scholarly journals The herbal extract KCHO-1 exerts a neuroprotective effect by ameliorating oxidative stress via heme oxygenase-1 upregulation

2016 ◽  
Vol 13 (6) ◽  
pp. 4911-4919 ◽  
Author(s):  
DONG-SUNG LEE ◽  
WONMIN KO ◽  
BONG-KEUN SONG ◽  
ILHONG SON ◽  
DONG-WOUNG KIM ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heme Oxygenase ◽  
Neuroprotective Effect ◽  
Herbal Extract ◽  
Heme Oxygenase 1

scholarly journals Heme Oxygenase-1 Deficiency and Oxidative Stress: A Review of 9 Independent Human Cases and Animal Models

2021 ◽  
Vol 22 (4) ◽  
pp. 1514 ◽  
Author(s):  
Akihiro Yachie
Keyword(s):  
Oxidative Stress ◽  
Animal Models ◽  
Heme Oxygenase ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Pharmacological Intervention ◽  
Heme Oxygenase 1 ◽  
Inflammatory Reactions

Since Yachie et al. reported the first description of human heme oxygenase (HO)-1 deficiency more than 20 years ago, few additional human cases have been reported in the literature. A detailed analysis of the first human case of HO-1 deficiency revealed that HO-1 is involved in the protection of multiple tissues and organs from oxidative stress and excessive inflammatory reactions, through the release of multiple molecules with anti-oxidative stress and anti-inflammatory functions. HO-1 production is induced in vivo within selected cell types, including renal tubular epithelium, hepatic Kupffer cells, vascular endothelium, and monocytes/macrophages, suggesting that HO-1 plays critical roles in these cells. In vivo and in vitro studies have indicated that impaired HO-1 production results in progressive monocyte dysfunction, unregulated macrophage activation and endothelial cell dysfunction, leading to catastrophic systemic inflammatory response syndrome. Data from reported human cases of HO-1 deficiency and numerous studies using animal models suggest that HO-1 plays critical roles in various clinical settings involving excessive oxidative stress and inflammation. In this regard, therapy to induce HO-1 production by pharmacological intervention represents a promising novel strategy to control inflammatory diseases.

scholarly journals Heme Oxygenase-1 Induction by Cobalt Protoporphyrin Ameliorates Cholestatic Liver Disease in a Xenobiotic-Induced Murine Model

2021 ◽  
Vol 22 (15) ◽  
pp. 8253
Author(s):  
Jung-Yeon Kim ◽  
Yongmin Choi ◽  
Jaechan Leem ◽  
Jeong Eun Song
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Heme Oxygenase ◽  
Murine Model ◽  
Liver Diseases ◽  
Transforming Growth Factor ◽  
Heme Oxygenase 1 ◽  
Cholestatic Liver Disease ◽  
Hepatocyte Apoptosis ◽  
Cobalt Protoporphyrin

Cholestatic liver diseases can progress to end-stage liver disease and reduce patients’ quality of life. Although their underlying mechanisms are still incompletely elucidated, oxidative stress is considered to be a key contributor to these diseases. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that displays antioxidant action. It has been found that this enzyme plays a protective role against various inflammatory diseases. However, the role of HO-1 in cholestatic liver diseases has not yet been investigated. Here, we examined whether pharmacological induction of HO-1 by cobalt protoporphyrin (CoPP) ameliorates cholestatic liver injury. To this end, a murine model of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet feeding was used. Administration of CoPP ameliorated liver damage and cholestasis with HO-1 upregulation in DDC diet-fed mice. Induction of HO-1 by CoPP suppressed the DDC diet-induced oxidative stress and hepatocyte apoptosis. In addition, CoPP attenuated cytokine production and inflammatory cell infiltration. Furthermore, deposition of the extracellular matrix and expression of fibrosis-related genes after DDC feeding were also decreased by CoPP. HO-1 induction decreased the number of myofibroblasts and inhibited the transforming growth factor-β pathway. Altogether, these data suggest that the pharmacological induction of HO-1 ameliorates cholestatic liver disease by suppressing oxidative stress, hepatocyte apoptosis, and inflammation.

scholarly journals Protective Effect of Osmundacetone against Neurological Cell Death Caused by Oxidative Glutamate Toxicity

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 328
Author(s):  
Tuy An Trinh ◽  
Young Hye Seo ◽  
Sungyoul Choi ◽  
Jun Lee ◽  
Ki Sung Kang
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Defense Mechanism ◽  
Neuroprotective Effect ◽  
Glutamate Release ◽  
Chromatin Condensation ◽  
Critical Role ◽  
Glutamate Toxicity ◽  
Heme Oxygenase 1 ◽  
Brain Functions

