Pathophysiological changes in experimental polycystic ovary syndrome in female albino rats: Using either hemin or <scp>L</scp>‐arginine

Ragy, Merhan; Abdel-Hamid, Heba A.; Toni, Nisreen D. M.

doi:10.1002/jcp.27757

Cited by 13 publications

(8 citation statements)

References 52 publications

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“…HEM was freshly dissolved in 0.1 mol/L NaOH, and pH was adjusted to 7.4 with 0.1 mol/L HCl and diluted with saline to the required volume. HEM was prepared in darkness and protected from light . GP and L‐NNA were dissolved in distilled water, and ISO was dissolved in saline immediately before administration.…”

Section: Methodsmentioning

confidence: 99%

“…The ISO+HEM+L‐NNA group was administered HEM (25 mg/kg/day) i.p . and L‐NNA (25 mg/kg/day) orally for 5 days and ISO (150 mg/kg/day) i.p . on the 4th and 5th day with 24 h between the two doses.…”

Section: Methodsmentioning

confidence: 99%

“…Previous studies detected the important role of HO1, K ATP channel, and eNOS in preventing tissue injury in different models . In addition, the mechanisms of ISO‐ induced MI and protective properties of HEM in several studies directed our attention to investigate the effect of HEM on ISO‐ induced MI and the possible mechanisms involved in it through evaluating the role of eNOS and K ATP . Until now, no studies have assessed such effects of HEM.…”

Section: Introductionmentioning

confidence: 99%

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Cardioprotective effect of hemin in isoprenaline‐induced myocardial infarction: role of ATP‐sensitive potassium channel and endothelial nitric oxide synthase

Refaie

Rifaai

Bayoumi

et al. 2020

Fundamemntal Clinical Pharma

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A B S T R A C TIschemic heart disease is a common cardiac health problem. Despite the significant advances in prevention and treatment of this disorder, its incidences and complications are very serious. So, the search for more antioxidants and anti-inflammatory agents with cardioprotective effects is an urgent task. We aimed to evaluate the effects of a heme oxygenase 1 (HO1) inducer, hemin (HEM), on isoprenaline (ISO)induced myocardial damage. Forty-five Wistar albino rats were used. Animals were treated with HEM (25 mg/kg/day) i.p. for 5 days and injected with ISO (150 mg/ kg/day) i.p. on 4th and 5th day of the experiment. Detection of the role of ATPsensitive potassium channel (K ATP ) was performed by administration of glibenclamide (GP) (5 mg/kg/day) orally 2 h before HEM. Moreover, the role of endothelial nitric oxide synthase (eNOS) was detected by coadministration of Nitro-x-L-arginine (L-NNA) (25 mg/kg/day) for 5 days. The ISO group showed increase in heart weight, cardiac enzymes, tumor necrosis factor alpha (TNFa), and malondialdehyde (MDA) with decrease in reduced glutathione (GSH), HO1, and total antioxidant capacity (TAC). In addition, there were increases in Bcl-2 associated X protein (Bax) and cleaved caspase-3, but decreases in B-cell lymphoma-2 (Bcl-2) and eNOS. Moreover, the histopathological examination of the ISO group showed degeneration of the cardiac muscle fibers and marked infiltration of the inflammatory cells. The biochemical and histopathological changes induced by ISO were markedly ameliorated in the HEM plus ISO group. This protective effect was diminished with coadministration of GP or L-NNA; thus, K ATP and eNOS might mediate HEM cardioprotection. I N T R O D U C T I O NCardiovascular diseases including myocardial infarction (MI) are among the most severe illnesses that could lead to death. MI occurs due to the imbalance between oxygen supply and oxygen demand followed by myocardial hypoxia [1]. This imbalance with the excessive release of reactive oxygen species (ROS) is a major contributing factor in the development of MI. Free radicals attack membrane lipids and mediate a chain of reactions of lipid peroxidation associated with disruption of the structure and permeability of cell membranes [2,3].Isoprenaline (ISO), a synthetic b-adrenergic agonist, causes severe oxidative stress and decreases oxygen supply in the myocardium leading to infarct-like necrosis in the heart muscles. The induction of MI using ISO is experimentally used to evaluate many cardiac ª 2019 Soci et e Franc ßaise de Pharmacologie et de Th erapeutique 302

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cardioprotective effect of hemin in isoprenaline‐induced myocardial infarction: role of ATP‐sensitive potassium channel and endothelial nitric oxide synthase

Refaie

Rifaai

Bayoumi

et al. 2020

Fundamemntal Clinical Pharma

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“…One study showed that a diet supplemented with L-arginine affected gene expression in the mTOR signaling pathway by suppressing the mRNA expression of cathepsin B and the 20S proteasome in the liver [ 52 ]. Our findings suggest that L-arginine can improve the oxidative state [ 53 ] and improve ovary development during sexual maturity. Homovanillic acid is related to tyrosine metabolism.…”

