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Ricardo De la, Cruz-Cordero
- Preclinical Safety Assessment of #946;-Hydroxyphospho-Carnitine
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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.
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