THE STUDY OF THE ACUTE AND SUB-ACUTE ORAL TOXICITIES OF THE NEBULIZED EXTRACT OF MYRACRODRUON URUNDEUVA ALLEMÃƒO IN RABBITS
Objective: The aim of this research was to evaluate the acute and sub-acute oral toxicities of the nebulized dried extract of Myracrodruon urundeuva (NDEMU) leaf obtained by the spray drying technique on rabbits.
Methods: In the acute toxicity study, the amount of nebulized dried extract (NDE) administered was adjusted to a dose of 2000 mg/kg of leaf powder of M. urundeuva to 6 rabbits once orally and were observed for 14â€‰days. In the sub-acute study, the amount of NDEMU administered was adjusted to a dose of 2000 mg/kg/day of to 6 rabbits once daily for 30â€‰day, orally. The appearance of toxic symptoms was observed every day, followed by each rabbits' food and drink intake. Haematological and biochemical analysis were observed and statistical analysis was performed on them. The rabbits were killed at the end of the study, and their organs were weighed and examined before organ histology were evaluated.
Results: No toxic signs and no mortality were observed in the acute and sub-acute study. In the sub-acute study, the amount of dried extract administered was adjusted to a dose of 2000 mg/kg of leaf powder of M. urundeuva to 6 rabbits once daily for 30â€‰days, orally. No toxic signs and no mortality were observed. There were no significant changes (pâ€‰<â€‰0.05) in the body weights, organ weights and haemato-biochemical parameters in any of the dose levels. No related histopathological lesions were observed.
Conclusion: The results indicate that the treatment of repeated doses with the dried NDEME showed low toxicity in rabbits.
2. Lorenzi H, Matos FJA. Plantas medicinais no Brasil-nativas e exÃ³ticas. 1st ed. Nova Odessa: Instituto Plantarum; 2002.
3. Diorge JM, Shanna B, Amanda CS, MÃ¡rcia IG, Claudete R. Medicinal plants of Renisus with analgesic activity. J Crit Rev 2016;3:1-4.
4. Viana GSB, Bandeira MAM, Matos FJA. Analgesic and antiinflammatory effects of chalcones isolated from Myracrodruon urundeuva AllemÃ£o. Phytomedicine 2003;10:189-95.
5. Cecilio AB, Faria DB, Oliveira PC, Caldas S, Oliveira DA, Sobral MEG, et al. Screening of Brazilian medicinal plants for antiviral activity against rotavirus. J Ethnopharmacol 2012;141:975-81.
6. Carlini EA, Duarte-Ameida JM, Rodrigues E, Tabach R. Antiulcer effect of the pepper trees Schinustere binthifolius Raddi (aroeira-da-praia) and Myracrodruon urundeuva AllemÃ£o, Anacardiaceae (aroeira-do-sertÃ£o). Rev Bras Farmacogn 2010;20:140-6.
7. Desmarrchelier C, RomÃ£o RL, Coussio J, Ciccia G. Antioxidant and free radical scavenging activities in extracts of medicinal trees used in the Caatinga region in northeastern, Brazil J Ethnopharmacol 1999;67:69-77.
8. Cavalcante ARSM, Rodrigues LV, Menezes DB, Cunha MPSS, Goes ACAM. Tension and morphological analysis of colonic anastomosis in 10% acetic acid-induced colitis in wistar rats treated with 10% aroeira-do-sertÃ£o aqueous extract (Myracrodruon urundeuva fr. All.). Acta Cir Bras 2005;20:180-6.
9. Nobre-JÃºnior HV, Oliveira RA, Maia FD, Nogueira MAS, Moraes MO, Bandeira MAM, et al. Neuroprotective effects of chalcones from Myracrodruon urundeuva on 6-Hydroxydopamine-Induced cytotoxicity in rat mesencephalic cells. Neurochem Res 2009;34:1066-75.
10. SÃ¡ RA, Argolo ACC, NapoleÃ£o TH, Gomes FS, Santos NDL, Melo CML, et al. Antioxidant, Fusarium growth inhibition and Nasutitermes corniger repellent activities of secondary metabolites from Myracrodruon urundeuva. Int Biodeterior Biodegrad 2009;63:470-7.
11. Renata S, Valmir GS, Agna HO, JosÃ© VCJ, Islaine SS, Rui OM, et al. Standardization and stability evaluation of dry extracts of Myracrodruon urundeuva AllemÃ£o obtained by a spray drier. Int J Pharm Pharm Sci 2017;9:154-9.
12. Monteiro JM, Lins Neto EMF, Amorim ELC, Strattmann RR, AraÃºjo EL, Albuquerque UP. Tannin content in three sympatric medicinal tree species of the caatinga. Tree Magazine 2005;29:999-1005.
13. JandÃº JJB, Silva LCN, Pereira APC, Souza RM, Silva JÃºnior CA, Figueiredo RCBQ. Myracrodruon urundeuvabark: anantimicrobial, antioxidantand non-cytotoxicagent. J Med Plants Res 2013;7:413-8.
14. Almeida AC, Sobrinho EM, Pinho L, Souza PNS, Martins ER, Duarte ER, et al. Acute toxicity of leaf hydroalcoholic extracts of Lippia sidoides, Myracroduon urundeuva, Stryphnodendro nadstringens and of Caryocar brasilliense administered by intraperitoneal route. CiÃªncia Rural 2010;40:200-3.
15. Andrade F, Albuquerque CAC, Maraschin M, Silva EL. Safety assessment of yerba mate (Ilex paraguariensis) dried extract: results of acute and 90 d subchronic toxicity studies in rats and rabbits. Food Chem Toxicol 2012;50:328-34.
