dehydroxymethylepoxyquinomicin and Dermatitis--Atopic

This study is aimed to further investigate the anti-atopic dermatitis (AD) activities of dehydroxymethylepoxyquinomicin (DHMEQ) ointment and compare its effect with that of tacrolimus ointment based on the previous study that DHMEQ improves AD-like lesions. AD were induced by 2,4-dinitroclilorobenzene/oxazolone (DNCB/OX) repeatedly on the ears of BABL/C mice while medical tape was additionally used to disrupt stratum corneum in order to exacerbate the lesions. The mice were randomly divided into groups, which are normal, vehicle, DHMEQ (0.1%) and tacrolimus (0.1%). Those in the last two groups were externally applied with DHMEQ ointment and tacrolimus ointment, respectively. The results showed that both of them significantly improved dermatitis symptoms of DNCB/OX-induced AD-like lesions, such as redness, itching, weeping, scaling and thickening of the skin, while reducing epidermis thickness, dermis thickness and the number of mast cells as well, which were examined histopathologically. In contrast with DHMEQ, tacrolimus led to a significant decrease in body weight after long-term application. Both DHMEQ and tacrolimus suppress DNCB-induced increase of serum total IgE and attenuate expression of inflammatory factors IL-4, IL-6, IL-13, IL-1β and interferon (IFN)-γ in the disrupted ear tissues. On the other hand, the mice applied with tacrolimus became obviously irritable, jumping up and down, and inflammatory exudation on the lesioned-skin surface of the mice was remarkably observed. Contrary to the side effects made by tacrolimus, DHMEQ didn't cause any adverse stimulus response. As a conclusion, DHMEQ is safer, milder and more suitable for long-term use than tacrolimus for the treatment of AD-like lesions.

Topics: Animals; Benzamides; Cyclohexanones; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Disease Models, Animal; Epidermis; Female; Humans; Immunoglobulin E; Immunosuppressive Agents; Inflammation Mediators; Mast Cells; Mice; Mice, Inbred BALB C; Ointments; Oxazolone; Tacrolimus

Dehydroxymethylepoxyquinomicin (DHMEQ) which is originally developed as an analog of antibiotic epoxyquinomicin C is a specific and potent inhibitor of NF-κB and has been shown to possess promising potential as an anti-inflammatory and anti-tumor agent.. This study examines DHMEQ's effect on therapeutic potential for atopic dermatitis (AD)-like lesions.. AD lesions were chronically induced by the repetitive and alternative application of 2,4-dinitrochlorobenzene (DNCB) and oxazolone (OX) on ears in BALB/c mice. The mice were then externally treated with DHMEQ ointment. Macroscopic and microscopic changes of the skin lesions were observed and recorded.. DHMEQ inhibited ear swelling and relieved clinical symptoms of the AD-like lesions induced by DNCB/OX in BALB/c mice. Histopathology examination illustrated that it significantly decreased DNCB/OX-induced epidermal thickness, the infiltration of inflammatory cells, and the count of mast cell. The elevated level of immunoglobulin E (IgE) in serum and the mRNA levels of interferon γ (IFN-γ), interleukin 4 (IL-4) and IL-13 in the ear tissues, were also suppressed by DHMEQ.. This study indicated that DHMEQ would be useful for the treatment of AD.

Topics: Animals; Benzamides; Cyclohexanones; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Epidermis; Mice; Mice, Inbred BALB C; NF-kappa B; Ointments; Oxazolone

Topics: Active Transport, Cell Nucleus; Administration, Topical; Animals; Benzamides; Cell Line; Cyclohexanones; Dermatitis, Atopic; Disease Models, Animal; Humans; Mice; NF-kappa B