Melatonin and circadian rhythms in liver diseases: Functional roles and potential therapies

Abstract

Circadian rhythms and clock gene expressions are regulated by the suprachiasmatic nucleus in the hypothalamus, and melatonin is produced in the pineal gland. Although the brain detects the light through retinas and regulates rhythms and melatonin secretion throughout the body, the liver has independent circadian rhythms and expressions as well as melatonin production. Previous studies indicate the association between circadian rhythms with various liver diseases, and disruption of rhythms or clock gene expression may promote liver steatosis, inflammation, or cancer development. It is well known that melatonin has strong antioxidant effects. Alcohol drinking or excess fatty acid accumulation produces reactive oxygen species and oxidative stress in the liver leading to liver injuries. Melatonin administration protects these oxidative stress‐induced liver damage and improves liver conditions. Recent studies have demonstrated that melatonin administration is not limited to antioxidant effects and it has various other effects contributing to the management of liver conditions. Accumulating evidence suggests that restoring circadian rhythms or expressions as well as melatonin supplementation may be promising therapeutic strategies for liver diseases. This review summarizes recent findings for the functional roles and therapeutic potentials of circadian rhythms and melatonin in liver diseases.

Pro-Oxidative Effect of KIO3 and Protective Effect of Melatonin in the Thyroid—Comparison to Other Tissues

“…Moreover, available studies show that disruption of the circadian rhythm or clock gene expression may lead to liver diseases, such as liver steatosis, inflammation or cancer development. These facts may suggest, that supplementation of melatonin not only prevents oxidative stress-induced liver damage (induced e.g., by alcohol drinking or excess fatty acid diet), but also through restoring the circadian rhythm may be a promising therapeutic strategy for liver diseases [ 59 ].…”

Melatonin inhibits proliferation, migration, and invasion by inducing ROS-mediated apoptosis via suppression of the PI3K/Akt/mTOR signaling pathway in gallbladder cancer cells

“…Melatonin is a well-known hormone that is generated by the pineal gland [ 29 ]. Recently, the antitumor effects of melatonin have gained significant attention and numerous studies reveal that melatonin exerts growth inhibition on tumor cells [ 9 , 30 , 31 ]. The potential mechanisms include stimulation of apoptosis, regulation of cancer immunity, cell cycle arrest, and modulation of pro-survival signaling [ 32 ].…”

Chondroprotective effect of melatonin and strontium ranelate in animal model of osteoarthritis

“…It was observed in the current study that its use in isolation or in association with the SR was not capable of modifying the cytoarchitecture of the hepatic and the renal tissues in experimental model of OA, which makes its utilization secure. The administration of melatonin presents several beneficial effects facing hepatic disorders, which are not limited to antioxidant effects [44].…”