**5. Oligoelements**

104 Liver Regeneration

and position of the methyl groups in the chromanol ring, designated as α, β, ∂, and (Figure

This vitamin forms part of the essential vitamins; thus, it should be acquired by means of its consumption in the daily diet. The distinct forms of vitamin E are not interchangeable among themselves in humans; in addition, they present distinct metabolic behaviors; therefore, other existing forms do not convert into α-tocopherol at any time and do not contribute to covering the vitamin E requirement. One of the main functions of α-tocopherol is that of its being a lipid antioxidant; on the other hand, it diminishes the production of thromboxanes and prostaglandins, is capable of inducing apoptosis directly or indirectly in tumor cells, modulates microsomal enzyme activity, inhibits protein kinase C activity, functions as a genetic regulator at the messenger RNA (mRNA) level, modulates the immunitary response during oxidative stress, and intervenes in the processes of fetal development and gestation, as well as in the processes of the formation of elastic and collagen fibers of the connective tissues, and in addition promotes the normal formation of erythrocytes; thus, the importance of this vitamin (Morales-González, 2009; Sayago, 2007).

Fig. 3. In tocopherol structure, the alpha (α) homologue possesses four methyl groups in

**CH3**

**α- Tocopherol**

**CH3 CH3**

Vitamin E is principally absorbed in the small intestine, with biliary secretion and micelle solubilization as indispensible. The bile acids, proceeding from the liver and segregated in the small intestine, favor the formation of micelles and facilitate the action of pancreatic lipases on lipids. Absorption of vitamin E within the erythrocyte is a passive process; αtocopherol and non-esterized -tocopherol are incorporated into the kilomicrons and for transport to the liver, in which the alpha-Tocopherol transfer protein (α-TTP) binds to the natural α-tocopherol stereoisomer or to the Golgi apparatus to incorporate it into Very-lowdensity lipoproteins (VLDL), from which is transferred to other circulating lipoproteins such as High-density (HDL) and Low-density lipoproteins (LDL) during their catabolism by the Lipoprotein lipase (LPL). LPL can also act on HDL and LDL in order for vitamin E to be able

α-Tocopherol inhibits lipid oxidation by means of two mechanisms. On the one hand, it eliminates the FR produced during peroxidation, thus inhibiting the oxidation chain reaction and, on the other hand, it acts as a singlet oxygen chelator. Polyunsaturated fatty

to accede to the peripheral tissues (Morales-González, 2009; Sayago, 2007).

3) (Morales-González, 2009).

positions 2, 5, and 7.

7

6

**HO**

8

**CH3**

5

**CH3**

**4.2 Antioxidant activity** 

**4.1 Absorption and metabolism** 

**O**

4

3

2

**CH3**

Oligoelements comprise nine micronutrients that are found in the organism in amounts of <0.01% of body weight, and are the following: iron; zinc; selenium; manganese; iodine; chromium; fluorine; copper, and molybdenum. Oligoelements are very important for the organism because they perform functions such as serving as co-factors in enzymatic systems or as vital molecular components (Morales-González, 2009).

#### **5.1 Selenium (Se)**

Selenium is localized within the group of micronutrients constituting a trace element or an essential micronutrient for all mammals. Selenium is defined as a non-volatile micromineral that fulfills numerous biological functions; thus, its best known function is its role as part of the glutathione peroxidase enzyme that protects cells from oxidative damage. Its presence in tissues such as liver, heart, lung, and pancreas is essential because it promotes the breakdown of toxic peroxides formed during metabolism, impeding cell membrane damage. Selenium protects against toxicity by means of mercury, cadmium, and silver (Morales-González, 2009; Manzanares-Castro, 2007).

#### **5.1.1 Absorption and metabolism**

Absorption is mainly carried out in the duodenum. This element enters into the body in two principal ways depending on its source: selenocysteine (in animals), and selenomethionine (in plants); once in the organism, sulfur replacement takes place in cysteine and methionine for the formation of amino acids and selenoproteins. It is excreted through the urine and when consumed in high quantities, it also can be eliminated through the breath (Manzanares-Castro, 2007).

