Induction of acantholysis in organ explant culture by penicillamine and captopril

Yokel, B. K.

doi:10.1001/archderm.125.10.1367

Cited by 33 publications

(25 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…With the non-immunological mechanism, the drug would interact directly on the epidermal antigens either by modifying the synthesis of the adhesion molecules or by binding the already synthesized ones [6]. Acantholysis, therefore, would dependent on a mere biochemical mechanism without any immunological involvement.…”

Section: Discussionmentioning

confidence: 99%

Fosinopril as a Possible Pemphigus-Inducing Drug

Parodi¹,

Cozzani²,

Milesi³

et al. 2002

Dermatology

View full text Add to dashboard Cite

Fosinopril has recently been added to the angiotensin-converting enzyme inhibitors inducing pemphigus. The observation of a patient in whom pemphigus vulgaris (PV) worsened after taking fosinopril prompted us to study an experimental way to assess its responsibility. Slices of normal human skin (NHS) were simultaneously incubated for 2, 6, 12 and 24 h at 4°C with progressively diluted fosinopril and captopril solutions and used as indirect immunofluorescence (IIF) substrates for 2 sera containing anti-desmoglein-3 (anti-Dsg3) antibodies at a dilution of 1/160. With captopril, IIF was negative, irrespective of dilution and time of incubation. Only at 1/40,000 dilution was IIF positive. With fosinopril, IIF was negative for the 2- and 6-hour-long incubations but turned positive after 12 h and so remained with all other solutions and incubation times. IIF negativity with captopril suggests that anti-Dsg3 antibodies contained in the PV sera were unable to find molecules in NHS to bind to. Captopril would therefore induce acantholysis by blocking the adhesion molecules. With fosinopril, instead, a partial block of the adhesion molecules was seen only with the very concentrated solution, unlikely to occur in vivo. Fosinopril, therefore, is probably unable to block the adhesion molecules in vivo. Our method might be used to verify the acantholytic properties of a drug.

show abstract

Section: Discussionmentioning

confidence: 99%

Fosinopril as a Possible Pemphigus-Inducing Drug

Parodi¹,

Cozzani²,

Milesi³

et al. 2002

Dermatology

View full text Add to dashboard Cite

show abstract

“…pyrazolon derivatives [51,52] and rifampicin [53][54][55][56]. It would be interesting to investigate whether these drugs cause intraepidermal acantholytic splits in vitro, as penicillamine and other thiol drugs [32][33][34][35][36],…”

Section: Penicillins and Cephalosporinsmentioning

confidence: 99%

“…When added to normal human skin cultured in vitro they provoke acantholytic splittings microscopically [32][33][34][35][36] and ultrastructurally [36] similar to those produced in vivo by pemphigus auto antibodies. It has been suggested that the above-mentioned drug interference with the keratinocyte membrane, the alteration of its biochemistry and antigenicity are the first links of a long chain of events that leads to the production of the clinical manifestations of the disease.…”

mentioning

confidence: 99%

An Active Amide Group in the Molecule of Drugs That Induce Pemphigus: A Casual or Causal Relationship?

Wolf¹,

Brenner²

1994

Dermatology

View full text Add to dashboard Cite

Traditionally, drugs that are capable of inducing pemphigus are divided into two main groups according to their chemical structure, in particular, the existence of a sulfhydryl group in their molecule. Thus, two groups are formed: (1) drugs containing a sulfhydryl radical (thiol drugs or SH drugs) and (2) nonthiol or other drugs. Much emphasis has been put on the role of the sulfhydryl group in the pathogenesis of drug-induced pemphigus. The effects of this group have been extensively studied, and a logical paradigm on the mode of its action has been created. However, no attempt has been made to search for other biochemical radicals which might have an influence on the activation/triggering of this disease. The aim of the present report is to draw attention to a chemical group common to the molecule of several drugs that have been associated with the induction of pemphigus. Careful analysis of the chemical structure of nonthiol drugs known to induce pemphigus revealed that several of them share an active amide group in their molecule. We believe that this group might be responsible for the induction of the disease; thus, a third group of drugs capable of triggering pemphigus can be formed, namely drugs containing an active amide group. Several drugs of this group are discussed

