Pesticides plays an important role in the modern agricultural system. Methyl parathion (MP), an organophosphorus insecticide, reported to impose various adverse effects on non-target organisms, including mutagenicity. In the present study, the possible antimutagenic activity of rutin, a flavonoid with potential antioxidant activity, was assessed against MP-induced mutagenicity by employing the Ames test. Salmonella typhimurium –TA 100 was used as the test strain representing the base-pair substitution. A concentration-response toxicity was performed by selecting 0.1, 0.5 and 1.0mg/ml of MP. The protective effect of rutin was assessed at 5, 10 and 20mg/ml against 0.5mg/ml of MP-induced mutagenicity with and without metabolic activation. The results indicated that MP induced concentration-dependent mutagenicity up to 0.5mg/mL (p<0.001). However, growth inhibition was observed in the highest concentration of MP, both in the presence and absence of S9 fraction, indicating the lethality. Rutin induced a concentration-dependent decrease in the frequency of revertant colonies at a significant level up to 1.0mg/ml (p<0.05 and p<0.01) compared with that of MP-treated strains in the presence of S9 fraction. Thus, rutin has the potency to minimize the base-pair substitution induced by MP after metabolic activation, with a threshold limit.
Cite this article:
Amritha Nair, Prashantha Naik. Rutin Imparts Attenuation of Methyl Parathion-Induced Base-pair substitution. Research J. Pharm. and Tech. 2020; 13(12):5680-5684. doi: 10.5958/0974-360X.2020.00989.0
1. Pimentel D, Greiner A and Bashore T. Economic and environmental costs of pesticide use. In Environmental Toxicology 1998 (pp. 133-164). CRC Press.
2. Inter-Organization Programme for the Sound Management of Chemicals, World Health Organization. WHO Recommended Classification of Pesticides by Hazard and Guidelines to Classification 2009. World Health Organization; 2010.
3. Akhgari M, Abdollahi M, Kebryaeezadeh A, Hosseini R, and Sabzevari O. Biochemical evidence for free radicalinduced lipid peroxidation as a mechanism for subchronic toxicity of malathion in blood and liver of rats. Human and experimental toxicology. 2003; (4):205-11.
4. Sharma Y, Bashir S, Irshad M, Gupta SD and Dogra TD. Effects of acute dimethoate administration on antioxidant status of liver and brain of experimental rats. Toxicology. 2005;206(1):49-57.
5. Fortunato JJ, Feier G, Vitali AM, Petronilho FC, Dal-Pizzol F and Quevedo J. Malathion-induced oxidative stress in rat brain regions. Neurochemical research. 2006; 31(5):671-8.
6. Velazquez A, Xamena N, Creus A and Marcos R. Indication for weak mutagenicity of the organophosphorus insecticide dimethoate in Drosophila melanogaster. Mutation Research/Genetic Toxicology. 1986;172(3):237-43.
7. Argentin G, Divizia M and Cicchetti R. Oxidative stress, cytotoxicity, and genotoxicity induced by methyl parathion in human gingival fibroblasts: protective role of epigallocatechin-3-gallate. Journal of Toxicology and Environmental Health, Part A. 2015;78(19):1227-40.
8. Rashid KA and Mumma RO. Genotoxicity of methyl parathion in short‐term bacterial test systems. Journal of Environmental Science and Health Part B. 1984;19(6):565-77.
9. Coral MN, Ucman S, Hasan Y, Haydar O and Semih D. Potential neoplastic effects of parathion-methyl on rat liver. Journal of Environmental Sciences. 2009; 21(5):696-9.
10. Deman J, Van Larebeke N. Carcinogenesis: mutations and mutagens. Tumor biology. 2001;22(3):191-202.
11. Poon SL, McPherson JR, Tan P, Teh BT, Rozen SG. Mutation signatures of carcinogen exposure: genome-wide detection and new opportunities for cancer prevention. Genome medicine. 2014;6(3):24.
12. Hallenbeck W H, Cunningham-Burns K M, 1985. Pesticides and Human Health. New York: Springer-Verlag.
13. Liu J, Lin RI and Milner JA. Inhibition of 7, 12-dimethylbenz [a] anthracene-induced mammary tumors and DNA adducts by garlic powder. Carcinogenesis. 1992; 13(10):1847-51.
14. Williamson G and Manach C. Bioavailability and bioefficacy of polyphenols in humans. II. Review of 93 intervention studies. The American journal of clinical nutrition. 2005;81(1):243S-55S.
15. Scholz. Interactions affecting the bioavailability of dietary polyphenols in vivo. International journal for vitamin and nutrition research. 2007;77(3):224-35.
16. Harborne JB. Nature, distribution and function of plant flavonoids. Progress in clinical and biological research. 1986; 213:15-24.
17. M. D. Mashkovskii, Drugs [in Russian], RIA Novaya Volna, Moscow 2007, pp. 629 – 631.
18. Francis AR, Shetty TK, Bhattacharya RK. Modifying role of dietary factors on the mutagenicity of aflatoxin B1: in vitro effect of plant flavonoids. Mutation Research/Genetic Toxicology. 1989;222(4):393-401.
