Alpha-lipoic acid promotes the growth of rat hepatic pre-neoplastic lesions in the choline-deficient model.

Abstract

alpha-lipoic acid (alpha-LA) is an antioxidant used in a number of conditions related to liver diseases. Herein, we investigated the effect of alpha-LA on the development of rat pre-neoplastic lesions generated by a model of hepatocarcinogenesis, which has similarities in its histopathological sequence to human hepatocellular carcinoma development with cirrhosis. Initiation of hepatocytes was achieved by treatment with a single dose of diethylnitrosamine and promotion by feeding a choline-methionine-deficient diet (CMD), with or without alpha-LA. Pre-neoplastic lesions were identified by their positivity to the placental form of glutathione S-transferase (GSTP) or to gamma glutamyl transpeptidase. alpha-LA given to rats fed a CMD for 6 weeks dramatically increased the number of GSTP-positive foci as compared with rats fed a CMD alone (96/cm(2) versus 7/cm(2)), the mean foci area (0.033 versus 0.008 mm(2)) and the percentage of GSTP-positive liver tissue (3.01 versus 0.07%). Essentially similar results were obtained after 10 weeks of treatment. Co-treatment with CMD + alpha-LA also resulted in the enhancement of fat accumulation, lipid peroxidation and hepatocyte death; increased expression of tumor necrosis factor-alpha, cytochrome 2E1 and cyclooxygenase-2, enhanced activation of c-jun N-terminal kinase and signal transducer activator of transcription 3, and chronic hepatocyte proliferation was also observed. No such effects were observed when alpha-LA was added to a choline-supplemented diet. In conclusion, administration of alpha-LA in conditions associated with hepatic damage aggravates liver injury and stimulates the development of pre-neoplastic lesions; the results also suggest caution in its use in the presence of chronic liver injury.

• Authors: Andrea Perra, Monica Pibiri, Pia Sulas, Gabriella Simbula, Giovanna Maria Ledda-Columbano, Amedeo Columbano
• Journal: Carcinogenesis (Carcinogenesis) Vol. 29 Issue 1 Pg. 161-8 (Jan 2008) ISSN: 1460-2180 [Electronic] England
• PMID: 17893235 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Thioctic Acid

Topics

• Animals
• Antioxidants (pharmacology)
• Cell Death
• Choline Deficiency (pathology)
• Lipid Peroxidation
• Liver Neoplasms (enzymology, metabolism, pathology)
• Precancerous Conditions (enzymology, metabolism, pathology)
• Rats
• Thioctic Acid (pharmacology)