| Title | Cytotoxic drugs (AII-Trans-R-A and hydroxyurea) on caspase-3 activity in pregnant rat (liver and kidney) | |
| Authors | H. Frangou¹, S. Massouridou¹, E.-N. Emmanouil² and M. Nikoloussis²
1. Department of General Biology, Faculty of Medicine, Aristotle University, Thessaloniki, Greece 2. Department of Histology, Embryology and Anthropology, Faculty of Medicine, Aristotle University, Thessaloniki, Greece |
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| Citation | Frangou, H., Massouridou, S., Emmanouil, E.-N., Nikoloussis, M.: Cytotoxic drugs (AII-Trans-R-A and hydroxyurea) on caspase-3 activity in pregnant rat (liver and kidney), Epitheorese Klin. Farmakol. Farmakokinet. 21(1): : 24-30 (2007) | |
| Publication Date | Accepted for publication (Final version): 15 January 2007 | |
| Full Text Language | English | |
| Order – Buy | Ηλεκτρονική Μορφή: pdf (10 €) – Digital Type: pdf (10 €)
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| Keywords | Cytotoxic drugs, caspase-3 activity, pregnant rat. | |
| Other Terms | review article | |
| Summary | Hydroxyurea (HU) is a drug that causes birth defects in a variety of animals. Its pharmacologic actions include rapid killing of proliferating cells and profound inhibition of the synthesis of DNA. All-Trans-R-A is a Retinoid acid, natural derivative of vitamin A, which affect biological processes such as development, cell growth, and differentiation. AII-Trans-R-A as well as HU induces apoptosis in some cell types and tissues. Caspases belongs to a family of aspartate-specific cysteine proteases. Caspase-3 is an active caspase, effector, which degrades intracellular substrates. In healthy cells, caspases normally lie dormant. In response to diverse stimuli they become activated when cell death is required. The late stages of apoptotic process typically involve cleavage of specific target protein like lamin, actin or poly(ADP-ribose)polymerase. To further understand the apoptotic molecular mechanisms of AII-Trans-R-A and HU on rat liver and kidneys, caspase-3 activity was tested by colorimetric assay on subcellular fractions. Pregnant rats (230-260 g) were treated on Gestational days (GD), 9th, 10th with: a) corn oil, b) AII-Trans-R-A 50 mg/k.b. weight, c) NaCl 9=, d) HU 4.56 mg/k.b. weight. The animals were sacrificed at 17th day of pregnancy. The subcellular fractions were taken according to the method of Nordlie and Lardy, and the caspase-3 activity was determined by a colorimetric assay (kit, Sigma) based on the hydrolysis of the peptide substrate acetyl-Asp-Glu-Val-Asp p-nitroanilide (Ac-DEVD-pNA) by caspase-3, resulting the release of the p-nitroaniline (pNA) moiety. According to our results the caspase-3 activity was observed increased only in renal nuclear fraction after HU admmistration. There was no found any statistically difference with AH-Trans-R-A. In pregnant rat liver the caspase-3 activity was decreased after treatment with the above drugs in crude as well as in subcellular fractions. Our findings suggest that: a) HU may induce apoptosis in pregnant rat kidney cells via caspase-3 process, and b) All-Trans-R-A may produce downregulation of this process. | |
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Online ISSN 1011-6575
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