Possible contribution of the neprilysin/ACE pathway to sepsis in mice

Uğan, Rüstem Anıl; Un, Harun; Gürbüz, Muhammed Ali; Kaya, Gokce; Kahramanlar, Aysenur; Aksakalli-Magden, Zeynep Berna; Halıcı, Zekai; Çadırcı, Elif

doi:10.1016/j.lfs.2020.118177

Cited by 11 publications

(10 citation statements)

References 41 publications

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“…In a study by Li et al, 45 In sepsis-induced lung injury, elevated levels of proinflammatory cytokines, such as TNF-α and IL-1β, play a crucial role in the development of ARDS and other complications. 46 The results showed that in this study treatment with MEL, ASA or MEL + ASA significantly reduced the levels of TNF-α and IL-1β in the lung tissue of septic rats, compared to the CLP group. The combination of MEL and ASA was found to have an enhanced effect in reducing inflammation and cytokine release in sepsis-induced lung injury, with the lowest levels of TNF-α and IL-1β observed in the MEL + ASA group.…”

Section: Discussionsupporting

confidence: 51%

“…In sepsis‐induced lung injury, elevated levels of proinflammatory cytokines, such as TNF‐α and IL‐1β, play a crucial role in the development of ARDS and other complications 46 . The results showed that in this study treatment with MEL, ASA or MEL + ASA significantly reduced the levels of TNF‐α and IL‐1β in the lung tissue of septic rats, compared to the CLP group.…”

Section: Discussionsupporting

confidence: 47%

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Protective effect of melatonin and ascorbic acid combination on sepsis‐induced lung injury: An Experimental study

Üstündağ

Demir

Çiçek

et al. 2023

Clin Exp Pharma Physio

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This study investigated the synergistic protective effects of melatonin (MEL) and ascorbic acid (vitamin C, ASA) in treating sepsis‐induced lung injury in rats. Rats were divided into five groups: control, cecal ligation and puncture (CLP), CLP + MEL, CLP + ASA and CLP + MEL + ASA. The effects of MEL (10 mg/kg), ASA (100 mg/kg) and their combination on oxidative stress, inflammation and histopathology were evaluated in septic rats’ lung tissues. Sepsis‐induced oxidative stress and inflammation were evident through increased levels of malondialdehyde (MDA), myeloperoxidase (MPO), total oxidant status (TOS) and oxidative stress index (OSI); decreased levels of superoxide dismutase (SOD), glutathione (GSH), catalase (CAT) and glutathione peroxidase (GPx); and elevated levels of tumour necrosis factor‐α (TNF‐α) and interleukin‐1 β (IL‐1β) in the lung tissue. Treatment with MEL, ASA and their combination significantly improved antioxidant capacity and reduced oxidative stress, with the combination treatment being more effective. The combination treatment also significantly reduced TNF‐α and IL‐1β levels and improved peroxisome proliferator‐activated receptor (PPAR), arylesterase (ARE) and paraoxonase (PON) levels in the lung tissue. Histopathological examination showed reduced oedema and lymphocyte infiltration with a lung tissue appearance similar to the control group. Immunohistochemical staining for caspase 3 demonstrated reduced immune positivity in the treatment groups. In conclusion, this study supports the potential synergistic protective effects of MEL and ASA in treating sepsis‐induced lung injury. The combination therapy could effectively reduce oxidative stress, inflammation and improve antioxidant capacity in septic rats, suggesting a promising strategy for treating sepsis‐induced lung injury.

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Section: Discussionsupporting

confidence: 51%

Section: Discussionsupporting

confidence: 47%

Protective effect of melatonin and ascorbic acid combination on sepsis‐induced lung injury: An Experimental study

Üstündağ

Demir

Çiçek

et al. 2023

Clin Exp Pharma Physio

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“…All chemicals were administered orally by gastric gavage. Omapatrilat was administered at 10, 20 and 40 mg/kg doses, according to previous experimental studies which showed that omapatrilat can influence oxidative stress parameters at similar doses (31)(32)(33). For NAC, two doses were administered at 140 mg/kg each, as per its recommended therapeutic application against paracetamol poisoning (7,34).…”

Section: Methodsmentioning

confidence: 99%

“…In contrast to the aforementioned drugs influencing RAAS, omapatrilat also inhibits NEP. The increase in natriuretic peptides due to this NEP inhibition and the decrease in Ang II by ACE inhibition both have beneficial effects in sepsis, as indicated by reductions in inflammation and oxidative stress (29)(30)(31). This combined inhibition of ACE and NEP suggests omapatrilat's hepatoprotective potential against paracetamol-induced toxicity.…”

Section: Potential Role Of Angiotensin Converting Enzyme/neprilysin P...mentioning

confidence: 98%

Potential role of angiotensin converting enzyme/neprilysin pathway and protective effects of omapatrilat for paracetamol‑induced acute liver injury

