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1.
Bioorg Med Chem Lett ; 48: 128256, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34256117

RESUMO

Acute kidney injury (AKI) is a common clinical problem that is associated with high mortality due to multiple complex mechanisms. Cisplatin is the most important and highly effective chemotherapeutic agent used for the treatment of various solid tumors; however, it is associated with dose-dependent adverse effects, particularly in the kidney where it can cause severe nephrotoxicity. The pathophysiological basis of cisplatin-induced nephrotoxicity has been investigated over the last few decades, and the key pathological occurrences in cisplatin nephrotoxicity include renal tubular cell injury and death. Necrostatin-1 (Nec-1) has been confirmed to act as a specific and potent small-molecule inhibitor of necroptosis. However, the effects of three structurally distinct necrostatins on cisplatin-induced nephrotoxicity remain ambiguous. The aim of this study was to determine if three types of necrostatins (Nec-1, Nec-3-A, and/or Nec-3-B) can exert protective effects in regard to the AKI induced by cisplatin. Our results indicated that necrostatins can prevent cisplatin induced nephrotoxicity via modulating apoptotic pathways through the suppression of cleaved caspase-3 and also by influencing the function of mitogen-activated protein kinase pathway members, including extracellular signal-regulated kinases, c-Jun N-terminal kinases, and p38, in the renal tubular epithelial cell line LLC-PK1. These findings suggest that necrostatins exert beneficial anti-apoptotic effects in the context of AKI induced by cisplatin.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Imidazóis/farmacologia , Indóis/farmacologia , Inflamação/tratamento farmacológico , Bibliotecas de Moléculas Pequenas/farmacologia , Animais , Antineoplásicos/química , Cisplatino/farmacologia , Relação Dose-Resposta a Droga , Imidazóis/química , Indóis/química , Túbulos Renais/efeitos dos fármacos , Células LLC-PK1 , Estrutura Molecular , Necroptose/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/química , Relação Estrutura-Atividade , Suínos
2.
Medicine (Baltimore) ; 97(17): e0391, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29702985

RESUMO

BACKGROUND: Suoquan is widely used to treat frequent urination, enuresis, and other diseases caused by kidney qi deficiency. Many clinical trials assessing the efficacy and safety of Suoquan for the treatment of enuresis have been reported. This review will assess the clinical evidence for and against the use of Suoquan as a treatment for enuresis. METHODS AND ANALYSIS: Fourteen databases will be searched until 2018. We will include randomized controlled trials (RCTs) examining Suoquan decoctions for any type of enuresis. All RCTs of decoctions or modified decoctions will be included. The methodological qualities of the RCTs will be assessed using the Cochrane Collaboration tool for assessing risk of bias. ETHICS AND DISSEMINATION: This systematic review will be published in a peer-reviewed journal. The review will be disseminated both electronically and in print. It will be updated to inform and guide healthcare practices. TRIAL REGISTRATION NUMBER: CRD42018087900.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Enurese Noturna/tratamento farmacológico , Projetos de Pesquisa , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto
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