(2e-4e-6e-10e)-3-7-11-15-tetramethyl-2-4-6-10-14-hexadecapentaenoic-acid and Liver-Diseases

The poor prognosis for patients with hepatocellular carcinoma (HCC) is associated with its high rate of recurrence in the cirrhotic liver. Therefore, more effective strategies need to be urgently developed for the chemoprevention of this malignancy. The malfunction of retinoid X receptor α, a retinoid receptor, due to phosphorylation by Ras/mitogen-activated protein kinase is closely associated with liver carcinogenesis and may be a promising target for HCC chemoprevention. Acyclic retinoid (ACR), a synthetic retinoid, can prevent HCC development by inhibiting retinoid X receptor α phosphorylation and improve the prognosis for this malignancy. Supplementation with branched-chain amino acids (BCAA), which are used to improve protein malnutrition in patients with liver cirrhosis, can also reduce the risk of HCC in obese cirrhotic patients. In experimental studies, both ACR and BCAA exert suppressive effects on HCC development and the growth of HCC cells. In particular, combined treatment with ACR and BCAA cooperatively inhibits the growth of HCC cells. Furthermore, ACR and BCAA inhibit liver tumorigenesis associated with obesity and diabetes, both of which are critical risk factors for HCC development. These findings suggest that pharmaceutical and nutraceutical approaches using ACR and BCAA may be promising strategies for preventing HCC and improving the prognosis of this malignancy.

Topics: Amino Acids, Branched-Chain; Carcinoma, Hepatocellular; Chronic Disease; Clinical Trials as Topic; Dietary Supplements; Humans; Liver Diseases; Liver Neoplasms; Phosphorylation; Retinoid X Receptor alpha; Retinoid X Receptors; Retinoids; Tretinoin

A study was conducted to examine the inhibitory effect of acyclic retinoid (polyprenoic acid) on the secretion of alpha-fetoprotein (AFP) in rats with chronic liver damage induced by CCl4. Oral administration of the compound brought about a significant reduction of serum AFP levels at the time when liver cirrhosis was formed. Acyclic retinoid also decreased the activities of serum aminotransferases and ornithine carbamyl transferase, while it increased serum albumin levels, demonstrating the reduction of hepatic parenchymal damage. Significant negative correlation was observed between serum AFP and albumin levels. This cytoprotective effect of the retinoid on the parenchymal cell may well be related to the inhibition of the synthesis and/or secretion of AFP. No significant side effect was observed, despite a long-term administration of the compound. The present finding will provide a potential scope for the future use of acyclic retinoid for the treatment of chronic liver damage.

Topics: alpha-Fetoproteins; Animals; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Liver; Liver Diseases; Male; Ornithine Carbamoyltransferase; Rats; Rats, Inbred Strains; Serum Albumin; Tretinoin