geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Effects of nifurtimox, benznidazole, and beta-lapachone on the metabolism of DNA, RNA and proteins in Trypanosoma cruzi


, : Effects of nifurtimox, benznidazole, and beta-lapachone on the metabolism of DNA, RNA and proteins in Trypanosoma cruzi. Revista Argentina de Microbiologia 15(4): 193-204

Nifurtimox and benznidazole have trypanostatic actions in vitro and inhibit the incorporation of [3H] thymidine, [3H] uridine and L-[3H] leucine in T. cruzi macromolecules. The effect of nifurtimox may be explained by (a) direct inhibition of nucleic acid biosynthesis, or (b) generation of the oxygen radicals in T. cruzi and therefore, only mechanism (a) should be valid. In order to obtain more information on the action of these drugs on T. cruzi, in the present study we examined the effect of nifurtimox and benznidazole on DNA, RNA and protein turnover in epimastigote (culture) forms of the parasite. Complementary experiments were performed with beta-lapachone that, like nifurtimox, generates oxygen radicals in T. cruzi. Epimastigotes (Tulahuen strain) at the exponential-phase of growth were cultured with [3H] thymidine, [3H] uridine or L-[3H] leucine to label DNA, RNA and protein, respectively. After incubation, the cells were washed free of radioactive precursor, resuspended in fresh medium and reincubated at 30 degrees C with nifurtimox (10 or 100 microM), benznidazole (38 or 380 microM) or beta-lapachone (1.6 or 7.8 microM), for 1-3 hours. Controls were incubated without drug. At one hour time intervals, sampler were taken, washed free of medium and filtered through 0.45 microns Metricel filters. The filters were washed with 10% trichloroacetic acid to remove the acid soluble material, and after drying, the radioactivity incorporated in DNA, RNA and protein was counted with a scintillation counter. The results show that after elimination of the labelled precursors, 3H activity in DNA, RNA and protein decayed as a function of the time of incubation. Nifurtimox, benznidazole and beta-lapachone, stimulated in all cases they decay of the incorporated radioactivity. Calculation of "half-life" values for DNA, RNA and protein(s) indicated that nifurtimox and beta-lapachone exerted their greatest effects on DNA while benznidazole increased the decay of DNA, RNA and protein to about the same extent. Taking into account the effects of nifurtimox and beta-lapachone on DNA stability, specific lesions (single-strand breaks) were investigated in DNA from control, nifurtimox, benznidazole or beta-lapachone treated epimastigotes. The number of single-strand breaks was (per 10(6)b) 25 with 100 microM nifurtimox, 1.4 with 380 microM benznidazole and 45 with 7.8 microM g-lapachone. Interestingly enough, after reincubation of nifurtimox-damaged epimastigotes in fresh medium for 24 hours, recovery of DNA lesions could be observed.(ABSTRACT TRUNCATED AT 400 WORDS)

US$29.90

PMID: 6086046


Other references

Neumayer H H.; Seher Thos U.; Blossei M.; Wagner K., 1988: Effect of human atrial natriuretic factor anf on postischemic acute failure in conscious dogs. Kidney International 33(1): 363

Teuscher, G.W., 2001: Communication is often illusory. Asdc Journal of Dentistry for Children 67(6): 384, 382-384, 382

Machemer, R., 1973: Subtotal vitrectomy through the pars plana. Transactions - American Academy of Ophthalmology and Otolaryngology. American Academy of Ophthalmology and Otolaryngology 77(2): Op198-Op201

Ebert, E.C.; Roberts, A.I., 2001: Differential regulation of IFNgamma and TNFalpha production by lamina propria lymphocytes as evidenced by IL-12-responsiveness and utilization of the CD40/CD154 interaction. Gastroenterology 120(5 Supplement 1): A 191, April

Larner Ken; Hale Dave; Zinkham Sharon Misener; Hewlett Charles, 1982: Desired seismic characteristics of an air gun source. Marine seismic data are generally contaminated with both 'bubble pulses' and 'tow noise.' Air gun sources are deployed in arrays designed to reduce the effective level of the bubble pulses. Because the signal from a source arra...

Xu, H.; Zhu, Y.S.; Huang, Y., 2004: Treatment of severe pain caused by herpes zoster of the head and face by blocking the astroganglion. Shanghai Kou Qiang Yi Xue 8(2): 107-107

Pearsall, D.J.; Costigan, P.A., 1999: The effect of segment parameter error on gait analysis results. The extent to which errors in predicting body segment parameters (SP) influence biomechanical analysis of human motion is unclear. Therefore, the current study quantitatively evaluated the differences in SP estimates using literature predictive fu...

Dragu, E.; Dănilă, M.M., 1980: Personality, Psychological characteristics of the third age. Viata Medicala; Revista de Informare Profesionala Si Stiintifica A Cadrelor Medii Sanitare 28(7): 145-148

D.Buendia, Primavara Grigoriu, 1998: Search for DNA repair pathways in Drosophila melanogaster. The knowledge about the existence of different pathways for the repairing of DNA lesions has made possible a better understanding of mutation processes. The double mutant method has been shown to be useful for grouping rad mutants in yeast. Throug...

Heneka, M.T., 2014: Macrophages derived from infiltrating monocytes mediate autoimmune myelin destruction. Journal of Experimental Medicine 211(8): 1500-1500