5027
Marwa Helmy Ahmed Ali Elazma
Molecular Physiological Studies on The Effect of Certain Medicinal Plant on Pregnant Diabetic Rat
Diabetes type two, pregnancy, rosiglitazone, alkaloid lupin, DNA sequencing, DNA alignment, RNA secondary structure, single nucleotide polymorphism, and protein structure
DM is the most common pre-existing medical condition complicating pregnancy as, pregnancy exerts a diabetogenic effect. This is because the normal decrease of insulin sensitivity in pregnancy. Maternal diabetes constitutes an unfavorable environment for embryonic and fetoplacental development, and for the mother herself. So, the glycemic control for the pregnant women is vital. Rosiglitazone, a PPARɣ agonist, used to treat type two diabetes. However different ranges of side effects in response to rosiglitazone appeared. Such as edema, weight gain, congestive heart failure, and bone fractures. Lupin alkaloids are good candidates to exert both hypoglycemic and hypolipediemic effects. Hence, the study aims to investigate whether the lupin alkaloids possess beneficial effects on the glycemic control of the pregnant diabetic rat or not. To avoid the hazard effects caused by hypoglycemic drugs during the emergency period. Eighty pregnant diabetic rats were allocated into eight groups (Control, Lupin, rosiglitazone, Buffer, STZ, STZ+Rosi, STZ+Lupin, and STZ+Lupin+Rosi groups). Some blood biochemistries and compartments, mutations in Rattus PPARɣ exon 3 and exon 4, and the morphological abnormalities of the fetuses were assessed.The study showed that the treatment with rosiglitazone and/or lupin alkaloids results in, the decrease of hyperglycemia in pregnant diabetic rats and improvement of HOMA-IR score. Moreover all groups treated with rosiglitazone and/or lupin alkaloids enhanced the renal functions and caused the decrease of the blood urea, creatinine, and uric acid. On the other hand, it revealed the increase of AIP, atherogenic profile, and liver toxicity in rosiglitazone treated groups (either diabetic or non diabetic groups), in comparison to lupin alkaloids groups (diabetic and non diabetic). The combined group had shown significant results in decreasing the hyperglycemia and ameliorating other complications associated with diabetes or rosiglitazone administration.The molecular and bioinformatics studies showed a SNP (A/G) in position no. 123 in Rattus PPARɣ exon 3, which was remarkable for all of the studied groups in comparison to NCBI database reference sequences. Although this SNP was silent mutation but it affected the RNA secondary structure and decreased the rate of the protein translation. Also, there was three distinguishable SNPs (G/T), (C/T), and (C/T) on positions 157,158, and 159 respectively in Rattus PPARɣ exon 4, which can differentiate between diabetic and non diabetic animals. These SNPs cause the replacement of the alanine (A) by phenylalanine (F) in position no. 23in the translated polypeptide chain of the Rattus PPARɣ exon 4. These SNPs were thought to exert differential responses to the antidiabetic and hypolipidemic drugs.The administration of the rosiglitazone induced many embryonic abnormalities. So, the current study recommends the usage of lupin alkaloids during the pregnancy to avoid the hazard effects of rosiglitazone. Also, there is an urgent need for more studies to explore the effect of rosiglitazone on lipids and cardiovascular risk.
2015
M.Sc
Benha
Science