A 90 day chronic toxicity study of Nigerian herbal preparation DAS-77 in rats

BMC Complementary and Alternative Medicine

Olufunmilayo O Adeyemi¹  Chidozie C Anunobi²  Olufunsho Awodele¹  Abidemi J Akindele¹  Saheed O Afolabi¹ 

[1] Department of Pharmacology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Lagos, P. M. B, 12003, Nigeria;Department of Morbid Anatomy, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Lagos, P. M. B, 12003, Nigeria

关键词: Chronic toxicity;    Acute toxicity;    Toxicological assessment;    Herbal preparation;    DAS-77;   

Others  :  1232136
DOI  :  10.1186/1472-6882-12-79

 received in 2012-01-17, accepted in 2012-06-15,  发布年份 2012

【 摘 要 】

Background

The herbal preparation DAS-77, used for the treatment of various ailments in Nigeria, contains the milled bark of Mangifera indica L. and root of Carica papaya L. Toxicological assessment of the preparation was carried out in this study.

Methods

In the acute toxicity study, DAS-77 was administered to mice p.o. up to 20 g/kg in divided doses and i.p. at 250–3000 mg/kg. Mortality within 24 h was recorded. In the chronic toxicity study, rats were treated p.o. for 90 days at doses of 80, 400 (therapeutic dose, TD) and 2000 mg/kg. By 90 days, animals were sacrificed and blood samples collected for hematological and biochemical analysis. Organs were harvested for weight determination, antioxidants and histopathological assessments.

Results

DAS-77 did not produce any lethality administered p.o. up to 20 g/kg in divided doses but the i.p. LD₅₀ was 1122.0 mg/kg. At TD, DAS-77 produced significant (p < 0.05) reductions in body weight, food intake and K⁺, and increases in ovary weight, neutrophils and HDL, which were reversible. Histopathological presentations were generally normal. Effects at the other doses were comparable to those at TD except for reversible increases in antioxidants in the liver, kidney and testes, and sperm abnormality, and reductions in liver enzymes, sperm motility and count.

Conclusions

Findings in this study revealed that DAS-77 is relatively safe with the potential for enhancing in vivo antioxidant activity. However, possibly reversible side-effects include electrolyte imbalance and sterility in males.

