Pharmacological studies on the anti-inflammatory and immunomodulatory role of pentoxifylline and its interaction with nitric oxide (NO) in experimental arthritis in rats

Inflammopharmacology. 2016 Oct;24(5):221-231. doi: 10.1007/s10787-016-0281-4. Epub 2016 Sep 26.

Abstract

Aim: Present study was designed to evaluate protective effects of pentoxifylline and its potentiation with low dose of nitric oxide (NO) modulators in adjuvant-induced experimental arthritis in rats.

Method: Wistar rats (200-300 g, n = 8 per group) of both sexes were used in the study. On day "0" experimental arthritis was induced by injecting 0.2 ml of Complete Freund's adjuvant (CFA) in sub-planter region of right hind paw of animals. Pentoxifylline treatment alone and in combination with NO modulators was given (i.p.) from day 14 to 28. Various arthritic parameters were recorded and blood and joint synovial fluid was collected for biochemical analysis.

Results: CFA inoculation significantly increases (1) arthritic index (2) ankle diameter (3) paw volume (4) histopathology score (5) serum TNF-α, IL-6, IL-1β and synovial TNF-α levels (p < 0.001) (6) serum Th1 and Th2 cytokine levels g) MDA levels in rat paw tissue homogenates (7) serum NF-κB levels. Significant decrease in serum IL-10 levels and SOD activity was observed in rats after CFA inoculation. Decrease in body weight and suppressed general quality of life of CFA inoculated rats was also observed. These CFA-induced arthritic changes were significantly reversed by pentoxifylline alone and in combination with low dose of NO modulators (p < 0.05).

Conclusion: These results are suggestive of protective effects of pentoxifylline and its potentiation in combination with low dose of NO modulators. These results may provide new pharmacological therapy for management of rheumatoid arthritis (RA).

Keywords: Arthritic index; Cytokines; NF-κB; Nitric oxide; Pentoxifylline; Rheumatoid arthritis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Arthritis, Experimental / drug therapy
  • Arthritis, Experimental / metabolism*
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Immunologic Factors / administration & dosage*
  • Inflammation Mediators / metabolism*
  • Male
  • NG-Nitroarginine Methyl Ester / administration & dosage
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / metabolism*
  • Pentoxifylline / administration & dosage*
  • Rats
  • Rats, Wistar

Substances

  • Anti-Inflammatory Agents
  • Immunologic Factors
  • Inflammation Mediators
  • Nitric Oxide
  • Pentoxifylline
  • NG-Nitroarginine Methyl Ester