Free radical biology for medicine: learning from nonalcoholic fatty liver disease

Abstract

Reactive oxygen species, when released under controlled conditions and limited amounts, contribute to cellular proliferation, senescence, and survival by acting as signaling intermediates. In past decades there has been an epidemic diffusion of nonalcoholic fatty liver disease (NAFLD) that represents the result of the impairment of lipid metabolism, redox imbalance, and insulin resistance in the liver. To date, most studies and reviews have been focused on the molecular mechanisms by which fatty liver progresses to steatohepatitis, but the processes leading toward the development of hepatic steatosis in NAFLD are not fully understood yet. Several nuclear receptors, such as peroxisome proliferator-activated receptors (PPARs) α/γ/δ, PPARγ coactivators 1α and 1β, sterol-regulatory element-binding proteins, AMP-activated protein kinase, liver-X-receptors, and farnesoid-X-receptor, play key roles in the regulation of lipid homeostasis during the pathogenesis of NAFLD. These nuclear receptors may act as redox sensors and may modulate various metabolic pathways in response to specific molecules that act as ligands. It is conceivable that a redox-dependent modulation of lipid metabolism, nuclear receptor-mediated, could cause the development of hepatic steatosis and insulin resistance. Thus, this network may represent a potential therapeutic target for the treatment and prevention of hepatic steatosis and its progression to steatohepatitis. This review summarizes the redox-dependent factors that contribute to metabolism alterations in fatty liver with a focus on the redox control of nuclear receptors in normal liver as well as in NAFLD.

Status of and candidates for cell therapy in liver cirrhosis: overcoming the “point of no return” in advanced liver cirrhosis

“…Damage to hepatocytes and cholangiocytes and the subsequent inflammatory response induce activated myofibroblasts. Antiviral therapy for hepatitis B and C virus infection and antioxidants such as vitamin E are the typical treatments for NASH [22,23]. In this context, many strategies, including a small molecule antagonist of NADPH oxidase [24] and a carbohydrate molecule that inhibits galectin-3 [25], are currently being evaluated in animal and human trials.…”

Oxidative stress caused by a SOD1 deficiency ameliorates thioacetamide-triggered cell death via CYP2E1 inhibition but stimulates liver steatosis

“…Introduction liver disease (NAFLD), a common chronic liver disease that is increasing worldwide (Serviddio et al 2013). Among a variety of etiology, elevated stress in the liver is a common underlying factor in the pathogenesis of NAFLD.…”

The mitochondrial-targeted antioxidant, MitoQ, increases liver mitochondrial cardiolipin content in obesogenic diet-fed rats

“…Linoleic acid is the primary 617 fatty acid constituent of CL as it represents up to 50% to 70% of CL acyl 618 chains in the liver [18]. In order for CL to achieve its specific acyl compo- MitoQ compared to HF maybe reflecting amelioration of mitochondrial 648 function as this has been already suggested [10].…”