A novel beneficial role of humanin on intestinal apoptosis and dysmotility in a rat model of ischemia reperfusion injury

Abozaid, Eman R.; Abdel-Kareem, Reham; Habib, Marwa

doi:10.1007/s00424-023-02804-0

Cited by 3 publications

(2 citation statements)

References 76 publications

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“…Moreover, Colivelin attenuated the inflammatory response, endothelial, and glycocalyx injury, and ameliorated glycocalyx density and mitochondrial structure among septic animals relative to shams. Similar findings were reported among male albino rats subject to an model of mesenteric artery ischemia reperfusion injury, wherein animals treated with HN analogue were reported to demonstrate reduced inflammation, apoptosis, and iNOS activity relative to shams (33). To the best of our knowledge, no studies have thus far evaluated whether HN directly influences platelet structure and function in shock and as such requires future mechanistic investigation.…”

Section: Discussionsupporting

confidence: 72%

Serum Humanin in Pediatric Septic Shock Associated Multiple Organ Dysfunction Syndrome

Atreya,

Piraino,

Cvijanovich

et al. 2023

Shock

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Background Multiple organ dysfunction syndrome (MODS) disproportionately contributes to pediatric sepsis morbidity. Humanin (HN) is a small peptide encoded by mitochondrial DNA and thought to exert cytoprotective effects in endothelial cells and platelets. We sought to test the association between serum HN (sHN) concentrations and MODS in a prospectively enrolled cohort of pediatric septic shock. Methods Human MT-RNR2 ELISA was used to determine sHN concentrations on day 1 and 3. The primary outcome was thrombocytopenia associated multi-organ failure (TAMOF). Secondary outcomes included individual organ dysfunctions on day 7. Associations across pediatric sepsis biomarker (PERSEVERE) based mortality risk strata and correlation with platelet and markers endothelial activation were tested. Results 140 subjects were included in this cohort, of whom 39 had TAMOF. The concentration of sHN was higher on day 1 relative to day 3, and among those with TAMOF phenotype in comparison to those without. However, the association between sHN and TAMOF phenotype was not significant after adjusting for age and illness severity in multivariate models. In secondary analyses, sHN was associated with presence of day 7 sepsis-associated acute kidney injury (SA-AKI) (p = 0.049). Further, sHN was higher among those with high PERSEVERE-mortality risk strata and correlated with platelet counts and several markers of endothelial activation. Conclusion Future investigation is necessary to validate the association between sHN and SA-AKI among children with septic shock. Further, mechanistic studies that elucidate the role of humanin may lead to therapies that promote organ recovery through restoration of mitochondrial homeostasis among those critically ill.

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Section: Discussionsupporting

confidence: 72%

Serum Humanin in Pediatric Septic Shock Associated Multiple Organ Dysfunction Syndrome

Atreya,

Piraino,

Cvijanovich

et al. 2023

Shock

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“…Similar ndings were reported among male albino rats subject to an model of mesenteric artery ischemia reperfusion injury, wherein animals treated with humanin analogue were reported to demonstrate reduced in ammation, apoptosis, and inducible nitric oxide synthase (iNOS) activity relative to shams. 25 To the best of our knowledge, no studies have thus far evaluated whether HN directly in uences platelet structure and function in shock. We observed that sHN was higher among patients with TAMOF phenotype relative to those without.…”

Section: Discussionmentioning

confidence: 99%

Serum Humanin in Pediatric Septic Shock Associated Multiple Organ Dysfunction Syndrome

Atreya

Cvijanovich

Fitzgerald

et al. 2023

Preprint

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Background Multiple organ dysfunction syndrome (MODS) disproportionately contributes to pediatric sepsis morbidity. Humanin (HN) is a small peptide encoded by mitochondrial DNA and thought to exert cytoprotective effects in endothelial cells and platelets. We sought to test the association between serum HN (sHN) concentrations and MODS in a prospectively enrolled cohort of pediatric septic shock. Methods Human MT-RNR2 ELISA was used to determine sHN concentrations on day 1 and 3. The primary outcome was thrombocytopenia associated multi-organ failure (TAMOF). Secondary outcomes included individual organ dysfunctions on day 7. Associations across pediatric sepsis biomarker (PERSEVERE) based mortality risk strata and correlation with platelet and markers endothelial activation were tested. Results 140 subjects were included in this cohort, of whom 39 had TAMOF phenotype. Concentration of sHN was higher on day 1 relative to day 3, and among those with TAMOF phenotype in comparison to those without. Although, the association between sHN and TAMOF phenotype was not significant after adjusting for age and PRISM-III score in multivariate models, we identified that sHN was independently associated with presence of day 7 sepsis-associated acute kidney injury (SA-AKI) (p = 0.032). Further, sHN was higher among those with high PERSEVERE-mortality risk strata and correlated with platelet counts and several markers of endothelial activation. Conclusion Among children with septic shock, sHN concentrations were higher among patients with TAMOF phenotype and independently associated with persistent SA-AKI. Pending further validation and rigorous mechanistic studies, interventions aimed at restoring humanin may have therapeutic implications in recovery of organ function among critically ill patients.

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Glutamine Alleviates I/R-Induced Intestinal Injury and Dysmotility Via the Downregulation of Xanthine Oxidase/Uric Acid Signaling and Lactate Generation in Wistar Rats

Akhigbe,

Adedamola Aminat,

Akhigbe

et al. 2024

Journal of Surgical Research

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A novel beneficial role of humanin on intestinal apoptosis and dysmotility in a rat model of ischemia reperfusion injury

Cited by 3 publications

References 76 publications

Serum Humanin in Pediatric Septic Shock Associated Multiple Organ Dysfunction Syndrome

Serum Humanin in Pediatric Septic Shock Associated Multiple Organ Dysfunction Syndrome

Serum Humanin in Pediatric Septic Shock Associated Multiple Organ Dysfunction Syndrome

Glutamine Alleviates I/R-Induced Intestinal Injury and Dysmotility Via the Downregulation of Xanthine Oxidase/Uric Acid Signaling and Lactate Generation in Wistar Rats

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