Inducible nitric oxide synthase (iNOS) mediates ethanol-induced redox imbalance and upregulation of inflammatory cytokines in the kidney

Silva, Carla Brigagão Pacheco da; Ceron, Carla S.; Mendes, Atlante S.; Martinis, Bruno De; Castro, Michele M.; Tirapelli, Carlos Renato

doi:10.1139/cjpp-2021-0108

Cited by 8 publications

(6 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alcohol abuse induces liver inflammation and has been associated with myopathy (49)(50)(51). A recent study by de Silva et al suggested a role of the inducible nitric oxide synthase in ethanol-induced oxidative stress and proinflammatory cytokines production in the kidney (51). These findings could explain our results since alcohol was the main cause of liver disease.…”

Section: Discussionsupporting

confidence: 57%

“…Alcohol consumption could explain the relationship between sarcopenia and renal impairment in the context of cirrhosis. Alcohol abuse induces liver inflammation and has been associated with myopathy (49)(50)(51). A recent study by de Silva et al suggested a role of the inducible nitric oxide synthase in ethanol-induced oxidative stress and proinflammatory cytokines production in the kidney (51).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Renal dysfunction independently predicts muscle mass loss in patients following liver transplantation

Nguyen

Mukaneza

Tremblay

et al. 2022

CanLivJ

View full text Add to dashboard Cite

BACKGROUND: Liver transplantation (LT) is the only curative treatment for cirrhosis. However, the presence of complications can impact outcomes following LT. Sarcopenia, or muscle mass loss, is highly prevalent in patients with cirrhosis and is associated with longer hospitalization stays and a higher infection rate post-surgery. We aimed to identify patients at higher risk of early sarcopenia post-LT. METHODS: This retrospective study included 79 cirrhotic patients who underwent LT. Muscle mass was evaluated using the third lumbar spine vertebra skeletal muscle mass index (SMI) and sarcopenia was defined using established cut-off values. Computerized tomography (CT) scans performed within six-month peri-operative period (three months pre- and post-LT) were included in the study. Complications and comorbidities were collected and correlated to SMI post-LT and predictive models for SMI post-LT were constructed. RESULTS: The overall prevalence of sarcopenia was 46% and 62% before and after LT, respectively. Newly developed sarcopenia was found in 42% of patients. Post-LT sarcopenia was associated with longer hospital stays (54±37 vs 29±10 days, p = 0.002), higher number of infection (3±1 vs 1±2, p = 0.027), and greater number of complications (5±2 vs 3±2, p <0.001) compared to absence of sarcopenia. Multivariate analyses showed that the SMI post-LT was independently associated with pre-LT renal function markers, the glomerular filtration rate (GFR) and creatinine (Model 1, GFR: β = 0.33; 95% CI = 0.04–0.17; p = 0.003; Model 2, Creatinine: β = –0.29; 95% CI = –0.10 to –0.02; p = 0.009). CONCLUSIONS: The present study highlights the potential role of renal dysfunction in the development and persistence of sarcopenia after LT.

show abstract

Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Renal dysfunction independently predicts muscle mass loss in patients following liver transplantation

Nguyen

Mukaneza

Tremblay

et al. 2022

CanLivJ

View full text Add to dashboard Cite

show abstract

“…NOS2 is an important intracellular messenger and molecular marker in the mechanism of inflammation ( Jiang et al, 2016 ). In the kidney, NO is involved in the regulation of renal vascular resistance, glomerular filtration rate and maintenance of renal structural integrity ( Da Silva et al, 2021 ). Many studies have shown that NOS2 plays a key role in the pathogenesis of metabolic nephropathy, and it has been found in the pathogenesis of chronic nephropathy that elevated NOS2 levels produce highly reactive NO, which is associated with chronic low-grade inflammatory states ( Zhang et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Integrating strategies of metabolomics, network pharmacology, and experiment validation to investigate the processing mechanism of Epimedium fried with suet oil to warm kidney and enhance yang

