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.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.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).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.