【 授权许可】

   
2012 Afolabi et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Heber D: Foreword. In PDR for Herbal Medicines. Fourthth edition edition. Montvale, NJ: Thomson Health care Inc; 2007.
• [2]Wambebe C: Development of standardized phytomedicines in Africa. J Pharm Res Dev 1998, 3:1-11.
• [3]Gilani AH, Rahman Atta-ur: : Trends in ethnopharmacology. J Ethnopharmacol 2005, 100(1–2):43-49.
• [4]Brevoort P: The blooming U.S. botanical market: a new overview. Herbalgram 1998, 44:33-46.
• [5]Glaser V: Billion-dollar market blossoms as botanicals take root. Nat Biotechnol 1999, 17:17-18.
• [6]Briskin DP: Medicinal plants and phytomedicines - Linking plant biochemistry and physiology to human health. Plant Physiol 2000, 124:507-514.
• [7]Adewunmi CO, Ojewole JAO: Safety of traditional medicines, complementary and alternative medicines in Africa. Afr J Tradit Complement Altern Med 2004, 1:1-3.
• [8]Adeyemi OO, Akindele AJ, Nwumeh KI: Acute and subchronic toxicological assessment of Byrsocarpus coccineus Schum. and Thonn. (Connaraceae) aqueous leaf extract. Int J Appl Res Nat Prod 2010, 3(2):1-11.
• [9]Fennell CW, Lindsey KL, McGaw LJ, Sparg SG, Stafford GI, Elgorashi EE, Grace OM, van Staden J: Assessing African medicinal plants for efficacy and safety: pharmacological screening and toxicology. J Ethnopharmacol 2004, 94:205-217.
• [10]Ibarrola DA, Hellión-Ibarrola MC, Montalbetti Y, Heinichen O, Alvarenga N, Figueredo A, Ferro EA: Isolation of hypotensive compounds from Solanum sisymbriifolium. J Ethnopharmacol 2000, 70:301-307.
• [11]Ahmed M, Khan MA, Arshad M, Zafar M: Ethnophytotherapical approaches for the treatment of diabetes by the local inhabitants of district Attock (Pakistan). Ethnobotanical Leaflets 2006, 10:41-48.
• [12]Perera LMS, Escobar A, Souccar C, Remigio MA, Mancebo B: Pharmacological and toxicological evaluation of Rhizophora mangle L., as a potential antiulcerogenic drug: Chemical composition of active extract. J Pharmacognosy Phytother 2010, 2(4):56-63.
• [13]National Research Council: A Guide for the Care and Use of Laboratory Animals. A report of the Institute of Laboratory Animal Resources Committee on Care and Use of Laboratory Animals. National Institutes of Health Publication No. 85-23. Washington D.C: National Academy Press; 1985.
• [14]Harborne JB: Phytochemical methods. London: Chapman and Hall, Ltd.; 1973.
• [15]Trease GE, Evans WC: Pharmacognsy. Eleventhth edition. Brailliar Tiridel Can: Macmillian Publishers; 1989.
• [16]Edeoga HO, Okwu DE, Mbaebie BO: Phytochemical constituents of some Nigerian medicinal plants. Afri J Biotechnol 2005, 4(7):685-688.
• [17]Litchfield JT, Wilcoxon F: A simplified method of evaluating dose effect experiment. J Pharmacol Exp Ther 1949, 96:99-113.
• [18]Adeyemi OO, Akindele AJ, Ogunleye EA: Evaluation of the antidiarrhoeal effect of Sanseviera liberica Gerome & Labroy (Agavaceae) root extract. J Ethnopharmacol 2009, 123:459-463.
• [19]Yemitan OK, Adeyemi OO: Toxicity studies of the aqueous root extract of Lecaniodiscus cupanioides. Nigerian J Health Biomed Sci 2004, 3:20-23.
• [20]Amida MB, Yemitan OK, Adeyemi OO: Toxicological assessment of the aqueous root extract of Sanseviera liberica Gerome and Labroy (Agavaceae). J Ethnopharmacol 2007, 113:171-175.
• [21]Cheesbrough M: Examination of semen. In District laboratory practice in tropical countries (Part 2). UK. UK: Cambridge University Press; 2000:130-132.
• [22]Baginsky ES, Marie SS, Clark WL, Zak B: Direct microdetermination of calcium. Clinica Chimiya Acta 1973, 46:49-54.
• [23]Cheesbrough M: District Laboratory Practice in Tropical Countries, Part 2. UK: Cambridge University Press; 2004.
• [24]Ikewuchi JC, Onyeike EN, Uwakwe AA, Ikewuchi CC: Effect of aqueous extract of the leaves of Acalypha wilkesiana ‘Godseffiana’ Muell Arg (Euphorbiaceae) on the hematology, plasma biochemistry and ocular indices of oxidative stress in alloxan induced diabetic rats. J Ethnopharmacol 2011, 137:1415-1424.
• [25]Ogli SA, Enyikwola O, Odeh SO: Evaluation of the efficacy of separate oral supplements compared with the combined oral supplements of vitamins C and E on sperm motility in Wistar rats. Niger J Physiol Sci 2009, 24:129-135.
• [26]Sedlak J, Lindsay RH: Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 1968, 25:1192-1205.
• [27]Sun M, Zigma S: An improved spectrophotometric assay of superoxide dismutase based on ephinephrine antioxidation. Anal Biochem 1978, 90:81-89.
• [28]Buege JA, Aust SD: Microsomal lipid peroxidation. Methods Enzymol 1978, 52:302-310.
• [29]Soon YY, Tan BKH: Evaluation of the hypoglycemic and antioxidant activities of Morinda officinalis in streptozocin-induced diabetic rats. Singapore Med J 2002, 43:077-085.
• [30]Gornall AG, Bardawill CJ, David MM: Determination of serum proteins by means of the biuret reaction. J Biol Chem 1949, 177(2):751-766.
• [31]Galigher AE, Kozloff EN: Essentials of Practical Microtechniques. Secondth edition edition. Philadelphia: Lea and Febiger; 1971:77.
• [32]Habbu PV, Shastry RA, Mahadevan KM, Joshi H, Das SK: Hepatoprotective and antioxidant effects of Argyreia speciosa in rats. Afri J Tradit Complement Altern Med 2008, 5:158-164.
• [33]Seeff LB, Lindsay KL, Bacon BR, Kresina TF, Hoofnagle JH: Complementary and alternative medicine in chronic liver disease. Hepatology 2001, 34(3):595-603.
• [34]Clarke EG, Clarke ML: Veterinary Toxicology. London: Cassel and Collier Macmillian Publishers; 1977:268-277.
• [35]Gupta AK, Hasler P, Holzgreve W, Hahn S, Hasler P, Holzgreve W, Hahn S: Neutrophil NETs: a novel contributor to preeclampsia-associated placental hypoxia? Semin. Immunopathol 2007, 29(2):163-167.
• [36]Greenberg JS, Bruess CE, Conklin SC: Exploring the dimensions of human sexuality. Thirdth edition. Boston: Jones & Bartlett; 2007:136-137.
• [37]McCall MR, Frei B: Can antioxidant vitamins materially reduce oxidative damage in humans? Free Rad Biol Med 1999, 26:1034-1053.
• [38]Knapp P: Amphetamine and addiction. J Nerv Ment Disord 1952, 115:406-409.
• [39]Barter P, Gotto AM, LaRosa JC, Maroni J, Szarek M, Grundy SM, Kastelein JJP, Bittner V, Fruchart J-C: HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. New Engl J Med 2007, 357(13):1301-1310.
• [40]Gaetani G, Ferraris A, Rolfo M, Mangerini R, Arena S, Kirkman H: Predominant role of catalase in the disposal of hydrogen peroxide within human erythrocytes. Blood 1996, 87(4):1595-1599.
• [41]Gaze DC: The role of existing and novel cardiac biomarkers for cardioprotection. Curr Opin Investig Drugs 2007, 8(9):711-717.
• [42]Giboney PT: Mildly elevated liver transaminase levels in asymptomatic patient. Am Fam Physician 2005, 71(6):1105-1110.