tretinoin and Protein-Energy-Malnutrition

Many patients with liver cirrhosis are in a state of protein and energy malnutrition and require careful nutritional support. Our research has revealed that approximately 30% of the patients have protein-energy malnutrition, 40% protein malnutrition, and 10% energy malnutrition; 20% are in a normal nutritional state. Supplementation with branched-chain amino acids alleviates chronic liver failure, improves the protein nutritional state, and subsequently prolongs survival. In contrast, therapeutic modalities for energy malnutrition have not yet been fully elucidated and await further studies. Improved survival of the cirrhotic patients essentially brings a higher incidence of hepatocellular carcinoma (HCC). A synthetic analogue of vitamin A (acyclic retinoid or 4,5-dehydrogeranyl geranoic acid) prevents at least the development of second primary tumors after curative treatment of preceding HCC. The mechanism of this cancer chemo-prevention is clonal deletion of premalignant and latent malignant cells by the retinoid. We describe our clinical experiences with these two nutritional pharmacotherapies of chronic liver diseases and review their basic mechanisms.

Topics: Amino Acids, Branched-Chain; Antineoplastic Agents; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Combined Modality Therapy; Humans; Liver Cirrhosis; Liver Failure; Liver Neoplasms; Nutritional Support; Protein-Energy Malnutrition; Randomized Controlled Trials as Topic; Survival Rate; Treatment Outcome; Tretinoin

The present study was designed to investigate the embryo-fetotoxicity of vitamin A in protein-energy malnourished animals. Retinyl palmitate (66, 99 and 132 mg/kg) suspended in corn oil was given by gavage to well-nourished and malnourished rats from gestational days 8 to 10 and cesarean sections were performed on day 20. All fetuses were weighed and examined for malformations before being prepared for skeletal evaluation. The proportion of malformed fetuses was higher in the malnourished group at each one of the three dose levels. The data indicate that malnourished animals are more susceptible to the toxic effects of retinyl esters.

Topics: Animals; Body Weight; Congenital Abnormalities; Diterpenes; Female; Hypervitaminosis A; Pregnancy; Protein-Energy Malnutrition; Rats; Rats, Inbred Strains; Retinyl Esters; Tretinoin; Vitamin A