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The effect of Cyclophilin D depletion on liver regeneration following associating liver partition and portal vein ligation for staged hepatectomy.
Daradics, Noemi; Horvath, Gergo; Tretter, Laszlo; Paal, Agnes; Fulop, Andras; Budai, Andras; Szijarto, Attila.
Afiliação
  • Daradics N; Department of Surgery, Transplantation and Interventional Gastroenterology, Semmelweis University, Hepato-Pancreatico-Biliary (HPB) Surgical Research Center Hungary, Budapest, Hungary.
  • Horvath G; Department of Medical Biochemistry, Semmelweis University, Budapest, Hungary.
  • Tretter L; Department of Medical Biochemistry, Semmelweis University, Budapest, Hungary.
  • Paal A; 2nd Department of Pathology, Semmelweis University, Budapest, Hungary.
  • Fulop A; Department of Surgery, Transplantation and Interventional Gastroenterology, Semmelweis University, Hepato-Pancreatico-Biliary (HPB) Surgical Research Center Hungary, Budapest, Hungary.
  • Budai A; 2nd Department of Pathology, Semmelweis University, Budapest, Hungary.
  • Szijarto A; Department of Surgery, Transplantation and Interventional Gastroenterology, Semmelweis University, Hepato-Pancreatico-Biliary (HPB) Surgical Research Center Hungary, Budapest, Hungary.
PLoS One ; 17(7): e0271606, 2022.
Article em En | MEDLINE | ID: mdl-35834573
ABSTRACT

AIM:

Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) is a modification of two-stage hepatectomy profitable for patients with inoperable hepatic tumors by standard techniques. Unfortunately, initially poor postoperative outcome was associated with ALPPS, in which mitochondrial dysfunction played an essential role. Inhibition of cyclophilins has been already proposed to be efficient as a mitochondrial therapy in liver diseases. To investigate the effect of Cyclophilin D (CypD) depletion on mitochondrial function, biogenesis and liver regeneration following ALPPS a CypD knockout (KO) mice model was created.

METHODS:

Male wild type (WT) (n = 30) and CypD KO (n = 30) mice underwent ALPPS procedure. Animals were terminated pre-operatively and 24, 48, 72 or 168 h after the operation. Mitochondrial functional studies and proteomic analysis were performed. Regeneration rate and mitotic activity were assessed.

RESULTS:

The CypD KO group displayed improved mitochondrial function, as both ATP production (P < 0.001) and oxygen consumption (P < 0.05) were increased compared to the WT group. The level of mitochondrial biogenesis coordinator peroxisome proliferator-activated receptor γ co-activator 1-α (PGC1-α) was also elevated in the CypD KO group (P < 0.001), which resulted in the induction of the mitochondrial oxidative phosphorylation system. Liver growth increased in the CypD KO group compared to the WT group (P < 0.001).

CONCLUSIONS:

Our study demonstrates the beneficial effect of CypD depletion on the mitochondrial vulnerability following ALPPS. Based on our results we propose that CypD inhibition should be further investigated as a possible mitochondrial therapy following ALPPS.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Mitocôndrias Hepáticas / Peptidil-Prolil Isomerase F / Hepatectomia / Neoplasias Hepáticas / Regeneração Hepática Idioma: En Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Hungria

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Mitocôndrias Hepáticas / Peptidil-Prolil Isomerase F / Hepatectomia / Neoplasias Hepáticas / Regeneração Hepática Idioma: En Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Hungria