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A 28-Day Repeated Dose Toxicity Evaluation of Creatinine Monohydrate and β-Hydroxy β-Methyl Butyrate Combination in Rodent Model


Affiliations
1 Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, Nilgiris - 643001, Tamil Nadu, India
2 Department of Orthopaedics, Mahatma Gandhi Medical College and Research Institute, Pondicherry - 607402, India
3 Department of Radio-diagnosis, JSS Medical College and Hospital, JSS Academy of Higher Education and Research, Mysuru - 570015, Karnataka, India
     

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Substance abuse is a global concern, having a significant influence on society, healthcare, and the economy. Athletes are increasingly using substances to improve their performance or to cope with stress. Therefore, having a thorough awareness of the often misused substances, their effects, and potential toxicities is essential. One such chemical is the mixture of Creatinine Monohydrate (CM) and -Hydroxy Methyl Butyrate (HMB), which is widely used by athletes to increase strength and performance. According to studies, the combination can boost athletic performance, build muscle, and offer several health advantages. To determine the chemicals’ long-term impacts on human health, more research is required because their safety and toxicity are not well-established. Using TOPKAT(Computer-Aided Toxicity Prediction) and Discovery Studio Version 4.0, this study examined the toxicity and pharmacokinetic profiles of CM and HMB. The interaction of HMB and CM may significantly reduce cell viability compared to either drug alone. There were no negative effects seen in the animal models used for the acute oral toxicity study, but additional research is needed to confirm these results and determine the compounds’ long-term safety for human use. The study also performed cytotoxicity studies of individual substances and combinations on VERO and HEP-G2 cell lines and a 28-day repeated dose toxicity study in Wistar albino rats. The study results provide valuable information for healthcare professionals to understand the physiological complications of exposure to such drugs. Overall, the article emphasizes the importance of understanding the potential toxicity of chemical compounds, particularly those used as nutritional supplements.