et al. 2023

View full text Add to dashboard Cite

Introduction: Epimedium, a traditional Chinese medicine (TCM) commonly used in ancient and modern China, is one of the traditional Chinese medicines clinically used to treat kidney yang deficiency syndrome (KYDS). There are differences in the efficacy of Epimedium before and after processing, and the effect of warming the kidney and enhancing yang is significantly enhanced after heating with suet oil. However, the active compounds, corresponding targets, metabolic pathways, and synergistic mechanism of frying Epimedium in suet oil to promote yang, remain unclear.Methods: Herein, a strategy based on comprehensive GC-TOF/MS metabolomics and network pharmacology analysis was used to construct an “active compounds-targets-metabolic pathways” network to identify the active compounds, targets and metabolic pathways involved. Subsequently, the targets in kidney tissue were further validated by real-time quantitative polymerase chain reaction (RT-qPCR). Histopathological analysis with physical and biochemical parameters were performed.Results: Fifteen biomarkers from urine and plasma, involving five known metabolic pathways related to kidney yang deficiency were screened. The network pharmacology results showed 37 active compounds (13 from Epimedium and 24 from suet oil), 159 targets, and 267 pathways with significant correlation. Importantly, integrated metabolomics and network pharmacologic analysis revealed 13 active compounds (nine from Epimedium and four from suet oil), 7 corresponding targets (ALDH2, ARG2, GSTA3, GSTM1, GSTM2, HPGDS, and NOS2), two metabolic pathways (glutathione metabolism, arginine and proline metabolism), and two biomarkers (Ornithine and 5-Oxoproline) associated with improved kidney yang deficiency by Epimedium fried with suet oil.Discussion: These finds may elucidate the underlying mechanism of yang enhancement via kidney warming effects. Our study indicated that the mechanism of action mainly involved oxidative stress and amino acid metabolism. Here, we demonstrated the novel strategies of integrating metabolomics and network pharmacology in exploring of the mechanisms of traditional Chinese medicines.

show abstract

“…Chronic ethanol consumption affects cardiac, hepatic, and urinary systems, as well as food and water intake in humans and rodents [49][50][51][52][53][54] . Therefore, we measured food and water intake, as well as liver, kidney, and heart masses.…”

Section: Discussionmentioning

confidence: 99%

Vascular injury associated with ethanol intake is driven by AT1 receptor and mitochondrial dysfunction

Awata,

Alves,

Costa

et al. 2023

Preprint

View full text Add to dashboard Cite

Background: Renin angiotensin (Ang II) aldosterone system (RAAS) is crucial for the cardiovascular risk associated with excessive ethanol consumption. Disturbs in mitochondria have been implicated in multiple cardiovascular diseases. However, if mitochondria dysfunction contributes to ethanol-induced vascular dysfunction is still unknown. We investigated whether ethanol leads to vascular dysfunction via RAAS activation, mitochondria dysfunction, and mitochondrial reactive oxygen species (mtROS). Methods: Male C57/BL6J or mt-keima mice (6 to 8-weeks old) were treated with ethanol (20% vol./vol.) for 12 weeks with or without Losartan (10 mg/kg). Results: Ethanol induced aortic hypercontractility in an endothelium-dependent manner. PGC1a; (a marker of biogenesis), Mfn2, (an essential protein for mitochondria fusion), as well as Pink-1 and Parkin (markers of mitophagy), were reduced in aortas from ethanol-treated mice. Disturb in mitophagy flux was further confirmed in arteries from mtkeima mice. Additionally, ethanol increased mtROS and reduced SOD2 expression. Strikingly, losartan prevented vascular hypercontractility, mitochondrial dysfunction, mtROS, and restored SOD2 expression. Both MnTMPyP (SOD2 mimetic) and CCCP (a mitochondrial uncoupler) reverted ethanol-induced vascular dysfunction. Moreover, L-NAME (NOS inhibitor) and EUK 134 (superoxide dismutase/catalase mimetic) did not affect vascular response in ethanol group, suggesting that ethanol reduces aortic nitric oxide (NO) and H2O2 bioavailability. These responses were prevented by losartan. Conclusion: AT1 receptor modulates ethanol-induced vascular hypercontractility by promoting mitochondrial dysfunction, mtROS, and reduction of NO and H2O2 bioavailability. Our findings shed a new light in our understanding of ethanol-induced vascular toxicity and open perspectives of new therapeutic approaches for patients with disorder associated with abusive ethanol drinking.

show abstract

Inducible nitric oxide synthase (iNOS) mediates ethanol-induced redox imbalance and upregulation of inflammatory cytokines in the kidney

Cited by 8 publications

References 49 publications

Renal dysfunction independently predicts muscle mass loss in patients following liver transplantation

Renal dysfunction independently predicts muscle mass loss in patients following liver transplantation

Integrating strategies of metabolomics, network pharmacology, and experiment validation to investigate the processing mechanism of Epimedium fried with suet oil to warm kidney and enhance yang

Vascular injury associated with ethanol intake is driven by AT1 receptor and mitochondrial dysfunction

Contact Info

Product

Resources

About