Abstract
This study aimed to stand on genetic effects important of cabergoline drug. This toxic effect was evaluated for three different doses (0.05, 0.1, 0.5 mg/ml) in comparison with control (PBS/ phosphate buffer saline) both in vivo and in vitro. In vivo study involved the cytogenetic evaluation of cabergoline in mice by examination of mitotic index percentage (MI), micronucleus formation (MN) and chromosomal aberrations. Result indicated that all the tested doses cause significant reduction in MI percentage, while significant rise was seen with both MN formation and all studied chromosomal aberrations. While in vitro study involved measuring the effect of cabergoline on normal cell line (REF/ Rat embryonic fibroblast) by studing cell viability through MTT assay and a TP53 codon 72 polymorphism (rs1042522) through (PCR-RFLP). Results recorded that cabergoline caused high proliferation of normal cells at all doses and p53 polymorphism showed that the Arg allele yielding two fragments 213 and 140 bp after cleaving with BstuI,, while the Pro allele had a single 353 bp band because it did not cleaved by BstuI. In conclusion and according to the results care should be taken while obtaining cabergoline as a results of its genetic side effects.
Highlights
Cabergoline brand names ( Dostinex and Cabase) was approved by the FDA on 1996 for treatment of prolactinemia which is characterized by hypersecretion of prolactin which is derived from lactotroph cells in the pituitary gland [1, 2]
The PBS and cabergoline were given orally for fourteen days, and the mice were sacrificed at the day fifteenth, and cytogenetic analysis was performed Cytogenetic Experiments Mitotic Index (MI) Assay: The procedure was done according to method described by [14] and the calculation of mitotic index percentage (MI) percentage was done as follows: under the high power (40X) of the compound light microscope the slides were examined and thousands of non-divided and divided cells were mesured and the rate of MI was counted in the following equation: nomber of divided cells
Extraction of DNA: After preparation of cell line and treatment with cabergoline from the previous step of cytotoxicity assay, the cells were harvested after treatment with trypsin, and transferred to a 1.5ml microcentrifuge tube followed by centrifugation at 13,000–16,000 × g for 10 seconds
Summary
Cabergoline brand names ( Dostinex and Cabase) was approved by the FDA on 1996 for treatment of prolactinemia which is characterized by hypersecretion of prolactin which is derived from lactotroph cells in the pituitary gland [1, 2].absorption of cabergoline from the gastrointestinal ( GIT) tract is highly different, usually occurring within half to four hours following a single oral dose and since the drug is intended for taken by mouth only, human bioavailability has not been determined [3].Long-acting dopamine D2 receptor agonist and direct inhibition on the prolactin secretion in the pituitary's lactotroph cells is cabergoline was shown in vivo experiments [4]. The PBS and cabergoline were given orally for fourteen days, and the mice were sacrificed at the day fifteenth, and cytogenetic analysis was performed Cytogenetic Experiments Mitotic Index (MI) Assay: The procedure was done according to method described by [14] and the calculation of MI percentage was done as follows: under the high power (40X) of the compound light microscope the slides were examined and thousands of non-divided and divided cells were mesured and the rate of MI was counted in the following equation: nomber of divided cells
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