scholarly journals The Potential Role of Hemopexin and Heme Oxygenase-1 Inducer in a Model of Sepsis

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Passainte S. Hassaan ◽  
Radwa A. Mehanna ◽  
Abeer E. Dief

Background and Aims. Sepsis can evoke disseminated intravascular coagulation, resulting in multiple organ failure and death. Heme oxygenase-1 (HO-1) and hemopexin (HPx) can mediate cytoprotective mechanisms against these deleterious effects. This study aims to determine a role for HO-1 and HPx in coagulopathy induced by septic inflammation and define whether they can enhance the production of anti-inflammatory cytokine IL-10. Materials and Methods. 48 healthy male albino rats were divided equally into 4 groups: control group: animals subjected to laparotomy and bowel manipulation; CLP group: severe sepsis induced by cecal ligation puncture (CLP); CLP + hemin group: animals received single intraperitoneal injection of hemin (50 µmol/kg) 12 h before sepsis induction; CLP + HPx group: animals received single HPx dose (150 µg/rat, i.v.) 30 min before sepsis induction. Survival rates were calculated. Prothrombin time (PT), activated partial thromboplastin time (APTT), and activated protein C (APC), liver HO-1, serum, and liver IL-10 levels were measured, 48 hrs after sepsis induction. Liver and lung were excised for histopathological examination. Results. Hemin and HPx administration upregulated liver HO-1 and IL-10. They prolonged PT, PTT and increased APC. They reduced the inflammatory infiltrate and thrombosis in liver and lung parenchyma. However, hemin was superior in controlling coagulopathy and HO-1 production, while HPx was more potent stimulant of IL-10 expression. Conclusions. Hemin and HPx have a potential beneficial effect in severe sepsis regarding coagulopathy and inflammation.

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Prasit Na-Ek ◽  
Chuchard Punsawad

Acute kidney injury (AKI) is one of the most serious complications of severe Plasmodium falciparum malaria, but the exact pathogenic mechanisms of AKI in P. falciparum infection have not been clearly elucidated. We hypothesized that oxidative stress is a potential mediator of acute tubular necrosis in P. falciparum-infected kidneys. Therefore, this study aimed to investigate the histopathological changes and markers of oxidative stress in kidney tissues from mice with experimental malaria. DBA/2 mice were divided into two groups: the mice in the malaria-infected group (n = 10) were intraperitoneally injected with 1 × 106P. berghei ANKA-infected red blood cells, and the mice in the control group (n = 10) were intraperitoneally injected with a single dose of 0.85% normal saline. Kidney sections were collected and used for histopathological examination and the investigation of 4-hydroxynonenal (4-HNE) and heme oxygenase-1 (HO-1) expression through immunohistochemistry staining. The histopathology study revealed that the P. berghei-infected kidneys exhibited a greater area of tubular necrosis than those of the control group ( p < 0.05 ). The positive staining scores for 4-HNE and HO-1 expression in tubular epithelial cells of the P. berghei-infected group were significantly higher than those found for the control group ( p < 0.05 ). In addition, significant positive correlations were found between the tubular necrosis score and the positive staining scores for 4-HNE and HO-1 in the kidneys from the P. berghei-infected group. In conclusion, this finding demonstrates that increased expression of 4-HNE and HO-1 might be involved in the pathogenesis of acute tubular damage in the kidneys during malaria infection. Our results provide new insights into the pathogenesis of malaria-associated AKI and might provide guidelines for the future development of a therapeutic intervention for malaria.


2017 ◽  
Vol 51 (1) ◽  
pp. 20-30 ◽  
Author(s):  
N. M. Aziz ◽  
M. Y. Kamel ◽  
R. A. Rifaai

AbstractObjective. The aim of the current study was to assess the protective outcome of hemin, a heme oxygenase-1 (HO-1) inducer on L-arginine-induced acute pancreatitis in rats. Acute pancreatitis (AP) is considered to be a critical inflammatory disorder with a major impact on the patient health. Various theories have been recommended regarding the pathophysiology of AP and associated pulmonary complications.Methods. Twenty-four adult male albino rats were randomly divided into four groups: control group, acute pancreatitis (AP), hemin pre-treated AP group, and hemin post-treated AP group.Results. Administration of hemin before induction of AP significantly attenuated the L-arginine- induced pancreatitis and associated pulmonary complications characterized by the increasing serum levels of amylase, lipase, tumor necrosis factor-α, nitric oxide, and histo-architectural changes in pancreas and lungs as compared to control group. Additionally, pre-treatment with hemin significantly compensated the deficits in total antioxidant capacities and lowered the elevated malondialdehyde levels observed with AP. On the other hand, post-hemin administration did not show any protection against L-arginine-induced AP.Conclusions. The current study indicates that the induction of HO-1 by hemin pre-treatment significantly ameliorated the L-arginine-induced pancreatitis and associated pulmonary complications may be due to its anti-inflammatory and antioxidant properties.