Section: Discussionmentioning

confidence: 76%

Untargeted Metabolomics Revealed Potential Biomarkers of Small Yellow Follicles of Chickens during Sexual Maturation

et al. 2023

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Sexual maturation provides economically important traits in poultry production. Research on the initiation mechanism of sexual maturity is of great significance for breeding high-yield laying hens. However, the underlying mechanisms are not fully clear. Here, one hundred and fifty Chahua No. 2 laying hens (the CH2 group, which has precocious puberty) and one hundred and fifty Wu Liang Shan black-bone laying hens (the WLS group, a late-maturing chicken breed) with similar weights and ages were randomly selected. ELISA was used to determine the secretion levels of luteinizing hormone (LH), estradiol (E2), and progesterone (P4) in 150-day-old serum and small yellow follicle (SYF) tissues. A histology examination, immunohistochemistry, and quantitative real-time PCR (qPCR) were used to explore the molecular mechanism of how some genes related to oxidative stress affect sexual maturation. The results showed that the secretion levels of LH, E2, and P4 in the CH2 group serum and SYF were higher than those in the WLS group. The results of the real-time PCR of all genes showed that the expression levels of cytochrome P450 family 11 subfamily A member 1, steroidogenic acute regulatory protein, follicle-stimulating hormone receptor, and cytochrome P450 family 19 subfamily A member 1 in the CH2 group were significantly higher than those in the WLS groups (p < 0.001). Untargeted metabolomics combined with multivariate statistical analysis was used to identify biomarkers of SYF tissues in the CH2 and WLS groups. A trajectory analysis of the principal component analysis (PCA) results showed that the samples within the group were clustered and that the samples were dispersed between the CH2 and the WLS groups, indicating that the results of the measured data were reliable and could be used for further research. Further analysis showed that a total of 319 metabolites in small yellow follicles of the CH2 and WLS groups were identified, among which 54 downregulated differential metabolites were identified. These 54 metabolites were found as potential CH2 biomarkers compared with WLS at 150 days, and the different expressions of L-arginine, L-prolinamide, (R)-4-hydroxymandelate, glutathione, and homovanillic acid were more significant. Twenty metabolic pathways were found when significantly differential metabolites were queried in the KEGG database. According to the impact values of the metabolic pathways, eighteen differential metabolites belonged to the mTOR signaling pathway, glutathione metabolism, ABC transporters, the cell ferroptosis pathway, and D-arginine and D-ornithine metabolism. Interestingly, we identified that the cell ferroptosis pathway played an important role in chicken follicle selection for the first time. The histology and immunohistochemistry of SYF showed that the number of granulosa cells increased in the CH2 groups and the expression levels of glutathione peroxidase 4, tumor protein p53, ribosomal protein S6 kinase, and sterol regulatory element binding protein 1 in the granulosa cell layer were upregulated in the CH2 group at the time of sexual maturation. Furthermore, we also speculated that the antioxidant system may play an indispensable role in regulating sexual maturity in chickens. Overall, our findings suggest differentially expressed metabolites and metabolic pathways between CH2 and WLS chickens, providing new insights into the initiation mechanism of sexual maturation.

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“…Increased HMOX1 mRNA levels correlate with a high BMI and insulin resistance, and may be a compensatory mechanism to reduce oxidative stress and inflammatory status in adipose tissue ( 47 ). In letrozole-induced PCOS rats, the administration of hemin ameliorated oxidative stress, reduced inflammatory responses, restored hormonal balance, normalized metabolic function, and improved ovarian function ( 48 ). Our study found that patients with PCOS with the AA or AG genotype of A-42G SNP had significantly higher E 2 , LH, FSH, LH/FSH ratio, TC, HDL-C, LDL-C, apoB, and/or apoB/apoA1 ratio than those with the GG genotype.…”

Section: Discussionmentioning

confidence: 99%

Heme oxygenase 2 genetic variants alter hormonal and metabolic traits in polycystic ovary syndrome

Zhang,

Li,

Liu

et al. 2024

Endocrine Connections

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Oxidative stress and metabolic disorders are involved in the pathogenesis of polycystic ovary syndrome (PCOS). Heme oxygenase 2 (HMOX2) plays a critical role in preserving heme metabolism as well as in modulating glycolipid metabolism, oxidative stress, and inflammation. This study examined the correlation between HMOX2 G554A(rs1051308) and A-42G(rs2270363) genetic variants with the risk of PCOS and assessed the effects of these genotypes on clinical, hormonal, metabolic, and oxidative stress indices using a case-control design that included 1014 patients with PCOS and 806 control participants. We found that the allelic and genotypic frequencies of the HMOX2 G554A and A-42G polymorphisms were comparable between the PCOS and control groups in Chinese women (P > 0.05). Nevertheless, it was discovered that patients with the AA or AG genotype of A-42G polymorphism had notably elevated levels of estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH ratio, high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (apo)B, and/or apoB/apoA1 ratio than those with the GG genotypes (P < 0.05). Patients with the GG or AG genotype of G554A polymorphism had elevated serum levels of LH, FSH, E2, LH/FSH ratio, TC, HDL-C, LDL-C, apoB, and/or apoB/apoA1 ratio and lower 2-h glucose concentration compared with those with the AA genotype (P < 0.05). Our findings indicate a potential association between the genetic variants and endocrine abnormalities in the reproductive system and metabolic irregularities in glycolipid levels in patients, thus suggesting their potential role in the pathogenesis of PCOS.

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Pathophysiological changes in experimental polycystic ovary syndrome in female albino rats: Using either hemin or L‐arginine

Cited by 13 publications

References 52 publications

Cardioprotective effect of hemin in isoprenaline‐induced myocardial infarction: role of ATP‐sensitive potassium channel and endothelial nitric oxide synthase

Cardioprotective effect of hemin in isoprenaline‐induced myocardial infarction: role of ATP‐sensitive potassium channel and endothelial nitric oxide synthase

Untargeted Metabolomics Revealed Potential Biomarkers of Small Yellow Follicles of Chickens during Sexual Maturation

Heme oxygenase 2 genetic variants alter hormonal and metabolic traits in polycystic ovary syndrome

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