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

Naunyn Schmiedebergs Arch Pharmacol. 2024 May;397(5):3275-3299. doi: 10.1007/s00210-023-02814-w. Epub 2023 Nov 6.

Abstract

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 × 108 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.

Keywords: Arthritis; Hepatoxicity; Immunosuppression; Nephrotoxicity; Probiotics; Steroid.

Publication types

  • Comparative Study

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Arthritis, Experimental* / drug therapy
  • Arthritis, Experimental* / pathology
  • Bacillus subtilis* / drug effects
  • Dexamethasone* / pharmacology
  • Dexamethasone* / therapeutic use
  • Female
  • Freund's Adjuvant*
  • Kidney* / drug effects
  • Kidney* / metabolism
  • Kidney* / pathology
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • NF-kappa B / metabolism
  • Oxidative Stress / drug effects
  • Spleen / drug effects
  • Spleen / immunology
  • Spleen / metabolism

Substances

  • Dexamethasone
  • Freund's Adjuvant
  • Adjuvants, Immunologic
  • Anti-Inflammatory Agents
  • NF-kappa B