Jong-Won Kim is currently a PhD candidate at the Chonbuk National University where he researches pathogenesis of several non-infectious diseases including acute or chronic hepatitis. He holds a BS degree in Molecular Biology and a Doctor of Veterinary Pathology from the same university. He has his expertise and tries to clarify the mechanism of non-infectious diseases and contributes to the development of new therapeutic strategies.
Reactive Oxygen Species (ROS) plays a key role in Non-Alcoholic Steatohepatitis (NASH). Inactivation of glutathione peroxidase-4 (GPX4) induces ferroptosis, which is an iron dependent and lipid peroxidation-mediated non-apoptotic form of cell death. The aim of this study was to investigate the impact of GPX4 on the progression of NASH at an early stage. C57BL6/J mice were fed a Methionine and Choline-Deficient (MCD) diet for 10 days to induce NASH. To determine the role of GPX4 on NASH progression, the inhibitor (RSL-3) and the activator (sodium selenite) of GPX4, the inhibitor of ferroptosis (Liproxstatin-1, Lip-1) and an iron chelator (deferoxamine mesylate salt, DFO) were used in current experiments. RSL-3 treatment showed decreased hepatic expression of GPX4, 12/15-lipoxygenase and apoptosis inducing factor, indicating that GPX4 plays, a key role in NASH-related lipid peroxidation and its-associated cell death. Consistently, serum biochemical analysis showed increased serum Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) levels in MCD-fed mice with RSL-3 treatment. In line with these results, NASH-related hepatic steatosis, inflammation and apoptosis were also increased in MCD-fed mice with RSL-3 treatment. However, sodium selenite treatment showed an opposite and protective effect on NASH progression in MCD-fed mice. Administration of DFO showed significantly lowered NASH severity and abolished the harmful effects of RSL-3-mediated GPX4 inhibition in MCD-fed mice. Finally, Lip-1 treatment showed repressed hepatic lipid peroxidation and its associated cell death resulting in decreased NASH severity. Consistent with in vivo findings, similar results were observed in palmitic acid-induced in vitro NASH condition. Taken together, we conclude that ferroptosis might play a major role in development of NASH. These results suggest that modulation of iron-mediated ferroptotic cell death might pave the way for a new strategy in treating NASH.
Jorge Arturo Hernandez is a General Surgeon and Member of the Mexican Association of General Surgery, certified by the Mexican Council of General Surgery. He is an Endoscopist in the 2nd year of training and also a Member of the Mexican Association of Phlebology and Lymphology.
Multiple biliary hamartomatosis or Meyenburg Complex was described in 1918 and consists of a deformation and disorganization of the bile ducts, forming cystic structures that vary in size. An incidence of 5.6% in adults and 0.9% in children is reported. The diagnosis of this disease has gone very far thanks to the technological advances of imaging. Previously the management was conservative, maintaining an expectant and continuous periodic behavior, however, at present, the increase in the number of cases, that there is a possible association with the development of cholangiocarcinoma. The treatment for isolated and unique lesions is surgical resection whenever is possible. A 56 years female without risk factors, controlled hypertension, without allergic or surgical history, assigned to the outpatient clinic with hepatobiliary ultrasound that reports hypoechoic, multiple images in the hepatic parenchyma, gallbladder and extrahepatic bile duct without alterations, the intrahepatic bile duct with multiple ectasias that deform the gland. It is protocolized for primary tumor search thinking about metastatic disease, basic paraclinical without alterations, liver function tests without alterations, normal tumor markers, normal panndoscopy and colonoscopy. Magnetic cholangiography is performed, which in T2 sequence shows multiple hyperintense images, alternating with areas of low signal uptake and in spin echo sequence with T2 reinforcement hyperintense images are identified coinciding with cystic lesions that cover more than 90% of the hepatic gland. Multiple biliary hamartomatosis had been considered and managed as benign behavior pathology, however, experience, technological progress and its relationship with the development of cholangiocarcinoma makes us question the need to consider its surgical treatment, including liver transplantation.