poisoning acute lung injury animal model to study the therapeutic effect of Salvia polyphenols acid salt of paraquat-induced acute lung injury. Methods: Adult male Wister rats 120, were randomly divided into three groups: the paraquat exposure group, the start of the experiment to give a one-time 20% paraquat dope orally 50 mg/kg body weight of rats; salvianolate treatment group, the start of the experiment paraquat to give a one-time 20% the stock solution orally 50 mg/kg body weight of rats, and then given daily intraperitoneal injection of 200 mg/kg body weight of rats salvianolate; blank control group was given the same amount normal saline. The exposure group, the treatment group and control group rats were sacrificed after anesthesia in the 3rd, 7th, 14th, 21st day from the beginning of the experiment respectively, and taken out and preserved venous blood specimens and lung tissue to be tested. Venous detection heme oxygenase-1 (HO-1) , the lung tissue detection heme oxygenase-1 (HO-1) , hydroxyproline (HYP) . And do biopsy specimens from some of the lung tissue, HE and Masson staining observed by optical microscope. Results: Compared with control group, model group 7, 14, 21 days had elevated levels of serum and lung tissue HO-1 (all P<0.05) ; Treatment group 3, 7, 14, 21 days increased (all P<0.05) , and 3, 7, 14 days is higher than the model group (compared with model group, P<0.05) . Compared with control group, treatment group 3 days and model group, 14, 21 days HYP content in lung tissue increased significantly (all P<0.05) ; 21 days, compared with model group, HYP content of treatment group reduce obviously, the difference was statistically significant (P<0.05) . Optical microscope observation, lung tissue damage and aggravated with the experimental increase in the number of days, inflammatory cell infiltration, alveolar septal fibrosis gradually formed. The treatment group experimental animal lung tissue to reduce inflammation, lung fibrosis relief. Conclusion: Paraquat (50 mg/kg body weight) to fill the stomach can be induced model of acute lung injury in the rats. The serum HO-1 expression and HO-1, HYP content in lung tissue increased obviously in model rats. Salvia miltiorrhiza polyphenols acid salt to a certain degree and stage influenced the expression of HO-1 and HYP, relieve acute lung injury and pulmonary fibrosis, has certain curative effect in the treatment of paraquat poisoning.

Serum heme oxygenase-1 levels in patients with primary dysmenorrhea.

Primary dysmenorrhea effects the life-quality of women negatively. The aim of this study was to evaluate heme oxygenase-1 (HO1) activity together with malondialdehyde (MDA) and nitric oxide (NO) levels in patients with primary dysmenorrhea. A total of 28 nulliparous women with the diagnosis of primary dysmenorrhea and 26 healthy controls were included in this study. On the first day of menstruation, all patients underwent ultrasound examination to exclude pelvic pathology and the visual analogue scale was applied to patients. Patient's visual analogue scale (VAS) scores, age, body mass index (BMI), menstrual cycle length (day), length of bleeding (day) were recorded. In the same day, fasting blood samples were taken from each patient for biochemical analysis. Serum MDA, NO and HO1 levels were found to be higher in women with primary dysmenorrhea compared to healthy controls (p = 0.012, p = 0.009, p < 0.001, respectively). There were no correlation among serum levels of HO1, NO and MDA, age, BMI, cycle length, pain score and menses duration in both groups. In Pearson's correlation analysis, positive correlation was found between HO1 levels with the NO levels (r = 0.316, p < 0.05) and VAS scores (r = 0.520, p < 0.01). Also, positive correlation was found between MDA levels and VAS scores (r = 0.327, p < 0.05). Serum HO1, NO and MDA levels increase in patients with primary dysmenorrhea. Antioxidant support might be helpful to reduce pain severity in primary dysmenorrhea.

Citrus leaf extract reduces blood pressure and vascular damage in repeatedly heated palm oil diet-Induced hypertensive rats.

Prolonged consumption of repeatedly heated vegetable oil increases blood pressure. This study aimed to determine the effects of Citrus leaf extract, (CLE) on blood pressure, blood pressure-regulating enzymes and mediators, as well as aortic histomorphometry in heated palm oil induced-hypertension. Male Sprague Dawley rats (n=56) were divided into seven groups; control group was given normal diet and the other groups were fed with palm oil-enriched diet (15% w/w) either fresh (FPO), five-time-heated (5HPO) or ten-time-heated (10HPO) with or without CLE (0.15%, w/w) supplementation. CLE supplementation reduced the heated oil-raising effect of blood pressure, plasma TBARS, thromboxane and angiotensin-1 converting enzyme in 5HPO but not in 10HPO group. CLE increased serum heme oxygenase-1 in both 5HPO and 10HPO groups. CLE supplementation reduced the increase in aortic intima-media thickness, intima-media area and circumferential wall tension in 5HPO group but not in 10HPO group. These findings suggested that CLE supplementation reduces the blood pressure-raising effects of 5HPO and vascular damage, possibly through its antioxidant effect by modulating vasoactive mediators and blood pressure-regulating enzymes.

