Published online Mar 5, 2022. doi: 10.4292/wjgpt.v13.i2.11
Peer-review started: July 7, 2021
First decision: October 3, 2021
Revised: October 18, 2021
Accepted: January 19, 2022
Article in press: January 19, 2022
Published online: March 5, 2022
Processing time: 237 Days and 9.4 Hours
Chronic liver diseases are characterized by a multistep process that involves several molecules and cellular events to transform a normal parenchyma into a parenchyma with steatosis, increased collagen deposition, fibrosis, and cirrhosis. Melatonin (MLT) is a potent antioxidant molecule that is shown to have a beneficial effect in various pathological situations, due to its action against free radicals.
To reduce the generation of reactive oxygen species would be a way to slow the progression of cell damage observed in liver diseases.
To study the effects of MLT on biochemical analysis, on serum zinc levels, and on oxidative stress in rats exposed to carbon tetrachloride (CCl4), and to evaluate the expression of proteins involved in cell damage, endoplasmic reticular stress, and unfolded protein response in animals with liver injury induced by CCl4 and treated with MLT.
Twenty male Wistar rats (230-250 g) were divided into four groups: Control rats, rats treated with MLT alone, rats treated with CCl4 alone, and rats treated with CCl4 plus MLT. CCl4 was administered as follows: Ten doses every 5 d, ten every 4 d, and 7 every 3 d. MLT was administered intraperitoneally at a dose of 20 mg/kg from the 10th wk to the end of the experiment (16th wk).
Administration of CCl4 caused an increase in liver enzyme levels, a reduction in serum zinc levels, and greater oxidative stress and ER stress. MLT treatment was able to reverse the changes promoted by the toxic agent CCl4.
We conclude that MLT acts as a potent antioxidant, promoting activation of the nuclear factor Nrf2, which allows the reduction in oxidative stress. Concomitantly, we observed the restoration of serum zinc levels, which contributes to numerous hepatic cytoprotective processes. With the reduction of oxidative stress, it is possible to attenuate the ER stress and the unfolded protein response, as well as the cell damage caused by the toxic agent CCl4.
MLT may offer a promising therapeutic approach to liver diseases, given its effectiveness in the attenuation of oxidative stress. A major limitation in the application of MLT is that most of the studies were designed especially on rats. More research is needed in clinical trials to approve the potentials of this indolamine in humans.