Protective effects of menthol against sepsis-induced hepatic injury: Role of mediators of hepatic inflammation, apoptosis, and regeneration

Matouk, Asmaa I.; El‐Daly, Mahmoud; Habib, Heba A.; Senousy, Shaymaa Ramzy; Hafez, Sara Mohamed Naguib Abdel; Kasem, AlShaimaa W.; Almalki, Waleed H.; Alzahrani, Abdulaziz; Alshehri, Ahmed; Ahmed, Al-Shaimaa F.

doi:10.3389/fphar.2022.952337

Cited by 13 publications

(11 citation statements)

References 77 publications

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“…Previous studies have demonstrated that hepatocyte death by apoptosis mechanism serves a crucial role in septic liver injury. 30,31 Conversely, inhibiting liver apoptosis can relieve septic liver injury. 32 Cleaved caspase-3 is a hallmark of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Deoxyribonuclease I Alleviates Septic Liver Injury in a Rat Model Supported by Venoarterial Extracorporeal Membrane Oxygenation

Zhang,

Yan,

Wang

et al. 2023

ASAIO Journal

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Sepsis is an unusual systemic reaction with high mortality and secondary septic liver injury is proposed to be the major cause of mortality. Extracorporeal membrane oxygenation (ECMO) can enhance terminal organ perfusion by elevating circulatory support which is used in severe sepsis patients. However, the interaction of blood components with the biomaterials of the extracorporeal membrane elicits a systemic inflammatory response. Besides, inflammation and apoptosis are the main mediators in the pathophysiology of septic liver injury. Therefore, we investigated the protective effect of Deoxyribonuclease I (DNase I) against septic liver injury supported by ECMO in rats. Sepsis was induced by lipopolysaccharide (LPS) and 24 hours after the administration, the rats were treated with ECMO. Then blood samples and liver tissues were collected. DNase I significantly attenuated the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and significantly decreased hepatic levels of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, myeloperoxidase (MPO), downstream inflammatory factor interleukin-1β (IL-1β) and interleukin-18 (IL-18), and improved neutrophil infiltration. Additionally, DNase I significantly reduced the expression of apoptosis key protein and terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL)-labeled apoptotic hepatocytes. In summary, our findings demonstrated that DNase I alleviates liver injury in ECMO-supported septic rats by reducing the inflammatory and apoptotic responses.

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Section: Discussionmentioning

confidence: 99%

Deoxyribonuclease I Alleviates Septic Liver Injury in a Rat Model Supported by Venoarterial Extracorporeal Membrane Oxygenation

Zhang,

Yan,

Wang

et al. 2023

ASAIO Journal

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show abstract

“…Sepsis, characterized by an overwhelming host response to infection, significantly impacts multiple organs, including the liver, kidneys, and heart. Liver damage in sepsis is a key factor in patient mortality, necessitating prompt and effective treatment strategies [ 12 , 13 ]. Excessive inflammatory response and oxidative stress play pivotal roles in the pathogenesis of liver injury, making them key targets for therapeutic intervention [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Rebastinib attenuates liver injury following cecal ligation and puncture in male mice

Hadi,

Zaini,

Jawad

et al. 2023

JMedLife

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Sepsis remains a public health issue with high morbidity and mortality. Liver injury due to sepsis is associated with poor outcomes and an increased risk of death among septic patients. Rebastinib is a small molecule inhibiting the Tie2 receptor and vascular endothelial growth factor receptor-2 (VEGFR2). The current study aimed to reveal the potential protective impact of Rebastinib against sepsis-induced liver injury. Twenty-four adult male mice were allocated into four groups (six per group) as follows: Sham group was exposed to anesthesia and laparotomy with no cecal ligation and puncture procedure (CLP); CLP group was subjected CLP procedure; vehicle-treated group was pretreated with vehicle (oral route) one hour prior to CLP procedure; Rebastinib group was pretreated with oral Rebastinib one hour before induction of CLP. Collected blood was used to measure the serum levels of AST, ALT, and angiopoietin 2. Homogenized liver tissues were used to investigate IL-6, TNF-α, ICAM-1, MIF, VEGF, F2-isoprostanes, and caspase-11 levels. Histological examination was used to determine the severity of liver damage. Compared to the sham group, mice subjected to CLP had high levels of these biomarkers with a high degree of liver injury. In contrast, Rebastinib markedly reduced these levels and mitigated the liver damage. Rebastinib may be a hepatoprotective agent against sepsis-associated liver injury.

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“…As a lipid peroxidation marker, MDA reacts with thiobarbituric acid in an acidic medium to form a colored adduct with maximal absorbance at 534 nm; the measured values were proportional to the amount of lipid peroxides [ 66 ]. Cardiac GSH was determined based on its ability to react with 5,5′-dithio-bis-2-nitrobenzoic acid (Ellman’s reagent) and form a yellow product [ 65 , 67 ]. Tissue NOx was determined as an indicator of cardiac • NO content.…”

Section: Methodsmentioning

confidence: 99%

Pregnenolone Inhibits Doxorubicin-Induced Cardiac Oxidative Stress, Inflammation, and Apoptosis—Role of Matrix Metalloproteinase 2 and NADPH Oxidase 1

et al. 2023

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The clinical usefulness of doxorubicin (DOX) is limited by its serious adverse effects, such as cardiotoxicity. Pregnenolone demonstrated both anti-inflammatory and antioxidant activity in animal models. The current study aimed to investigate the cardioprotective potential of pregnenolone against DOX-induced cardiotoxicity. After acclimatization, male Wistar rats were randomly grouped into four groups: control (vehicle-treated), pregnenolone (35 mg/kg/d, p.o.), DOX (15 mg/kg, i.p, once), and pregnenolone + DOX. All treatments continued for seven consecutive days except DOX, which was administered once on day 5. The heart and serum samples were harvested one day after the last treatment for further assays. Pregnenolone ameliorated the DOX-induced increase in markers of cardiotoxicity, namely, histopathological changes and elevated serum levels of creatine kinase-MB and lactate dehydrogenase. Moreover, pregnenolone prevented DOX-induced oxidative changes (significantly lowered cardiac malondialdehyde, total nitrite/nitrate, and NADPH oxidase 1, and elevated reduced glutathione), tissue remodeling (significantly decreased matrix metalloproteinase 2), inflammation (significantly decreased tumor necrosis factor-α and interleukin 6), and proapoptotic changes (significantly lowered cleaved caspase-3). In conclusion, these findings show the cardioprotective effects of pregnenolone in DOX-treated rats. The cardioprotection achieved by pregnenolone treatment can be attributed to its antioxidant, anti-inflammatory, and antiapoptotic actions.

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Protective effects of menthol against sepsis-induced hepatic injury: Role of mediators of hepatic inflammation, apoptosis, and regeneration

Cited by 13 publications

References 77 publications

Deoxyribonuclease I Alleviates Septic Liver Injury in a Rat Model Supported by Venoarterial Extracorporeal Membrane Oxygenation

Deoxyribonuclease I Alleviates Septic Liver Injury in a Rat Model Supported by Venoarterial Extracorporeal Membrane Oxygenation

Rebastinib attenuates liver injury following cecal ligation and puncture in male mice

Pregnenolone Inhibits Doxorubicin-Induced Cardiac Oxidative Stress, Inflammation, and Apoptosis—Role of Matrix Metalloproteinase 2 and NADPH Oxidase 1

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