Gandouling Tablets Inhibit Excessive Mitophagy in Toxic Milk (TX) Model Mouse of Wilson Disease via Pink1/Parkin Pathway.

OBJECTIVE: Gandouling (GDL) tablet is a Chinese patent medicine approved by the National Medical Product Administration, which is used to treat Wilson disease (WD) in China. In this study, we aimed to investigate the effects of GDL on mitophagy in the hippocampus in the toxic milk (TX) mouse model of WD. METHODS: Mice were randomly divided into the following four groups: control, Wilson (model group), D-penicillamine (DPA), and GDL groups. The animal behaviors were evaluated by the water maze experiment, traction test, and pole test. Transmission electron microscopy was used for the detection of mitochondrion structure. An enzyme-linked immunosorbent assay (ELISA) was performed for the analysis of the changes in liver function. Colocalization of mitophagy-related proteins was detected by fluorescence microscopy. Western blotting (WB) and reverse transcription-polymerase chain reaction (RT-PCR) were conducted for the detection of protein expression and mRNA levels, respectively. RESULTS: Significant reduction in neurological impairments was observed in the WD model group. All of these results were significantly reversed by GDL intervention. Compared with the levels in the Wilson group, the levels of alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), and albumin (ALB) changed obviously. Colocalization between mitophagy-related proteins pink1, parkin, and mitochondria was changed significantly. The mitophagy-related mRNA (pink1, parkin, and LC3II) and protein expression levels (pink1, parkin, and the rate of LC3II/LC3I) were decreased significantly, while p62 was remarkably increased after GDL intervention. CONCLUSION: Our findings indicated that the neuroprotective mechanism of GDL may occur via the inhibition of excessive mitophagy through the regulation of the pink1/parkin pathway in the TX mouse brain of WD.

Successful Treatment of Hypersplenism in Wilson's Disease by Partial Splenic Embolization.

AIM: Hypersplenism can occur in patients with Wilson's disease (WD). Surgical splenectomy is a conventional treatment for this condition; however, emotional and neurological deterioration may follow splenectomy. In recent years, partial splenic embolization (PSE) has been increasingly performed as a nonsurgical alternative treatment for hypersplenism. The aim of this study was to evaluate the effectiveness and safety of PSE compared with splenectomy in the treatment of hypersplenism in WD patients. METHODS: Fifty WD patients with hypersplenism were randomly divided into two groups (group A and group B), each including 25 patients. Patients in groups A and B were treated with PSE and splenectomy, respectively. Data were collected on the clinical efficacy of each procedure, adverse reactions, hematologic and blood chemistry test results, and abdominal computed tomography (CT) scan findings (group A only). RESULTS: Marked improvements in the platelet and leukocyte counts after PSE and splenectomy were observed in all patients. PSE was associated with improved liver function without severe complications, and no significant changes in emotional and neurological symptoms were observed. In contrast, seven WD patients suffered neurological deterioration after splenectomy. CONCLUSIONS: Hypersplenism in WD patients was successfully treated by PSE, which appears to be a safe and effective alternative treatment for WD-induced hypersplenism.