Dogs with Atopic Dermatitis: Effects of Oclacitinib Maleate on Serum Total Antioxidant and Total Oxidant Status Levels

Abstract

Background: Canine atopic dermatitis (AD) is a chronic, pruritic, inflammatory skin disease associated with epidermal barrier dysfunction, immune dysregulation, and oxidative stress. Total antioxidant status (TAS) and total oxidant status (TOS) are useful biomarkers for assessing systemic redox balance. Oclacitinib maleate, a selective Janus kinase 1 (JAK1) inhibitor, is widely used to control pruritus and inflammation in canine AD; however, its effects on oxidative balance remain unclear. This study aimed to evaluate the effects of short-term oclacitinib treatment on serum TAS and TOS levels in dogs with AD.

Materials, Methods & Results: Dogs diagnosed with AD (n = 10) according to Favrot criteria and age-matched healthy control dogs (n = 10; 1-3 years-old) were included in the study. To ensure that oxidative parameters reflected primary atopic disease rather than concurrent conditions, secondary bacterial, fungal, and parasitic infections were excluded through detailed microbiological, mycological, and parasitological examinations. Dogs in the AD group received oral oclacitinib maleate at a dose of 0.5 mg/kg twice daily (q12h) for 7 days. Blood samples were collected from the control group once and from the AD group at three time points: before treatment (day 0), day 7, and day 14. Serum TAS and TOS levels were determined spectrophotometrically using commercially available ELISA kits. Pre-treatment TAS levels in dogs with AD were significantly higher than those of healthy controls and post-treatment values (P < 0.05). During the treatment period, TAS levels showed a significant progressive decrease and reached values comparable to those of healthy dogs by day 14. In contrast, no statistically significant differences were detected in TOS levels either between groups or across sampling time points (P > 0.05).

Discussion: The elevated pre-treatment TAS levels observed in dogs with AD may represent a compensatory upregulation of systemic antioxidant defenses in response to chronic inflammation and increased oxidative burden. Inflammatory cytokines and activated immune cells promote reactive oxygen species (ROS) production, which can stimulate antioxidant mechanisms. Therefore, increased TAS levels before treatment may reflect an adaptive response to ongoing systemic inflammation. The significant decline in TAS during oclacitinib therapy suggests reduced inflammatory activity and, consequently, a decreased requirement for compensatory antioxidant defense. By inhibiting JAK1-dependent cytokine signaling, oclacitinib suppresses mediators involved in inflammation and pruritus and may thereby indirectly reduce oxidative stress. Moreover, its reported suppressive effects on CD4⁺ and CD8⁺ T lymphocytes suggest that the reduction in TAS may also be associated with modulation of immune-mediated antioxidant responses. Thus, decreased TAS following treatment may reflect both attenuation of inflammatory stimuli and immunomodulatory effects on effector immune cells. In contrast, the absence of significant changes in TOS throughout the study suggests that oclacitinib may not directly affect oxidant production or ROS generation. Its influence on redox balance may therefore occur mainly through modulation of inflammatory and immune pathways rather than through direct alteration of oxidant status. Overall, these findings suggest that oclacitinib treatment may modify systemic antioxidant balance in dogs with AD by reducing inflammation and immune activation. Further large-scale, long-term, and mechanistic studies are needed to clarify the relationship between JAK1 inhibition, immune modulation, and redox homeostasis in canine AD. Additional oxidative biomarkers may help characterize these treatment-related changes furthe.

Keywords: atopic dermatitis, canine, total antioxidant status, total oxidant status, oclacitinib.