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 ◽  
...  

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.


2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Xiongwei Yu ◽  
Wenjun Han ◽  
Changli Wang ◽  
Daming Sui ◽  
Jinjun Bian ◽  
...  

Hemin, an inducer of heme oxygenase-1 (HO-1), can enhance the activation of HO-1. HO-1 exhibits a variety of activities, such as anti-inflammatory, antioxidative, and antiapoptotic functions. The objective of this study was to investigate the effects of hemin on sepsis-induced skeletal muscle wasting and to explore the mechanisms by which hemin exerts its effects. Cecal ligation and perforation (CLP) was performed to create a sepsis mouse model. Mice were randomly divided into four groups: control, CLP, CLP plus group, and CLP-hemin-ZnPP (a HO-1 inhibitor). The weight of the solei from the mice was measured, and histopathology was examined. Cytokines were measured by enzyme-linked immunosorbent assay (ELISA). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting were used to assess the expression levels of HO-1 and atrogin-1. Furthermore, we investigated the antioxidative effects of HO-1 by detecting malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity. CLP led to dramatic skeletal muscle weakness and atrophy, but pretreatment with hemin protected mice against CLP-mediated muscle atrophy. Hemin also induced high HO-1 expression, which resulted in suppressed proinflammatory cytokine and reactive oxygen species (ROS) production. The expression of MuRF1 and atrogin-1, two ubiquitin ligases of the ubiquitin-proteasome system- (UPS-) mediated proteolysis, was also inhibited by increased HO-1 levels. Hemin-mediated increases in HO-1 expression exert protective effects on sepsis-induced skeletal muscle atrophy at least partly by inhibiting the expression of proinflammatory cytokines, UPS-mediated proteolysis, and ROS activation. Therefore, hemin might be a new treatment target against sepsis-induced skeletal muscle atrophy.


2019 ◽  
Vol 97 (12) ◽  
pp. 1159-1168
Author(s):  
Fatma F. Ali ◽  
Walaa Yehia Abdelzaher ◽  
Randa Ahmed Ibrahim ◽  
Doaa Mohamed Elroby Ali

Although heme oxygenase-1 (HO-1) is part of an endogenous defense system implicated in the homeostatic response, its role in cell proliferation and tumor progression is still controversial. Endometrial hyperplasia (EH) is associated with high risk of endometrial cancer (EC). Therefore, we aimed to evaluate the effect of hemin, a HO-1 inducer, against EH. Thirty-two female rats (60–70 days old) were divided into 4 groups treated for 1 week: vehicle control group, hemin group (25 mg/kg; i.p. 3 times/week), estradiol valerate (EV) group (2 mg/kg per day, p.o.), and hemin plus EV group. Sera were obtained for reduced glutathione level. Uterine malondialdehyde, superoxide dismutase, total nitrite/nitrate, and interleukin-1β levels were estimated. HO-1 and p38 mitogen-activated protein kinase expressions were obtained in uterine tissue. Uterine histological and immunohistochemical assessment of iNOS and Ki67 were also done. Results demonstrated that upregulation of HO-1 expression in hemin plus EV rats led to amelioration of EH which was confirmed with histological examination. This was associated with significant decrease in oxidative stress parameters, p38 mitogen-activated protein kinase expression, and interleukin-1β level. Also, uterine iNOS and Ki67 expressions were markedly suppressed. In conclusion, upregulation of HO-1 expression via hemin has ameliorative effect against EH through its antioxidant, anti-inflammatory, and antiproliferative actions.


