Assessment of the Genotoxic Potential of <i>Rasamanikya</i>, an Ayurvedic Arsenical Formulation in Albino Rats
Keywords:Chromosomal Aberration, Genotoxicity, Orpiment, <i>Rasamanikya</i>, Safety
AbstractShodhita Haratala (processed orpiment) is a single ingredient of Rasamanikya (RM). Arsenicals are known for producing toxic effects in humans, if not processed as per classical text therefore, the present study was aim to generate data for the safety of RM in albino rats. In the present study, two samples of RM were prepared by using two different purification media of orpiment, i.e., juice of Benincasa hispida (Thunb.) Cong. and lime water. Extract of Tinospora cordifolia Linn. (GG) was used as an adjuvant. Both the samples of RM along with GG were administered to the albino rats for 60 consecutive days at the therapeutic dose, TED (90 mg/kg) and TED×5 (450 mg/kg) orally in albino rats. Sample of RM along with GG not having the potential to produce any mutagenic or genotoxicity effects in albino rats. Further, there is no significant difference found in the safety of the orpiment on changing of media for purification.
Sharma SN. Rasa Tarangini, 11/88-89, Shastri K N, Hindi commentary. Varanasi: Motilal Banarasi Das Publication; 2009. p. 257.
Mehta M, Hundal SS. Assessment of genotoxic potential of arsenic in female albino rats at permissible dose levels. Toxicol Int. 2014; 21(1):24–28. https://doi.org.org/10.4103/0971-6580.128787. PMid:24748731. PMCid:PMC3989911
Jagtap CY, Ashok BK, Patgiri BJ, Prajapati PK, Ravishankar B. Acute and subchronic toxicity study of tamra bhasma (Incinerated copper) prepared from Ashodhita (Impurified) and Shodhita (Purified) tamra in rats. Indian J Pharm Sci. 2013; 75:346–352. https://doi.org.org/10.4103/0250-474X.117433. PMid:24082351. PMCid:PMC3783753
Sud S, Reddy S, Sujatha K, Honwad S. A comparative toxicological study of Rasamanikya prepared with three different methods. AYU. 2013; 34(3):309–315. https://doi.org.org/10.4103/0974-8520.123134. PMid:24501530. PMCid:PMC3902601
Chaudhari SY, Biradar S, Nariya M, Galib R, Prajapati PK. Acute and chronic toxicity of rasamanikya, an ayurvedic arsenical formulation in rats. Indian J Pharm Sci. 2018; 80(2):325333. https://doi.org/10.4172/pharmaceuticalsciences. 1000361
Chaudhari SY, Nariya M, Galib R, Prajapati PK. Acute and sub-chronic toxicity of Tamra Bhasma (Incinerated copper) prepared with and without Amritikarana. J Ayurveda Integr Med. 2016; 7:23–29. https://doi. org/10.1016/j.jaim.2015.11.001. PMid:27297506. PMCid:PMC4910297
Gokarn RA, Nariya M, Patgiri BJ, Prajapati PK. Toxicological studies of Rasasindura, an ayuvedic formulation. Indian J Pharm Sci. 2017; 79(4):633–640. https://doi.org.org/10.4172/pharmaceutical-sciences.1000272
Deshpnde SW, Gandhi N. Drug and cosmetic Act 1940 and rules 1945. The medical devices rules 2017. Drug and magic remedies (objectionable advertisement) Act, 1954 Drugs (prices control) order 2013. Mumbai:Susmit publishers; 2018.
Anonymous. The Gazette of India: Extraordinary, Part II-Section 3-Sub-section (i). Ministry of health and family welfare. New Delhi; 2008. p.11.
Chaudhari SY, Jagtap C, Thakkar JH, Galib R, Prajapati PK. Assessment of genotoxic potential of Tamra Bhasma (incinerated copper). Int J Green Pharm. 2015; 9:175– 179. https://doi.org/10.4103/0973-8258.161235
Jagtap CY, Chaudhari SY, Thakkar JH, Galib R, Prajapati PK. Assessment of genotoxic potential of hridayarnava rasa (A herbo-mineralo-metallic ayurvedic formulation) using chromosomal aberration and sperm abnormality assays. Toxicol Int. 2014; 21:242–247. https://doi.org.org/10.4103/0971-6580.155331. PMid:25948961. PMCid:PMC4413405
Savalgi PB, Patgiri BJ, Thakkar JH, Ravishankar B, Gupta VB. Evaluation of subchronic genotoxic potential of Swarna Makshika Bhasma. AYU. 2012; 33:418–422. https://doi.org/10.4103/0974-8520.108858. PMid:23723652. PMCid:PMC3665102
Paget, GE. Barnes JM. Toxicity tests. In: Laurence DR, Bacharach AL, editors. Evaluation of drug activities pharmacometries. Vol.1. New York: Academic Press, London; 1964. p. 50. https://doi.org/10.1016/B978-1- 4832-2845-7.50012-8
OECD. Guidelines for the Testing of Chemical (483) — Mammalian spermatogonial Chromosomal Aberration Test, Published on 29 july 2016. Retrieved from: https://www.oecd.org/env/test-no-483-mammalian-spermatogonial-chromosomal-aberration-test- 9789264264847-en.htm
Tijio JH, Whang J. Direct chromosomal preparation of bone marrow cells. Stain Technique. 1962; 37:17–20. https://doi.org/10.3109/10520296209114563. PMid:13921436
Wyrobek AJ, Bruce WR. Chemical induction of sperm abnormalities in mice. Proc. Nat. Acad. Sci. USA. Nov 1975; 22(11):4425–4429. https://doi.org.org/10.1073/pnas.72.11.4425 PMid:1060122. PMCid:PMC388734
Pandey S, Sharma V, Chudhari AK. Chelation therapy and chelating agent of Ayurveda. Int. J. Green Pharm. 2016; 10(3):143–150.
