The vascular impact of dapagliflozin, liraglutide, and atorvastatin alone or in combinations in type 2 diabetic rat model

Diabetic dyslipidemia is a significant contributor in the pathogenesis of type 2 diabetes (T2D). The study aimed at comparing the effect of dapagliflozin, liraglutide, and atorvastatin alone or their combinations on lipids and inflammatory markers and their vascular impact in T2D rats. There were 56...

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Published in:	Fundamental & clinical pharmacology Vol. 36; no. 4; pp. 731 - 741
Main Authors:	El Medany, Azza Mohammed Hafez, Hammadi, Sami Hussein Mahmoud, Khalifa, Hoda Mahmoud, Ghazala, Rasha Abdelmawla, Zakaria Mohammed, Hend Samir
Format:	Journal Article
Language:	English
Published:	England Wiley Subscription Services, Inc 01-08-2022
Subjects:	Advanced glycosylation end products Albumins Animals Atorvastatin Atorvastatin - pharmacology Atorvastatin - therapeutic use Benzhydryl Compounds C-Reactive Protein - metabolism Cholesterol Cholesterol, LDL - therapeutic use Corpuscles Creatinine dapagliflozin Density Diabetes Diabetes mellitus Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Experimental - chemically induced Diabetes Mellitus, Experimental - drug therapy Diabetes Mellitus, Type 2 - drug therapy diabetic dyslipidemia Dyslipidemia Glucosides Glycated Hemoglobin - metabolism Glycated Hemoglobin - therapeutic use Glycosylation Hemoglobin High density lipoprotein Inflammation Kidneys Lipids Lipoproteins liraglutide Liraglutide - pharmacology Liraglutide - therapeutic use Low density lipoprotein Male Nicotinamide Parameters Pathogenesis Pharmacology Pyrroles Rats Rodents Streptozocin Subgroups Thyroid-stimulating hormone Thyrotropin - therapeutic use liraglutide atorvastatin dapagliflozin diabetic dyslipidemia
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Summary:	Diabetic dyslipidemia is a significant contributor in the pathogenesis of type 2 diabetes (T2D). The study aimed at comparing the effect of dapagliflozin, liraglutide, and atorvastatin alone or their combinations on lipids and inflammatory markers and their vascular impact in T2D rats. There were 56 male albino rats included in the study and divided into two main groups. Group A (8 rats) served as normal control. Group B (48 rats) were streptozotocin–nicotinamide‐induced diabetic rats. Subgroups (B‐1, B‐2, B‐3, B‐4, B‐5, and B‐6) received (no medications, dapagliflozin, liraglutide, atorvastatin, dapagliflozin + atorvastatin, and liraglutide + atorvastatin), respectively. Urine albumin/creatinine ratio (UACR), glycosylated hemoglobin (HBA1c), fasting serum glucose (FSG), serum low‐density lipoprotein‐cholesterol (LDL‐C), high‐density lipoprotein‐cholesterol (HDL‐C), TGs, lipoprotein(a) Lp (a), serum thyrotropin (TSH), highly sensitive C‐reactive protein (hs‐CRP) and advanced glycation end products (AGEs), were assessed. Qualitative and quantitative histological examination of kidneys focused on renal corpuscles. Dapagliflozin improved the studied parameters but with statistically insignificant increase in LDL‐C, Lp (a) and significant increase in UACR. Atorvastatin improved the studied parameters but with statistically insignificant increase in FSG and HbA1C. Liraglutide and the combination groups significantly improved all studied parameters. Histologically, liraglutide and atorvastatin produced therapeutic effect, while dapagliflozin depicted nephrotoxic effect. Combination groups resulted in better effects with normalization of most of renal corpuscles. There were positive correlations between LDL‐C and hs‐CRP, AGEs, TSH and mesangial expansion. Combination of atorvastatin with liraglutide can improve its vasculoprotective effect. Moreover, combination of atorvastatin with dapagliflozin can ameliorate its possible nephrotoxic effect.
ISSN:	0767-3981 1472-8206
DOI:	10.1111/fcp.12765