Nebivolol Exerts Hepatoprotective Activity During CLP-Induced Sepsis by Modulating Oxidative Stress, Liver Regeneration, and AKT/MAPK Pathways in Rats DOI Creative Commons

Rahma Tharwat Sabra,

Amany Abdlrehim Bekhit,

Nourhan Tharwat Sabra

и другие.

Stresses, Год журнала: 2024, Номер 4(4), С. 800 - 815

Опубликована: Дек. 2, 2024

Sepsis is a potentially catastrophic organ dysfunction arising from an infection-induced immunologic reaction leading to severe inflammation, progression of septic shock, and damage body organs. marked by noticeable hepatotoxicity caused activating oxidative stress, apoptotic mechanisms. Through Cecal Ligation Puncture (CLP) in rats, our study the first investigate potential preventive effect antihypertensive medicine “Nebivolol” on sepsis-induced at molecular level. Six groups sixty albino Wistar rats (male) were randomly assigned. Biochemical stress markers liver function measured. Additionally, apoptosis- inflammatory-related gene protein expressions examined. Finally, tissues examined for histological assessments. The hepatic architecture was considerably altered CLP, which also resulted elevations blood aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total direct bilirubin levels, malondialdehyde (MDA). In contrast, it decreased serum albumin level, superoxide dismutase (SOD) activity, glutathione (GSH) It significantly elevated all inflammatory mediators (Interlukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), Interlukin-1 beta (IL-1β)) alleviated Interlukin-10 (IL-10). magnified expression p-AKT/t-AKT, p-JNK1/2/t-JNK1/2, p-p38/t-p38 proteins, raised Matrix Metalloproteinase 2/9 (MMP 2/9) nuclear factor-kappa B (NF-κB) transcriptions, lessened Vascular Endothelial Growth Factor (VEGF) expression. Nebivolol administration dramatically mitigated biochemical changes obtained CLP. present finding demonstrated that succeeded, time, improving injury CLP-evoked sepsis through modulating mediators, pathways targeting crosstalk between kinase (AKT), NF-κB, mitogen-activated (MAPK), making hopeful treatment injury.

Язык: Английский

Vincamine exerts hepato-protective activity during colon ligation puncture-induced sepsis by modulating oxidative stress, apoptosis, and TNFα/Nrf-2/Keap-1 signaling pathways DOI Creative Commons
Rania Alaaeldin, Reham H. Mohyeldin,

Ehab E. Sharata

и другие.

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Авг. 23, 2024

Abstract Sepsis is a pathological and biochemical disorder induced by numerous infections, leading to critical illness high mortality rate worldwide. Vincamine an indole alkaloid compound obtained from the leaves of Vinca minor. The present study aims investigate hepato-protective activity vincamine during colon ligation puncture (CLP)-induced sepsis at molecular level. was using CLP model. Liver function enzymes such as ALT AST were analyzed. hepatic antioxidant status (SOD GSH), lipid peroxidation (MDA), pro-inflammatory cytokines (TNFα, IL-6, IL-1β), bax, bcl2, cleaved caspase 3 proteins estimated. Nrf-2 Keap-1 protein expression evaluated western blotting. Histopathological investigation liver tissues also performed. CLP-induced led injury through elevation enzymes. Oxidative stress initiated via suppression GSH content SOD MDA. inflammatory condition activated upregulation TNFα, IL-1β, downregulation proteins. apoptosis activation bax inhibition bcl2 expression. However, significantly improved histological abnormalities decreased (ALT AST). It ameliorated oxidative stress, evidenced reducing MDA increasing content. Moreover, reduced increased Additionally, it upregulated downregulated exhibited potential cross-connection antioxidant, anti-inflammatory, anti-apoptotic activities modulating TNFα/IL-6/IL-1β/Nrf-2/Keap-1 regulating bax/bcl2/cleaved signaling pathways.

Язык: Английский

Процитировано

7
Alkaloids from the genus Vinca L. (Apocynaceae): a comprehensive biological and structural review DOI Creative Commons
Rudolf Vrabec, Pavel Drašar, Lubomı́r Opletal

и другие.

Phytochemistry Reviews, Год журнала: 2025, Номер unknown

Опубликована: Март 29, 2025

Язык: Английский

Процитировано

0
Nebivolol ameliorates sepsis-evoked kidney dysfunction by targeting oxidative stress and TGF-β/Smad/p53 pathway DOI Creative Commons

Rahma Tharwat Sabra,

Amany Abdlrehim Bekhit,

Nourhan Tharwat Sabra

и другие.

