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


METHODS
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 Th1and Th2cytokine 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).


CONCLUSIONS
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).
Department of Pharmacology & Therapeutics, King George's Medical University, Lucknow, UP, 226003, India. rishipal@kgmcindia.edu.
Rishi
R
Pal
Department of Physiology, Government Medical College, Tirwa Road, Kannauj, UP, India.
Manju J
MJ
Chaudhary
Department of Pharmacology & Therapeutics, King George's Medical University, Lucknow, UP, 226003, India.
Prafulla Chandra
PC
Tiwari
Department of Pharmacology & Therapeutics, King George's Medical University, Lucknow, UP, 226003, India.
Rajendra
R
Nath
Department of Pathology, King George's Medical University, Lucknow, UP, 226003, India.
Suresh
S
Babu
Department of Pharmacology & Therapeutics, King George's Medical University, Lucknow, UP, 226003, India.
Kamlesh Kumar
KK
Pant
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D007155:Immunologic Factors / Q000008:administration & dosage*; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010431:Pentoxifylline / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar
D000893:Anti-Inflammatory Agents; D007155:Immunologic Factors; D018836:Inflammation Mediators; D009569:Nitric Oxide; D010431:Pentoxifylline; D019331:NG-Nitroarginine Methyl Ester
Arthritic index; Cytokines; NF-κB; Nitric oxide; Pentoxifylline; Rheumatoid arthritis
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