Abstract
Podocyte injury represents the main reason for proteinuria and renal disease in diabetic and non-diabetic patients. Recently Liraglutide as a GLP-1 analog is hypothesized to play a vital role in preventing kidney damage by anti-inflammatory and anti-apoptotic effect mechanisms. This study was established to evaluate the effect of Liraglutide on deterioration that happens with time in chronic kidney disease. 36 male Wister rats with a weight of 250-300 g were used in this study. All selected animals were examined and determined to be normal on general examination. Rats were divided into three groups (12rats/group): control group: negative control group injected normal saline I.P, induction group: single I.P dose (7.5 mg/kg) of doxorubicin for 14 days then administered 0.5ml/kg normal saline intraperitoneal for 28 days, and treatment group: single I.P dose (7.5 mg/kg) of doxorubicin for 14 days then administered I.P Liraglutide 200μg/kg/day freshly dissolve in 0.5ml /kg normal saline 28 days. The treatment group appeared significantly decreased (P< 0.05) in the pro-inflammatory expression of TNF-α as compared with the induction group, while the treatment group revealed a significant increased (P< 0.05) in the expression of anti-apoptotic BCL-2 in the proximal tubule of the kidney. Besides the effect of Liraglutide on renal deterioration by lowering blood glucose, the main causes of oxidative stress, Liraglutide as GLP-1 analog can reduce the consequence of proteinuria in the cases of glomerulosclerosis and tubulointerstitial damage by decreased pro-inflammatory TNF-α expression and increase expression of BCL-2 in that cell.
Highlights
Podocyte injury playing role in the immune and none immune pathological glomerulonephritis in renal failure[1]
Renal fibrosis is related to chronic kidney disease (CKD), glomerulosclerosis, and tubulointerstitial fibrosis characterized by excessive deposition of protein in the extracellular matrix (ECM) of interstitial tubule and glomeruli
Regarding immune staining intensity of TNF alpha, the induction group without treatment observed a significant increased (P< 0.05) in the expression of TNF alpha in the epithelial cell of tubule when compared with other groups while the treatment group by Liraglutide for 28 days after induction revealed a significant decreased (P< 0.05) in the pro-inflammatory expression of TNF alpha when compared with induction group, otherwise still a significant higher (P< 0.05) than the control group, Figure 1, 2
Summary
Podocyte injury playing role in the immune and none immune pathological glomerulonephritis in renal failure[1]. Podocyte injury is the main reason for the occurrence of proteinuria and is developed in diabetic and non-diabetic patients with renal failure[5] It is decreased in the early diagnoses of type 1 and 2 diabetes with albumin excretion and decline podocyte injury[6, 7] Increased albumin in the tubule which responsible to consequence progression of kidney deleterious[8]. Renal fibrosis is related to chronic kidney disease (CKD), glomerulosclerosis, and tubulointerstitial fibrosis characterized by excessive deposition of protein in the extracellular matrix (ECM) of interstitial tubule and glomeruli. The sequence of tubulointerstitial fibrosis includes inflammatory cell infiltration; fibroblast activation and deposition of a huge amount of extracellular matrix (ECM), tubular degeneration, and microvascular rarefaction[14]. Aim of this study was to evaluate the effect of Liraglutide on deterioration that happen with time in chronic kidney disease through anti- inflammatory and anti -apoptotic protected mechanism
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