Perindopril ameliorates lipopolysaccharide-induced brain injury through modulation of angiotensin-II/angiotensin-1-7 and related signaling pathways

El-Shoura, Ehab A.M.; Messiha, Basim Anwar Shehata; Sharkawi, Souty M.Z.; Hemeida, Ramadan A.M.

doi:10.1016/j.ejphar.2018.07.046

Cited by 19 publications

(15 citation statements)

References 67 publications

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“…In contrast, we observed a decrease in the numbers of damaged cardiomyocytes in heart tissues treated with PER. This finding was consistent with Ehab A. M. El-Shoura et al who reported that PER reversed the effects of lipopolysaccharide-based cardiopulmonary damage (40).…”

Section: Discussionsupporting

confidence: 92%

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The Cardioprotective Effects of Perindopril in a Model of Polymicrobial Sepsis: The Role of Radical Oxygen Species and the Inflammation Pathway

Topçu¹,

Kostakoğlu²,

Mercantepe³

et al.

Authorea

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Mortality rates associated with myocardial dysfunction due to sepsis and septic shock are generally high across the world.Although symptomatic therapies are employed in an attempt to cope with the resulting complications, there is an urgent need for effective and reliable novel agents regulating oxidative stress and the inflammatory process in cardiac damage to be discovered and developed. The present study focused on the antioxidant and anti-inflammatory effects of perindopril for the purpose of preventing the adverse effects of sepsis on the myocardium and developing new alternatives in treatment. The control group received only saline solution via the oral route for four days. The second group underwent cecal ligation puncture (CLP), and the third underwent CLP and received PER (2 mg/kg). Rats in the third group received 2 mg/kg PER p.o. from four days before induction of sepsis. TBARS, total -SH, IL-1β, IL-6 and 8-OHdG levels increased in the CLP groups. In contrast, PER (2 mg/kg) administered reduced the levels of biochemical parameters, apart from -SH, in rat heart tissues, and lowered 8-OHdG immunopositivity. The data from this study show that impairment of the antioxidant/antioxidant balance and inflammatory cytokine levels in favor of inflammation in heart tissue under septic conditions results in severe tissue damage. Per administration before sepsis was shown to exhibit antioxidant and anti-inflammatory properties by reducing these effects. This in turn increased the importance of PER as new evidence of its protective effects in heart tissue.

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Section: Discussionsupporting

confidence: 92%

“…This effect may be due to endogenous antioxidant systems and producing a protective effect in association with an increasing oxidant effect at the cellular level. This was also compatible with Ehab A M El-Shoura et al's study showing the antioxidant effects of PER (40).…”

Section: Discussionsupporting

confidence: 91%

The Cardioprotective Effects of Perindopril in a Model of Polymicrobial Sepsis: The Role of Radical Oxygen Species and the Inflammation Pathway

Topçu¹,

Kostakoğlu²,

Mercantepe³

et al.

Authorea

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“…It was reported that PER possesses anticancer activity through inhibition of angiogenesis in murine hepatocarcinogenesis (Saber et al, ). In addition, PER has protective effects on the liver (Saber et al, ), the respiratory tract (Abdel‐Fattah et al, ), and the brain (El‐Shoura et al, ) injuries.…”

Section: Introductionmentioning

confidence: 99%

Perindopril Ameliorates Hepatic Ischemia Reperfusion Injury Via Regulation of NF‐κB‐p65/TLR‐4, JAK1/STAT‐3, Nrf‐2, and PI3K/Akt/mTOR Signaling Pathways

