Acute and Subacute Toxicity of Ruta Montana Extract to Female Rats: Effect on Liver, Kidneys and Ovaries

Authors

DOI:

https://doi.org/10.24925/turjaf.v11i10.1862-1870.5768

Keywords:

Ruta montana L., toxicity, LD50, liver, kidneys, ovaries.

Abstract

Ruta montana L. is an annual aromatic plant of the family rutaceae. Quantitative analysis of the methanolic crude extract of Ruta montana L. yielded 8.43%, whereas the qualitative analysis revealed the presence of alkaloid or coumarin. The Litchfield and Wilcoxon method calculated the LD50 of the crude methanolic extract of Ruta montana L. in Wistar albino female rats at 393.18 mg/kg. This allows the plant to be classified as moderately toxic. The subacute toxicity study of the methanolic crude extract of Ruta montana L. in female Wistar albino rats treated with 100 mg/kg (≈ 1/4 LD50) and intraperitoneally showed a significant increase in body weight of the rats treated at the 4th week. Animals treated and sacrificed after 30 days showed a disturbance of the relative mass of the organs. Biochemical parameters of hepatic function assessment showed a significant increase in PAL with elevation of AST and ALT, whereas those of renal function revealed a significant decrease in creatinine with an increase in urea. Hematologic parameters recorded a decrease in RBC, HGB and HCT. The histological sections of the treated rats reveal the existence of blood congestion in the central veins and liver tissues, foci of necrosis and steatosis in the liver, blood congestion and some glomerular atrophy in the kidneys, as well as blood congestions and developed follicles without oocytes in the ovaries.

References

Almança CCJ, Saldanhab SV, Sousaa DR, Trivilin LO, Nunesa LC, Porfírio LC, Marinhoc B. G. 2011.Toxicological evaluation of acute and sub-chronic ingestion of hydroalcoholic extract of Solanum cernuum Vell in mice. Journal of Ethnopharmacology, 138 (2): 508– 512. doi: 10.1016/j.jep.2011.09.045 .

Aragon G, Younossi ZM. 2010. When and how to evaluate mildly elevated liver enzymes in apparently healthy patients. Cleveland Clinic Journal of Medicine, 77 (3): 195-204. doi: 10.3949/ccjm.77a.09064 .

Atsamo AD, Nguelefacka TB, Dattéb JY, Kamanyia A. 2011. Acute and subchronic oral toxicity assessment of the aqueous extract from the stem bark of Erythrina senegalensis DC (Fabaceae) in rodents. Journal of Ethnopharmacology, 134(3): 697–702. doi: 10.1016/j.jep.2011.01.023.

Baxmann AC, Ahmed MS, Marques NC, Menon VB, Pereira AB, Kirsztajn GM, Heilberg IP. 2008. Influence of muscle mass and physical activity on serum and urinary creatinine and serum cystatin C. Clinical Journal of the American Society of Nephrology, 3(2):348-354. doi: 10.2215/CJN.02870707 .

Bellakhdar J. 2020. La pharmacopée marocaine traditionnelle. Médecine arabe ancienne et savoirs populaires. Casablanca : Le Fennec. ISBN 978-9920-755-22-1.

Brown PN, Murch S J, Shipley P. 2012. Phytochemical diversity of cranberry (Vaccinium macrocarponAiton) cultivars by anthocyanin determination and metabolomic profiling with chemometric analysis. Journal of Agricultural and Food Chemistry, 60(1):261- 271. doi: 10.1021/jf2033335.

Chandra P, Sachan N, Kishore K, Ghosh AK. 2012. Acute, sub-chronic oral toxicity studies and evaluation of antiulcer activity of Sooktyn in experimental animals, Journal of Advanced Pharmaceutical Technology & Research, 3(2):117-123. doi: 10.4103/2231-4040.97290.

Da Silva AFS, De Andrade JP, Bevilaqua LRM, De Souza MM, Izquierdo I, Henriques AT. Zuanazzi JAS. 2006. Anxiolytic, antidepressant and anticonvulsant-like effects of the alkaloid montanine isolated from Hippeastrumvittatum. Pharmacology, Biochemistry and Behavior, 85: 148-154. doi:10.1016/j.pbb.2006.07.027.

Diallo A. 2005. Etude de la phytochimie et des activités biologiques de Syzygium guineense Willd (Myrtaceae). PhD thesis in Pharmacy. University of Bamako, Bamako, Mali.

