FETAL TOXICITY OF HYDROALCOHOLIC EXTRACT OF AGERATUM CONYZOIDES L. LEAVES (ASTERACEAE) IN RATS
Keywords:Ageratum conyzoides, Pyrrolizidine alkaloids, Fetal toxicity
Objective: Ageratum conyzoides is known to possess pharmacological and therapeutic pro perties in Africa. Some pyrrolizidine alkaloids, chemicals known to induce fetuses toxicity, have been identified in A. conyzoides. This study aims to evaluate the fetal toxicity of A. conyzoides.
Methods: Mated females were randomly assigned to three experimental groups of 8 animals each. Pregnant rats received orally 500 or 1000â€‰mg/kg of 80% hydroalcoholic extract of A. conyzoides, daily from the 17th to the 20th day of gestation. On day 21 of pregnancy, the females were sacrificed. Laparotomy was performed and uterine horns were removed. The number of implants, resorptions, and dead and live fetuses was then recorded. The ovaries were also observed and the corpora lutea were counted.
Results: No visible signs of toxicity were observed in females and their pups throughout the study period. However, A. conyzoides (500 and 1000 mg/kg) caused a significant decrease (p<0.01) of fetal weight compared with the control. For the implantation, resorption and morta-lity there was no significant difference between groups.
Conclusion: The administration of hydroalcoholic extract of A. conyzoides to female rats in late pregnancy is toxic to the fetuses. This fetal toxicity can be due to the oxidative stress induced by pyrrolizidine alkaloids present in this plant.
Bull LB, Dick AT. The chronic pathological effects on the liver of the rat of the pyrrolizidine alkaloids heliotrine, lasiocarpine, and their N-oxides. J Pathol Bacteriol 1959;78:483-502.
Willmott FC, Robertson GW. Senecio disease or cirrhosis of the liver due to Senecio poisoning. Lancet 1920;23:848-9.
Milenkov SM, Kizhaikin Y. Toxic hepatitis with ascites. Proc Sympos V M Molotov Med Inst; 1952.
Mohabbat O, Srivastava RN, Younos MS, Sediq GG, Menzad AA, Aram GN. An outbreak of hepatic veno-occlusive disease in north-western afghanistan. Lancet 1976;7:269-71.
Chauvin P, Dillon J-C, Moren A. Ã‰pidÃ©mie dâ€™intoxication alimen-taire Ã¡ lâ€™hÃ©liotrope, Tadjikistan, Novembre 1992-Mars 1993. Cahiers SantÃ© 1994;4:263-8.
Fu PP, Yang YC, Xia Q, Chou MW, Cui YY, Lin G. Pyrrolizidine Alkaloids-tumorigenic components in Chinese herbal medi-cines and dietary supplements. J Food Drug Anal 2002a;10:198â€“210.
Fu, PP, Xia Q, Lin G, Chou MW. Genotoxic pyrrolizidine alkalo-ids-mechanisms leading to DNA adduct formation and tumori-genicity. Int J Mol Sci 2002b;3:948â€“64.
Quijano L, Calderson JS, Gomez GF, Soria IE, Rios T. Highly oxygenated flavonoids from Ageratum conyzoides. Phytochemistry 1980;19:2439-42.
Roeder E. Medicinal plants in China containing pyrrolizidine alkaloids. Pharmazie 2000;55:711-26.
Abena AA, Ouamba JM, Keita A. Anti-inflammatory, analgesic and antipyretic activities of essential oil of Ageratum con-yzoides. Phytother Res 1996;10:S164-S65.
Igoli JO, Ogaji OG, Tor-Anyiin TA, Igoli NP. Traditional medicine practice amongst the igede people of Nigeria. Part II. Afr J Tradit Complementary Altern Med 2005;2:134-52.
Diallo A, Eklu-Gadegbeku K, Agbonon A, Aklikokou K, Creppy EE, Gbeassor M. Acute and sub-chronic (28-day) oral toxicity studies of hydroalcoholic extract of Ageratum conyzoides L. (Asteraceae) leaves. Trop J Pharmacol Res 2010;9(5):463-67.
Moura ACA, Silva ELF, Fraga MCA, Wanderley AG, Afiatpour P, Maia MBS. Anti-inflammatory and chronic toxicity study of leaves of Ageratum conyzoides L. in rats. Phytomedicine 2005;12:138-42.