Kamel

Hassanein

Ahmed

et al. 2019

The Anatomical Record

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Hepatic ischemia reperfusion (IR) is an inevitable clinical problem for surgical procedures such as liver transplantation and liver resection. This study was designed to evaluate the protective effect of perindopril (PER) against hepatic IR injury. Thirty‐two rats were used and randomly allocated into four groups. Sham control group was subjected to sham operation and received saline only, IR group was subjected to IR and received vehicle, PER group was pretreated with PER (one milligram per kilogram per day i.p. for 10 consecutive days), and IR+PER group was pretreated with PER then subjected to IR. Liver function biomarkers (aspartate aminotransferase and alanine aminotransferase), oxidative stress (glutathione, malondialdehyde, myeloperoxidase, and superoxide dismutase) and inflammation markers (tumor necrosis factor‐alpha, interferon‐gamma, and inteleukin‐10 [IL‐10]), mRNA expression of NF‐κB‐p65 and TLR‐4, as well as protein expression of JAK1, STAT‐3, PI3K, mTOR, Akt, and Nrf‐2 were investigated concomitantly with histopathological examination. The results indicated that, hepatic IR induced a significant alteration in liver function biomarkers and structure, oxidative stress, and inflammation. At the molecular level, up‐regulation of NF‐κB‐p65, TLR‐4, JAK1, and STAT‐3 concomitantly with down‐regulation of Nrf‐2, IL‐10, PI3K, Akt, and mTOR were observed. These disturbances were alleviated by pretreatment of IR rats with PER in concomitant with hepatic structural improvement. Conclusively, the protective effect of PER presumably may be relevant to its ability to reduce oxidative stress, ameliorate the inflammatory processes, and modify the related signaling pathways. Anat Rec, 2019. © 2019 American Association for Anatomy Anat Rec, 303:1935–1949, 2020. © 2019 American Association for Anatomy

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“…RAS stimulation mediates oxidative and inflammatory damage, mostly via activation of NADPH oxidase and the inhibition of endothelial nitric oxide synthase (12,13). Interestingly, interference with localized RAS in different animal models using ACEIs was shown to offer protective effects in the liver (14), respiratory tract (15), joints (16) and the brain (13). The aim of the present study was to examine the possible modulatory effects of perindopril on cisplatin-induced acute nephrotoxicity in mice and the potential mechanisms behind this modulation.…”

mentioning

confidence: 96%

“…Accumulated evidence suggests the role of localized renin-angiotensin system (RAS) in the progression of different pathologies. RAS stimulation mediates oxidative and inflammatory damage, mostly via activation of NADPH oxidase and the inhibition of endothelial nitric oxide synthase (12,13). Interestingly, interference with localized RAS in different animal models using ACEIs was shown to offer protective effects in the liver (14), respiratory tract (15), joints (16) and the brain (13).…”

mentioning

confidence: 99%

Modulatory effects of perindopril on cisplatin-induced nephrotoxicity in mice: Implication of inflammatory cytokines and caspase-3 mediated apoptosis

et al. 2020

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Cisplatin-induced nephrotoxicity limits its anticancer effectiveness, thus this study’s aim was to assess the potential modulatory effect of perindopril on cisplatin-induced nephrotoxicity and to elucidate the possible underlying mechanisms. Renal dysfunction was induced in mice by a single injection of cisplatin (10 mg kg−1, i.p.) and perindopril was administered orally (2 mg kg−1, once daily) for 5 days. Perindopril remarkably ameliorated cisplatin-induced perturbations in renal histology, renal levels of tumor necrosis factor-alpha, interleukin-6 and interleukin-10, apoptosis-regulating protein expressions (Bax and Bcl2), and partially normalized Bax to Bcl2 ratio and active caspase 3 protein expression. Conversely, perindopril had no significant effect on cisplatin-induced elevations in serum creatinine and urea, microalbuminuria, kidney to body weight ratio, lipid peroxidation marker, superoxide dismutase and catalase activities and reduced glutathione content. In conclusion, perindopril may be safely used with cisplatin in mice since it ameliorated cisplatin-induced histopathological changes, inflammation and apoptosis without affecting renal biomarkers or oxidative stress.

show abstract

Perindopril ameliorates lipopolysaccharide-induced brain injury through modulation of angiotensin-II/angiotensin-1-7 and related signaling pathways

Cited by 19 publications

References 67 publications

The Cardioprotective Effects of Perindopril in a Model of Polymicrobial Sepsis: The Role of Radical Oxygen Species and the Inflammation Pathway

The Cardioprotective Effects of Perindopril in a Model of Polymicrobial Sepsis: The Role of Radical Oxygen Species and the Inflammation Pathway

Perindopril Ameliorates Hepatic Ischemia Reperfusion Injury Via Regulation of NF‐κB‐p65/TLR‐4, JAK1/STAT‐3, Nrf‐2, and PI3K/Akt/mTOR Signaling Pathways

Modulatory effects of perindopril on cisplatin-induced nephrotoxicity in mice: Implication of inflammatory cytokines and caspase-3 mediated apoptosis

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