Author(s):  
S. W. Hassan ◽  
A. N. Ukwuani-Kwaja ◽  
U. D. Nuhu ◽  
R. D. Jabaka

Combretum collinum root extract has been recognized long ago as traditional medicinal plant in curing several diseases among the indigenous people of Alela-land (Zuru), Kebbi State, Nigeria. This research work was carried out to evaluate the toxicological effects of Combretum collinum methanol root extract (CCME) in albino rats. Acute toxicity was performed by a fixed single oral administration at a dose of 10, 100, 1000 mg/Kg and 1600, 2900, 5000 mg/Kg. Subchronic toxicity studies of CCME was conducted at doses of 32, 63, 126 and 253 mg/Kg for 28 days. The result showed that acute administration of CCME resulted at mortality and general behavioral changes at 1000 to 5000 mg/Kg. Therefore, the estimated lethal dose (LD50) of CCME was 316.23 mg/Kg. Subchronic oral administration of CCME revealed a significant (P<0.01) decrease in body weight in rats receiving 63 to 253 mg/Kg throughout the study period compared with the control group. The results also showed a significant (P<0.01) increase in serum ALT, AST, creatinine, potassium and bicarbonate in rats administered with 126 and 253 mg/Kg of the extract. Haematological analysis of the same extract revealed a significant (P<0.01) increase in WBC, HCT, MCV, MCH, MCHC, PLT, LYM and NEUT in rats receiving 126 and 253 mg/Kg only. Histopathological examination of liver revealed severe periportal inflammation, hypertrophy, areas of hydropic changes, cancerous tumor, areas of infiltration and necrosis of the hepatic cells while the kidney showed a mild mesengial hyperplasia, compressed blood vessels, glomerular degeneration, tubular degeneration and tubular widened lumen in rats treated with 63 to 253 mg/Kg. Therefore, caution should be applied as C. collinum root extract has a low mean lethal dose and would be toxic at higher concentrations.


2019 ◽  
Vol 1 (2) ◽  
pp. 16-33 ◽  
Author(s):  
Nawal A. A. Elghazaly ◽  
Eman H. Radwan ◽  
Hala H. Zaatout ◽  
Mohamed M. Elghazaly ◽  
Nour El din Allam

Obesity is associated with a number of serious medical complications, which are often referred to as the “insulin resistance syndrome”. The aim of the present study was performed to investigate the possible interaction between a conventional drug used for management of cholesterol and traditional herbal remedies on the obesity. This was carried through out: through estimation of blood test; Estimation of serum tests; Determination of oxidative stress biomarkers and the antioxidant enzymes activities in the liver were assayed; Histopathological examination of the liver and kidney of adult male albino rats were done. In the present study, the serum levels of the total protein and albumin in the obesity group (7.1± 0.2) and (4.78 ± 0.19); respectively were significantly (p ≤ 0.05) more than those of the control group (6.5±0.1) and (3.95± 0.1).The administration of (fennel group) revealed significant (P<0.05) decrease in the serum levels of the albumin and total protein (4.38± 0.1) and (6.65± 0.2); respectively as compared to the obesity group (4.78 ± 0.19) and (7.1± 0.2(. The total cholesterol of the group(5) (fennel and ator) after two weeks from a high fat diet than treatment with fennel and Ator through six weeks equal 142.86±5.9, 100.4±8.68, 93.29±5.99, 87.1±11.28, 80.4±21.55, 78.1±6.7 and 77.1±6.87; respectively. The present study showed a significant (P<0.05) increase in the activities of ALT, AST and ALP in the obesity group which recorded as (60.5±11.45), (57.25±6.3) and (845.0±49.47); respectively as compared to the control group (28.25±1.7), (38.5±3.87) and (537.0±41.5); respectively. The fennel group caused significant decrease in the activities of these enzymes (41.0± 2.9), (42.25+3.2) and (717.75+48.6); respectively compared to the obesity group. Ator group showed a significant decrease in the activities of these enzymes (40.0±2.16), (42.5±3.1) and (679.25±41.16); respectively compared as obesity group. The activity of AlT, AST and ALP in the fennel and ator group (32.75±2.5), (40.5±2.38) and (601.25±17.5); respectively were near to the control group.