Keywords

Creatinine Monohydrate, β-Hydroxy β-Methyl Butyrate, Substance Abuse, Toxicity Study.
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  • Reardon CL, Creado S. Drug abuse in athletes. Substance Abuse and Rehabilitation. 2014; 5:95-105. https://doi.org/10.2147/SAR.S53784 PMid:25187752 PMCid:PMC4140700
  • Green G, Uryasz F, Petr T, Bray C. NCAA study of substance use and abuse habits of college student-athletes. PubMed- NCBI; 2001. https://doi.org/10.1097/00042752-200101000-00009 PMid:11176146
  • Villa L, Thomas S. Addiction and drug use among athletes. Drug Rehab Options. 2019.
  • Trevino S. Athletes and drug abuse: A disturbing trend in modern sports | MTR Blog. More Than Rehab; 2019
  • Kalman DS, Campbell B. Sports Nutrition: What the future may bring. J Int Soc Sports Nutr. 2004 Jun 1;1(1). https:// doi.org/10.1186/1550-2783-1-1-61 PMCid:PMC2129143
  • FSSAI Regulations for Nutraceuticals: A Complete Overview. Available from: https://corpbiz.io/learning/fssairegulations- for-nutraceuticals/
  • Dhar R, Stout CW, Link MS, Homoud MK, Weinstock J, Estes NAM. Cardiovascular toxicities of performance-enhancing substances in sports. Mayo Clin Proc. 2005; 80(10):1307-15. https://doi.org/10.4065/80.10.1307 PMid:16212144
  • Martin SJ, Sherley M, McLeod M, Adverse effects of sports supplements in men. Australian Prescriber. 2018; 41(1):10-3 https://doi.org/10.18773/austprescr.2018.003 PMid:29507454 PMCid:PMC5828928
  • McDowall JA. Supplement use by young athletes. Journal of Sports Science and Medicine. 2007; 6(3):337-42
  • Mielgo-Ayuso J, Calleja-Gonzalez J, Del Coso J, Urdampilleta A, León-Guereño P, Fernández-Lázaro D. Caffeine Supplementation and Physical Performance, Muscle Damage and Perception of Fatigue in Soccer Players: A Systematic Review. Nutrients. 2019 Feb 1; 11(2). https://doi.org/10.3390/nu11020440 PMid:30791576 PMCid:PMC6412526
  • Mangine GT, Vandusseldorp TA, Hester GM, Julian JM, Feito Y. The addition of β-Hydroxy β-Methylbutyrate (HMB) to creatine monohydrate supplementation does not improve anthropometric and performance maintenance across a collegiate rugby season. J Int Soc Sports Nutr. 2020 May 27; 17(1). https://doi.org/10.1186/s12970-020-00359-4 PMid:32460801 PMCid:PMC7254750
  • Portal S, Eliakim A, Nemet D, Halevy O, Zadik Z. Effect of HMB supplementation on body composition, fitness, hormonal profile and muscle damage indices. Journal of Pediatric Endocrinology and Metabolism. 2010; 23(7):641-50. https://doi.org/10.1515/JPEM.2010.23.7.641 PMid:20857835
  • Kreider RB, Kalman DS, Antonio J, Ziegenfuss TN, Wildman R, Collins R, et al. International society of sports nutrition position stand: Safety and efficacy of creatine supplementation in exercise, sport, and medicine. J Int Soc Sports Nutr. 2017 Jun 13; 14(1). https://doi.org/10.1186/ s12970-017-0173-z PMid:28615996 PMCid:PMC5469049
  • Ich. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use Ich Harmonised Tripartite Guideline Duration of Chronic Toxicity Testing in Animals (rodent and non-rodent toxicity testing) s4; 1998
  • Shibuya M. Vascular Endothelial Growth Factor (VEGF) and its Receptor (VEGFR) signalling in angiogenesis: A crucial target for anti- and pro-angiogenic therapies. Genes Cancer. 2011; 2(12):1097-105. https:// doi.org/10.1177/1947601911423031 PMid:22866201 PMCid:PMC3411125
  • Egan WJ, Merz KM, Baldwin JJ. Prediction of drug absorption using multivariate statistics. J Med Chem. 2000; 43(21):3867-77. https://doi.org/10.1021/jm000292e PMid:11052792
  • Cheng A, Diller DJ, Dixon SL, Egan WJ, Lauri G, Merz KM. Computation of the physio‐chemical properties and data mining of large molecular collections. J Comput Chem. 2002; 23(1):172-83. https://doi.org/10.1002/jcc.1164 PMid:11913384
  • Egan WJ, Lauri G. Prediction of intestinal permeability. Adv Drug Deliv Rev. 2002; 54(3):273-89. https://doi.org/10.1016/S0169-409X(02)00004-2 PMid:11922948
  • Zeb A, Park C, Rampogu S, Son M, Lee G, Lee KW. Structure-based drug designing recommends HDAC6 inhibitors to attenuate microtubule-associated tau-pathogenesis. ACS Chem Neurosci. 2019; 10(3):1326-35. https:// doi.org/10.1021/acschemneuro.8b00405 PMid:30407786
  • Jubie S, Prabha T, Palanisamy S, Latha S, Ayyamperumal S. A strategy to treat the breast cancer through inhibiting the over expression of protein estrogen via schiff base fused coumarin: an in-silico based synthetic approach. International Journal of Pharmaceutical Sciences and Research, 2020; 11(9):4349-58.
  • Ammerman NC, Beier-Sexton M, Azad AF. Growth and maintenance of Vero cell lines. Curr Protoc Microbiol. 2008; 11(1): A.4E.1-A.4E.7. https://doi. org/10.1002/9780471729259.mca04es11 PMid:19016439 PMCid:PMC2657228
  • Donato MT, Tolosa L, Gómez-Lechón MJ. Culture and functional characterization of human hepatoma HEPG2 Cells. Methods in Molecular Biology. 2015; 77-93. https:// doi.org/10.1007/978-1-4939-2074-7_5 PMid:26272135
  • Senthilraja P, Kathiresan K. In vitro cytotoxicity MTT assay in Vero, HEPG2 and MCF -7 cell lines study of Marine Yeast. Journal of Applied Pharmaceutical Science. 2015; 080-084. https://doi.org/10.7324/JAPS.2015.50313
  • OECD. Test No. 423: Acute oral toxicity - acute toxic class method. OECD Guideline for Testing of Chemicals. 2002; 1-14.
  • Delhi N, Act C, Rules C, X-a P. Drugs and cosmetics (iind amendment) rules. Control. 2005; 32(Appendix IV):1-37.
  • Test No. 407: Repeated Dose 28-day Oral Toxicity Study in Rodents; 2008.
  • Ramakrishnan S, Setty RS. Toxicological studies of drugs of abuse: Sub-chronic and chronic toxicity study of benzocaine- caffeine combination. 2015.
  • Mary LAG, Charles B, Clifford. Clinical laboratory parameters for Crl: WI(HAN). Charles Liver Accelerating Drug Development; 2008.
  • Kiss A, Kasza G, Töreki K, Lakner Z. Use and abuse of dietary supplements for adolescents- Results of a survey among Hungarian recreational athletes. Acta Alimentaria. 2017; 46:214-22. https://doi.org/10.1556/066.2017.46.2.11
  • Karimian J, Esfahani PS. Supplement consumption in body builder athletes. Journal of Research in Medical Sciences: The Official Journal of Isfahan University of Medical Sciences. 2011; 16(10):1347-53.
  • Jovanov P, Dordic V, Barak O. Prevalence, knowledge and attitudes towards using sports supplements among young athletes. Journal of the International Society of Sports Nutrition. 2019. https://doi.org/10.1186/s12970-019- 0294-7 PMid:31272457 PMCid:PMC6611041
  • Pal S, Kumar V, Kundu B, Bhattacharya D, Preethy N, Reddy MP, Talukdar A. Ligand-based pharmacophore modeling, virtual screening and molecular docking studies for discovery of potential topoisomerase I inhibitors. Computational and Structural Biotechnology Journal. 2019; 17:291-310. https://doi.org/10.1016/j.csbj.2019.02.006 PMid:30867893 PMCid:PMC6396084
  • Raies AB, Bajic VB. In silico toxicology: Computational methods for the prediction of chemical toxicity. Wiley Interdiscip Rev Comput Mol Sci. 2016; 147-72. https://doi.org/10.1002/wcms.1240 PMid:27066112 PMCid:PMC4785608
  • Yang H, Sun L, Li W, Liu G, Tang Y. Corrigendum: In silico prediction of chemical toxicity for drug design using machine learning methods and structural alerts. Front Chem. 2018; 6:30 https://doi.org/10.3389/ fchem.2018.00129 PMid:29515993 PMCid:PMC5826228
  • Kim S, Chen J, Cheng T, Gindulyte A, He J, He S, Li Q, Shoemaker BA, Thiessen PA, Yu B, Zaslavsky L, Zhang J, Bolton EE. Improved access to chemical data. Nucleic Acids Research. 2019; 47(D1):D1102-D1109.
  • Giknis MLA, Clifford CB. Clinical laboratory parameters for CrlWI (Han). Charles River Laboratories; 2008. Available from: https://www. scirp.org/(S(351jmbntvnsjt1aadkposzje))/reference/ ReferencesPapers.aspx?ReferenceID=523684
  • Bernardi M, Maggioli C, Zaccherini G. Human albumin in the management of complications of liver cirrhosis. Crit Care. 2012; 16(2). Available from: https://pubmed.ncbi. nlm.nih.gov/22429536/ https://doi.org/10.1186/cc11218 PMid:22429536 PMCid:PMC3681351
  • Buford TW, Kreider RB, Stout JR, Greenwood M, Campbell B, Spano M, et al. International society of sports nutrition position stand: Creatine supplementation and exercise. J Int Soc Sports Nutr. 2007 Aug 30; 4(1):6. https://doi.org/10.1186/1550-2783-4-6 PMid:17908288 PMCid:PMC2048496
  • Ammerman NC, Beier-Sexton M, Azad AF. Growth and maintenance of Vero cell lines. Curr Protoc Microbiol. 2008 Nov. https://doi.org/10.1002/9780471729259.mca04es11 PMid:19016439 PMCid:PMC2657228

