Combination of telmisartan with sildenafil ameliorate progression of diabetic nephropathy in streptozotocin-induced diabetic model.
Diabetic nephropathy (DN) is a leading cause of end-stage renal disease in the world. Several signaling pathways are involved in the pathogenesis of DN including elevation in level of angiotensin II, formation of advanced glycation end products (AGE), activation of protein kinase c (PKC), and lipid accumulation. These pathways activate one another mutually leading to oxidative stress, increasing expression of transforming growth factor beta-1(TGF-β 1) and release of interleukins and adhesion molecules, so the aim of this study is to interrupt more than pathogenic pathway to ameliorate the progression of DN. In the present study, white male rats (N=48) were divided into six groups (8 rats each), the first two groups served as normal control and a control vehicle group while the remaining four groups were rendered diabetic by a single intraperitoneal injection of Streptozotocin (STZ) and being left for 4 weeks to develop DN. Thereafter, the rats were divided into DN group, DN group receiving Telmisartan or Sildenafil or Telmisartan Sildenafil combination. After the specified treatment period, urine samples were collected (using metabolic cages) to measure proteinuria, animals were then euthanized, blood and tissue samples were collected for measurement of Blood glucose,BUN, S.Cr, LDL, NO, TGF-β1, IL-1β, AGEPs, and SOD. The combination therapy showed significant decrease in BUN, S.Cr,LDL, TGF-β1, IL-1β, Proteinuria and AGEPs and significant increase in SOD and NO. The findings showed that combination therapy was able to ameliorate DN and that the effects were superior to the single drugs alone.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
Nageh Ahmed
NA
El-Mahdy
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
Magda El-Sayed
ME
El-Sayad
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt. Electronic address: aya_111222333@yahoo.com.
Aya Hassan
AH
El-Kadem
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D001565:Benzoates / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood; D003404:Creatinine / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D003928:Diabetic Nephropathies / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D004359:Drug Therapy, Combination; D017127:Glycation End Products, Advanced / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011507:Proteinuria / Q000097:blood / Q000150:complications / Q000188:drug therapy; D051381:Rats; D000068677:Sildenafil Citrate / Q000494:pharmacology / Q000627:therapeutic use*; D013311:Streptozocin; D013482:Superoxide Dismutase / Q000378:metabolism; D000077333:Telmisartan; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D001562:Benzimidazoles; D001565:Benzoates; D001786:Blood Glucose; D008078:Cholesterol, LDL; D017127:Glycation End Products, Advanced; D053583:Interleukin-1beta; D053773:Transforming Growth Factor beta1; D009569:Nitric Oxide; D013311:Streptozocin; D003404:Creatinine; D000068677:Sildenafil Citrate; D013482:Superoxide Dismutase; D000077333:Telmisartan
Cytokines; Diabetic nephropathy; Nitric oxide; Oxidative stress; Sildenafil