Author(s):  
Samar S Ibrahim ◽  
Alshaimaa M Said

Background: The present study was designed to evaluate the relative ameliorating efficacy of lycopene against the deleterious effects of boldenone, an androgenic steroid, on the rat testis and kidney.  Materials and Methods: 40 male albino rats were divided into four groups; control group received intramuscular (i.m) injection of olive oil once a week; lycopene (Lc) group received lycopene (10 mg/kg b.w p.o daily); boldenone (Bol) group received (5 mg/kg b.w i.m once a week); Bol + Lc group received boldenone (5 mg/kg b.w i.m once a week) and lycopene (10 mg/kg b.w p.o daily) all for four weeks. Results: intramuscular injection of boldenone significantly induced lipid peroxidation and DNA fragmentation as well as inhibited total antioxidant capacity (TAC) and catalase (CAT) activity in testis and kidney tissue. Additionally, up-regulation of Bax and down-regulation of Bcl-2 gene expression after Bol injection along with marked increase in serum inflammatory cytokines and decrease in serum testosterone. These alterations were confirmed by the histopathological examination of testis and kidney. On the other hand, lycopene oral administration attenuated the testicular and renal injuries induced by boldenone injection. Conclusion: administration of antioxidants as lycopene effectively ameliorated the adverse effects of boldenone on testis and kidney tissues. Key words: Boldenone undecylenate, lycopene, DNA fragmentation, interleukin-1β, tumor necrosis factor-α, apoptosis.


2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Nur Adiba Hanum ◽  
Ismalayani Ismalayani ◽  
Rahmad Aswin Juliansyah ◽  
Syokumawena Syokumawena ◽  
Marta Pastari ◽  
...  

Kerokan is an alternative therapy done by rubbing and pressing the skin surface using oil and a blunt object. This treatment has a hepatoprotective effect as it increases heme oxygenase-1, an essential enzyme in heme catabolism. In hepatitis B, heme oxygenase-1 plays a vital role to fight oxidative stress. Hence the damage on liver cells can be reduced or even prevented. Damaged cells indicate by the production of aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) enzymes that accumulated in the bloodstream. This study aimed to investigate the effect of kerokan to liver function by analyzing SGOT and SGPT levels in hepatitis B patients. These were an experimental study with a pre-test post-test control group design conducted in the public health center in Palembang in October 2016. Statistical analysis used the unpaired t test and paired. The research subjects were 30 patients with inactive carrier and chronic hepatitis B. The levels of SGOT and SGPT were determined using the IFCC method. The levels of SGOT in control (19.53±3.44 U/L) and treatment group (20.46±4.53 U/L, Δ=0.93) after 24–48 hours were not statistically different (p=0.53). Also, the levels of SGPT in control (18.66±5.40 U/L) and treatment group (19.80±9.25 U/L, Δ=1.13) after 24–48 hours were also not statistically different (p=0.68) as well. In conclusion, the liver cells of inactive carrier and chronic hepatitis B patients were not damaged (necrosis) after kerokan therapy, and the levels of SGOT and SGPT were still in the normal range. EFEK KEROKAN TERHADAP FUNGSI HEPAR PASIEN HEPATITIS BKerokan merupakan terapi alternatif yang dilakukan dengan menggosok dan menekan permukaan kulit menggunakan minyak dan benda tumpul. Pengobatan ini bersifat hepatoprotektif, yaitu meningkatkan produksi enzim heme oxygenase-1 dalam katabolisme heme. Pada hepatitis B, heme oxygenase-1 berperan penting dalam menangkal radikal bebas sehingga dapat mengurangi atau mencegah kerusakan sel hepar. Kerusakan sel hepar diindikasikan oleh produksi enzim aspartate aminotransferase (AST/SGOT) dan alanine aminotransferase (ALT/SGPT) yang terakumulasi dalam pembuluh darah. Penelitian ini bertujuan mengetahui pengaruh kerokan pada fungsi hepar dengan menganalisis kadar SGOT dan SGPT pada pasien hepatitis B. Penelitian eksperimental ini menggunakan desain pre-test post-test control group yang dilakukan di puskesmas di Palembang pada Oktober 2016. Analisis statistik menggunakan uji t berpasangan dan tidak berpasangan. Subjek penelitian meliputi 30 pasien inactive carrier dan kronik hepatitis B. Kadar SGOT dan SGPT diukur dengan menggunakan metode IFCC. Kadar SGOT pada kontrol (19,53±3,44 U/L) dan grup perlakuan (20,46±4,53 U/L; Δ=0,93) setelah 24–48 jam tidak terdapat perbedaan signifikan (p=0,53). Selain itu, kadar SGPT pada kontrol (18,66±5,40 U/L) dan grup perlakuan (19,80±9,25 U/L; Δ=1,13) setelah 24–48 jam tidak menunjukkan perbedaan signifikan (p=0,68). Simpulan, sel hepar pada pasien inactive carrier dan kronik hepatitis B tidak mengalami kerusakan setelah terapi kerokan, serta kadar SGOT dan SGPT tetap dalam kondisi normal.


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