Frank CL. 1991. Toxicologie, données générales procédures d’évaluation, organes cibles, évaluation du risque. Paris : Masson. ISBN : 2-225-82520-3.

Ghedjati N, Mahdeb N, Bouzidi A. 2022. Acute and Subchronic Toxicity Study of Methanol Extract of the Aerial Parts of Ruta montana L. on Adult Female Wistar Rats. Tropical Journal of Natural Product Research, 6(8):1203-1209. doi.org/10.26538/tjnpr/v1i4.5.

Girish C, Koner BC, Jayanthi S, Rao KR, Rajesh B, Pradhan SC. 2009. Hepatoprotective activity of six polyherbal formulations in paracetamol induced liver toxicity in mice. Indian Journal of Medical Research, 129(5): 569-578. PMID: 19675387.

Goulle JP, Gilbert P, Christian L. 2004. Botanique, chimie et toxicologie des solanacées hallucinogènes: Belladone, Datura, jusquiame, Mandragore. Annales de toxicologie analytique, 16(1): 55- 65. doi:10.1051/ata/2004023.

Hardman JG, Limbird LE, Molinoff PB, Ruddon RW, Gilman AG. 1998. Les bases pharmacologiques de l’utilisation des médicaments, London : McGraw-Hill. ISBN : 2-7042-1326-7.

Heywood VH. 1996. Les plantes à Fleurs. Paris : Nathan. ISBN 2092410563

Hor SY, Ahmad M, Farsi E, Yam MF, Hashim MA, Lim CP, Sadikun A, Asmawi MZ. 2012. Safety assessment of methanol extract of red dragon fruit (Hylocereus polyrhizus): Acute and subchronic toxicity studies. Regulatory Toxicology and Pharmacology, 63:106–114. doi: 10.1016/j.yrtph.2012.03.006.

Kara Ali W, Ihoual S, Abidli N. 2016. Antioxidant and MDR reversal activity in resistant human ovarian cancer cells of methanolic extract from Ruta montana located in the North of Algeria. Der Pharma Chemica, 8(12): 215-223. http://derpharmachemica.com/archive.html.

Kalt W, Ryan DAJ, Duy JC, Prior RL, Ehlenfeldt M K, Vander Kloet SP. 2001. Interspecific variation in anthocyanins, phenolics, and antioxidant capacity among genotypes of highbush and lowbush blueberries (Vaccinium section Cyanococcus spp.). Journal of Agricultural and Food Chemistry, 49(10): 4761–4767. doi: 10.1021/jf010653e.

Kifayatullah M, Mohd SM, Pinaki S, Moklesur MRS, Arindam D, Sreemoy KD. 2015. Evaluation of the acute and sub-acute toxicity of the ethanolic extract of Pericampylus glaucus (Lam.) Merr. in BALB/c mice. Journal of Acute Disease, 4(4): 309–315. doi: 10.1016/j.joad.2015.06.010.

Kulkarni YA, Veeranjaneyulu A. 2012. Toxicological evaluation of the methanol extract of Gmelina arborea Roxb Bark in mice and rats. Toxicology International, 19(2):125-31. doi: 10.4103/0971-6580.97203.

Kumar G, Sharmila B, Vanitha PP, Sundararajan M, Rajasekara PM. 2004. Hepatoprotective activity of Trianthema portulacastrum L. against paracetamol and thioacetamide intoxication in albino rats. Journal of ethnopharmacology, 92(1): 37-40. doi: 10.1016/j.jep.2003.12.009.

Kurt R.1971. Chromatographie sur couches minces. Paris : Gauthier-Villars.

Lahsissene H, Kahouadj A, Tijane M, Hseini S. 2009. Catalogue des plantes médicinales utilisées dans la région de Zaër (Maroc occidental). Revue de Botanique Lejeunia, N°186. https://popups.uliege.be/0457-4184/index.php?id=710.

Landray MJ, Toescu V, Kendall MJ. 2002. The cardioprotective role of beta-blockers in patients with diabetes mellitus. Journal of Clinical Pharmacy and Therapeutics, 27(4): 233-242. doi: 10.1046/j.1365-2710.2002.00419.x.

