Topical Sildenafil in Comparison with Tacrolimus on Induced Atopic Dermatitis in Mice
Abstract
Background: Atopic dermatitis (AD) is characterized by xerosis (increased water loss through the skin) and is characterized by a chronic, recurring itchy skin inflammatory skin disease. It is a very difficult-to-treat skin disorder that affects a lot of infants and young children. Atopic dermatitis has a multifaceted cause, including genetic issues, immunological disruptions, skin barrier degradation, and environmental triggers. Atopic dermatitis is characterized by elevated production of cytokines related to the T helper 2 pathway, namely interleukin-4 and interleukin-13. It's possible to divide the onset of AD into three distinct phases: acute, subacute, and chronic. It is generally accepted that glucocorticoids and calcineurin inhibitors are the first lines of treatment for atopic dermatitis. However, there may be side effects from using calcineurin inhibitors or corticosteroids for an extended period of time. As a result, there is a pressing need for the development of a novel, but safe, approach to the treatment of atopic dermatitis that may provide desirable clinical results while minimizing undesirable adverse effects. Sildenafil is a selective, reversible inhibitor of the phosphodiesterase type 5 (PDE5) enzyme. It has been shown to effectively treat a wide range of medical conditions, such as erectile dysfunction and pulmonary arterial hypertension.
Aim of the Study: The goal of this study was to see how well sildenafil treat atopic dermatitis in a mouse model that had been given the disease.
Methods: The most current research uses a randomized, controlled design using animals. 50 male Albino mice (weighing in at 20–30g) were taken from the Veterinary Medicine Animal House at the University of Baghdad and randomly split into five groups. Fifty mice had their dorsal skin treated with 1-chloro-2,4-dinitrobenzene (DNCB) to induce atopic dermatitis, and the mice were then randomly split into five groups. There were 10 control (apparently healthy) mice in Group I and 10 induced atopic dermatitis mice in Group II, both of which received no therapy. Group III: 10 mice with atopic dermatitis developed on day 6 were given tacrolimus 0.1% ointment topically For the next 21 days, every morning at 9:00 a.m. Group IV: Ten mice with induced atopic dermatitis on day 6 of the induction period received topical ointment containing 2% Sildenafil once daily at 9:00 a.m. for the next 21 days, whereas Group v : received the same treatment but with vehicle ointment beginning on day six of induction. Histopathology, immunohistochemistry for interleukin-4 and interleukin-13, an observational severity score, and the number of neutrophils, lymphocytes, monocytes, and eosinophils in the mice's blood were all looked at at 9:00 a.m. for the next 21 days.
Results: Changes in the percentages of several types of white blood cells in the blood, including neutrophils, lymphocytes, and monocytes When contrasting the group with induced, untreated AD with the control (apparently healthy) group, statistically significant elevations in eosinophil count, as well as immunohistochemistry for interleukin 13( IL-13) and interleukin 4 (IL-4), were observed and histopathological scores (epidermal thickness, hyperkeratosis, parakeratosis, erosion, and inflammation).
Compared to the untreated AD-induced group, sildenafil 2%, and Tacrolimus-treated groups all had significantly lower CBC counts, immunohistochemical (IHC) IL-4 and IL-13 staining, and histopathological scores. Immediately after treatment with sildenafil or Tacrolimus, P < 0.05. Tacrolimus and sildenafil treatment groups show the greatest improvements (P <0.05) in histopathological scores for inflammation and hyperkeratosis and observational severity scores, respectively.
Conclusions: It seems that sildenafil 2% ointment, and tacrolimus 0.1% all work to treat the induced AD mouse model, with sildenafil being a bit more effective than tacrolimus.
