Melatonin application in targeting oxidative‐induced liver injuries: A review

Abstract

It is believed that oxidative stress is a key causing factor of liver damage induced by a variety of agents, and it is a major contributing factor in almost all conditions compromising liver function, including ischemia-reperfusion injury (IRI), nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), liver fibrosis, liver cirrhosis, and hepatocellular carcinoma (HCC). Liver is the organ that high concentration of melatonin (N-acetyl-5-methoxytryptamine) accumulates, and it is the sole organ where circulating melatonin is metabolized. Melatonin is one of the best antioxidants that protects liver, and its metabolites also have antioxidative function. Melatonin exerts its antioxidative function directly through its radical scavenging ability and indirectly through stimulation of antioxidant enzymes. The antioxidative response from melatonin in liver affects from various factors, including its dosage, route, time and duration of administration, the type of oxidative-induced agent and species aging. This indoleamine is also an effective and promising antioxidative choice for targeting liver IRI, NAFLD, NASH, fibrosis, cirrhosis, and HCC.

Human hepatocellular carcinoma: Protection by melatonin

“…Melatonin is a secretory product of the pineal gland and gastrointestinal tract during night and daytime, respectively (Margheri et al, ). Melatonin is responsible for a variety of physiological functions (Mortezaee, Khanlarkhani, Sabbaghziarani et al, ; Mortezaee, Sabbaghziarani et al, ), including antioxidant (Mortezaee & Khanlarkhani, ; Mortezaee et al, ; Mortezaee, Khanlarkhani, Beyer, & Zendedel, ), anti‐apoptotic (Mortezaee, Majidpoor, Daneshi, Abouzaripour, & Abdi, ), and pro‐apoptotic (Lin et al, ) activities. Melatonin is the only known chronobotic hormone for regulation of neoplastic cell growth (Blask, Sauer, & Dauchy, ).…”

“…In some situations melatonin reduces the huge amount of antioxidant enzymes generated as a response to augmented ROS production. This diverse response for melatonin is possibly due to normalizing antioxidant activity in liver (Mortezaee & Khanlarkhani, ) as well as suppressing cancer cell proliferation and promoting their apoptosis. Therefore, having both pro‐oxidative and anti‐oxidative characteristics is a unique virtue for melatonin that shows its functional versatility so as to target HCC in a meticulous manner.…”

Reduced delivery of epididymal adipocyte‐derived exosomal resistin is essential for melatonin ameliorating hepatic steatosis in mice

“…In addition to ER stress, oxidative stress and mitochondrial stress are able to initiate multiple inflammatory processes after excess fat accumulation in liver . Since high‐level resistin has a positive correlation with oxidative stress and inflammation, resistin may trigger steatosis progression into liver fibrogenesis via activating inflammatory processes . Along with obvious fat accumulation in liver, we do not detect statistical differences of multiple inflammatory, fibrosis, and cell apoptosis markers among the control, Exos resistin groups, and Exos MT groups, confirming that Exos MT ‐mediated amelioration of hepatic steatosis may be located in the upstream of oxidative stress and inflammatory processes.…”

Protective role of germinated mung bean against progression of non-alcoholic steatohepatitis in rats: A dietary therapy to improve fatty liver health

“…ROS are generated during metabolic process of the cells, if it is unchecked by antioxidant defense system, cell will incline toward oxidative stress (Alcala et al, ; Lubos, Loscalzo, & Hand, ; Mortezaee & Khanlarkhani, ). In few conditions ROS could react with nitric oxide and generate higher reactive nitrogen species (RNS) known as peroxy nitrite (Chance, Sies, & Boveris, ; Hansen et al, ; Liochev & Fridovich, ).…”