Luteolin protects mice from severe acute pancreatitis by exerting HO-1-mediated anti-inflammatory and antioxidant effects.

Reseda odorata L. has long been used in traditional Asian medicine for the treatment of diseases associated with oxidative injury and acute inflammation, such as endotoxemia, acute lung injury, acute myocardial infarction and hepatitis. Luteolin, the main component of Reseda odorata L., which is also widely found in many natural herbs and vege tables, has been shown to induce heme oxygenase-1 (HO-1) expression to exert anti-inflammatory and antioxidant effects. In this study, we aimed to examine the effects of luteolin on mice with severe acute pancreatitis (SAP), and to explore the underlying mechanisms. Cerulein and lipopolysaccharide were used to induce SAP in male Institute of Cancer Research (ICR) mice in the SAP group. The SAP group was divided into 4 subgroups, as follows: the vehicle, luteolin, zinc protoporphyrin (ZnPP) only, and luteolin (Lut) + ZnPP (luteolin plus zinc protoporphyrin treatment) groups. The wet/dry weight ratios, hematoxylin and eosin staining and pathological scores of pancreatic tissues were assessed and compared to those of the control mice. Amylase, lipase, nuclear factor-κB (NF-κB) and myeloperoxidase activities, and malondialdehyde, tumor necrosis factor α (TNFα), interleukin (IL)-6, IL-10 and HO-1 levels, as well as the expression of HO-1 were determined in serum and/or pancreatic tissue samples. SAP was successfully induced in male mice compared to normal control mice. The wet/dry weight ratios, pathological scores, and amylase and lipase activity, as well as the levels of TNFα and IL-6 were significantly reduced in the pancreatic tissues of the mice in the Lut group compared with those of the mice in the vehicle group. The Lut group exhibited a significant increase in HO-1 expression in the pancreas and enhanced serum HO-1 and IL-10 levels compared with the vehicle group. The suppression of HO-1 activity in the ZnPP group significantly abolished the protective effects of luteolin. NF-κB expression in the pancreatic tissues from the mice in the Lut + ZnPP group was significantly increased following the suppression of HO-1 activity. On the whole, our findings demonstrate that luteolin protects mice from SAP by inducing HO-1-mediated anti-inflammatory and antioxidant activities, in association with the suppression of the activation of the NF-κB pathway.

Obesity, Oxidative Stress, and Their Effect on Serum Heme Oxygenase-1 Concentrations and Insulin in Children Aged 3 to 5 Years in a Pediatric Hospital of the Ministry of Health CDMX.

Obesity during early stages of life may condition states of oxidative stress. Heme oxygenase-1 (HO-1) is an enzyme involved in oxidative metabolism; it has antioxidant and anti-inflammatory functions and is related in sensitivity to insulin. However, a high concentration of this enzyme has been described to cause alterations such as insulin resistance. The objective of this work was to study the relationship between obesity, oxidative stress, HO-1, and insulin in children aged 3 to 5 years. To achieve our objective, we studied a control group of children (n = 50) and a group of obese children (n = 50) who underwent an anthropometric evaluation. Additionally, we quantified peroxidized lipids, oxidized low-density lipoproteins (Ox-LDLs), oxidized and reduced glutathione, HO-1, and insulin. We also calculated the homeostasis model assessment of insulin resistance (HOMA-IR), HOMA-%B, and HOMA-%S indices. According to the data distribution, nonparametric and Spearman's rank correlation coefficient tests were conducted. The results demonstrate that obese children show a statistically relevant increase in BMI/age, serum concentrations of peroxidized lipids, Ox-LDLs, oxidized glutathione, HO-1, and insulin (p < 0.005). In addition, there was an increase in the HOMA-IR and HOMA-%B (p < 0.0001) indices and a decrease of reduced glutathione, as well as a reduction in the HOMA-%S, compared with the children of the control group (p < 0.003). With the results obtained, we can conclude that obese preschool children show a chronic state of oxidative stress, an increase of HO-1, and an incipient state of insulin resistance. Finally, the increased reactive oxygen species could be one of the leading factors involved in insulin resistance and Ox-LDL increase from the preschool stage.

Association of the microsatellite (GT)n repeat polymorphisms of the HO-1 gene promoter and corresponding serum levels with the risk of laryngeal squamous cell carcinoma

Conclusion: Long (GT)n repeat polymorphisms in the heme oxygenase-1 (HO-1) gene promoter and decreased serum HO-1 levels are associated with a higher susceptibility to laryngeal squamous cell carcinoma (LSCC). Objective: In this case-control study, the association of HO-1 microsatellite (GT)n repeat polymorphisms and serum levels with the risk of LSCC was investigated. Methods: A total of 142 LSCC patients, 54 vocal leukoplakia patients and 98 healthy controls, were examined for (GT)n polymorphisms by sequencing, and the serum HO-1 levels were detected in a sub-set from participants above by ELISA. Results: Compared with the controls, the LSCC group had significantly higher frequencies of L-allele (> 29 repeats) and L-allele carriers (p < 0.001, OR = 2.037 and p = 0.005, OR = 2.152, respectively). The frequencies of lymph node metastasis and of moderate or poor differentiation were significantly higher in L-allele carriers compared to non-L-allele carriers (p < 0.05). Significantly lower serum HO-1 levels were detected in LSCC patients (p < 0.001), and patients with lower serum HO-1 levels had more advanced cancer stage and a higher lymph node metastasis rate (p < 0.05). Furthermore, the L-allele carriers had lower serum HO-1 concentrations compared with the non-L-allele carriers (p = 0.019).