16. Shahina P, Anwar S, Anamica U, Vikas Y. Gas chromatography-mass spectrometry analysis of methanolic leaf extract of Cassia angustifolia Vahl. Asian J Pharm Clin Res 2016;9:111-6.
17. Gallo L, Llabot JM, Allemandi D, BucalÃ¡ V, PiÃ±a J. Influence of spray-drying operating conditions on Rhamnus purshiana (CÃ¡scarasagrada) extract powder physical properties. Powder Technol 2011;208:205-14.
18. American Chemical Society (ACS). Subcommittee on Environmental Analytical Chemistry. Guidelines for data acquisition and data quality evaluation in environmental chemistry. Anal Chem 1980;52:2242-9.
19. ICH Q2B. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation Research. Guidance for industry: ICH Q2B Validation of analytical procedures: methodology. Rockville; 1995.
20. Megha S, Neeraj M. Development and validation of stability indicating a RP-HPLC method for determination of Î²-acetyldigoxin. Int J Appl Pharm 2017;9:54-9.
21. General Guidelines for Methodologies on Research and Evaluation of Traditional Medicine. 1st ed. Geneva: World Health Organization; 2000.
22. Organisation for economic cooperation and development (OECD). Repeated dose 28-day oral toxicity test method guideline 407. In: OECD, Guidelines for testing of chemicals. Paris: Organisation for Economic Cooperation and Development; 1995.
23. Organisation for Economic Cooperation and Development (OECD). Guidelines for the Testing of Chemicals/Section 4: Health Effects Test No. 423: Acute oral toxicity-acute toxic class method. Paris: Organization for Economic Cooperation and Development; 2002.
24. Koo MH, Park YK. Investigation of flavonoid aglycones in propolis collected by two different varieties of bees in the same region. Biosci Biotechnol Biochem 1997;61:367-9.
25. MinistÃ©rio da SaÃºde, Anvisa-Brasil. ResoluÃ§Ã£o n Â° 899-Guia para ValidaÃ§Ã£o de MÃ©todos AnalÃticos e BioanalÃticos, Anvisa: BrasÃlia; 2003.
26. AgÃªncia Nacional de VigilÃ¢ncia SanitÃ¡ria. Anvisa-Brasil). FarmacopÃ©ia brasileira. 5nd ed. Anvisa: BrasÃlia; 2010.
27. Yuangang Z, Chunying L, Yujie F, Chunjian Z. Simultaneous determination of Catechin, rutin, quercetin kaempferol and isorhamnetin in the extract of sea buckthorn (Hippophae rhamnoides L.) leaves by RP-HPLC with DAD. J Pharm Biomed Anal 2006;41:714-9.
28. Marina S, Svetlana K, Trajce S. Assay of flavonols and quantification of quercetin in medicinal plants by HPLC with UV-DIODE array detection. J Liq Chromatogr Relat Technol 2001;24:2283-92.
29. Menezes MAS, Rao VSN, Fonteles MC. Antiinflammatory activity of Astronium urundeuva Fr. All. possible mechanisms involved. Braz J Med Biol Res 1985;18:861-4.
30. Clarke EGC, Clarke ML. Veterinary toxicology. 1st ed. London: Bailliere Tindall; 1975. p. 438.
31. Jahn AI, Gunzel PKH. The value of spermatology in male reproductive toxicology: do spermatologic examinations in fertility studies provide new and additional information relevant for safety assessment. Reprod Toxicol 1997;11:171â€“8.
32. Kayarohanam S, Kavimani S. Acute and sub-acute toxicity study of aqueous methanolic leaf and bark extract of dolichandrone atrovirens. Int J Pharm Sci 2015;7:63-5.
33. Al-Habori M, Al-Aghbari A, Al-Mamary M, Maker M. Toxicological evaluation of Catha edulis leaves a long-term feeding experiment in animals. J Ethnopharmac 2002;83:209-17.
34. Emanuelli MP, Lopes STA, Macel RM, Garmatz BC, Tavares MO. Toxicological evaluation of Catha edulis leaves a long-term feeding experiment in animals. J Ethnopharmac 2002;83:209â€“17.
35. Havel RJ, Kita T, Kotite L, Kane JP, Hamilton RL. Serum concentration of alkaline phosphatase, gama-glutamyl transferase, urea and creatinin in rabbits (Oryctolagus cuniculus). CiÃªncia Animal Bras 2008;9:251-5.
36. Kaneko JJ, Harvey JW, Bruss LM. Clinical biochemistry of domestic animals. 5nd ed. San Diego: Academic; 1997. p. 895-9.
37. Prabu PC, Panchapakesan S, Raj CD. Acute and sub-acute oral toxicity assessment of the hydroalcoholic extract of Withania somniferaroots in Wistar rats. Phytother 2013;27:1169â€“78.
38. Carlton WW, McGavin MD. Patologia VeterinÃ¡ria Especial de Thonson. 2nd ed. Artmed; 1998. p. 635.
39. Dobereiner J, Peixoto PV, Tokarnia CH. Experimental poisoning by Arrabidae abilabiata (Bignoniaceae) in rabbits. Pesq Vet Bras 1984;4:89-96.
40. Maxie MG. The urinary system. In: Jugg KVF, Kennedy PC, Palmer N. Pathology of domestic animals. 4nd ed. San Diego: Academic Press; 1993. p. 447-538.
41. Jones TC, Hunt RD, King NW. Patologia VeterinÃ¡ria. 1nd ed. SÃ£o Paulo: Malone; 2000. p. 586.