Okunade AL. Review: Ageratum conyzoides L. (Asteraceae). Fitoterapia 2002;2:1-16.
Smith LW, Culvenor CC. Plant sources of hepatotoxic pyrrolizi-dine alkaloids. J Nat Prod 1981;44:129-52.
Diallo A, Eklu-Gadegbeku K, Agbonon A, Napo Koura G, Akliko-kou K, Creppy EE, et al. Repeated-dose toxicological studies of hydroalcoholic extract of Lannea kerstingii Engl and K. Krause (Anacardiaceae) and identification of toxicity mechanism. Int J Pharm Sci Res 2015;6(2):1000-8.
Amacher DE, Schomaker SJ, Boldt SE, Mirsky M. The relation-ship among microsomal enzyme induction, liver weight and histological change in cynomolgus monkey toxicology studies. Food Chem Toxicol 2006;44:528-37.
Juberg DR, Mudra DR, Hazelton GA, Parkinson A. The effect of Fenbuconazole on cell proliferation and enzyme induction in the liver of female CD1 mice. Toxicol Appl Pharmacol 2006;214:178-87.
Diallo A, Divakar S, Venkadesh G, Syamala GJ, Eklu-Gadegbeku K, Ramanathan M, et al. Edmond. In vitro and in vivo genotoxicity assessment of total alkaloids of Ageratum conyzoides L. (Asteraceae) leaves by alkaline comet assay. Int J Pharm Sci Res 2015;6(7):1000-7.
Rasenack R, MÃ¼ller C, Kleinschmidt M, Rasenack J, Wiedenfeld H. Veno-occlusive disease in a fetus caused by pyrrolizidine al-kaloids of food origin. Fetal Diagn Ther 2003;18(4):223-5.
Guo Y, Ma Z, Kou H, Sun R, Yang H, Smith CV, et al. Synergistic effects of pyrrolizidine alkaloids and lipopolysaccharide on preterm delivery and intrauterine fetal death in mice. Toxicol Lett 2013;221(3):212-8.
OCDE. Repeated dose oral toxicity test method. In: OCDE Guidelines for testing of chemicals, N Â° 408, Organization for Economic Cooperation and Development, Paris, France; 1998.
OECD. Repeated dose oral toxicity test method. In OECD Guide-lines for testing of chemicals, N Â° 407. Organization for Eco-nomic Cooperation and Development, Paris, France; 2008.
Gleich J, Frohberg H. General teratological techniques. In: Neubert D. et al. Ed. Methods in prenatal toxicology. Evaluation of embryotoxic effects in experimental animal. Massachusetts: PSG Publishing; 1977. p. 94-102.
Kato H, Morishige WK, Rotchild I. A quantitative relationship between the experimentally determined number of conceptus-es and corpus luteum activity in pregnant rat. Endocrinol 1979;105:846-50.
Khera KS. Maternal toxicity: a possible factor in fetal malformations in mice. Teratology 1984;29:411-6.
Manson JM, Kang YJ. Test methods for assessing female repro-ductive and developmental toxicology. In: Hayes AW. Ed. Prin-ciples and Methods of Toxicology, New York: Raven Press; 1994. p. 989-1034.
Niesink RJM, de Vries J, Holliger MA. Toxicology: Principles and applications. CRC Press; 1996. p. 3-317, 694-5.
Diallo A, Kwashie Eklu-Gadegbeku, Koffi Amegbor, Amegnona Agbonon, Aklikokou K, Creppy EE, et al. In vivo and in vitro toxicological evaluation of the hydroalcoholic leaf extract of Ageratum conyzoides L. (Asteraceae). J Ethnopharmacol 2014;155(2):1214-8.
Blanco-Kelly F, Matesanz F, Alcina A, Teruel M, DÃaz-Gallo LM. CD40:novel association with Crohn's disease and replication in multiple sclerosis susceptibility. PloS One 2010:5(7):e11520.
Brocardo PS, Gil-Mohapel J, Christie BR. The role of oxidative stress in fetal alcohol spectrum disorders. Brain Res Rev 2011;67(1-2):209-25.
Dennery PA. Effects of oxidative stress on embryonic develop-ment. Birth Defects Res Part C 2007;81(3):155-62.