Pal Rishi, Chaudhary Manju J, Tiwari Prafulla Chandra, Nath Rajendra, Babu Suresh, Pant Kamlesh Kumar
Department of Pharmacology & Therapeutics, King George's Medical University, Lucknow, UP, 226003, India.
Department of Physiology, Government Medical College, Tirwa Road, Kannauj, UP, India.
Inflammopharmacology. 2016 Oct;24(5):221-231. doi: 10.1007/s10787-016-0281-4. Epub 2016 Sep 26.
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.
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.
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 Th and Th 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).
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).
本研究旨在评估己酮可可碱及其与低剂量一氧化氮(NO)调节剂联合使用对佐剂诱导的大鼠实验性关节炎的保护作用。
本研究使用了体重200 - 300克的雌雄Wistar大鼠(每组n = 8)。在“0”天,通过在动物右后爪足底皮下注射0.2毫升完全弗氏佐剂(CFA)诱导实验性关节炎。从第14天至28天,单独给予己酮可可碱以及将其与NO调节剂联合给予(腹腔注射)。记录各种关节炎参数,并采集血液和关节滑液进行生化分析。
接种CFA后显著增加了(1)关节炎指数(2)踝关节直径(3)爪体积(4)组织病理学评分(5)血清TNF-α、IL-6、IL-1β以及滑膜TNF-α水平(p < 0.001)(6)大鼠爪组织匀浆中血清Th和Th细胞因子水平、丙二醛(MDA)水平(7)血清NF-κB水平。接种CFA后的大鼠血清IL-10水平和超氧化物歧化酶(SOD)活性显著降低。还观察到接种CFA的大鼠体重下降且总体生活质量受到抑制。己酮可可碱单独使用以及与低剂量NO调节剂联合使用可显著逆转这些由CFA诱导的关节炎变化(p < 0.05)。
这些结果提示己酮可可碱及其与低剂量NO调节剂联合使用具有保护作用。这些结果可能为类风湿性关节炎(RA)的治疗提供新的药物疗法。