et al. 2022

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The renin-angiotensin-aldosterone system (RAAS) is an important pathway that contributes to the pathophysiology of acute liver injury due to paracetamol toxicity. Omapatrilat, a RAAS-acting agent, inhibits both angiotensin converting enzyme (ACE) and neprilysin/neutral endopeptidase (NEP). The aim of the present study was to investigate the hepatoprotective effects of omapatrilat and examine the role of ACE/NEP pathway on the physiopathology of paracetamol toxicity. A total of 56 BALB/c mice were separated into seven groups: Control, 40 mg/kg omapatrilat only, 400 mg/kg paracetamol only, paracetamol and 140 mg/kg N-acetylcysteine and three groups with paracetamol and 10-40 mg/kg omapatrilat. Blood and liver tissue samples were studied through histopathological imaging, alanine transaminase (ALT) and aspartate transaminase (AST) liver function tests and oxidant/antioxidant biomarker measurements including superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA). ACE and NEP activities were also measured. Histopathological analysis revealed that paracetamol toxicity resulted in a number of apoptotic and necrotic cells in liver tissue samples. By contrast, with 40 mg/kg omapatrilat administration in toxicity-induced mice, hepatocytes were significantly improved and exhibited similar appearance to the control group. Biochemical measurements also supported these histopathological results. Omapatrilat pretreatment provided a dose-dependent reduction in oxidative stress and reversed paracetamol toxicity indications by reducing ALT and AST activities, increasing SOD activity and GSH levels and reducing MDA levels. Dose-dependent increase of ACE and NEP enzymes in omapatrilat groups was also observed. The results demonstrated promotion of antioxidant activity by omapatrilat and suppression of oxidative stress associated with acute liver injury. These findings revealed the potential role of ACE/NEP pathway in paracetamol toxicity and hepatoprotective effects of omapatrilat against oxidative stress.

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“…Daha sonra santrifüj edildi ve supernatant kısım biyokimyasal ölçümlerimizde kullanıldı. Glutatyon (GSH) 31 ve MDA 32 seviyeleri daha önceki çalışmalardaki manuel yöntemler modifiye edilerek ölçüldü [33][34][35]…”

Section: Biyokimyasal Analizlerunclassified

Sıçanlarda letrozolün indüklediği polikistik over sendromunda fisetinin etkileri

Çelikçi

Uğan

Toktay

2021

Cukurova Medical Journal

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The aim of this study is to evaluate the antioxidant effects of fisetin on letrozole induced PCOS (polycystic ovarian syndrome) in rats. Materials and Methods: A total of 36 Albino Wistar female rats were used in the study. Letrozole at a dose of 1 mg/kg dissolved in 1% carboxymethyl cellulose (2ml/kg) was administered orally to rats for 21 days to induce the PCOS model. After 21 days, metformin and fisetin were administered to their groups for 7 days. The ovaries of the animals were removed and stored under suitable conditions for biochemical and histological examinations. Results: The glutathione (GSH) levels decreased and the malondialdehyde (MDA) levels increased in the PCOS group compared to the healthy group. It was determined that GSH levels increased and MDA levels decreased in PCOS+MET+FIS25 (PCOS+metformin 20 mg/kg+fisetin 25 mg/kg) and PCOS+MET+FIS50 (PCOS+metformin 20 mg/kg+fisetin 50 mg/kg) groups in a dose dependent manner. Histological findings showed that the PCOS group contained more cystic follicles than the control group. It was observed that cystic follicles and the apoptotic and necrotic cells contained in follicles decreased in the PCOS+MET+FIS25 and PCOS+MET+FIS50 groups in a dose dependent manner. Conclusion: As a result, fisetin showed beneficial effects in the treatment of PCOS by preventing the oxidative damage that metformin cannot eliminate. Fisetin prevented and protected new cells from going to necrosis by showing antioxidant activity. Therefore, it would be beneficial to add fisetin to the metformin treatment.. Amaç: Bu çalışmanın amacı sıçanlarda letrozolle oluşturulmuş PKOS (polikistik over sendromu) üzerinde fisetinin antioksidan etkilerini değerlendirmektir. Gereç ve Yöntem: Çalışmada 36 adet Albino Wistar dişi sıçan kullanıldı. Dişi sıçanlara, PKOS modelini indüklemek için 21 gün boyunca %1 karboksimetil selüloz (2 mL/kg) içinde çözülmüş 1 mg/kg dozunda letrozol oral yolla uygulanmıştır. PKOS oluşturulduktan sonra 7 gün boyunca metformin ve fisetin kendi gruplarına uygulandı. Hayvanların overleri alındı ve biyokimyasal, histolojik incelemeler için uygun koşullarda saklandı. Bulgular: PKOS grubunda sağlıklı gruba göre glutatyon (GSH) seviyelerinde düşüş, malondialdehit (MDA) seviyelerinde artış görüldü. PKOS+MET+FIS25 (PKOS+20 mg/kg metformin+25 mg/kg fisetin) ve PKOS+MET+FIS50 (PKOS+20 mg/kg metformin+50 mg/kg fisetin) gruplarında doza bağlı olarak GSH seviyelerinin yükseldiği, MDA seviyelerinin düştüğü tespit edildi. Histolojik bulgularda PKOS grubunda kontrol grubuna göre çok sayıda kistik folikül içerdiği görüldü. PKOS+MET+FIS25 ve PKOS+MET+FIS50 gruplarında doza bağlı olarak kistik foliküllerin ve foliküllerin içerdiği apoptotik ve nekrotik hücrelerin azaldığı görüldü. Sonuç: Sonuç olarak, fisetin metforminin ortadan kaldıramadığı oksidatif hasarı engelleyerek faydalı etkiler göstermiştir. Fisetin antioksidan aktivite göstererek yeni hücrelerin nekroza gitmesini engellemiş ve korumuştur. Bundan dolayı metformin tedavisine fisetin eklenmesi faydalı olacaktır.

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Possible contribution of the neprilysin/ACE pathway to sepsis in mice

Cited by 11 publications

References 41 publications

Protective effect of melatonin and ascorbic acid combination on sepsis‐induced lung injury: An Experimental study

Protective effect of melatonin and ascorbic acid combination on sepsis‐induced lung injury: An Experimental study

Potential role of angiotensin converting enzyme/neprilysin pathway and protective effects of omapatrilat for paracetamol‑induced acute liver injury

Sıçanlarda letrozolün indüklediği polikistik over sendromunda fisetinin etkileri

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