Serum Heme Oxygenase-1 and BMP-7 Are Potential Biomarkers for Bone Metabolism in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis.

Backgrounds. Heme oxygenase-1 (HO-1) has been reported to play a regulatory role in osteoclastogenesis. Bone morphogenetic protein (BMP) pathways induce osteoblastic differentiation and bone remodeling. Aims. To identify serum levels of HO-1, BMP-7, and Runt related-transcription factor 2 (Runx2) in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and to investigate the relationships between HO-1, BMP-7, Runx2, and other common biomarkers for bone metabolism. Results. Serum levels of HO-1 and BMP-7 were revealed to be significantly higher in patients with RA or AS than in healthy controls (p < 0.01). In RA group, HO-1 was positively correlated with BMP-7, Runx2, and tartrate-resistant acid phosphatase-5b (TRAP-5b) (p < 0.05, resp.), BMP-7 was positively correlated with Runx2 and TRAP-5b (p < 0.05, resp.), and Runx2 was negatively correlated with N-terminal midfragment of osteocalcin (NMID) (p < 0.05). In AS group, we observed identical correlation between HO-1 and BMP-7, but opposite correlations between BMP-7 and TRAP-5b and between Runx2 and NMID, when comparing with the RA cohort. Conclusion. Our findings suggest that HO-1 and BMP-7 are potential biomarkers for bone metabolism in patients with RA and AS. The different correlations between the bone markers point to distinct differences in bone remodeling pathways in the two types of arthritis.

Higher Level of Serum Heme Oxygenase-1 in Patients With Intracerebral Hemorrhage.

The objective of this paper was to investigate the association of the serum level of heme oxygenase-1 in patients with intracerebral hemorrhage (ICH) with the risk of ICH. Heme oxygenase-1(HO-1) metabolizes heme into biliverdin, bilirubin, carbon monoxide, and iron, our recent study showed that serum level of HO-1 was increased in stroke patients, yet the association of HO-1 level with risk of intracerebral hemorrhage (ICH) is poorly known. Forty patients with ICH and another 40 patients without ICH were recruited. The serum level of HO-1, total, and direct bilirubin were measured. The level of HO-1, serum total bilirubin, and direct bilirubin, as well as blood pressure were increased in ICH group than in control group (P < 0.001). The level of HO-1, both systolic and diastolic blood pressure had a significant difference between subgroups (P < 0.05). Multivariate regression analysis showed that poor compliance to medicine for hypertension, the serum level of HO-1, and systolic blood pressure were associated with the prevalence of ICH. Blood pressure, serum HO-1, serum total bilirubin, and direct bilirubin were raised in patients with ICH who did not take medicine for hypertension compared with those who did, and increased in ICH patients in comparison with control group. Further investigation in multiple medical centers with large number of cohorts is warranted to verify these results.

The level of serum heme oxygenase-1 and carbon monoxide in children with mycoplasma pneumoniae infection

Objective To investigate the role of heme oxygenase-1(HO-1) and carbon monoxide(CO) in children with mycoplasma pneumoniae infection. Methods A total of 198 cases with mycoplasma pneumoniae infection under 3 years were enrolled in this study.According to whether with wheezing, all cases were divided into wheezing group(n=58) and no wheezing group(n=140). According to having hypoxemia, wheezing group was divided into mild wheezing group(n=34) and severe wheezing group(n=24). And no wheezing group was set as control group.The serum COHb levels were measured by dual-wavelength spectrophotometry.The serum HO-1 were measured by ELISA. Results The levels of serum HO-1 and COHb% in severe wheezing group were(2 734.10±707.59) ng/L, (3.88±0.83)%, and(1 130.03±671.02) ng/L, (1.16±0.63)% in mild wheezing group, and(931.32±451.67) ng/L, (1.04±0.37)% in no wheezing group, respectively.There were significant differences in serum HO-1 and COHb% between severe wheezing group and mild wheezing group(P 0.05, respectively). There was significant positive correlation between serum HO-1 and COHb%(r=0.875, P<0.01). Conclusion With mycoplasma pneumoniae infection, the expression of HO-1 and COHb% increase by the wheezing disease progression.HO-1 and CO may participate in the development process of infantile wheezing diseases. Key words: Heme oxygenase-1; Carbon monoxide; Mycoplasma pneumoniae