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  • A 28-Day Repeated Dose Toxicity Evaluation of Creatinine Monohydrate and β-Hydroxy β-Methyl Butyrate Combination in Rodent Model

Abstract Views: 139  |  PDF Views: 0

Authors

Shivaramakrishnan Balasubramanian
Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, Nilgiris - 643001, Tamil Nadu, India
Kavitha Giridharan
Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, Nilgiris - 643001, Tamil Nadu, India
K. D. Kavya
Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, Nilgiris - 643001, Tamil Nadu, India
Venkataram Vellaipandi
Department of Orthopaedics, Mahatma Gandhi Medical College and Research Institute, Pondicherry - 607402, India
Gurumurthy Balasubramanian
Department of Radio-diagnosis, JSS Medical College and Hospital, JSS Academy of Higher Education and Research, Mysuru - 570015, Karnataka, India

Abstract


Substance abuse is a global concern, having a significant influence on society, healthcare, and the economy. Athletes are increasingly using substances to improve their performance or to cope with stress. Therefore, having a thorough awareness of the often misused substances, their effects, and potential toxicities is essential. One such chemical is the mixture of Creatinine Monohydrate (CM) and -Hydroxy Methyl Butyrate (HMB), which is widely used by athletes to increase strength and performance. According to studies, the combination can boost athletic performance, build muscle, and offer several health advantages. To determine the chemicals’ long-term impacts on human health, more research is required because their safety and toxicity are not well-established. Using TOPKAT(Computer-Aided Toxicity Prediction) and Discovery Studio Version 4.0, this study examined the toxicity and pharmacokinetic profiles of CM and HMB. The interaction of HMB and CM may significantly reduce cell viability compared to either drug alone. There were no negative effects seen in the animal models used for the acute oral toxicity study, but additional research is needed to confirm these results and determine the compounds’ long-term safety for human use. The study also performed cytotoxicity studies of individual substances and combinations on VERO and HEP-G2 cell lines and a 28-day repeated dose toxicity study in Wistar albino rats. The study results provide valuable information for healthcare professionals to understand the physiological complications of exposure to such drugs. Overall, the article emphasizes the importance of understanding the potential toxicity of chemical compounds, particularly those used as nutritional supplements.

Keywords


Creatinine Monohydrate, β-Hydroxy β-Methyl Butyrate, Substance Abuse, Toxicity Study.

References





DOI: https://doi.org/10.18311/ti%2F2023%2Fv30i2%2F32418