Systemic Administration of Neutral Electrolyzed Saline as a Novel Treatment for Rheumatoid Arthritis Reduces Mechanical and Inflammatory Damage to the Joints: Preclinical Evaluation in Mice

Abstract

Rheumatoid arthritis is globally present in about 1% of the population. This autoinflammatory disease modifies the connective tissue, causing pain and inflammation of the joints. Over time, it causes the loss of joint cartilage and bone mass, decreasing the patient's quality of life. Treatment options now available either give symptomatic alleviation or alter the disease process. Nonetheless, adherence to chronic treatment is typically limited due to adverse effects. As a result, new therapy approaches, such as systemic administration of neutral electrolyzed saline to improve patients’ quality of life, are being investigated. The study is a randomized prospective preclinical trial with a single-blind and a 4-arm parallel group using a collagen-induced mice model to generate rheumatoid arthritis. It was carried out on 36 male BALB/c mice, with the primary outcome measure being a scoring system for histopathologic assessment. When all groups are compared, there are significant differences. In addition, the animal model was validated by the healthy group. The animals treated with neutral electrolyzed saline had much less cartilage degradation, bone erosion, pannus development, and inflammation than the placebo-treated mice. Serum IL-6 levels were evaluated in parallel with disease severity expressed as synovitis grading of the affected joints. Spearman’s rank correlation coefficient (Rs) = 0.399 ( $P=0.016$ ) between serum IL-6 levels and the synovitis grading suggests a direct correlation between IL-6 production and disease severity. An additional trial of 20 male BALB/c mice (10 treated with placebo and 10 with neutral electrolyzed saline for 30 days) showed no clinical nor histopathological evidence of adverse effects. According to histopathological and blood test results, we conclude that neutral electrolyzed saline minimizes mechanical and inflammatory damage to the joint and may be helpful as an alternative to rheumatoid arthritis therapy.