Immunostimulant, hepatoprotective, and nephroprotective potential of Bacillus subtilis (NMCC-path-14) in comparison to dexamethasone in alleviating CFA-induced arthritis

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 2024-05, Vol.397 (5), p.3275-3299
• Main Authors: Mazhar, Muhammad Usama, Naz, Sadaf, Zulfiqar, Tayyaba, Khan, Jehan Zeb, Ghazanfar, Shakira, Tipu, Muhammad Khalid
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - pharmacology; Animals; Ankle; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Arthritis; Arthritis, Experimental - drug therapy; Arthritis, Experimental - pathology; Bacillus subtilis; Bacillus subtilis - drug effects; Biomedical and Life Sciences; Biomedicine; Dexamethasone; Dexamethasone - pharmacology; Dexamethasone - therapeutic use; Dual energy X-ray absorptiometry; Female; Freund's Adjuvant; GA-binding protein; Immunohistochemistry; Immunostimulants; Immunosuppression; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Liver - drug effects; Liver - metabolism; Liver - pathology; Lymphocytes B; Male; Mice; Neurosciences; NF-kappa B - metabolism; NF-κB protein; Oxidative stress; Oxidative Stress - drug effects; Pharmacology/Toxicology; Side effects; Spleen - drug effects; Spleen - immunology; Spleen - metabolism; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 0028-1298; 1432-1912; 1432-1912
• DOI: 10.1007/s00210-023-02814-w

To investigate and compare efficacy as well as safety of Bacillus subtilis and dexamethasone (Dexa) in complete Freund’s adjuvant (CFA)-induced arthritis, we used glucocorticoid monotherapy (Dexa 5 mg/kg/day) and B. subtilis (1 × 10 8  CFU/animal/day p.o) as pre-treatment and concurrent treatment for a duration of 35 days. Specific emphasis was on chronic aspect of this study since long-term use of Dexa is known to produce undesirable side effects. Treatment with Dexa significantly attenuated the arthritic symptoms but produced severe side effects like weight loss, increased mortality, immunosuppression, and altered histology of liver, kidney, and spleen. Oxidative stress was also elevated by Dexa in these organs which contributed to the damage. Treatment with B. subtilis improved symptoms of arthritis without producing any deleterious side effects as seen with Dexa therapy. Immunohistochemistry (IHC) profile revealed decreased expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin (IL)-1β, tumor necrosis factor alpha (TNF-α), and increased nuclear factor erythroid 2–related factor 2 (Nrf-2) expression by B. subtilis and Dexa treatment in ankle joint of arthritic mice. Radiological scores were also improved by both treatments. This study concludes that B. subtilis could be an effective alternative for treating arthritis than Dexa since it does not produce life-threatening side effects on prolong treatment.