Vol 6-1 Original Research Article

Topical Application of Aprepitant Inhibits Erlotinib-induced Facial Dermatitis/Hair Loss

Iu Tong Mak*, Jay H. Kramer*, Joanna J. Chmielinska*, William B. Weglicki

Department of Biochemistry and Molecular Medicine, The George Washington University, School of Medicine and Health Sciences, Ross Hall, Rm 228, 2300 Eye Street, NW. Washington DC 20037; USA

Erlotinib, an EGFR-TKI, has been used as an effective anti-tumorigenesis agent against several cancers including lung, colon, head and neck. However, it has been reported to cause significant and severe cutaneous side effects. Our previous studies implicated substance P, a neuropeptide, as a significant mediator of skin toxicity. Our present study was designed to determine if the topical application of aprepitant, a specific substance P receptor blocker, would be protective against these skin side effects. Erlotinib in the diet was administered to the rats for 12 weeks. Facial rash and hair loss began to occur after 6 weeks and were most severe at 12 weeks when animals were sacrificed. Topical treatment of aprepitant to the facial area 3 times a week showed dose-dependent and progressive inhibition up to 70% of the induced dermatitis/hair loss. These results were comparable to the effects produced by oral doses in our prior study. At sacrifice, we also found significant elevations of neutrophil superoxide, that were inhibited by topical aprepitant, along with elevated plasma 8-isoprostane levels, that were also suppressed. Facial skin samples revealed increased leukocyte (CD11b positive) infiltration in the erlotinib-treated rats, which were substantially reduced by the topical aprepitant. In conclusion, the indicators of reactive oxidative species (ROS) suggest that neurogenic inflammation played a critical role in causing EGFR-TKI-induced toxicity; it also confirmed that the systemic inhibition of ROS production due to blockade of substance P action was significantly protective against the dermatitis/hair loss pathology.

DOI: 10.29245/2767-5092/2024/1.1174 View / Download Pdf
Vol 6-1 Review Article

Role of Actives in Emollients in Atopic Dermatitis

B. S. Chandrashekar1, Thomas Luger2, S. C. Rajendran3, Anchala Parathasaradhi4, Jayakar Thomas5, Anil Ganjoo6, Divya Sharma7, Rajetha Damishetty8, Nazima Ruby9, Vijayalakshmi Sujay10, Snehal Sriram11, Satish Udare12, Dhara Shah13, Jayesh Rajgopal*14

1Chief Dermatologist / Medical Director: Cutis, Academy of Cutaneous Sciences, Bengaluru

2Department of Dermatology, University of Muenster, Muenster, Germany

3Director and Senior Consultant Dermatologist at Cosmetic Skin Care Clinic, Koramangala, Bengaluru

4Senior Consultant Dermatologist at Anchala’s Skin Institute, Hyderabad

5Professor & Head, Chettinad Hospital and Research Institute, Chennai

6Director, Skinnovation Clinics, New Delhi

7Chief Consultant at Dr Divya’s Skin and Hair Solutions, Bangalore

8Additional Medical director, Oliva chain of 23 Hair and Skin Clinics

9Consultant Dermatologist, Radiant Skin Clinic, Bengaluru

10Consultant Dermatologist and Cosmetologist, Shree Skin and Cosmetic Clinic, Bengaluru

11Consultant and Head of Cosmetic Dermatology Department at Nahar Medical Center, Mumbai

12Medical Director of ‘Sparkle’ Skin and Aesthetic Centre, Vashi and ‘Disha Skin and Laser Institute’ Thane, Mumbai

13Head Medical Affairs, Mylan Pharmaceuticals Private Limited - A Viatris Company

14Senior Medical Manager, Mylan Pharmaceuticals Private Limited - A Viatris Company

The prevalence of atopic dermatitis (AD) in India is 2.7% (age 6–7 years) and 3.6% (age 13–14 years). Emollients remain mainstay treatment for atopic dermatitis. The present review article focuses on the role of active ingredients in emollients towards the management of AD. Article were selected by searching in database like Google Scholar and PubMed and were reviewed by the authors. Daily use of emollients from birth may significantly reduce the incidence of AD in a high-risk population. Emollients with a variety of active ingredients to target AD pathophysiology have been developed which contain active ingredients like liquorice extract (anti-inflammatory and anti-pruritic), niacinamide (restoration of barrier function), sterols (restoration of barrier function), laureth-9-polydocanol (anti-pruritic), xylitol (microbiome maintenance) and galacto-oligosaccharide (GOS) (microbiome maintenance). Emollient plus may be a useful adjunct to pharmacological therapy in AD and as maintenance therapy, providing rapid and significant improvements in skin moisture, epidermal barrier function, and signs and symptoms of AD.

DOI: 10.29245/2767-5092/2024/1.1178 View / Download Pdf
Vol 6-1 Short Communication

Autophagy Regulates Transglutaminase-1 Expression and Vitamin C Enhances Autophagic Activity in Keratinocytes

Akira Hagino*, Mitsuhiro Gomi

Central R&D Laboratories, KOBAYASHI Pharmaceutical Co., Ltd., 1-30-3, Toyokawa, Ibaraki 567-0057, Japan

Vitamin C, known for its various effects on the skin, promotes epidermal differentiation and enhances skin barrier function. However, the underlying mechanism remains unclear. Autophagy is an intracellular degradation system that maintains cellular homeostasis. Although autophagy decrement has been associated with barrier defects in skin diseases, the mechanism by which autophagy regulates skin barrier function remains insufficiently understood. Therefore, this study aimed to investigate the relationship between autophagy and transglutaminase-1 (TGase-1), a molecule required to form the cornified envelope that contributes to skin barrier function. We also examined the effect of vitamin C on autophagy in epidermal keratinocytes. Autophagy modulation through the knockdown of autophagy-related molecules (ATG5, ATG7, and ATG13) significantly decreased TGase-1 expression in human epidermal keratinocytes. Furthermore, vitamin C treatment enhanced the autophagic activity of epidermal keratinocytes and suppressed TGase-1 expression decrease in ATG13 knockdown cells. In conclusion, TGase-1 expression can be regulated by autophagy, and vitamin C may be involved in skin barrier function through autophagy activation.

Abbreviations: TGase-1: transglutaminase-1; CE: cornified envelope; ATG5: autophagy related 5; ATG7: autophagy related 7, ATG13: autophagy related 13, LOR: loricrin; FLG: filaggrin; TBP: TATA-box binding protein; LC3: microtubule-associated protein 1 light chain 3; CQ: chloroquine; VC: vitamin C; CTL: control.

DOI: 10.29245/2767-5092/2024/1.1177 View / Download Pdf