#### **5.1.2 Antioxidant action**

Selenium (Se) possesses a potent antioxidant power, which is associated with the so-called selenoenzymes. To date, approximately 35 selenoenzymes have been described; these are proteins contain a selenocysteine residue in their active site and in which Se constitutes their enzymatic co-factor. Among the selenoenzymes, the best characterized and studied are Glutathione peroxidase (GPx) and Selenoprotein P (SePP). Another two very important enzymes are thioredoxin reductase, whose function is to reduce nucleotides during DNA synthesis, and iodothyronine deiodinase, which is responsible for the peripheral conversion

The Protective Effect of Antioxidants in Alcohol Liver Damage 107

that glycine blocks the activation of Kupffer cells, which produce FR. Likewise, glycine exercises an ascorbate oxidation protector effect by means of cupric ions; consequently, it diminishes hydroxyl radical generation. In addition to this, glycine forms part of glutathione, tripeptidic and intracellular, that combats FR and maintains some essential

A group of researchers demonstrated the hepatoprotector effect of glycine and vitamin E in a study conducted in rats in which Partial hepatoctomy (PH) was practiced with subsequent administration of these antioxidants; finally, it was observed that treatment with either of the two antioxidants causes an increase in the peroxidase dismutase enzyme; it diminishes Thiobarbituric acid (TBARS) levels, exhibiting the protector effect in hepatic regeneration

Flavonoids are compounds that make up part of the polyphenols and are also considered essentials nutrients. Their basic chemical structure consists of two benzene rings bound by means of a three-atom heterocyclic carbon chain. Oxidation of the structure gives rise to several families of flavonoids (flavons, flavonols, flavanons, anthocyanins, flavanols, and isoflavons), and the chemical modifications that each family can undergo give rise to >5,000

Flavonoid digestion, absorption, and metabolism have common pathways with small differences, such as, for example, unconjugated/non-conjugated flavonoids can be absorbed at the stomach level, while conjugated flavonoids are digested and absorbed at the intestinal level by extracellular enzymes on the enterocyte brush border. After absorption, flavonoids are conjugated by methylation, sukfonation, ands glucoronidation reactions due to their biological activity, such as facilitating their excretion by biliary or urinary route. The conjugation type the site where this occurs determine that metabolite's biological action, together with the protein binding for its circulation and interaction with cellular membranes and lipoproteins. Flavonoid metabolites (conjugated or not) penetrate the tissues in which they possess some function (mainly antioxidant), or are metabolized (Morales-González, 2009).

Silymarin is a compound of natural origin extracted from the *Silybum marianum* plant, popularly known as St. Mary's thistle, whose active ingredients are flavonoids such as silybin, silydianin, and silycristin. This compound has attracted attention because of its possessing antifibrogenic properties, which have permitted it to be studied for its very promising actions in experimental hepatic damage. In general, it possesses functions such as its antioxidant one, and it can diminish hepatic damage because of its cytoprotection as well

Silymarin is an active principle that possesses hepatoprotector and regenerative action; its mechanism of action derives from its capacity to counterarrest the action of FR, which are formed due to the action of toxins that damage the cell membranes (lipid peroxidation), competitive inhibition through external cell membrane modification of hepatocytes; it forms

as due to its inhibition of Kupffer cell function (Sandoval, 2008).

**7.1.1 Antioxidant and hepatoprotector action** 

compounds identified by their particular properties (Morales-González, 2009).

biological molecules in a reduced chemical state (Morales-González, 2009).

(Parra-Vizuet et al., 2009).

**7. Flavonoids** 

**7.1 Silymarin** 

of T4 in active T3. Selenium, together with vitamin E, protects cells from peroxidation because the former destroys peroxides through the cytoplasm, while the latter prevents peroxide formation (Manzanares-Castro, 2007).

The biological role that selenium presents is based on two fundamental properties: the antioxidant protector function from oxidative damage, and immunomodulation; in this case, it had the antecedent of a study carried out in rats in whom oxidative damage was induced and by means of Selenium (Se); a significant diminution of the enzymes aspartate aminotransferse (AST), Alkaline phosphatase (ALT), and Alanine aminotransferase (ALP) was observed, as well as an improvement in the antioxidant state. The results suggested that administration of Se to hepatic tissue protects against intoxication due to its antioxidant properties (Mahfoud et al., 2010).
