Gingerol suppresses sepsis-induced acute kidney injury by modulating methylsulfonylmethane and dimethylamine production

Acute kidney injury (AKI) and metabolic dysfunction are critical complications in sepsis syndrome; however, their pathophysiological mechanisms remain poorly understood. Therefore, we evaluated whether the pharmacological properties of 6-gingerol (6G) and 10-gingerol (10G) could modulate AKI and met...

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Detalles Bibliográficos
Autores: Rodrigues, Francisco Adelvane de Paulo, Santos, Alan Diego da Conceição, Medeiros, Pedro Henrique Quintela Soares de, Prata, Mara de Moura Gondim, Santos, Tailane Caína de Souza, Silva, James Almada da, Brito, Gerly Anne de Castro, Santos, Armênio Aguiar dos, Silveira, Edilberto Rocha, Lima, Aldo Ângelo Moreira, Havt, Alexandre
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:Brasil
Institución:Universidade Federal do Ceará (UFC)
Repositorio:Repositório Institucional da Universidade Federal do Ceará (UFC)
Idioma:inglés
OAI Identifier:oai:repositorio.ufc.br:riufc/35900
Acceso en línea:http://www.repositorio.ufc.br/handle/riufc/35900
Access Level:acceso abierto
Palabra clave:Sepse
Sepsis
Acute Kidney Injury
Lesão Renal Aguda
Descripción
Sumario:Acute kidney injury (AKI) and metabolic dysfunction are critical complications in sepsis syndrome; however, their pathophysiological mechanisms remain poorly understood. Therefore, we evaluated whether the pharmacological properties of 6-gingerol (6G) and 10-gingerol (10G) could modulate AKI and metabolic disruption in a rat model of sepsis (faecal peritonitis). Animals from the sham and AKI groups were intraperitoneally injected with 6G or 10G (25 mg/kg). Septic AKI decreased creatinine clearance and renal antioxidant activity, but enhanced oxidative stress and the renal mRNA levels of tumour necrosis factor-α, interleukin-1β, and transforming growth factor-β. Both phenol compounds repaired kidney function through antioxidant activity related to decreased oxidative/nitrosative stress and proinflammatory cytokines. Metabolomics analysis indicated different metabolic profiles for the sham surgery group, caecal ligation and puncture model alone group, and sepsis groups treated with gingerols. 1H nuclear magnetic resonance analysis detected important increases in urinary creatine, allantoin, and dimethylglycine levels in septic rats. However, dimethylamine and methylsulfonylmethane metabolites were more frequently detected in septic animals treated with 6G or 10G, and were associated with increased survival of septic animals. Gingerols attenuated septic AKI by decreasing renal disturbances, oxidative stress, and inflammatory response through a mechanism possibly correlated with increased production of dimethylamine and methylsulfonylmethane.