Published online Mar 28, 2020. doi: 10.13105/wjma.v8.i2.78
Peer-review started: September 17, 2019
First decision: November 4, 2019
Revised: February 3, 2020
Accepted: February 28, 2020
Article in press: February 28, 2020
Published online: March 28, 2020
Processing time: 224 Days and 3.1 Hours
The liver is considered a vital organ and is the hub for multiple chemical functions, such as intermediary metabolism and the detoxification of ingested toxins, which are essential for the preservation of life, hence, the origin or the word “liver”. The liver has enormous, highly diversified catalytic potential. This enormous catalytic potential generates massive oxidative stress, which is important for the functions of the liver but is detrimental to the viability of the liver. The liver receives approximately 80% of its blood supply from the portal vein, which brings less saturated blood from the gastrointestinal tract. Hepatocytes operate in a relatively hypoxic microenvironment due to this portal inflow. The development of this hypoxic microenvironment of the liver is an important evolutionary adaptation for its detoxification function that is not recognized in the literature as a defence mechanism against the oxidative stress generated during the detoxification process. This review describes liver function in relation to its oxidative catalytic potential and the oxidative stress generated by it as well as the evolutionary defence mechanisms present in the liver against this oxidative stress to provide new insights into liver function.
Core tip: This review presents a prototypic view of the role of hypoxia as a regulator and a defence mechanism against oxidative stress in the gastrointestinal tract, including in the liver. The functional significance of having an anaerobic gut lumen for the preservation of energy sources is described in the article. Furthermore, the significance of the hepatic arterial buffer response in the maintenance of the hypoxic microenvironment of hepatocytes to regulate the oxidative stress generated by the enormous catalytic potential of the liver and other hypoxia-mediated defences against this oxidative stress are described.