Refine your search
Collections
Co-Authors
Year
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z All
Miguel Angel, Duarte-Vazquez
- Preclinical Safety Assessment of #946;-Hydroxyphospho-Carnitine
Abstract Views :439 |
PDF Views:0
Authors
Reyes-Esparza Jorge
1,
Mendoza-Rivera Brissa
1,
Cruz-Cordero Ricardo De la
1,
Duarte-Vazquez Miguel Angel
1,
Jorge L. Rosado
1,
Rodriguez-Fragoso Lourdes
1
Affiliations
1 Av. Universidad 1001 Chamilpa, Cuernavaca, Morelos, MX
1 Av. Universidad 1001 Chamilpa, Cuernavaca, Morelos, MX
Source
Toxicology International (Formerly Indian Journal of Toxicology), Vol 23, No 2 (2016), Pagination: 170-177Abstract
β-hydroxyphospho-carnitine(β-HPC) has been shown therapeutic potential. However, safety information is lacking. Acute toxicity, chronic toxicity, embryotoxicity, teratogenicity and genotoxicity of β-HPC were evaluated. For the acute toxicity, β-HPC was orally administered to mice at a dose range of 5-9000 mg/kg. For the repeated dose toxicity study, male rats were orally administered with β-HPC at the doses of 100 mg/kg for a period of 24 weeks. The effects on body weight, food and water consumption, organ weight, hematology, clinical chemistry as well as histology were studied. For embryiotoxicity and teratogenicity, β-HPC was administered to fertile chicken eggs (range 60-480 μg/mL). The genotoxic potential was tested using a comet assay. Data of each parameter were analyzed by oneway ANOVA followed by Tukey-Kramer test to compare the difference between treated groups. In general toxicity studies, orally administered β-HPC showed no sign of toxicity in any of the analyzed parameters involved in rodent single- and repeated-dose studies. Chicken embryos exposed to β-HPC in ovo showed alterations in growth and development during the early stage and at the end of their development in a dose dependent manner. In some cases, embryonic development terminated at stages 40/45 on the Hamburger-Hamilton scale and there were no associated malformations. β-HPC was not genotoxic to THP-1 cells. The results of the toxicological research confirmed that the safety profile of β-HPC. This safety evaluation results support the implementation of an exploratory Phase I clinical trial and underscore the potential of β-HPC as a new drug.Keywords
Acute Oral Toxicity, Chronic Toxicity, β-Hydroxyphospho-Carnitine, L-Carnitine, Preclinical, Safety.
References
- Han TS, Lean ME. A Clinical perspective of obesity, metabolic syndrome and cardiovascular disease. JRSM Cardiovasc Dis 2016 Feb 25;5:2048004016633371
- Gallagher EJ, LeRoith D. Obesity and Diabetes: the increased risk of cancer and cancer-related mortality. Physiol Rev 2015 Jul;95(3):727-8.
- Brown L, Poudyal H, Panchal SK. Functional foods as potential therapeutic options for metabolic syndrome. Obes Rev 2015 Nov;16(11):914-41.
- Radzhabkadiev RM, Korosteleva MM, Evstratova VS, Nikityuk DB, Khanferyan RA. L-carnitine: properties and perspectives for use in sports practice. Vopr Pitan 2015;84:4-12
- Moghaddas A, Dashti-Khavidaki S. Potential protective effects of l-carnitine against neuromuscular ischemia-reperfusion injury: from experimental data to potential clinical applications. Clin Nutr 2015 Jul 10:SO261-5614 (5) 00175-2.
- McCoin CS, Knotts TA, Adams SH. Acylcarnitines—old actors auditioning for new roles in metabolic physiology. Nat Rev Endocrinol 2015 Oct;11(10):617-25.
- Gomez Solis A, De la Cruz Cordero R, Duarte Fajardo M, Reyes-Esparza J, Rodriguez-Fragoso L. Efficacy and safety of two analogues of L-carnitine on rats made insulin-resistant by a high fructose diet. Pharmacology 2011;88(1-2):10-7.
- Reyes-Esparza J, Mendoza-Rivera B, De la Cruz-Cordero R, Rosado JL, Duarte-Vázquez MA, et al.Pharmacological Evaluation of a β-Hydroxyphosphonate Analogue of L-Carnitine in Obese Zucker fa/fa Rats.Basic ClinPharmacolToxicol 2013 Apr;112(4):222-8.
- Reyes-Esparza J, Mendoza-Rivera B, De la Cruz-Cordero R, Duarte-Vázquez MA, Rosado JL, et al. Pharmacokinetic and pharmacodinamic study of β-hydroxyphospho-carnitine in animal models. Pharmacology 2014 Jan 7;94:90-8.
- Bayne K. Revised guide for the care and use of laboratory animals available. Am PhysiolSocPhysiol 1996 Aug;39(4):208-11.
- Jelinek R. Marhan O. Validation of the chick embryotoxicity screening test (CHEST): a comparative study. FunctDevMorphol 1994;4(4):317-23.
- Hamburger V, Hamilton HL. A series of normal stages in the development of the chick embryo (repr from 1951).DevDyn 1992 Dec;195(4):231-72.
- Moller P, Molller L, Godschalk RW, Jones GD.Assessment and reduction of comet assay variation in relation to DNA damage: studies from the European Comet Assay Validation Group. Mutagenesis 2010 Mar;25(2):109-11.
- Manakova E, Hubickova L, Kostalova J, Zemanova Z. Embryotoxicity of mirtazapine: a study using chick embryotoxicity screening test. NeuroEndocrinolLett 2010; 31(Suppl2): 8-10.
- Keralapurath MM, Corzo A, Pulikanti R, Zhai W, Peebles ED. Effects of in ovo injection of l-carnitine on hatchability and subsequent broiler performance and slaughter yield. Poult Sci 2010 Jul;89(7):1497-501.
- Keralapurath MM, Keirs RW, Corzo A, Bennett LW, Pulikanti R, et al. Effects of in ovo injection of L-carnitine on subsequent broiler chick tissuenutrient profiles. Poult Sci 2010 Feb;89(2):335-41.
- de Bruyn A, Jacquemyn Y, Kinget K, Eyskens F.Carnitine deficiency and pregnancy. Case Rep ObstetGyneecol 2015; 2015:101468.
- Kepka A, Chojnowska S, Okungbowa OE, Zwierz K. The role of carnitine in the perinatal period. Dev Period Med 2014 Oct-Dec;18(4):417-25.
- Dooley M, Peebles ED, Zhai W, Mejia L, Zumwalt CD, et al. Effects of l-carnitine via in ovo injection with or without l-carnitine feed supplementation on broiler hatchability and posthatch performance. J Appl Poult Res 2011;20: 491-7.
- Moraes e Luz EW, Vieira LR, Semedo JG, Bona SR, Forgiarini LF, et al. Neurobehavioral effects of L-carnitine and its ability to modulate genotoxicity and oxidative stress biomarkers in mice.PharmacolBiochemBehav 2013 Sep;110:40-5.
- Mescka CP, Guerreiro G, Hammerschmidt T, Faverzani J, de Moura Coelho D, et al. L-carnitine ssuplementation decreases DNA damage in treated MSUD patients. Mut Res 2015 May;775:43-7.