Oxidative stress is one of the main causes of brain cell death in neurological disorders. The use of natural antioxidants to maintain redox homeostasis contributes to alleviating neurodegeneration. Glutamate is an excitatory neurotransmitter that plays a critical role in many brain functions. However, excessive glutamate release induces excitotoxicity and oxidative stress, leading to programmed cell death. Our study aimed to evaluate the effect of osmundacetone (OAC), isolated from Elsholtzia ciliata (Thunb.) Hylander, against glutamate-induced oxidative toxicity in HT22 hippocampal cells. The effect of OAC treatment on excess reactive oxygen species (ROS), intracellular calcium levels, chromatin condensation, apoptosis, and the expression level of oxidative stress-related proteins was evaluated. OAC showed a neuroprotective effect against glutamate toxicity at a concentration of 2 μM. By diminishing the accumulation of ROS, as well as stimulating the expression of heat shock protein 70 (HSP70) and heme oxygenase-1 (HO-1), OAC triggered the self-defense mechanism in neuronal cells. The anti-apoptotic effect of OAC was demonstrated through its inhibition of chromatin condensation, calcium accumulation, and reduction of apoptotic cells. OAC significantly suppressed the phosphorylation of mitogen-activated protein kinases (MAPKs), including c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 kinases. Thus, OAC could be a potential agent for supportive treatment of neurodegenerative diseases.

scholarly journals Resveratrol Protects C6 Astrocyte Cell Line against Hydrogen Peroxide-Induced Oxidative Stress through Heme Oxygenase 1

PLoS ONE ◽  
2013 ◽  
Vol 8 (5) ◽  
pp. e64372 ◽  
Author(s):  
André Quincozes-Santos ◽  
Larissa Daniele Bobermin ◽  
Alexandra Latini ◽  
Moacir Wajner ◽  
Diogo Onofre Souza ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Cell Line ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1

Dexrazoxane does not protect against doxorubicin-induced damage in young rats

2003 ◽  
Vol 285 (2) ◽  
pp. H499-H506 ◽  
Author(s):  
Stéphanie Héon ◽  
Martin Bernier ◽  
Nicolas Servant ◽  
Stevan Dostanic ◽  
Chunlei Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Weight Gain ◽  
Heme Oxygenase ◽  
Caspase 3 ◽  
Exercise Program ◽  
Female Rats ◽  
Male Rats ◽  
Heme Oxygenase 1 ◽  
Cardiac Damage

Doxorubicin (DOX), an anticancer drug, causes a dose-dependent cardiotoxicity. Some evidence suggests that female children have an increased risk for DOX-mediated cardiac damage. To determine whether the iron chelator dexrazoxane (DXR) could reduce DOX-induced cardiotoxicity in the young, we injected day 10 neonate female and male rat pups with a single dose of saline or DOX, DXR, or DXR + DOX (20:1). We followed body weight gain with growth, measured cardiac hypertrophy after a 2-wk swim exercise program, markers of apoptosis (Bcl-2, BAX, BNIP1, caspase 3 activation), oxidative stress (heme oxygenase 1, protein carbonyl levels), the chaperone protein clusterin, and the transcriptional activator early growth response gene-1 (Egr-1) in hearts of nonexercised and exercised rats on neonate day 38. All DOX-alone and DXR + DOX-treated rats showed decreased weight gain, with female rats affected earlier than male rats. DXR-alone, DOX-alone, and DXR + DOX-treated rats had an increased heart weight-to-body weight (heart wt/body wt) ratio after the exercise program with female rats showing the largest increase in heart wt/body wt. Drug-treated females also showed increased cardiac apoptosis, as measured by the increased expression of the proapoptotic proteins BAX and BNIP1 and the appearance of caspase 3 activation products, and oxidative stress, as measured by increased heme oxygenase 1 expression, and reduced Egr-1 and clusterin expression when compared with the similarly treated male rats. We conclude that DXR preinjection did not reduce DOX-induced noncardiac and cardiac damage and that young female rats were more susceptible to DXR and DOX toxicities than age-matched male rats.