19. Mladenović M, Matić S, Stanić S, Solujić S, Mihailović V, Stanković N, Katanić J. Combining molecular docking and 3-D pharmacophore generation to enclose the in vivo antigenotoxic activity of naturally occurring aromatic compounds: myricetin, quercetin, rutin, and rosmarinic acid. Biochemical pharmacology. 2013;86(9):1376-96.
20. Khan MS, Qais FA, Ahmad I, Hussain A, Alajmi MF. Genotoxicity inhibition by Syzygium cumini (L.) seed fraction and rutin: understanding the underlying mechanism of DNA protection. Toxicology research. 2018;7(2):156-71.
21. Ashoka C, Mustak M. Antigenotoxic effects of rutin against methotrexate genotoxicity in Swiss albino mice. Current Trends in Biotechnology and Pharmacy. 2019;13(2).
22. Batra P, Sharma AK. Anti-cancer potential of flavonoids: recent trends and future perspectives. 3 Biotech. 2013;3(6):439-59.
23. Sugiyama KI, Yamada M, Awogi T, Hakura A. The strains recommended for use in the bacterial reverse mutation test (OECD guideline 471) can be certified as non-genetically modified organisms. Genes and Environment. 2016;38(1):2.
24. Sharma S, Ali A, Ali J, Sahni JK, Baboota S. Rutin: therapeutic potential and recent advances in drug delivery. Expert opinion on investigational drugs. 2013 Aug 1;22(8):1063-79.
25. Agar G, Gulluce M, Aslan A, Bozari S, Karadayi M, and Orhan F. Mutation preventive and antigenotoxic potential of methanol extracts of two natural lichen. Journal of Medicinal Plants Research. 2010;4(20):2132-7.
26. Issazadeh K, Aliabadi MA, Darsanaki RK and Pahlaviani MR. Antimutagenic activity of olive leaf aqueous extract by Ames test. Advanced Studies in Biology. 2012; 4(9):397-405.
27. Akin D, Durak Y, Uysal A, Gunes E and Aladag MO. Assessment of antimutagenic action of Celtis glabrata Steven ex Planch (Cannabaceae) extracts against base pair exchange and frame shift mutations on Salmonella typhimurium TA98 and TA100 strains by Ames test. Drug and chemical toxicology. 2016; 39(3):312-21.
28. Ames BN. Identifying environmental chemicals causing mutations and cancer. science. 1979; 204(4393):587-93.
29. Maron DM, Ames BN. Revised methods for the Salmonella mutagenicity test. Mutation Research/Environmental Mutagenesis and Related Subjects. 1983;113(3-4):173-215.
30. Agar G, Gulluce M, Aslan A, Bozari S, Karadayi M, Orhan F. Mutation preventive and antigenotoxic potential of methanol extracts of two natural lichen. Journal of Medicinal Plants Research. 2010;4(20):2132-7.
31. Zeiger E. Mutagens that are not carcinogens: faulty theory or faulty tests? Mutation Research/Genetic Toxicology and Environmental Mutagenesis. 2001;492(1-2):29-38.
32. Tejs S. The Ames test: a methodological short review. Environmental Biotechnology. 2008; 4:7-14.
33. Zeiger E. Historical perspective on the development of the genetic toxicity test battery in the United States. Environmental and molecular mutagenesis. 2010;51(8‐9):781-91.
34. Ojha A, Gupta YK. Study of commonly used organophosphate pesticides that induced oxidative stress and apoptosis in peripheral blood lymphocytes of rats. Human and experimental toxicology. 2017;36(11):1158-68.
35. Shrivastav N, Li D and Essigmann JM. Chemical biology of mutagenesis and DNA repair: cellular responses to DNA alkylation. Carcinogenesis. 2009;31(1):59-70.
36. Yang ZP and Dettbarn WD. Diisopropylphosphorofluoridate-induced cholinergic hyperactivity and lipid peroxidation. Toxicology and applied pharmacology. 1996;138(1):48-53.
37. Edwards FL, Yedjou CG, Tchounwou PB. Involvement of oxidative stress in methyl parathion and parathion‐induced toxicity and genotoxicity to human liver carcinoma (HepG2) cells. Environmental toxicology. 2013;28(6):342-8.
38. Mader JA, Macdonald IA. Effect of bile acids on formation of the mutagen, quercetin, from two flavonol glycoside precursors by human gut bacterial preparations. Mutation Research/Genetic Toxicology. 1985;155(3):99-104.
39. Snijman PW, Swanevelder S, Joubert E, Green IR, Gelderblom WC. The antimutagenic activity of the major flavonoids of rooibos (Aspalathus linearis): some dose–response effects on mutagen activation–flavonoid interactions. Mutation Research/Genetic Toxicology and Environmental Mutagenesis. 2007;631(2):111-23.
40. Bartoli S, Bonora B, Colacci A, Niero A, Grilli S. DNA damaging activity of methyl parathion. Research communications in chemical pathology and pharmacology. 1991;71(2):209-18.