**11. Inhibition of hepatic regeneration by ethanol**

When there is an important, functional hepatic mass loss, such as occurs in PH, the remnant tissue undergoes a regeneration process in which the removed tissue is replaced in its totality; during this process, DNA synthesis increases notably, reaching a maximal peak of 23 at 25 hours postsurgery. After PH, hepatic tissue become more vulnerable to the damage caused by consumption of xenobiotics, particularly ethanol administration, which causes damage to HR, above all in the early regenerative process phase (Morales-González et al., 2001; Morales-González et al., 1999).

Studies performed in animals in which PH was carried out suggest that the acute ethanol administration rapidly inhibits the result of the HR after surgery; this has been assessed by a frank diminution of the cell proliferation parameters in the remnant liver. Although the exact mechanism by which ethanol inhibits HR, it is reasonable to assume that this hepatotoxicity could alter the total metabolism of the regenerating liver, which includes ethanol oxidation into acetaldehyde, catalyzed by ADH, and the later conversion of this into acetate by means of the mitochondrial ALDH (Gutiérrez-Salinas, 1999).

Acute ethanol administration produces structural and biochemical changes such as partial inhibition of protein and DNA synthesis, which indicates the diminution of the mitotic index, transitory accumulation of fat, the presence of inflammation, modifications in hepatocellular organization, diminution of weight gain in the regenerating liver, and inhibition of hepatic regeneration (Morales-González et al., 2001).

Some physiological processes that are altered by ethanol are metabolite levels in serum (glucose, triglycerides, albumin, and bilirubin), in addition to causing modification of the serum activity of enzymes that reflect liver integrity (alanine and aspartate aminotransferase, lactate dehydrogenase, ornithine carbamoyltransferase, and glutamate dehydrogenase); also, on inhibiting DNA synthesis and the activity of enzymes intimately related with this process, such as Thymidine synthetase (TS) and Thymidine kinase (TK), in addition to diminution of the mitotic index (Morales-González et al., 2001).

A sole dose of ethanol is capable of significantly inhibiting the synthesis of the protein ornithine decarboxylase, in addition to causing thyrosine aminotransferase degradation, which suggests that acute ethanol consumption inhibits protein synthesis and regenerating liver activity on transcriptional levels, interfering with RNA synthesis in the nucleus (Morales-González et al., 2001; Morales-González et al., 1999).

Investigations that have been conducted have demonstrated that the acute as well as the chronic ethanol administration jeopardize the incorporation of thymidine into the DNA of hepatocytes of rats on which PH had been performed with or without diminution of the DNA contents, in addition to reporting that chronic consumption of this substance inhibits regeneration 24 hours after the PH due to delay in the induction of ornithine carbamoyltransferase activity (Yoshida et al., 1997).

It has been suggested that damage cause by FR as the product of ethanol consumption occurs at the early phase of HR; on the other hand, a transcending increase has been reported in mitochondrial lipoperoxidation of the liver in rats after PH. In the same study, a diminution was also observed in the early HR phase of mitochondrial glutathione levels (Guerrieri et al., 1998).
