Skip to main content
Log in

Morin protects acute liver damage by carbon tetrachloride (CCl4) in rat

  • Research Articles
  • Drug Efficacy and Safety
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

The purpose of this study was to investigate possible beneficial effects of morin on CCl4-induced acute hepatotoxicity in rats. Rats received a single dose of CCl4 (150 μL/100 g 1:1 in corn oil). Morin treatment (20 mg/kg) was given at 48, 24, and 2 h before CCl4 administration. CCl4 challenge elevated serum alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) levels, but these effects were prevented by the pretreatment of rats with morin. To identify the mechanism of protective activity of morin in CCl4-induced hepatotoxicity in rats, we investigated expressions of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and inducible nitric oxide (iNOS). The expressions of TNF-α, IL-1β, IL-6, and iNOS were increased by CCl4 treatment and increased expressions of those were decreased by morin. These findings suggest that morin prevents acute liver damage by inhibiting the production of TNF-α, IL-1β, IL-6, and iNOS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Chamulitrat, W., Blazka, M. E., Jordan, S. J., Luster, M. I., and Mason, R. P., Tumor necrosis factor-alpha and nitric oxide production in endotoxin-primed rats administered carbon tetrachloride. Life Sci, 57, 2273–2280 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Dong, W., Simeonova, P. P., Gallucci, R., Matheson, J., Flood, L., Wang, S., Hubbs, A., and Luster, M. I., Toxic metals stimulate inflammatory cytokines in hepatocytes through oxidative stress mechanisms. Toxicol Appl Pharmacol, 151, 359–366 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Drotman, R. B. and Lawhorn, G. T., Serum enzymes as indicators of chemically induced liver damage. Drug Chem Toxicol, 1, 163–171 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Edwards, M. J., Keller, B. J., Kauffman, F. C., and Thurman, R. G., The involvement of Kupffer cells in carbon tetrachloride toxicity. Toxicol Appl Pharmacol, 119, 275–279 (1993).

    Article  PubMed  CAS  Google Scholar 

  • Fang, S. H., Hou, Y. C., Chang, W. C., Hsiu, S. L., Chao, P. D., and Chiang, B. L., Morin sulfates/glucuronides exert anti-inflammatory activity on activated macrophages and decreased the incidence of septic shock. Life Sci, 74, 743–756 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Galvez, J., Coelho, G., Crespo, M. E., Cruz, T., Rodriguez-Cabezas, M. E., Concha, A., Gonzalez, M., and Zarzuelo, A., Intestinal anti-inflammatory activity of morin on chronic experimental colitis in the rat. Aliment Pharmacol Ther, 15, 2027–2039 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Gutteridge, J. M., and Halliwell, B., Free radicals and antioxidants in the year 2000. A historical look to the future. Ann N Y Acad Sci, 899, 136–147 (2000).

    PubMed  CAS  Google Scholar 

  • Hierholzer, C., Harbrecht, B., Menezes, J. M., Kane, J., MacMicking, J., Nathan, C. F., Peitzman, A. B., Billiar, T. R., and Tweardy, D. J., Essential role of induced nitric oxide in the initiation of the inflammatory response after hemorrhagic shock. J Exp Med, 187, 917–928 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Hishinuma, I., Nagakawa, J., Hirota, K., Miyamoto, K., Tsukidate, K., Yamanaka, T., Katayama, K., and Yamatsu, I., Involvement of tumor necrosis factor-alpha in development of hepatic injury in galactosamine-sensitized mice. Hepatology, 12, 1187–1191 (1990).

    Article  PubMed  CAS  Google Scholar 

  • Kawabata, K., Tanaka, T., Honjo, S., Kakumoto, M., Hara, A., Makita, H., Tatematsu, N., Ushida, J., Tsuda, H., and Mori, H., Chemopreventive effect of dietary flavonoid morin on chemically induced rat tongue carcinogenesis. Int J Cancer, 83, 381–386 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Kuo, H. M., Chang, L. S., Lin, Y. L., Lu, H. F., Yang, J. S., Lee, J. H., and Chung, J. G., Morin inhibits the growth of human leukemia HL-60 cells via cell cycle arrest and induction of apoptosis through mitochondria dependent pathway. Anticancer Res, 27, 395–405 (2007).

    PubMed  CAS  Google Scholar 

  • Laughton, M. J., Evans, P. J., Moroney, M. A., Hoult, J. R., and Halliwell, B., Inhibition of mammalian 5-lipoxygenase and cyclo-oxygenase by flavonoids and phenolic dietary additives. Relationship to antioxidant activity and to iron ion-reducing ability. Biochem Pharmacol, 42, 1673–1681 (1991).

