The Combined Effect of Topical CX-659S, a Novel Diaminouracil Derivative, With Topical Corticosteroid on the Three Types of Allergic Responses in Mice or Guinea Pigs

Abstract

Abstract. CX-659S ((S)-6-amino-5-(6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxamido)-3-methyl-1-phenyl-2,4(1H,3H)-pyrimidinedione), a newly discovered anti-inflammatory compound, exerts inhibitory effects against picryl chloride-, oxazolone-, and dinitrochlorobenzeneinduced acute contact hypersensitivity responses (CHRs) characterized by Th1-type reactions. Furthermore, this compound suppressed chronic CHRs characterized by Th2-type reactions, which is well known to mimic many, if not all, events occurring within the lesional skin of patients with atopic dermatitis (AD). The present study was conducted to determine the combined effect of topical CX-659S with topical corticosteroid on immediate type (ITR), late type (LTR), and delayed type hypersensitivity (DTHR) allergic reactions that are involved in AD. An ineffective dose of CX-659S (0.03 mg / ear) combined with betamethasone valerate (BV) significantly potentiated inhibitory activity of BV alone (0.1 m g / ear and 0.3 m g / ear) on both the ITR and the LTR in mice with the ovalbumin (OVA)-induced biphasic cutaneous reaction. Furthermore, the combined effect of CX-659S with BV was also observed on dinitrochlorobenzene (DNCB)-induced DTHR in guinea pigs. These results indicate that CX-659S has a combined effect with corticosteroids on every ITR, LTR, and DTHR. Proper treatment with corticosteroids for a safe and effective treatment of AD is needed. Thus, the combination therapy of topical CX-659S with topical corticosteroid would be one of the potential approaches for devising a proper treatment with corticosteroids.

Pimecrolimus kremin (%1) atopik dermatit tedavisindeki etkinliği

“…DNCB is an agent that was previously used in many studies to form induced allergic dermatitis in mice [23,24]. In our study we successfully formed atopic dermatitis through the use of local DNCB in all the trial subjects.…”

Synthesis and structure–activity relationship of tricyclic carboxylic acids as novel anti-histamines

“…Furthermore, compounds that exhibited good bioavailability in rats (>20%) were examined for their anti-inflammatory potential in mice OVA-induced biphasic cutaneous reaction model. 19 Finally, promising compounds were evaluated for their H 1 receptor occupancy in the mouse brain.…”

Fingolimod hydrochloride gel shows promising therapeutic effects in a mouse model of atopic dermatitis

“…The gels were tested in an animal model of AD where AD‐like skin lesions were induced with a strong sensitizer (DNBC) . It has been reported that following DNBC challenge, the mice skin expression of both TH 1 and TH 2 immune responses as well as the production of IgE and TH 2 cytokines is similar to that observed in human patients of AD . On the macroscopic level, the skin of mice treated with DNBC exhibits an AD‐like lesion; that is, it appears dry, red and rough: topical signs of a compromised barrier function .…”

“…[34,44,45] It has been reported that following DNBC challenge, the mice skin expression of both TH 1 and TH 2 immune responses as well as the production of IgE and TH 2 cytokines is similar to that observed in human patients of AD. [5,34,46,47] On the macroscopic level, the skin of mice treated with DNBC exhibits an AD-like lesion; that is, it appears dry, red and rough: topical signs of a compromised barrier function. [46,48,49] The results of this study show that the AD-like lesions were successfully induced in the mice models as all the indexes of skin AD lesions (pH, TEWL and EASI) remarkably increased after 1 week of DNCB application compared with both the measurements performed before the application and the negative control group (group 6).…”