Abstract
C57BL/10 mice develop inflammatory and necrotic changes in the liver, as well as raised serum ALT activities, after 9 days of exposure to ethanol vapour. If mice were injected twice with liposomes containing dichloromethylene diphosphonate (DMDP), with an interval of 5 days between the injections, there was complete elimination of Kupffer cells (hepatic macrophages) for a 9-day period starting 1 day after the first injection. The inflammatory and necrotic changes were significantly reduced in mice injected with liposomes containing DMDP as compared to uninjected mice or mice injected with empty liposomes; serum ALT activities were also significantly reduced. No significant difference was seen in serum tumour necrosis factor-alpha levels between the different groups. Kupffer cells therefore play a significant role in the development of the liver damage resulting from exposure to ethanol. Acetaldehyde production by Kupffer cells is one way in which these cells can damage hepatocytes and further work needs to be done to investigate this and other mechanisms.
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- Classen E., Van Rooijen N. Preparation and characteristics of dichloromethylene diphosphonate-containing liposomes. J Microencapsul. 1986 Apr-Jun;3(2):109–114. doi: 10.3109/02652048609031565. [DOI] [PubMed] [Google Scholar]
- Decker K. Biologically active products of stimulated liver macrophages (Kupffer cells). Eur J Biochem. 1990 Sep 11;192(2):245–261. doi: 10.1111/j.1432-1033.1990.tb19222.x. [DOI] [PubMed] [Google Scholar]
- Fox E. S., Broitman S. A., Thomas P. Bacterial endotoxins and the liver. Lab Invest. 1990 Dec;63(6):733–741. [PubMed] [Google Scholar]
- Goldin R. D., Wickramasinghe S. N. Hepatotoxicity of ethanol in mice. Br J Exp Pathol. 1987 Dec;68(6):815–824. [PMC free article] [PubMed] [Google Scholar]
- Hendriks H. F., Horan M. A., Durham S. K., Earnest D. L., Brouwer A., Hollander C. F., Knook D. L. Endotoxin-induced liver injury in aged and subacutely hypervitaminotic A rats. Mech Ageing Dev. 1987 Dec;41(3):241–250. doi: 10.1016/0047-6374(87)90044-3. [DOI] [PubMed] [Google Scholar]
- Lieber C. S., DeCarli L. M. Hepatotoxicity of ethanol. J Hepatol. 1991 May;12(3):394–401. doi: 10.1016/0168-8278(91)90846-4. [DOI] [PubMed] [Google Scholar]
- Martinez F., Abril E. R., Earnest D. L., Watson R. R. Ethanol and cytokine secretion. Alcohol. 1992 Nov-Dec;9(6):455–458. doi: 10.1016/0741-8329(92)90080-t. [DOI] [PubMed] [Google Scholar]
- Peters T. J., Ward R. J. Role of acetaldehyde in the pathogenesis of alcoholic liver disease. Mol Aspects Med. 1988;10(2):179–190. doi: 10.1016/0098-2997(88)90022-2. [DOI] [PubMed] [Google Scholar]
- Van Rooijen N., Kors N., vd Ende M., Dijkstra C. D. Depletion and repopulation of macrophages in spleen and liver of rat after intravenous treatment with liposome-encapsulated dichloromethylene diphosphonate. Cell Tissue Res. 1990 May;260(2):215–222. doi: 10.1007/BF00318625. [DOI] [PubMed] [Google Scholar]
- Wickramasinghe S. N., Mawas F., Hasan R., Brown I. N., Goldin R. D. Macrophages are a major source of acetaldehyde in circulating acetaldehyde-albumin complexes formed after exposure of mice to ethanol. Alcohol Clin Exp Res. 1994 Dec;18(6):1463–1467. doi: 10.1111/j.1530-0277.1994.tb01451.x. [DOI] [PubMed] [Google Scholar]
- Yamada S., Mochida S., Ohno A., Hirata K., Ogata I., Ohta Y., Fujiwara K. Evidence for enhanced secretory function of hepatic macrophages after long-term ethanol feeding in rats. Liver. 1991 Aug;11(4):220–224. doi: 10.1111/j.1600-0676.1991.tb00520.x. [DOI] [PubMed] [Google Scholar]