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Morphological and enzymatic changes caused by a long-term treatment of female rats with a low dose of gonadoliberin agonist and antagonist
BACKGROUND: Long-term treatment with gonadoliberin analogs is used to block the hypothalamic-pituitary-gonadal axis. The use of these agents is generally considered to be safe; however, some observations suggest the possibility of adverse effects. MATERIAL/METHODS: We investigated whether a 3-months...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Scientific Literature, Inc.
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3560692/ https://www.ncbi.nlm.nih.gov/pubmed/22847193 http://dx.doi.org/10.12659/MSM.883264 |
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author | Suszka-Œwitek, Aleksandra Czekaj, Piotr Pająk, Jacek Skowronek, Rafał Wrona-Bogus, Katarzyna Plewka, Danuta Kozłowska-Rup, Danuta Wiaderkiewicz, Ryszard Jankowski, Andrzej |
author_facet | Suszka-Œwitek, Aleksandra Czekaj, Piotr Pająk, Jacek Skowronek, Rafał Wrona-Bogus, Katarzyna Plewka, Danuta Kozłowska-Rup, Danuta Wiaderkiewicz, Ryszard Jankowski, Andrzej |
author_sort | Suszka-Œwitek, Aleksandra |
collection | PubMed |
description | BACKGROUND: Long-term treatment with gonadoliberin analogs is used to block the hypothalamic-pituitary-gonadal axis. The use of these agents is generally considered to be safe; however, some observations suggest the possibility of adverse effects. MATERIAL/METHODS: We investigated whether a 3-months administration of a low dose (6 μg/kg b.w.) of dalarelin – a new agonist, and cetrorelix – a known antagonist of GnRH to female rats causes morphological changes in pituitary gland, ovaries, uterus and liver (HE and VG staining); effects on pituitary, hepatic and blood enzyme activities (histochemical and kinetic methods, respectively), and on the blood lipid profile (colorimetric methods); and to what extent these changes are reversible. RESULTS: Applying analogs effectively inhibited ovulation, affected the uterine endometrium and changed histological appearance of the liver (e.g., steatosis). They altered activities of marker enzymes of cellular respiration, gluconeogenesis and intracellular digestion in the liver and, partially in the pituitary gland, caused undesirable changes in the activities of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and creatine kinase, and a concentration of cholesterol HDL fraction and triglycerides in the blood. Both morphological and enzymatic effects were more evident after antagonist administration; changes in the blood lipid profile were more evident after agonist administration. In both analogs histological and enzymatic changes persisted a relatively long time after the discontinuation of the treatment. CONCLUSIONS: The low dose of dalarelin and cetrorelix is sufficient to cause limited damage of hepatic cells and may modify the function of pituitary, ovaries, uterus and liver as well as other organs, even after discontinuation of the treatment. |
format | Online Article Text |
id | pubmed-3560692 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | International Scientific Literature, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-35606922013-04-24 Morphological and enzymatic changes caused by a long-term treatment of female rats with a low dose of gonadoliberin agonist and antagonist Suszka-Œwitek, Aleksandra Czekaj, Piotr Pająk, Jacek Skowronek, Rafał Wrona-Bogus, Katarzyna Plewka, Danuta Kozłowska-Rup, Danuta Wiaderkiewicz, Ryszard Jankowski, Andrzej Med Sci Monit Basic Research BACKGROUND: Long-term treatment with gonadoliberin analogs is used to block the hypothalamic-pituitary-gonadal axis. The use of these agents is generally considered to be safe; however, some observations suggest the possibility of adverse effects. MATERIAL/METHODS: We investigated whether a 3-months administration of a low dose (6 μg/kg b.w.) of dalarelin – a new agonist, and cetrorelix – a known antagonist of GnRH to female rats causes morphological changes in pituitary gland, ovaries, uterus and liver (HE and VG staining); effects on pituitary, hepatic and blood enzyme activities (histochemical and kinetic methods, respectively), and on the blood lipid profile (colorimetric methods); and to what extent these changes are reversible. RESULTS: Applying analogs effectively inhibited ovulation, affected the uterine endometrium and changed histological appearance of the liver (e.g., steatosis). They altered activities of marker enzymes of cellular respiration, gluconeogenesis and intracellular digestion in the liver and, partially in the pituitary gland, caused undesirable changes in the activities of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and creatine kinase, and a concentration of cholesterol HDL fraction and triglycerides in the blood. Both morphological and enzymatic effects were more evident after antagonist administration; changes in the blood lipid profile were more evident after agonist administration. In both analogs histological and enzymatic changes persisted a relatively long time after the discontinuation of the treatment. CONCLUSIONS: The low dose of dalarelin and cetrorelix is sufficient to cause limited damage of hepatic cells and may modify the function of pituitary, ovaries, uterus and liver as well as other organs, even after discontinuation of the treatment. International Scientific Literature, Inc. 2012-08-01 /pmc/articles/PMC3560692/ /pubmed/22847193 http://dx.doi.org/10.12659/MSM.883264 Text en © Med Sci Monit, 2012 This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. |
spellingShingle | Basic Research Suszka-Œwitek, Aleksandra Czekaj, Piotr Pająk, Jacek Skowronek, Rafał Wrona-Bogus, Katarzyna Plewka, Danuta Kozłowska-Rup, Danuta Wiaderkiewicz, Ryszard Jankowski, Andrzej Morphological and enzymatic changes caused by a long-term treatment of female rats with a low dose of gonadoliberin agonist and antagonist |
title | Morphological and enzymatic changes caused by a long-term treatment of female rats with a low dose of gonadoliberin agonist and antagonist |
title_full | Morphological and enzymatic changes caused by a long-term treatment of female rats with a low dose of gonadoliberin agonist and antagonist |
title_fullStr | Morphological and enzymatic changes caused by a long-term treatment of female rats with a low dose of gonadoliberin agonist and antagonist |
title_full_unstemmed | Morphological and enzymatic changes caused by a long-term treatment of female rats with a low dose of gonadoliberin agonist and antagonist |
title_short | Morphological and enzymatic changes caused by a long-term treatment of female rats with a low dose of gonadoliberin agonist and antagonist |
title_sort | morphological and enzymatic changes caused by a long-term treatment of female rats with a low dose of gonadoliberin agonist and antagonist |
topic | Basic Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3560692/ https://www.ncbi.nlm.nih.gov/pubmed/22847193 http://dx.doi.org/10.12659/MSM.883264 |
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