Protective Effects of Plant Extracts against Isoniazid- and Nitrofurantoin-Induced Cytotoxicity in HepG2 Cells

Isoniazid와 Nitrofurantoin으로 유발되는 간 세포독성에 대한 식물추출물의 보호효과

  • Byun, Erisa (College of Pharmacy, Wonkwang University) ;
  • Jeong, Gil-Saeng (Zoonosis Research Center, Wonkwang University) ;
  • Lee, Dong-Sung (College of Pharmacy, Wonkwang University) ;
  • Li, Bin (College of Pharmacy, Wonkwang University) ;
  • Yang, Suk-Hyun (College of Pharmacy, Wonkwang University) ;
  • Beom, Jin-Seon (College of Pharmacy, Wonkwang University) ;
  • Lv, Hui-zi (Zoonosis Research Center, Wonkwang University) ;
  • An, Ren-Bo (Zoonosis Research Center, Wonkwang University) ;
  • Kim, Youn-Chul (Key Laboratory of Organism Functional Factors of the Changbai Mountain, College of Pharmacy, Yanbian University)
  • Published : 2009.06.30

Abstract

Isoniazid was discovered in 1950's and since then it has been widely used as a synthetic bactericidal agent in the treatment of tuberculosis. However, the adverse effect of isoniazid has been reported to show significant hepatotoxicity in approximately 1-2% of patients. Nitrofurantoin {1-(5-nitro-2-furfurylideneamino)-hydantoin} is a synthetic nitrofuran that is commonly used for the treatment and prophylaxis of urinary tract infections, but its use is associated with liver cirrhosis and fatal liver necrosis. Therefore, studies for natural products with protective effect on the isoniazid- and/or nitrofurantoin-induced hepatotoxcity would be valuable as the potential therapeutic use. 107 plants sources were collected at Mt. Baekdu, and extracted with methanol. These extracts had been screened for the protective effects against isoniazid- and/or nitrofurantoin-induced cytotoxicity in HepG2 cells at the both 100 and $300{\mu}g/ml$. Five methanolic extracts, Acanthopanax senticosus, Acer mono, Asparagus schoberioides, Fagopyrum tataricum, Potentilla centigrana, showed significant protective effects against isoniazidinduced hepatotoxicity. Two methanolic extracts, Acer mono and Leonurus artemisia, showed significant protective effects against nitrofurantoin-induced cytotoxicity in HepG2 cells.

Keywords

References

  1. Jim, L. K. and Gee, J. P. (1995) Adverse effects of drugs on the liver. In young, L. Y and Koda-Kimble, M. A. (ed.), Applied therapeutics: The clinical use of drugs, 26-1-26-17, Applied Therapeutics, Inc., Vancouver
  2. Mitchell, J. R., Long, M. W., Thorgeirssonm U. P. and Jollow, D. J. (1975) Acetylation rates and monthly liver function tests during on year of isoniazid preventive therapy. Chest. 68: 181-190 https://doi.org/10.1378/chest.68.2.181
  3. Edoute Y., Karmon Y., Roguin A. and Ben-Ami H. (2001) Fatal liver necrosis associated with the use of nitrofurantoin. Isr. Med. Assoc. J. 3: 382-383
  4. Grant, M. H., Duthie, S. J., Gray, A. G. and Burke, M. D. (1988) Mixed function oxidase and UDP-glucuronyltransferase activities in the human HepG2 hepatoma cell line. Biochem. Pharmacol. 37: 4111-4116 https://doi.org/10.1016/0006-2952(88)90103-7
  5. 주팅청, 옌중카이, 주서우뵤우 (2005) 백두산 식물도감, 10-12. 도서출판 일진사, 서울
  6. An, R. B., Oh, H. and Kim, Y. C. (2005) Phenolic constituents of Galla Rhois with hepatoprotective effects on tacrine- and nitrofurantoin-induced cytotoxcity in HepG2 cells. Biol. Pharm. Bull. 28: 2155-2157 https://doi.org/10.1248/bpb.28.2155
  7. Bardou, F., Raynaud, C., Ramos, C., Lsneelle, M. A. and Laneelle, G. (1998) Mechanism of isoniazid uptake in Mycobacterium tuberculosis. Microbiology 144: 2539-2544 https://doi.org/10.1099/00221287-144-9-2539
  8. Snodgrass, W., Poter, W. Z., Timbrell, J., Jollow, D. J. and Mitchell, J. R. (1974) Possible mechanism of isoniazid related hepatic injury. Clin. Res. 323: 22
  9. Barlow, P. B., Black, M., Brummer, D. L., Comstock, G. W., Dubin, I. N., Enterline, P., Gibson, M. L., Hardy, G. E., Harrel, J. A., Johnston, R. F., Kent, D. C., Marvin, V. A., Mc Caig, N. C., Mitchel, J. R., Mosley, J. W., Ogasawara, F. R., Popper, H., Reichmen, L. B. and Zillmerman, H. J. (1974) Preventive therapy of tuberculis infection. Am. Rev. Resp. Dis. 110: 371-374
  10. Shoeb, H. A., Browman, B. U., Ottolenghi, A. C. and Merola, A. J. (1985) Peroxidase mediated oxidation of isoniazid. Antimicrob. Agents. Chemother. 27:399-403
  11. Tu, Y. and McCalla, D. R. (1975). Effect of activated nitrofurans on DNA. Biochem. Biophys. Acta 402: 142-49 https://doi.org/10.1016/0005-2787(75)90032-5
  12. Carbonera, D., Angrilli, A. and Azzone, G. F. (1988) Mechanism of nitrofurantoin toxicity and oxidative stress in mitochondria. Biochim. Biophys. Acta 936: 139-147 https://doi.org/10.1016/0005-2728(88)90261-7
  13. Lim, L. O., Bortell, R. and Neims, A. H. (1986) Nitrofurantoin inhibition of mouse liver mitochondrial respiration involving NAD-linked substrates. Toxicol. Appl. Pharmacol. 84: 493-499 https://doi.org/10.1016/0041-008X(86)90254-1
  14. Okuda, T., Kimura, Y., Yoshida, T., Hatano, T., Okuda, H. and Arichi, S. (1983) Studies on the activities of tannins and related compounds from medicinal plants and drugs. I. Inhibitory effects on lipid peroxidation in mitochondria and microsomes of liver. Chem. Pharm. Bull. 31: 1625-1631
  15. Yang, H., Lee, M. K. and Kim, Y. C. (2005) Protective activities of stilbene glycosides from Acer mono leaves against $H_2O_2$-induced oxidative damage in primary cultured rat hepatocytes. J. Agric. Food Chem. 53: 4182-4186 https://doi.org/10.1021/jf050093+
  16. Yang, H., Sung, S. H. and Kim, Y. C. (2005) Two new hepatoprotective stilbene glycosides from Acer mono leaves. J. Nat. Prod. 68: 101-103 https://doi.org/10.1021/np0497907