Lazare T, Jacques DY, Michel OA. 2011. Alcoolisation chronique des rats (Rattus norvegicus) de souche Wistar à une eau-de-vie traditionnelle produit en Côte d’Ivoire (Koutoukou). Journal of Applied Biosciences, 41: 2772-2779. ISSN 1997–5902

Litchfield JT, Wilcoxon FA. 1949. A simplified method of evaluating dose effect experiments. Journal of Pharmacology and Experimental Therapeutics, 96(2): 99-113. PMID: 18152921.

Lullmann H, Mohr K, Ziegler A.1998. Atlas de poche de pharmacologie. Paris : Flammarion Médecine - Science. ISBN-10 ‏ : ‎ 2257121198.

Magdy MEG . 2013. Acute and repeated-doses (28 Days). Toxicity of thymol formulation in male albino rats. Australian Journal of Basic and Applied Sciences, 7(10): 594-601, 2013. ISSN 1991-8178.

Masri W, Belwaer I, Khlifi F, Nouioui A, Ben salah D, Amira D, Hedhili A. 2015. Acute poisoning by Ruta montana: A case report, Phytothérapie, 13(1): 36-38. doi.org/10.1007/s10298-014-0903-1.

Nussey GJ, Vuren JHJ, Du Preez HH.1995. Effects of copper on the haematology and osmoregulation of the Mozambicus tilapia, Oreochromis mossambicus (Cichlidae). Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology, 111 (3): 359-367. doi:10.1016/0742-8413(95)00063-1.

Oduola T, Adeniyi F, Ogunyemi E, Bello IS, Idowu T, Subair H. 2007. Toxicity studies on an unripe Carica papaya aqueous extract: biochemical and hematological effects in Wistar albino rats. Journal of. Medicinal Plants Research, 1(1): 001-004. doi.org/10.5897/JMPR.9001254.

Özcan M, Chaichat JC. 2005. Effect of different locations on the chemical composition of essential oils of Laurel (Laurus nobilis L.) leaves growing wild in Turkey. Journal of Medicinal Food, 8(3): 408–411. doi: 10.1089/jmf.2005.8.408.

Ozenda P. 2000. Les Végétaux : Organisation et diversité biologiquE. Paris : Dunod. ISBN : 2-10-004684-5.

Pelletier SW. 1983. Alkaloïds, Chemical, Biological Perspectives. London: Pergamon. ISBN: 9780080527000.

Pollio A, De Natale A, Appetiti E, Aliotta G, Touwaide A. 2008. Continuity and change in the mediterranean medical tradition: Ruta spp. (rutaceae) in Hippocratic medicine and present practices, Journal of Ethnopharmacology. 116(3): 469-482. doi.org/10.1016/j.jep.2007.12.013.

Quezel P, Santa S. 1963. Nouvelle flore de l’Algérie et des régions désertiques et méridionales. Paris : CNRS.

Selamoglu Z. 2018.The Natural Products and Healthy Life. Journal of Traditional Medicine Clinical Naturopathy, 7(2): 1-2. doi: 10.4172/2573-4555.1000e146.

Touati D, Atta-ur-Rahman, Ulubelen A. 2000. Alkaloids from Ruta montana .Phytochemistry , 53(2):277-279. doi: 10.1016/s0031-9422(99)00486-0.

Ulubelen A, Ertugrul L, Birman H, Yigit R, Erseven G,. Olgac V. 1994. Antifertility Effects of Some Coumarins Isolated from Ruta chalepensis and Ruta chalepensis var. Latifolia in Rodents. Phytotherapy Research, 8: 233-236. https://doi.org/10.1002/ptr.2650080409.

Voigt GL. 2000. Anemias Polychythenias. In: Voigt G, Willey (Editors). Hematology Techniques and Concepts for Veterinary Technicians. Iowa: State University Press. pp. 95–101. ISBN: 0813804914, 9780813804910 (Print).

Wagner H, Bladt S. 1996. Plant drug analysis. A thin layer chromatography atlas. Berlin: Springer-Verlag. http://dx.doi.org/10.1007/978-3-642-00574-9.

Downloads

Published

22.10.2023

How to Cite

Nadia, M., Attafi, K., Bouhouhou, S., Rima, A., & Bouzidi, A. (2023). Acute and Subacute Toxicity of Ruta Montana Extract to Female Rats: Effect on Liver, Kidneys and Ovaries. Turkish Journal of Agriculture - Food Science and Technology, 11(10), 1862–1870. https://doi.org/10.24925/turjaf.v11i10.1862-1870.5768

Issue

Section

Research Paper