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L-Carnitine protects against tacrolimus-induced renal injury by attenuating programmed cell death via PI3K/AKT/PTEN signaling.
Zheng, Hai-Lan; Zhang, Hai-Yue; Zhu, Chun-Lian; Li, Hui-Ying; Cui, Sheng; Jin, Jian; Piao, Shang-Guo; Jiang, Yu-Ji; Xuan, Mei-Ying; Jin, Ji-Zhe; Jin, Ying-Shun; Lee, Jung-Pyo; Chung, Byung-Ha; Choi, Bum-Soon; Yang, Chul-Woo; Li, Can.
Afiliação
  • Zheng HL; Department of Nephrology, Yanbian University Hospital, Yanji, 133000, China.
  • Zhang HY; College of Chemical and Life Science, Changchun University of Technology, Changchun, 130000, China.
  • Zhu CL; Department of Nephrology, Yanbian University Hospital, Yanji, 133000, China.
  • Li HY; Department of Nephrology, Yanbian University Hospital, Yanji, 133000, China.
  • Cui S; Department of Nephrology, Yanbian University Hospital, Yanji, 133000, China.
  • Jin J; Transplantation Research Center, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, 06591, Korea.
  • Piao SG; Department of Nephrology, Yanbian University Hospital, Yanji, 133000, China.
  • Jiang YJ; Department of Nephrology, Yanbian University Hospital, Yanji, 133000, China.
  • Xuan MY; Department of Nephrology, Yanbian University Hospital, Yanji, 133000, China.
  • Jin JZ; Department of Nephrology, Yanbian University Hospital, Yanji, 133000, China.
  • Jin YS; Department of Health Examination Central, Yanbian University, Yanji, 133000, China.
  • Lee JP; Department of Nephrology, Yanbian University Hospital, Yanji, 133000, China.
  • Chung BH; Department of Nephrology, Yanbian University Hospital, Yanji, 133000, China.
  • Choi BS; Division of Nephrology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, 07061, Korea.
  • Yang CW; Transplantation Research Center, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, 06591, Korea.
  • Li C; Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 06591, Korea.
Acta Pharmacol Sin ; 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32555441
ABSTRACT
Reducing immunosuppressant-related complications using conventional drugs is an efficient therapeutic strategy. L-carnitine (LC) has been shown to protect against various types of renal injury. In this study, we investigated the renoprotective effects of LC in a rat model of chronic tacrolimus (TAC) nephropathy. SD rats were injected with TAC (1.5 mg · kg-1 · d-1, sc) for 4 weeks. Renoprotective effects of LC were assessed in terms of renal function, histopathology, oxidative stress, expression of inflammatory and fibrotic cytokines, programmed cell death (pyroptosis, apoptosis, and autophagy), mitochondrial function, and PI3K/AKT/PTEN signaling. Chronic TAC nephropathy was characterized by severe renal dysfunction and typical histological features of chronic nephropathy. At a molecular level, TAC markedly increased the expression of inflammatory and fibrotic cytokines in the kidney, induced oxidative stress, and led to mitochondrial dysfunction and programmed cell death through activation of PI3K/AKT and inhibition of PTEN. Coadministration of LC (200 mg · kg-1 · d-1, ip) caused a prominent improvement in renal function and ameliorated histological changes of kidneys in TAC-treated rats. Furthermore, LC exerted anti-inflammatory and antioxidant effects, prevented mitochondrial dysfunction, and modulated the expression of a series of apoptosis- and autophagy-controlling genes to promote cell survival. Human kidney proximal tubular epithelial cells (HK-2 cells) were treated with TAC (50 µg/mL) in vitro, which induced production of intracellular reactive oxygen species and expression of an array of genes controlling programmed cell death (pyroptosis, apoptosis, and autophagy) through interfering with PI3K/AKT/PTEN signaling. The harmful responses of HK-2 cells to TAC were significantly attenuated by cotreatment with LC and the PI3K inhibitor LY294002 (25 µM). In conclusion, LC treatment protects against chronic TAC nephropathy through interfering the PI3K/AKT/PTEN signaling.
Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Idioma: Inglês Assunto da revista: Farmacologia Ano de publicação: 2020 Tipo de documento: Artigo País de afiliação: China

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Idioma: Inglês Assunto da revista: Farmacologia Ano de publicação: 2020 Tipo de documento: Artigo País de afiliação: China