Aminaftone, a Derivative of??4-Aminobenzoic Acid, Downregulates??Endothelin-1 Production in??ECV304 Cells

Abstract

Aminaftone inhibits ET-1 production in cell cultures by interfering with transcription of the PPET-1 gene. These findings may account for the clinical efficacy of aminaftone in the treatment of capillary disorders and may encourage conduct of further clinical trials.

Aminaphtone therapy in patients with type 1 diabetes and albuminuria: a case report

“…He was re-evaluated 2 months after discontinuation of the drug and, again, showed an increase in proteinuria (from 98.3mg/dL to 573mg/dL = +474.7mg/dL), substantially the same GFR and creatinine values, and a new increase in arterial blood pressure to 140/85mmHg: this kind of re-challenge clearly demonstrates the relationship between proteinuria and aminaphtone therapy. The recent preclinical findings about aminaphtone (anti-ET-1 and anti-E-selectin activities together with a significant endothelial antiphlogistic effect) [ 19 – 23 ] seem to correlate with this result, confirming that microangiopathy is the leading cause of microalbuminuria in patients with IDDM.…”

“…Aminaphtone (2-hydroxy-3-methyl-1,4-napthohydroquinone-2-p-aminobenzoate) is a synthetic molecule derived from four aminobenzoic acids which is currently employed for “capillary disorders” and for chronic venous insufficiency [ 18 ]. This drug has recently demonstrated the ability to downregulate ET-1 production in ECV304 cells by interfering with transcription of preproET-1 (PPET-1) gene expression [ 19 ]. At the same time, cytofluorometry has shown that aminaphtone significantly reduces the expression of E-selectin (endothelial-leukocyte adhesion molecule 1; ELAM-1) both in resting and in ET-B -activated ECV304 cells in a dose-dependent manner [ 20 ].…”

Aminaftone in the Treatment of Raynaud’s Phenomenon in Systemic Sclerosis: New Perspectives

“…Another molecule, Aminaftone, compound 2-hydroxy-3-methyl1-1,4-napthohydroquinone-2-p-aminobe nzoatate (C18-H15-N-O4) used in the treatment of capillary disorders, has been reported to be effective in reducing vessel permeability and the number and size of leg ulcers in patients with chronic venous insufficiency [12,13,14]. Results from preliminary and open label studies suggested that the activity of aminaftone may be related to downregulation of ELAM-1 and VCAM-1 expression and to endothelium remodelling induced by down-regulates ET-1 [15,16].…”

Endothelin-1 Role in Human Eye: A Review

“…In a recent study, Scorza et al [80] analyzed the influence of aminaphtone, a 4-aminobenzoic acid derivative clinically used for the treatment of capillary disorders, on ET-1 protein production, pre pro endothelin (PPET-1) gene expression and ECE activity in human ECV304 cells after incubation with physiological concentrations of interleukin-1 β (IL-1 β ). ECV304 cells originate from endothelial cells of human umbilical vein by spontaneous transformation and have been widely used for in vitro studies of the endothelium and ET-1 pathways, since they are able to produce ET-1 and express the mRNA and the α -isoform of ECE.…”

“…They demonstrated that addition of different concentrations of aminaphtone to ECV304 cells reduces production of ET-1 and downregulates PPET-1 gene expression in a concentration-dependent manner. Moreover they observed that aminaphtone at a concentration of 6  μ g/mL, which roughly represents the peak plasma concentration reached after oral administration of 75 mg of the drug, reverts production of ET-1 to baseline values [80]. This may encourage clinical trials on the efficacy of this molecule in the downregulation of ET-1 levels in eye disorders.…”