Kaushik S, Singh R, Yadav P, Galib R, Prajapti PK. Safety concerns on Ayurvedic herbomineral formulations- Myth or reality. J. Drug Res. Ayurvedic Sci. 2018; 3(4):234–241.
Chaudhari SY, Biradar S, Nariya M, Galib R, Prajapati PK. Acute and chronic toxicity of rasamanikya, an ayurvedic arsenical formulation in rats. Indian J Pharm Sci. 2018; 80(2):325–333. https://doi.org/10.4172/pharmaceuticalsciences. 1000361
Guimarães AP, Guimarães AC, Alcântara DA, Cunha LR, Lima PL, Vasconcellos MC, et al. Chromosomal aberration test utilities in vitro and in vivo. Genotoxicity and DNA Repair. 2014:115–139. https://doi.org/10.1007/978- 1-4939-1068-7_7. PMid:25488217
OECD. Guideline for testing of chemicals 483-Mammalian spermatogonial chromosomal aberration test. 2016. Retrieved from: https://www.oecd.org/ env/test-no-483-mammalian-spermatogonial-chromosomal- aberration-test-9789264264847-en.htm
CCRAS. General guideline for safety/toxicity evaluation of ayurvedic formulations. New Delhi: Ministry of AYUSH, Govt. of India; 2018. Retrieved from: https://www.ayush.gov.in/docs/guideline_safety_toxicity. pdf
Deshpnde SW, Gandhi N. Drug and cosmetic AC,1940 and rules 1945. The medical devices rules 2017. Drug and magic remedies (objectionable advertisement) Act, 1954 Drugs (prices control) order 2013. Mumbai:Susmit publishers; 2018.
Abdella EM. Short term comparative study of cyclophosphamide genotoxicity administered free and liposome-encapsulated in mice. Iran J Cancer Prev. 2012; 5(2):51–60.
Simula AP, Priestly BG. Species differences in the genotoxicity of cyclophosphamide and styrene in three in vivo assays. Mutation Research/ Environmental Mutagenesis and related Subjects 1992; 271(1):49–58. https://doi. org/10.1016/0165-1161(92)90031-G
Bonfoco E, Ceccatelli S, Manzo L, Nicotera P. Colchicine induces apoptosis in cerebellar granule cells. Experimental Cell Research. 1995; 218(1):189– 200. https://doi.org/10.1006/excr.1995.1147. PMid:7537689
Ballav S, Maity G, Mondal N. Toxicological and human risk assessment of Haratala (orpiment/AS2S3). Int J Res Ayurveda Pharm. 2019; 10(1):55–58. https://doi. org/10.7897/2277-4343.100113
Parekh D, Patgiri BJ, Bederakar P, Nariya M. Pharmaceutical standardization of Rasamanikya prepared by two different media shodhita Haratala and its clinical efficacy in Ekakustha (psoriasis). MD dissertation 2019. IPGT & RA, Gujarat Ayurved University, Jamnagar.
Fraser IEB. The use of colchicine and colcemid for metaphase stasis in the matrix cells of wool follicles. Aust J Biol Sci. 1963; 16(1):211–217. https://doi.org/10.1071/ BI9630211
Mueller GA, Mary EG, Wanzer D. The effect of varying concentrations of colchicine on the progression of grasshopper neuroblasts into metaphase. Int J Cell Biol.1971; 48:259–265. https://doi.org/10.1083/jcb.48.2.253. PMid:5551659. PMCid:PMC2108180
Palestis BG, Brut A, Jones RN, Trivers R. B chromosomes are more frequent in mammals with acrocentric karyotypes: Support for the theory of centromeric drive. Proc Biol Sci. 2004; 271(Suppl 3):S22–S24. https://doi.org.org/10.1098/rsbl.2003.0084. PMid:15101408. PMCid:PMC1810000
Sharpe RM. Sperm counts and fertility in men: a rocky road ahead. EMBO Rep. 2012; 13(5):398–403. https://doi.org.org/10.1038/embor.2012.50. PMid:22491033. PMCid:PMC3343360
Sharma SN. Rasa Tarangini, 11/7, Shastri K N, Hindi commentary. Varanasi: Motilal Banarasi Das Publication; 2009. p. 245.
Bhavprakasha. Bhav Praksah Nighantu, Madhu Verga 22/3-4, Chunekar K. Varanasi: Chaukhamba Bharti Academy; 2013. p.772.