Abstract TP102: Modulation of Neuroinflammation by Haptoglobin Reduces Oxidative Stress and Improves ICH Outcomes

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Jenna Leclerc ◽  
Alex Dang ◽  
Juan Santiago-Moreno ◽  
Sylvain Dore
Keyword(s):  
Oxidative Stress ◽  
Heme Oxygenase ◽  
Functional Outcomes ◽  
Ferric Iron ◽  
Heme Oxygenase 1 ◽  
High Morbidity ◽  
Blood Components ◽  
Autologous Whole Blood ◽  
The Brain ◽  
Histological Staining

Intracerebral hemorrhage (ICH) is a stroke subtype associated with high morbidity and mortality. With breakdown of the blood-brain barrier and entry of toxic blood components and metabolites within the brain, a highly oxidative environment ensues and leads to a toxic neuroinflammatory cascade. A major cause of the debilitation following brain hemorrhage is due to the direct toxicity of blood components, notably hemoglobin (Hb), the most upstream precipitating factor in the cascade. The acute phase plasma protein haptoglobin (Hp) binds Hb and inhibits its cytotoxic, pro-oxidative, and pro-inflammatory properties. In this study, we investigated whether the local and specific overexpression of Hp would aid in the safe detoxification and clearance of free Hb, thereby protecting the neuropil from Hb-mediated oxidative stress and improving ICH outcomes. Hp was overexpressed locally within the brain using uniquely designed adeno-associated viral vectors and ICH was induced using the intrastriatal autologous whole blood injection model. Functional outcomes were assessed by a 24-point neurological deficit score. At 72h post-hemorrhage, mice were sacrificed and brains collected for histological staining. Hp-overexpressing mice demonstrated smaller lesion volumes (p<0.05) with less blood accumulation (p<0.05) and improve neurologic status after ICH (p<0.05) when compared to an identically treated control group (n=11-13/group). Histological staining for Iba-1, GFAP, heme oxygenase-1, 4-hydroxynonenal, ferric iron, and myeloperoxidase was performed and revealed: 1) significantly less heme oxygenase-1 expression and lipid peroxidation, 2) a trend towards reduced peripheral neutrophil infiltration, 3) significantly increased cortical microgliosis and cortical and striatal astrogliosis, and 4) no changes in ferric iron content or striatal microgliosis. In conclusion, Hp overexpression in the brain reduces ICH-induced brain injury and improves functional outcomes. Locally modulating brain Hp levels could represent an important clinically relevant strategy for the treatment of ICH.

scholarly journals Evaluation of the heme oxygenase-1 expression in esophagitis and esophageal cancer induced by different reflux experimental models and diethylnitrosamine

2010 ◽  
Vol 25 (3) ◽  
pp. 304-310 ◽  
Author(s):  
Cleber Rosito Pinto Kruel ◽  
Luis Felipe Ribeiro Pinto ◽  
Tania Cristina Moita Blanco ◽  
Theresa Christina Barja-Fidalgo ◽  
Levi Lourenzo Melo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Experimental Model ◽  
Heme Oxygenase ◽  
Inflammatory Cells ◽  
Acid Reflux ◽  
Experimental Models ◽  
Control Group ◽  
Heme Oxygenase 1 ◽  
Duodenal Reflux ◽  
Esophageal Carcinogenesis

PURPOSE: To study the expression of heme-oxygenase-1 (HO-1), an enzyme induced by oxidative stress, in specimens obtained from an experimental model in rats that evaluated the role of gastric and duodenal reflux in esophageal carcinogenesis. METHODS: Esophageal specimens embedded in paraffin obtained from different experimental groups of rats were used for immunohistochemistry analysis of HO-1 expression. The rats had been divided into the following groups and were killed after 22 weeks: (1) cardioplasty to induce acid reflux; (2) esophagoduodenal anastomosis to induce duodenal reflux; (3) no treatment; (4) cardioplasty + diethylnitrosamine (DEN); (5) esophagoduodenal anastomosis + DEN; and (6) DEN. The study sample comprised 3 specimens from each group with the most severe histopathological lesions found on each study branch. RESULTS: The expression of HO-1 was seen only in rat specimens submitted to esophagoduodenal anastomosis (Groups 2 and 5), and the analysis of mean fluorescence intensity revealed a significant increase of HO-1 expression (4.8 and 4.6 fold, respectively) when compared with the control group (Group 3) (p<0.05). The main target for HO-1 induction was the inflammatory cells inside the tumor or in subepithelial areas. Rats exposed to gastric reflux had no HO-1 expression. CONCLUSION: Reflux esophagitis induced by reflux of duodenal contents, which provoked considerable oxidative stress, may play an important role in esophageal carcinogenesis. Acid reflux did not induce oxidative stress in this experimental model.

scholarly journals Vascular function and arginine and dimethylarginines in gentamicin-induced renal failure: a possible effect of heme oxygenase 1 inducer hemin

