# Medical Ozone Increases Methotrexate Effects in Rheumatoid Arthritis Through a Shared New Mechanism Which Involves Adenosine

## TL;DR

Medical ozone and methotrexate work together to treat rheumatoid arthritis by reducing inflammation through a shared mechanism involving adenosine.

## Contribution

The study identifies a new shared mechanism involving adenosine that explains the combined therapeutic effects of medical ozone and methotrexate in rheumatoid arthritis.

## Key findings

- Medical ozone and methotrexate share a common mechanism via adenosinergic regulation in treating rheumatoid arthritis.
- Combined therapy with methotrexate and medical ozone reduces ROS and proinflammatory cytokines through adenosine A1 receptors.
- The integrative analysis links experimental and clinical findings to propose a novel pharmacological mechanism for rheumatoid arthritis treatment.

## Abstract

Medical ozone is a redox regulator with beneficial effects in oxidative etiology diseases such as rheumatoid arthritis (RA). The aim of this study is to conduct a holistic review of different pharmacological trials involving ozone in model diseases, as well as the clinical responses of RA patients. The ROS (reactive oxygen species) involved in RA and their relationship with the main pathological pathways of this autoimmune disease are considered here. The integrative analysis of experimental results from animals with clinical findings reveals that both methotrexate (MTX) and medical ozone share common mechanisms via adenosinergic regulation. This finding enables us to propose a new pharmacological mechanism in the treatment of RA. We conclude that MTX + medical ozone combined therapy reduces ROS overproduction and the generation of proinflammatory cytokines and decreases anti-cyclic citrullinate peptide levels by a mutual mechanism involving adenosine A1 receptors.