Metabolic dysfunction-associated steatotic liver disease: ferroptosis related mechanisms and potential drugs

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is considered a “multisystem” disease that simultaneously suffers from metabolic diseases and hepatic steatosis. Some may develop into liver fibrosis, cirrhosis, and even hepatocellular carcinoma. Given the close connection between metabolic diseases and fatty liver, it is urgent to identify drugs that can control metabolic diseases and fatty liver as a whole and delay disease progression. Ferroptosis, characterized by iron overload and lipid peroxidation resulting from abnormal iron metabolism, is a programmed cell death mechanism. It is an important pathogenic mechanism in metabolic diseases or fatty liver, and may become a key direction for improving MASLD. In this article, we have summarized the physiological and pathological mechanisms of iron metabolism and ferroptosis, as well as the connections established between metabolic diseases and fatty liver through ferroptosis. We have also summarized MASLD therapeutic drugs and potential active substances targeting ferroptosis, in order to provide readers with new insights. At the same time, in future clinical trials involving subjects with MASLD (especially with the intervention of the therapeutic drugs), the detection of serum iron metabolism levels and ferroptosis markers in patients should be increased to further explore the efficacy of potential drugs on ferroptosis.

The clinician's view on the advantages and contradictions of the new nomenclature of steatotic liver disease: A review

“…Предложенный подход основывался на том факте, что NAFLD является главным образом следствием системной метаболической дисфункции, в частности наличия МС [1,3,[18][19][20][21]. Другим обстоятельством, которое необходимо учитывать при обсуждении данной нозологии, представляется многофакторность этиопатогенеза, который включает особенности питания и потребления алкоголя, нарушение целостности кишечного барьера и особенности микробиоты кишечника, дисфункцию субклеточных структур (митохондрий, эндоплазматического ретикулума), а также нарушение обмена веществ и/или гормональные расстройства [20,[22][23][24][25][26][27]. Выдвинуты предложения по изменению термина NAFLD с заменой определения «неалкогольная» на один из вариантов, указывающих на основной вклад в поражение печени одного из перечисленных факторов патогенеза [28,29].…”