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Assessment of Pharmacokinetics and Toxicology of Sadat-Habdan Mesenchymal Stimulating Peptide (SHMSP) in Rats and Goats
BACKGROUND: Sadat-Habdan Mesenchymal Stimulating Peptide (SHMSP) was discovered and patented with USPTO in 2008. Studies have shown that SHMSP works as an angiogenesis factor. This study was done to evaluate pharmacokinetics (PK) in rats and toxicology studies in goats and rats. METHODS: In 80 skele...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Master Publishing Group
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199474/ https://www.ncbi.nlm.nih.gov/pubmed/25324697 |
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author | Al-Habdan, Ibrahim Sadat-Ali, Mir Safar Alghamdy, Mastour Randhawa, Akram Chathoth, Shahanas |
author_facet | Al-Habdan, Ibrahim Sadat-Ali, Mir Safar Alghamdy, Mastour Randhawa, Akram Chathoth, Shahanas |
author_sort | Al-Habdan, Ibrahim |
collection | PubMed |
description | BACKGROUND: Sadat-Habdan Mesenchymal Stimulating Peptide (SHMSP) was discovered and patented with USPTO in 2008. Studies have shown that SHMSP works as an angiogenesis factor. This study was done to evaluate pharmacokinetics (PK) in rats and toxicology studies in goats and rats. METHODS: In 80 skeletally mature Sprague Dawley rats 5 milligram/kg body weight of SHMSP was injected intramuscularly. Blood samples were collected at 0, 30, 60, 120, 240, 320 minutes and 480 minutes. The plasma calibration curves were prepared at concentrations of 6.25, 3.12, 1.56, 0.78 and 0.39 ng/mL by spiking 190 µL of rat plasma with 10µL of working standard and 200 µL of deionized water. Samples were vortexed for five seconds, centrifuged at 14000 rpm for 30 minutes at 4°C and the supernatant was collected analyzed using High-performance liquid chromatography (HPLC). After injection of 20 µL sample, the peptide was eluted with 15ml linear gradient up to 36% of eluent A. The time between injections was 25 min. and the eluent was monitored at a wavelength of 215 nm. The concentration of peptide present in the rat plasma samples collected at different time intervals were quantified using standard curve method. The goats were injected deep intramuscularly 100 mg/kg-body weight of the SHMSP dissolved in injection solution. In 10 Sprague Dawley rats of ≥250 grams of weight, 20 mg/kg/day SHMSP was injected for 7 consecutive days. All the animals were kept at a close watch. Clinical observation at least once daily and as necessary was undertaken. After 2 weeks animals were euthanized and major organs were harvested and histopathology samples were obtained and processed. RESULTS: There were no deaths is either of the study and control group of animals. The gross observations of the various organs appeared normal and histopathological studies did not show any toxicity in the organs tested. The plasma concentration-time profile of SHMSP after intramuscular injection, the level of SHMSP in an initial high phase reaching the highest at 30 minutes 2.3184 ng/ml and 60 minutes 1.7447 ng/ml at 60 minutes. The lowest level was at 360 minutes of 0.0879 ng/ml. CONCLUSIONS: The dose of SHMSP at 20 times the recommended dose was not toxic and secondly the peak time and level was at 30 minutes to 120 minutes and the plasma half-life of SHMSP was 90 minutes. |
format | Online Article Text |
id | pubmed-4199474 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Master Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-41994742014-10-16 Assessment of Pharmacokinetics and Toxicology of Sadat-Habdan Mesenchymal Stimulating Peptide (SHMSP) in Rats and Goats Al-Habdan, Ibrahim Sadat-Ali, Mir Safar Alghamdy, Mastour Randhawa, Akram Chathoth, Shahanas Int J Biomed Sci Original Article BACKGROUND: Sadat-Habdan Mesenchymal Stimulating Peptide (SHMSP) was discovered and patented with USPTO in 2008. Studies have shown that SHMSP works as an angiogenesis factor. This study was done to evaluate pharmacokinetics (PK) in rats and toxicology studies in goats and rats. METHODS: In 80 skeletally mature Sprague Dawley rats 5 milligram/kg body weight of SHMSP was injected intramuscularly. Blood samples were collected at 0, 30, 60, 120, 240, 320 minutes and 480 minutes. The plasma calibration curves were prepared at concentrations of 6.25, 3.12, 1.56, 0.78 and 0.39 ng/mL by spiking 190 µL of rat plasma with 10µL of working standard and 200 µL of deionized water. Samples were vortexed for five seconds, centrifuged at 14000 rpm for 30 minutes at 4°C and the supernatant was collected analyzed using High-performance liquid chromatography (HPLC). After injection of 20 µL sample, the peptide was eluted with 15ml linear gradient up to 36% of eluent A. The time between injections was 25 min. and the eluent was monitored at a wavelength of 215 nm. The concentration of peptide present in the rat plasma samples collected at different time intervals were quantified using standard curve method. The goats were injected deep intramuscularly 100 mg/kg-body weight of the SHMSP dissolved in injection solution. In 10 Sprague Dawley rats of ≥250 grams of weight, 20 mg/kg/day SHMSP was injected for 7 consecutive days. All the animals were kept at a close watch. Clinical observation at least once daily and as necessary was undertaken. After 2 weeks animals were euthanized and major organs were harvested and histopathology samples were obtained and processed. RESULTS: There were no deaths is either of the study and control group of animals. The gross observations of the various organs appeared normal and histopathological studies did not show any toxicity in the organs tested. The plasma concentration-time profile of SHMSP after intramuscular injection, the level of SHMSP in an initial high phase reaching the highest at 30 minutes 2.3184 ng/ml and 60 minutes 1.7447 ng/ml at 60 minutes. The lowest level was at 360 minutes of 0.0879 ng/ml. CONCLUSIONS: The dose of SHMSP at 20 times the recommended dose was not toxic and secondly the peak time and level was at 30 minutes to 120 minutes and the plasma half-life of SHMSP was 90 minutes. Master Publishing Group 2014-09 /pmc/articles/PMC4199474/ /pubmed/25324697 Text en © Ibrahim Al-Habdan et al. Licensee Master Publishing Group http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Original Article Al-Habdan, Ibrahim Sadat-Ali, Mir Safar Alghamdy, Mastour Randhawa, Akram Chathoth, Shahanas Assessment of Pharmacokinetics and Toxicology of Sadat-Habdan Mesenchymal Stimulating Peptide (SHMSP) in Rats and Goats |
title | Assessment of Pharmacokinetics and Toxicology of Sadat-Habdan Mesenchymal Stimulating Peptide (SHMSP) in Rats and Goats |
title_full | Assessment of Pharmacokinetics and Toxicology of Sadat-Habdan Mesenchymal Stimulating Peptide (SHMSP) in Rats and Goats |
title_fullStr | Assessment of Pharmacokinetics and Toxicology of Sadat-Habdan Mesenchymal Stimulating Peptide (SHMSP) in Rats and Goats |
title_full_unstemmed | Assessment of Pharmacokinetics and Toxicology of Sadat-Habdan Mesenchymal Stimulating Peptide (SHMSP) in Rats and Goats |
title_short | Assessment of Pharmacokinetics and Toxicology of Sadat-Habdan Mesenchymal Stimulating Peptide (SHMSP) in Rats and Goats |
title_sort | assessment of pharmacokinetics and toxicology of sadat-habdan mesenchymal stimulating peptide (shmsp) in rats and goats |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199474/ https://www.ncbi.nlm.nih.gov/pubmed/25324697 |
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