    Article  PubMed  CAS  Google Scholar 

  • Li, J., and Billiar, T. R., Nitric Oxide. IV. Determinants of nitric oxide protection and toxicity in liver. Am J Physiol, 276, G1069–G1073 (1999).

    PubMed  CAS  Google Scholar 

  • Lutz, L. M., Glende, E. A., Jr., and Recknagel, R. O., Protection by diethyldithiocarbamate against carbon tetrachloride lethality in rats and against carbon tetrachloride-induced lipid peroxidation in vitro. Biochem Pharmacol, 22, 1729–1734 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Manna, S. K., Aggarwal, R. S., Sethi, G., Aggarwal, B. B., and Ramesh, G. T., Morin (3,5,7,2′,4′-Pentahydroxyflavone) abolishes nuclear factor-kappaB activation induced by various carcinogens and inflammatory stimuli, leading to suppression of nuclear factor-kappaB-regulated gene expression and up-regulation of apoptosis. Clin Cancer Res, 13, 2290–2297 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Mizuoka, H., Shikata, N., Yang, J., Takasu, M., Inoue, K., and Tsubura, A., Biphasic effect of colchicine on acute liver injury induced by carbon tetrachloride or by dimethylnitrosamine in mice. J Hepatol, 31, 825–833 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Ocete, M. A., Galvez, J., Crespo, M. E., Cruz, T., Gonzalez, M., Torres, M. I., and Zarzuelo, A., Effects of morin on an experimental model of acute colitis in rats. Pharmacology, 57, 261–270 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Rao, P. S., Mangipudy, R. S., and Mehendale, H. M., Tissue injury and repair as parallel and opposing responses to CCl4 hepatotoxicity: a novel dose-response. Toxicology, 118, 181–193 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Shito, M., Balis, U. J., Tompkins, R. G., Yarmush, M. L., and Toner, M., A fulminant hepatic failure model in the rat: involvement of interleukin-lbeta and tumor necrosis factor-alpha. Dig Dis Sci, 46, 1700–1708 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Simpson, K. J., Lukacs, N. W., Colletti, L., Strieter, R. M., and Kunkel, S. L., Cytokines and the liver. J Hepatol, 27, 1120–1132 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Steel, D. M. and Whitehead, A. S., The major acute phase reactants: C-reactive protein, serum amyloid P component and serum amyloid A protein. Immunol Today, 15, 81–88 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Thompson, D., Whicher, J. T., and Banks, R. E., Acute phase reactants in predicting disease outcome. Baillieres Clin Rheumatol, 6, 393–404 (1992).

    Article  PubMed  CAS  Google Scholar 

  • Tiegs, G., Wolter, M., and Wendel, A., Tumor necrosis factor is a terminal mediator in galactosamine/endotoxin-induced hepatitis in mice. Biochem Pharmacol, 38, 627–631 (1989).

    Article  PubMed  CAS  Google Scholar 

  • Wu, T. W., Zeng, L. H., Wu, J., and Fung, K. P., Morin: a wood pigment that protects three types of human cells in the cardiovascular system against oxyradical damage. Biochem Pharmacol, 47, 1099–1103 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Wu, T. W., Zeng, L. H., Wu, J., and Fung, K. P., Morin hydrate is a plant-derived and antioxidant-based hepatoprotector. Life Sci, 53, PL213-8 (1993).

    Google Scholar 

  • Yang, S. Q., Lin, H. Z., Yin, M., Albrecht, J. H., and Diehl, A. M., Effects of chronic ethanol consumption on cytokine regulation of liver regeneration. Am J Physiol, 275, G696–G704 (1998).

    PubMed  CAS  Google Scholar 

  • Yu, Z., Fong, W. P., and Cheng, C. H., The dual actions of morin (3,5,7,2′,4′-pentahydroxyflavone) as a hypouricemic agent: uricosuric effect and xanthine oxidase inhibitory activity. J Pharmacol Exp Ther, 316, 169–175 (2006).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Soon-Sun Hong.

Additional information

These authors contributed equally to this article.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, H.S., Jung, KH., Hong, SW. et al. Morin protects acute liver damage by carbon tetrachloride (CCl4) in rat. Arch. Pharm. Res. 31, 1160–1165 (2008). https://doi.org/10.1007/s12272-001-1283-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12272-001-1283-5

Key words

Navigation