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Interference with TGF beta 1-Mediated Inflammation and Fibrosis Underlies Reno-Protective Effects of the CB1 Receptor Neutral Antagonists AM6545 and AM4113 in a Rat Model of Metabolic Syndrome
Faculty
Pharmacy
Year:
2021
Type of Publication:
ZU Hosted
Pages:
Authors:
Hany Mohamed Abdelmalek Mahmoud ElBassossy
Staff Zu Site
Abstract In Staff Site
Journal:
MOLECULES MDPIST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
Volume:
Keywords :
Interference with , beta 1-Mediated Inflammation , Fibrosis
Abstract:
The role of cannabinoid receptors in nephropathy is gaining much attention. This study investigated the effects of two neutral CB1 receptor antagonists, AM6545 and AM4113, on nephropathy associated with metabolic syndrome (MetS). MetS was induced in rats by high-fructose high-salt feeding for 12 weeks. AM6545, the peripheral silent antagonist and AM4113, the central neutral antagonist were administered in the last 4 weeks. At the end of study, blood and urine samples were collected for biochemical analyses while the kidneys were excised for histopathological investigation and transforming growth factor beta 1 (TGF beta 1) measurement. MetS was associated with deteriorated kidney function as indicated by the elevated proteinuria and albumin excretion rate. Both compounds equally inhibited the elevated proteinuria and albumin excretion rate while having no effect on creatinine clearance and blood pressure. In addition, AM6545 and AM4113 alleviated the observed swelling and inflammatory cells infiltration in different kidney structures. Moreover, AM6545 and AM4113 alleviated the observed histopathological alterations in kidney structure of MetS rats. MetS was associated with a ten-fold increase in urine uric acid while both compounds blocked this increase. Furthermore, AM6545 and AM4113 completely prevented the collagen deposition and the elevated expression of the TGF beta 1 seen in MetS animals. In conclusion, AM6545 and AM4113, possess reno-protective effects by interfering with TGF beta 1-mediated renal inflammation and fibrosis, via peripheral action.
Author Related Publications
Hany Mohamed Abdelmalek Mahmoud ElBassossy, "Nitric-Oxide-Mediated Vasodilation of Bioactive Compounds Isolated from Hypericum revolutum in Rat Aorta", MDPIST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND, 2021
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Hany Mohamed Abdelmalek Mahmoud ElBassossy, "Self-Nanoemulsifying Drug Delivery System Loaded with Psiadia punctulata Major Metabolites for Hypertensive Emergencies: Effect on Hemodynamics and Cardiac Conductance", FRONTIERS MEDIA SAAVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE CH-1015, SWITZERLAND, 2021
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Hany Mohamed Abdelmalek Mahmoud ElBassossy, "Rp-HPLC Determination of Quercetin in a Novel D-alpha-Tocopherol Polyethylene Glycol 1000 Succinate Based SNEDDS Formulation: Pharmacokinetics in Rat Plasma", MDPIST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND, 2021
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Hany Mohamed Abdelmalek Mahmoud ElBassossy, "Modulation of preeclampsia by the cholinergic anti-inflammatory pathway: Therapeutic perspectives", PERGAMON-ELSEVIER SCIENCE LTD, 2021
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Hany Mohamed Abdelmalek Mahmoud ElBassossy, "A Nano-Pharmaceutical Formula of Quercetin Protects from Cardiovascular Complications Associated with Metabolic Syndrome", FRONTIERS MEDIA SAAVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE CH-1015, SWITZERLAND, 2021
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