In Vivo and In Vitro Study of the Genetic Effects of Cabergoline Drug

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.

Associations of TP53 codon 72 polymorphism with complications and comorbidities in patients with type 1 diabetes

Wild-type TP53 plays an important role in the regulation of immune response and systemic inflammation. In type 1 diabetes (T1D), TP53 pathways are upregulated and an increased susceptibility to apoptosis is observed. We hypothesize that TP53 codon 72 polymorphism could be associated with complications and comorbidities in patients with T1D. We have investigated the associations of the TP53 codon 72 polymorphism with the T1D complications and comorbidities (retinopathy, nephropathy, hypertension, dyslipidemia, autoimmune thyroiditis, and celiac disease) in 350 patients. The key results of our approach are as follows: (1) In diabetic subjects, the Pro/Pro genotype is associated with an increased risk of microvascular complications, dyslipidemia, and celiac disease; (2) the Arg/Arg variant is associated with a decreased risk of autoimmune thyroiditis and celiac disease; (3) the Pro allele is associated with an increased risk of dyslipidemia, autoimmune thyroiditis, and celiac disease. Although further studies are required, our results for the first time indicate that the TP53 codon 72 polymorphism could be considered a genetic marker to predict the increased susceptibility to some T1D complications and comorbidities. Key messages We analyzed the TP53 codon 72 polymorphism in patients with T1D. Pro/Pro genotype is associated with an increased risk of microvascular complications, dyslipidemia, and celiac disease. The Arg/Arg variant is associated with a decreased risk of autoimmune thyroiditis and celiac disease. The Pro allele is associated with an increased risk of dyslipidemia, autoimmune thyroiditis, and celiac disease.