show abstract

“…enalapril) (24)(25)(26)(27)(28)(29). Interestingly, most drugs implicated in inducing pemphigus, when added to normal human skin specimens cultured in vitro, were able to cause acantholytic splitting very similar to that produced by pemphigus antibodies both in vivo and in vitro in the absence of pemphigus antibodies or any other immunological factors (24)(25)(30)(31)(32). In these experiments, the drugs tested started a biochemical chain of events that culminated in loss of desmosomal function with no apparent intervention of immune mediators (biochemical acantholysis) (33-38).…”

mentioning

confidence: 99%

Tannic Acid Induces in vitro Acantholysis of Keratinocytes via IL-1α and TNF-α

Feliciani

Ruocco

Zampetti

et al. 2007

Int J Immunopathol Pharmacol

View full text Add to dashboard Cite

The mechanism of acantholysis in pemphigus vulgaris (PV) is an intriguing argument since several chemical mediators are implicated. We previously reported a central role for IL-la and TNF-a, both able to regulate complement activation and plasminogen activators. Very little is known about what triggers the disease (drugs, viruses or food). In this study, we evaluate the molecular role of tannins in acantholysis. By HPLC chromatography we measured tannic acid (TA) and gallic acid (GA) in blister fluid of 4 groups of patients divided according to their dietary habits, including a regular diet, a diet rich in tannins, a diet free of tannins, and a group of pemphigus patients. Blister fluid was obtained from patients using a suction blister apparatus. We show that people with a diet rich in tannins have increased tannin metabolites (TA and GA) in the skin in respect to controls (tannin-rich diet: GA = 194.52±2.39 nmol/ml; TA = 348.28±1.4 nmol/ml versus tannin-Mediterranean diet: GA = 15.28±1.63 nmol/ml; TA = 22.81±1.68 nmol/ml). PV patients showed similar values to the Mediterranean diet population (PV patients: GA = 95.8±1.97 nmol/ml; TA = 199.09±4.15 nmol/ml versus Mediterranean diet: GA = 83.53±2.35 nmol/ml; TA = 195.1±2.50 nmol/ml). In an in vitro acantholysis system using TA and PVIgG we show that TA 0.1 mM in NHEK culture is able to induce acantholysis. This effect was able to amplify the acantholytic action of PV-IgG in vitro. A blocking study using anti IL-la and anti TNF-a antibodies showed a reduction in TA-induced acantholysis. Taken together, these results suggest that a diet rich in tannins could be a trigger in genetically predisposed patients. If these data are confirmed, a complementary diet poor in tannins may be useful in patients affected by PV.Immunoglobulin-G deposition on desmoglein (Dsg) protein 3, and sometimes Dsg-l, is the main diagnostic criterion for pemphigus vulgaris (PV), and IgG-Dsg linkage is the most important phase in the development of this bullous disease. To date, we do not know which may be the triggering factors able to induce acantholysis in pemphigus.Acantholysis is a morpho functional change of malpighian epithelia which results in the loss of intercellular cohesion and brings cell keratinization to a standstill. Although acantholytic changes may be seen in numerous heterogeneous clinical conditions, the pemphigus group is the mucocutaneous disorder where acantholysis may be considered the histologic

show abstract

Induction of acantholysis in organ explant culture by penicillamine and captopril

Cited by 33 publications

References 0 publications

Fosinopril as a Possible Pemphigus-Inducing Drug

Fosinopril as a Possible Pemphigus-Inducing Drug

An Active Amide Group in the Molecule of Drugs That Induce Pemphigus: A Casual or Causal Relationship?

Tannic Acid Induces in vitro Acantholysis of Keratinocytes via IL-1α and TNF-α

Contact Info

Product

Resources

About