Saeed Abdel-Aziz, El-Shafey Mohamed, Helal Gouda K, Akool El-Sayed
Pharmacology and Toxicology Department, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
Pharmacology and Toxicology Department, Faculty of Pharmacy, Heliopolis University, Cairo, Egypt.
J Pharm Res Int. 2021;33(42A):370-382. doi: 10.9734/jpri/2021/v33i42a32415. Epub 2021 Aug 30.
The present work was designed to examine of the potential anti-inflammatory effect of rosuvastatin (ROSV) and/or Lefleunamide (LFLU) against Complete Freunds Adjuvant (CFA)-induced arthritis in rats.
The mRNA level of perxisome proliferator-activated receptor-alpha (PPAR-α) was determined using Real-time PCR. The levels of NF-κB, iNOS, IL-6, TNF-α and SOD activity were measured using ELISA. The swollen paws were measured using caliper. The GSH level was measured using colorimetric assay. The level of malondialdehyde (MDA) was determined using thiobarbituric acid reactive substances assay kit.
ROSV induced the expression of PPAR-α that suppresses NF-κB as demonstrated by a strong reduction in NF-κB level in animals treated with ROSV. Also, ROSV administration reduced the levels of the inflammatory mediators IL-6 and TNF-α. In addition, iNOS and MDA content as well as expression of MMP-9 and MMP-2 induced by CFA is abrogated in animals treated with ROSV. Also GSH content and SOD activity were highly increased in ROSV-treated animals. Furthermore, the size of right paw induced by CFA was reduced in ROSV-treated rats. Moreover, the histopathological alterations induced by CFA were highly improved in animals treated with ROSV. Similar results were also found in animals treated with LFLU. Importantly, similar effects were obtained in rats treated with both ROSV and LFLU in half doses.
This study demonstrates that ROSV as well as LFLU has the ability to inhibit rheumatoid arthritis in experimental model induced by CFA. Importantly, concomitant administration of ROSV and LFLU in half doses synergize against rheumatoid arthritis.
本研究旨在探讨瑞舒伐他汀（ROSV）和/或来氟米特（LFLU）对完全弗氏佐剂（CFA）诱导的大鼠关节炎的潜在抗炎作用。
采用实时定量聚合酶链反应（Real-time PCR）检测过氧化物酶体增殖物激活受体α（PPAR-α）的mRNA水平。采用酶联免疫吸附测定（ELISA）法检测核因子κB（NF-κB）、诱导型一氧化氮合酶（iNOS）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）水平及超氧化物歧化酶（SOD）活性。用游标卡尺测量大鼠肿胀的爪子。采用比色法测定谷胱甘肽（GSH）水平。使用硫代巴比妥酸反应物质检测试剂盒测定丙二醛（MDA）水平。
ROSV诱导PPAR-α的表达，PPAR-α可抑制NF-κB，这在接受ROSV治疗的动物中NF-κB水平显著降低得到证实。此外，给予ROSV可降低炎症介质IL-6和TNF-α的水平。另外，接受ROSV治疗的动物中，CFA诱导的iNOS和MDA含量以及基质金属蛋白酶-9（MMP-9）和基质金属蛋白酶-2（MMP-2）的表达均被消除。而且，接受ROSV治疗的动物中GSH含量和SOD活性显著增加。此外，接受ROSV治疗的大鼠中，CFA诱导的右爪大小减小。此外，接受ROSV治疗的动物中，CFA诱导的组织病理学改变得到显著改善。在接受LFLU治疗的动物中也发现了类似结果。重要的是，在接受半剂量ROSV和LFLU联合治疗的大鼠中也获得了类似效果。
本研究表明，ROSV和LFLU均有能力在CFA诱导的实验模型中抑制类风湿性关节炎。重要的是，半剂量的ROSV和LFLU联合给药对类风湿性关节炎具有协同作用。