2017 ◽  
Vol 95 (12) ◽  
pp. 1406-1413 ◽  
Author(s):  
Esra Aycan-Ustyol ◽  
Merve Kabasakal ◽  
Seldag Bekpinar ◽  
F. Ilkay Alp-Yıldırım ◽  
Ozge Tepe ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heme Oxygenase ◽  
Vascular Function ◽  
Asymmetric Dimethylarginine ◽  
Vascular Dysfunction ◽  
Cardiovascular Complication ◽  
Heme Oxygenase 1 ◽  
Antioxidant Enzyme Activities ◽  
Symmetric Dimethylarginine ◽  
Inflammatory Changes

Increased oxidative stress and disturbance in nitric oxide bioavailability lead to endothelial dysfunction and cardiovascular complication in renal disease. Gentamicin (GM), a commonly used antibiotic, exhibits a toxic effect on renal proximal tubules. Prevention of its nephrotoxicity is important. Therefore, we investigated whether heme oxygenase 1 HO-1) induction influenced kidney and vascular function in GM-administered rats. GM (100 mg·kg–1·day–1; i.p.) was given to rats alone or together with hemin (20 mg·kg–1 on alternate days; i.p.) for 14 days. Plasma and kidney l-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) as well as kidney 4-hydroxynonenal (HNE) levels and myeloperoxidase (MPO) activity were measured. Histopathological examinations of kidney and relaxation and contraction responses of aorta were also examined. GM increased serum SDMA, urea nitrogen (BUN), and creatinine levels and caused histopathological alterations in the kidney. GM elevated HO-1 protein and mRNA expressions, 4-HNE level, and MPO activity and decreased antioxidant enzyme activities and l-arginine levels in the kidney. Decreased relaxation and contraction were detected in the aorta. Hemin restored renal oxidative stress and inflammatory changes together with vascular dysfunction, but did not affect SDMA, BUN, or creatinine levels. We conclude that HO-1 induction may be effective in improving renal oxidative stress, inflammation, and vascular dysfunction mediated by GM.

scholarly journals Neuroinflammation associates with antioxidant heme oxygenase-1 response throughout the brain in persons living with HIV

2020 ◽  
Vol 26 (6) ◽  
pp. 846-862
Author(s):  
Analise L. Gruenewald ◽  
Yoelvis Garcia-Mesa ◽  
Alexander J Gill ◽  
Rolando Garza ◽  
Benjamin B. Gelman ◽  
...  
Keyword(s):  
Heme Oxygenase ◽  
Neuroprotective Effect ◽  
Expression Patterns ◽  
Distinct Pattern ◽  
Heme Oxygenase 1 ◽  
Type I ◽  
Persons Living With Hiv ◽  
Living With Hiv ◽  
Lower Expression ◽  
Hiv Negative

AbstractPrevious studies showed that persons living with HIV (PLWH) demonstrate higher brain prefrontal cortex neuroinflammation and immunoproteasome expression compared to HIV-negative individuals; these associate positively with HIV levels. Lower expression of the antioxidant enzyme heme oxygenase 1 (HO-1) was observed in PLWH with HIV-associated neurocognitive impairment (HIV-NCI) compared to neurocognitively normal PLWH. We hypothesized that similar expression patterns occur throughout cortical, subcortical, and brainstem regions in PLWH, and that neuroinflammation and immunoproteasome expression associate with lower expression of neuronal markers. We analyzed autopsied brains (15 regions) from 9 PLWH without HIV-NCI and 7 matched HIV-negative individuals. Using Western blot and RT-qPCR, we quantified synaptic, inflammatory, immunoproteasome, endothelial, and antioxidant biomarkers, including HO-1 and its isoform heme oxygenase 2 (HO-2). In these PLWH without HIV-NCI, we observed higher expression of neuroinflammatory, endothelial, and immunoproteasome markers in multiple cortical and subcortical regions compared to HIV-negative individuals, suggesting a global brain inflammatory response to HIV. Several regions, including posterior cingulate cortex, globus pallidus, and cerebellum, showed a distinct pattern of higher type I interferon (IFN)-stimulated gene and immunoproteasome expression. PLWH without HIV-NCI also had (i) stable or higher HO-1 expression and positive associations between (ii) HO-1 and HIV levels (CSF, plasma) and (iii) HO-1 expression and neuroinflammation, in multiple cortical, subcortical, and brainstem regions. We observed no differences in synaptic marker expression, suggesting little, if any, associated neuronal injury. We speculate that this may reflect a neuroprotective effect of a concurrent HO-1 antioxidant response despite global neuroinflammation, which will require further investigation.

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