TOKSISITAS AKUT ORAL DUA SENYAWA BISANTRAKUINON (+)-2,2’-EPISITOSKIRIN A DAN (+)-1,1’-BISLUNATIN [Oral Acute Toxicity of Two Bisanthraquinones (+)-2,2’-Epicytoskyrin A and (+)-1,1’-Bislunatin]

Praptiwi Praptiwi, Arif Nurkanto, Dewi Wulansari, Andria Agusta
| Abstract views: 429 | PDF views: 937

Abstract

Bisanthraquinones (+) - 2,2'-epicytoskyrin A and (+) -1,1'bislunatin produced by the endophytic fungus Diaporthe sp. GNBP-10 showed potent antibacterial activity on in-vitro test and have the opportunity to become new antibiotics candidates. The aspects of safety and toxicity of drug candidates have to be examined before applying to human. This study was conducted to determine the safety aspects of the compounds through acute oral toxicity testing in mice (Mus musculus). Acute toxicity of (+) - 2,2'-epicytoskyrin A and (+) - 1,1'-bislunatin evaluated by the method of Up and Down Procedure with limit test at a dose of 2000 mg / kg. Results of acute toxicity test showed that the LD50 of (+) - 2,2'-epicytoskyrin A and (+) - 1,1'-bislunatin were of 1638.87 mg / kg and > 2000 mg / kg respectively. Administration of (+)- 2,2'-epicytoskyrin A resulted in increased miliari multifocal hepatitis, fatty degeneration and necrosis of liver cells, and the renal tubule epithelial degeneration. Administration of (+) - 1,1'-bislunatin at a dose of 2000 mg / kg resulted in multifocal accumulation of inflammatory cells in the liver and degeneration of cells in the islets of Langerhans although not resulting in death. The administration of those compounds indicated the changes in the organs, but based on the UN/ECE classification of LD50 value showed that (+) 2,2'- epicytoskyrin A and (+) -1,1'-bislunatin included as low acute toxicity substance.

Keywords

(+)-2,2’-Epicytoskyrin A, (+)-1,1’-bislunatin, antimicrobial, oral acute toxicity.

Full Text:

PDF

References

Abdel-Daim MM, SMM Abuzead and SM Halawa. 2013. Protective Role of Spirulina platensis Against Acute Deltamethrin-Induced Toxicity in Rats,” PLOS ONE vol. 8( 9), Article ID e72991,.

Agusta, A, K Ohashi and H Shibuya. 2006, Bisanthraquinone Metabolites Produced by the Endophytic Fungus Diaporthe sp. Chemical and Pharmaceutical Bulletin 54(4), 579-582.

Agusta, A, D Wulansari, Y Jamal, A Nurkanto, Praptiwi and A Fathoni. 2015. Antibacterial Activity and Mode of Action of (+)-2,2’-Epicytoskyrin A. Microbiology Indonesia 9(1), 1-9.

Anonimous. 2001. OECD Guideline 425 for Testing of Chemicals. Acute Oral Toxicity- Up-and-Down Procedure. https://ntp.niehs.nih.gov/iccvam/suppdocs/feddocs/oecd/ oecd_gl425-508.pdf. (Diunduh 14 November2014).

Anonimus, 2015. Acute Tocixity. http://www.ilo.org/legacy/english/protection/safework/ghs/ ghsfinal/ghsc05.pdf(Diunduh 2 Februari 2015).

Arsad SS, NM Esa and H Hamzah. 2014. Histopathologic Changes in Liver and Kidney Tissues from Male Sprague Dawley Rats Treated with Rhaphidophora Decursiva (Roxb.) Schott Extract. Journal of Cytology & Histology S4: 001. doi:10.4172/2157-7099.

Canadian Center for Occupational Health and Safety. 2010. A Guide to the management Hazardous Substances. http://www.labour.gc.ca/eng/health_safety/pubs_hs/manage_guide.shtml. (Diunduh 2 April 2015).

Chowdhary K, N Kaushik, AG Coloma, and CM Raimundo. 2012. Endophytic fungi and their metabolites isolated from Indian medicinal plant. Phytochemistry Reviews 11:467-485. http://link.springer.com/article/10.1007%2Fs11101-012-9264-2#page-1 (Diunduh 2 April2015).

Churchill, J. 1990. Pet Sense. Caring for Pets and Native Fauna. Angus and Robertson Publisher. Australia. Harada T, A Enomoto, GA Boorman and RR Maronpot. 1999. Liver and Gallbladder, In: Pathology of the Mouse. RR Maronpot (Ed.), 119–83. Cache River Press, Vienna, IL.Jones TC,

Jones TC, DH Ronald and WK Norval. 2006. Veterinary Pathology p. 337. Blackwell Publishing. USA.

Kharwar RN, A Mishra, SK Gond, A Stierle and D Stierle. 2011. Anticancer Compounds Derived from Fungal Endophytes: Their Importance and Future Challenges. Natural Product Reports 28, 1208-1228.

Lu, FC. 1995. Toksikologi Dasar, 224-236. Universitas Indonesia Press. Jakarta.

Paul CW and BC Didia. 2012. The Effect of Methanolic Extract of Moringa oleifera Lam. Roots on the Histology of Kidney and Liver of Guinea Pigs. Asian Journal of Medical Sciences 4(1), 55-60.

Praptiwi, Y Jamal, A Fathoni, A Nurkanto and A Agusta. 2013. Antibacterial Activity of Bisanthraquinone (+)-1,1-Bislunatin. Microbiology Indonesia 7(4), 159-166.

Ressang, AA. 1984. Patologi Khusus Veteriner. Percetakan Bali. Denpasar.

Saidu Y, LS Bilbis, M Lawal, SA Isezuo and R A Umar. 2007. Hematotoxicity Study of the Leaf Extract of Albizia chevalieri. Biochemia Medica 17(2), 139–270.

Ueno Y, N Sato, T Ito, I Ueno, M Enomoto and H Tsunoda. 1980. Chronic Toxicity and Hepatocarcinogenicity of (+) Rugulosin, an Anthraquinoid Mycotoxin from Penicillium species: Preliminary Surveys in Mice. Journal of Toxicology and Environmental Health Sciences 5(4), 295–302 http:// www.ncbi.nlm.nih.gov/pubmed/7218376 (Diunduh 4 Desember 2014).

United Nations- Economic Commission for Europe (UN/ECE). 2003. Globally Harmonized System of Classification and Labelling of Chemicals (GHS) 7. New York and Geneva. United Nations.

Uraguchi K, M Saito, Y Noguchi, K Takahashi, M Enomoto and T Tatsuno. 1971. Chronic Toxicity and Carcinogenicity in Mice of the Purified Mycotoxins, Luteosyirin and Cyclochlorotine. Food and Cosmetics Toxicology 10, 193-207.

Zhao J, T Shan, Y Mou and L Zhou. 2011. Plant-Derived Bioactive Compounds Produced by Endophytic Fungi. Mini Reviews in Medicinal Chemistry 11, 159-168.


Refbacks

  • There are currently no refbacks.