The role of isotretinoin in acne therapy: why not as first-line therapy? facts and controversies

Rigopoulos, Dimitrios; Larios, George; Katsambas, Andreas

doi:10.1016/j.clindermatol.2009.03.005

Cited by 77 publications

(64 citation statements)

References 77 publications

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“…Furthermore, it is already in use in many countries in clinical practice without any significant side effects (Sativex) (16). This is especially promising, because the currently available, most effective anti-acne agent, isotretinoin, is known to cause serious side effects (2,69,70). These data, together with our current findings, point to a promising, costeffective, and, likely, well-tolerated new strategy for treating acne vulgaris, the most common human skin disease.…”

Section: Discussionmentioning

confidence: 52%

Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes

Oláh¹,

Tóth²,

Borbíró³

et al. 2014

J. Clin. Invest.

229

236

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Section: Discussionmentioning

confidence: 52%

Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes

Oláh¹,

Tóth²,

Borbíró³

et al. 2014

J. Clin. Invest.

229

236

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“…Isotretinoin leads to sebaceous gland atrophy through inhibiting basal sebocyte proliferation, and decreases the release of pro-inflammatory mediators through reduction of neutrophil migration and P. acnes population. [171827] Because beta-defensin release was influenced by pro-inflammatory cytokines, isotretinoin could be effective in the release of hBD through all of these abovementioned mechanisms. Harder et al .…”

Section: Discussionmentioning

confidence: 99%

Comparison of efficacy of doxycycline and isotretinoin on cutaneous human beta-defensin-1 and -2 levels in acne vulgaris

et al. 2018

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Background:Recent studies have shown that human beta-defensin-1 (hBD-1) and (human beta-defensin-2 hBD-2), which are antimicrobial peptides produced by the skin, play a role in the pathogenesis of acne vulgaris (AV).Objective:The aim of this study was to determine the role of antimicrobial peptides in the pathogenesis of AV and enlighten the effects of doxycycline and isotretinoin in the expression of these defensins in AV.Materials and Methods:A total of 44 patients (22 patients in each group) with Grade 6 and 8 AV who were indicated doxycycline or isotretinoin for their treatment, and 20 healthy volunteers were included in this study. Pretreatment cutaneous samples were obtained from pustular lesions and uninvolved skin of AV patients and were repeated after the treatment. Only one biopsy was obtained from controls.Results:Cutaneous levels of hBD-1 and hBD-2 were significantly increased in AV patients when compared with healthy controls (P<0.05). Doxycycline therapy achieved a decrease in hBD-1 levels (P<0.05), whereas isotretinoin therapy achieved a reduction in hBD-2 levels when compared with pretreatment levels (P<0.05). Posttreatment hBD-1 and hBD-2 levels were not different between doxycycline and isotretinoin groups (P>0.05).Conclusion:In the light of these results, it was reasonable to assume the role of hBD-1 and hBD-2 in the pathogenesis of AV. Our results showing a significant reduction in hBD-1 staining with doxycycline treatment and in hBD-2 with isotretinoin suggested that some part of their anti-acne effect worked through these mechanisms.

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“…In addition, delivery of retinoids is relatively inefficient as distribution is restricted by their high lipophilicity and limited absorption from oral administration. Consequently, the dose of a 13cRA regimen is relatively high (40-80 mg/day; Rigopoulos et al 2010); there are promising innovations in drug delivery methods, such as cyclodextrins, to improve the plasma concentrations of smaller doses of 13cRA (Lin et al 2007, Trichard et al 2007.…”

Section: Discussionmentioning

confidence: 99%

13-cis-Retinoic acid specific down-regulation of angiotensin type 1 receptor in rat liver epithelial and aortic smooth muscle cells

Snyder

Thekkumkara²

2011

Journal of Molecular Endocrinology

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Transcriptional repression through cis-and trans-acting factors enabling an alternate approach to control angiotensin type 1 receptor (AT1 or AGTR1 as listed in the MGI database) expression has not been studied. In previous investigations, treatment with retinoic acid was found to be associated with enhanced insulin sensitivity. In our previous study, expression of AT1 was found to be inversely correlated with intracellular glucose concentrations. Therefore, we hypothesized that 13-cis-retinoic acid (13cRA), an antioxidant, enhances insulin-sensitive glucose-mediated downregulation of the AT1. In this study, we used continuously passaged rat liver epithelial cells. Our study shows that cells exposed to 13cRA specifically down-regulated the AT1 protein in a dose-and time-dependent manner, independently of any change in receptor affinity. Down-regulation of the AT1 expression leads to reduced AngII-mediated intracellular calcium release, a hallmark of receptor-mediated intracellular signaling. Similarly with receptor down-regulation, we observed a significant reduction in AT1 mRNA; however, the AT1 down-regulation was independent of insulin-sensitive glucose uptake and retinoic acid receptor activation (RAR/RXR). Treatment with 13cRA resulted in phosphorylation of p42/p44 MAP kinases in these cells. Subsequent studies using MEK inhibitor PD98059 prevented 13cRA-mediated AT1 down-regulation and restored AngII-mediated intracellular calcium response. Furthermore, 13cRA-mediated inhibitory effects on AT1 were validated in primary rat aortic smooth muscle cells. In summary, our results demonstrate for the first time that 13cRA has a glucose-and RAR/RXR-independent mechanism for transcriptional inhibition of AT1, suggesting its therapeutic potential in systems in which AT1 expression is deregulated in insulin-sensitive and -insensitive tissues.

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The role of isotretinoin in acne therapy: why not as first-line therapy? facts and controversies

Cited by 77 publications

References 77 publications

Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes

Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes

Comparison of efficacy of doxycycline and isotretinoin on cutaneous human beta-defensin-1 and -2 levels in acne vulgaris

13-cis-Retinoic acid specific down-regulation of angiotensin type 1 receptor in rat liver epithelial and aortic smooth muscle cells

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