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Июнь 26, 2024

Abstract Sepsis is a potential fetal organ destruction brought on through an overzealous immunologic reaction to infection, causing severe inflammation, septic shock, and damage different organs. Although there has been progress in the identification controlling of clinical sepsis, fatality rates are still significant. This study, for first time, intended examine possible ameliorative impact Nebivolol, β1-adrenergic antagonist antihypertensive drug, against nephrotoxicity resulted from cecal ligation puncture (CLP)-induced sepsis rats, molecular basis. Sixty male Wistar albino rats were chosen. Oxidative stress indicators biochemical markers kidney activity evaluated. Inflammatory mediators, fibrosis- apoptosis-related proteins gene expressions investigated. Moreover, renal histopathological investigation was performed. CLP-induced characterized by markedly elevated serum levels creatinine, blood urea nitrogen, uric acid, malondialdhyde. On other hand, it decreased total protein level, superoxide dismutase reduced glutathione level. Additionally, significantly inflammatory mediators (tumor necrosis factor-alpha, ilnerlukin (IL)-6, IL-1β) Caspase-3 protein, IL-10 amplified expression transforming growth factor-beta 1 (TGF-β1), p-Smad2/3 alpha-smooth-muscle actin proteins, downregulated B cell lymphoma-2 (Bcl-2) transcription Bcl-2-associated X-protein (Bax) , p53 Nuclear factor-kappa ( NF-κB ) genes. Furtheremor, tissues exhibited significant changes with CLP. contrary, Nebivolol improved all these enhanced alterations obtained research showed, that effectively mitigated dysfunction via its antioxidant, antifibrotic anti-apoptotic modulation oxidative stress, TGF-β/NF-κB TGF-β/Smad/p53 signaling pathways.

Язык: Английский

Процитировано

2
The protective role of two oxindole derivatives is mediated by modulating NLRP3/caspase-1 and PI3K/AKT pathways in a preclinical animal model of hepatic ischemia reperfusion injury DOI

Nardeen Eldafashi,

Shaimaa Waaz,

Taha F. S. Ali

и другие.

Life Sciences, Год журнала: 2024, Номер 352, С. 122872 - 122872

Опубликована: Июнь 26, 2024

Язык: Английский

Процитировано

1
The Impact of Methamphetamine on Liver Injury in Iraqi Male Addicts DOI Creative Commons
Nawar S. Mohammed,

Zahraa Qasim Ali,

Aseel Sameer Mohamed

и другие.

Toxicology Reports, Год журнала: 2024, Номер 13, С. 101806 - 101806

Опубликована: Ноя. 8, 2024

Язык: Английский

Процитировано

0
Nebivolol Exerts Hepatoprotective Activity During CLP-Induced Sepsis by Modulating Oxidative Stress, Liver Regeneration, and AKT/MAPK Pathways in Rats DOI Creative Commons

Rahma Tharwat Sabra,

Amany Abdlrehim Bekhit,

Nourhan Tharwat Sabra

и другие.

Stresses, Год журнала: 2024, Номер 4(4), С. 800 - 815

Опубликована: Дек. 2, 2024

Sepsis is a potentially catastrophic organ dysfunction arising from an infection-induced immunologic reaction leading to severe inflammation, progression of septic shock, and damage body organs. marked by noticeable hepatotoxicity caused activating oxidative stress, apoptotic mechanisms. Through Cecal Ligation Puncture (CLP) in rats, our study the first investigate potential preventive effect antihypertensive medicine “Nebivolol” on sepsis-induced at molecular level. Six groups sixty albino Wistar rats (male) were randomly assigned. Biochemical stress markers liver function measured. Additionally, apoptosis- inflammatory-related gene protein expressions examined. Finally, tissues examined for histological assessments. The hepatic architecture was considerably altered CLP, which also resulted elevations blood aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total direct bilirubin levels, malondialdehyde (MDA). In contrast, it decreased serum albumin level, superoxide dismutase (SOD) activity, glutathione (GSH) It significantly elevated all inflammatory mediators (Interlukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), Interlukin-1 beta (IL-1β)) alleviated Interlukin-10 (IL-10). magnified expression p-AKT/t-AKT, p-JNK1/2/t-JNK1/2, p-p38/t-p38 proteins, raised Matrix Metalloproteinase 2/9 (MMP 2/9) nuclear factor-kappa B (NF-κB) transcriptions, lessened Vascular Endothelial Growth Factor (VEGF) expression. Nebivolol administration dramatically mitigated biochemical changes obtained CLP. present finding demonstrated that succeeded, time, improving injury CLP-evoked sepsis through modulating mediators, pathways targeting crosstalk between kinase (AKT), NF-κB, mitogen-activated (MAPK), making hopeful treatment injury.

Язык: Английский

Процитировано

0