Ahmed Yasmin Moustafa, Messiha Basim Anwar Shehata, Abo-Saif Ali Ahmed
a Department of Pharmacology and Toxicology, Faculty of Pharmacy , Nahda University , Beni-Suef , Egypt.
b Department of Pharmacology and Toxicology, Faculty of Pharmacy , Beni-Suef University , Beni-Suef , Egypt.
Immunopharmacol Immunotoxicol. 2017 Apr;39(2):97-104. doi: 10.1080/08923973.2017.1286502. Epub 2017 Feb 9.
Rheumatoid arthritis (RA), a disabling autoimmune disorder of the joints as well as other organs, affects about 1% of population. Unfortunately, all current treatments of RA cause severe gastrointestinal, renal and other complications.
We aimed to evaluate the possible antiarthritic effects of a serotonin 5-HT receptor blocker, granisetron, and a nonselective adrenergic receptor blocker, carvedilol, on complete Freund's adjuvant-induced RA in adult female albino rats.
Rats were allocated into a normal control group, an arthritis control group, two reference treatment groups receiving dexamethasone (1.5 mg/kg/day) and methotrexate (1 mg/kg/day), and two treatment groups receiving granisetron (2.5 mg/kg/day) and carvedilol (10 mg/kg/day). Serum-specific rheumatoid, immunological, inflammatory and oxidative stress biomarkers were assessed. A confirmatory histopathological study on joints and spleens was performed.
Granisetron administration significantly improved all the measured biomarkers, with the values of rheumatoid factor, matrix metalloproteinase-3, cartilage oligomeric matrix protein, immunoglobulin G, antinuclear antibody and myeloperoxidase being restored back to normal levels. Carvedilol administration significantly improved all biomarkers, with serum MPO value restored back to normal levels.
Serotonin 5-HT receptor blockers and adrenergic receptor blockers, represented by granisetron and carvedilol, may represent new promising protective strategies against RA, at least owing to immune-modulator, anti-inflammatory and antioxidant potentials.
类风湿性关节炎(RA)是一种会导致关节以及其他器官功能丧失的自身免疫性疾病,影响着约1%的人口。不幸的是,目前所有治疗RA的方法都会引发严重的胃肠道、肾脏及其他并发症。
我们旨在评估5-羟色胺5-HT受体阻滞剂格拉司琼和非选择性肾上腺素能受体阻滞剂卡维地洛对成年雌性白化大鼠完全弗氏佐剂诱导的RA可能产生的抗关节炎作用。
将大鼠分为正常对照组、关节炎对照组、两个接受地塞米松(1.5毫克/千克/天)和甲氨蝶呤(1毫克/千克/天)的参考治疗组,以及两个接受格拉司琼(2.5毫克/千克/天)和卡维地洛(10毫克/千克/天)的治疗组。评估血清特异性类风湿、免疫、炎症和氧化应激生物标志物。对关节和脾脏进行了验证性组织病理学研究。
给予格拉司琼显著改善了所有测量的生物标志物,类风湿因子、基质金属蛋白酶-3、软骨寡聚基质蛋白、免疫球蛋白G、抗核抗体和髓过氧化物酶的值恢复到正常水平。给予卡维地洛显著改善了所有生物标志物,血清髓过氧化物酶值恢复到正常水平。
以格拉司琼和卡维地洛为代表的5-羟色胺5-HT受体阻滞剂和肾上腺素能受体阻滞剂可能代表了针对RA的新的有前景的保护策略,至少因其具有免疫调节、抗炎和抗氧化潜力。