**The Protective Effect of Antioxidants in Alcohol Liver Damage**

José A. Morales González1 , Liliana Barajas-Esparza1, Carmen Valadez-Vega1, Eduardo Madrigal-Santillán1, Jaime Esquivel-Soto2, Cesar Esquivel-Chirino2, Ana María Téllez-López1, Maricela López-Orozco1 and Clara Zúñiga-Pérez1 *1Instituto de Ciencias de la Salud, UAEH, 2Facultad de Odontología, UNAM México* 

#### **1. Introduction**

98 Liver Regeneration

Yoneda, A., Ogawa, H., Matsumoto, I., Ishizuka, I., Hase, S. & Seno, N. (1993) Structures of

797-806.

the *N*-linked oligosaccharides on porcine plasma vitronectin. *Eur. J. Biochem.*, 218,

The term antioxidant was originally utilized to refer specifically to a chemical product that prevented the consumption of oxygen (Burneo, 2009); thus, antioxidants are defined as molecules whose function is to delay or prevent the oxygenation of other molecules. The importance of antioxidants lies in their mission to end oxidation reactions that are found in the process and to impede their generating new oxidation reactions on acting in a type of sacrifice on oxidating themselves. There are endogenous and exogenous antioxidants in nature. Some of the best-known exogenous antioxidant substances are the following: β‐ carotene (pro‐vitamin A); retinol (vitamin (A); ascorbic acid (vitamin C); α‐tocopherol (vitamin E); oligoelements such as selenium; amino acids such as glycine, and flavonoids such as silymarin, among other organic compounds (Venereo, 2002).

Historically, it is known that the first investigations on the role that antioxidants play in Biology were centered on their intervention in preventing the oxidation of unsaturated fats, which is the main cause of rancidity in food (Wolf, 2005). However, it was the identification of vitamins A, C, and E as antioxidant substances that revolutionized the study area of antioxidants and that led to elucidating the importance of these substances in the defense system of live organisms (Jacob, 1996).

Due to their solubilizing nature, antioxidant compounds have been divided into hydrophilics (phenolic compounds and vitamin C) and lipophilics (carotenoids and vitamin E). The antioxidant capacity of phenolic compounds is due principally to their redox properties, which allow them to act as reducing agents, hydrogen and electron donors, and individual oxygen inhibitors, while vitamin C's antioxidant action is due to its possessing two free electrons that can be taken up by Free radicals (FR), as well as by other Reactive oxygen species (ROS), which lack an electron in their molecular structure. Carotenoids are deactivators of electronically excited sensitizing molecules, which are involved in the generation of radicals and individual oxygen, and the antioxidant activity of vitamin A is characterized by hydrogen donation, avoiding chain reactions (Burneo, 2009).

The Protective Effect of Antioxidants in Alcohol Liver Damage 101

Because vitamin A is a liposoluble vitamin, retinol digestion and absorption is intimately linked to that of lipids. Retinol esters dissolved in fat from the diet arrive in the small intestine, forming micelles with the aid of bile salts. Later, hydrolysis is produced in which the pancreatic lipase enzyme participates, acting on formed micelles, causing the absorption of 90% of dietary fats. Vitamin A, together with the additional products of enzymatic hydrolysis, enter the enterocyte after passing through the cellular membrane, whether by facilitated diffusion or passively depending on the concentrations present (Morales-

**CH2OH**

Fig. 1. The chemical structure of vitamin A is made up of a 6-carbon-atom cyclic nucleus

**Retinol**

**CH3 CH3 CH3 CH3**

**CH3**

catabolism and excretion as retinoic acid (Allende-Martínez 1997).

Carotenes as such are absorbed passively, and once in the cytoplasm, are transformed into retinol. Within the intestinal cell, the greater part of the retinol is esterified with saturated fatty acids such as palmitic acid and is incorporated in lymphatic kilomicrons, which enter into the bloodstream and are transported to the liver, where it is stored in parenchymatous cells and in the adiposites in the form of retinyl ester. The greater part of this is taken up by the hepatocytes of kilomicron fragments and is transferred in the form of light retinol to the Retinol binding protein (RBP) and toward the Kupffer cells, whose main function appears to be storage of these. When the tissues require retinol, this is transported by means of RBP and Transthyretin (TTR, prealbumin) for transport in the circulation of the target cells. The tissues are capable of taking this up through surface receptors, where the retinol is transferred to a retinol membrane binding protein and becomes a retinyl ester. Later, a hydrolase related with the membrane unfolds the latter. RBP exists in nearly all tissues; the exceptions comprise cardiac and skeletal muscle. In addition to its uptake of retinol, the RBP functions as a reservoir for cellular retinol and releases the vitamin to the appropriate sites for its conversion into active compounds. In the retina, retinol becomes 11-cis-retinal, which is incorporated into the rhodospin. In other target tissues, retinol apparently is oxidized into retinoic acid, which is transported to the nucleus. It is noteworthy that the RBP plasma concentration is crucial for regulation of the retinol in plasma and its transport to the tissues (Morales-González, 2009). In general, within the organism retinol can follow three processes; esterification and storage in the liver; conversion into active metabolites (retinal), and/or

**2.2 Digestion, absorption, and metabolism** 

González 2009).

with an 11-carbon side-chain.

The antioxidant defense system is composed of a group of substances that, on being present at low concentrations with respect to the oxidizable substrate, delay or significantly prevent oxygenation of the latter. Given that FR such as ROS are inevitably produced constantly during metabolic processes, in general it may be considered as an oxidizable substrate to nearly all organic or inorganic molecules that are found in living cells, such as proteins, lipids, carbohydrates, and DNA molecules. Antioxidants impede other molecules from binding to oxygen on reacting or interacting more rapidly with FR and ROS than with the remainder of molecules that are present in the microenvironment in which they are found (plasma membrane, cytosol, the nucleus, or Extracellular fluid [ECF]). Antioxidant action is one of the sacrifices of its own molecular integrity in order to avoid alterations in the remainder of vitally functioning or more important molecules. In the case of the exogenic antioxidants, replacement through consumption in the diet is of highest importance, because these act as suicide molecules on encountering FR, as previously mentioned (Venereo, 2002).

This is the reason that, for several years, diverse researchers have been carrying out experimental studies that demonstrate the importance of the role of antioxidants in protection and/or hepatic regeneration in animals. Thus, in this chapter, the principal antioxidants will be described that play an important role in the regeneration of hepatic cells and in the prevention of damage deriving from alcohol (Burneo, 2009; Venereo 2002).
