title: Effect of S-methylisothiourea, an inducible nitric oxide synthase inhibitor, in joint pain and pathology in surgically induced model of osteoarthritis.
abstract: The aim of the present study was to evaluate in vivo modulatory effect of S-methylisothiourea (SMT), a preferential inhibitor of inducible nitric oxide synthase (iNOS) on pain and pathology in the surgical model of osteoarthritis (OA) in rats. The OA was produced by the anterior cruciate ligament transection (ACLT) and medial meniscectomy (MMx) of right knee. SMT was administered 1 day prior to the production of OA and continued up to day 42 postoperation. Mechanical hyperalgesia, thermal hyperalgesia, tail flick latency after repeated flexion and extension of OA knee and knee diameter of right knee were determined at weekly intervals. Serum levels of IL-1β, TNF-α and nitrite concentration were determined at the end of the experiment. Glycosaminoglycan (GAG) content, collagen content and histopathological evaluation of articular cartilage were also determined at the end of the experiment. SMT reduced mechanical hyperalgesia and the serum levels of IL-1β, TNF-α and nitrite. Further, SMT reduced the loss of GAG from articular cartilage. Microscopically, SMT reduced the severity of the cartilage lesion. The results indicate the effectiveness of SMT in attenuating the pain and pathology of experimental OA phase by reducing the production of nitric oxide and interleukin-1β and tumor necrosis factor-α, which are known to play a major role in the pathophysiology of OA.
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute , Izatnagar, Uttar Pradesh , India.
authors.forename: Venkanna
authors.initials: V
authors.lastname: Balaganur
authors.forename: Nitya Nand
authors.initials: NN
authors.lastname: Pathak
authors.forename: Madhu C
authors.initials: MC
authors.lastname: Lingaraju
authors.forename: Amar Sunil
authors.initials: AS
authors.lastname: More
authors.forename: Najeeb
authors.initials: N
authors.lastname: Latief
authors.forename: Rashmi Rekha
authors.initials: RR
authors.lastname: Kumari
authors.forename: Dinesh
authors.initials: D
authors.lastname: Kumar
authors.forename: Surendra K
authors.initials: SK
authors.lastname: Tandan
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016118:Anterior Cruciate Ligament / Q000601:surgery; D018771:Arthralgia / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D006652:Histological Techniques; D006930:Hyperalgesia / Q000188:drug therapy; D053583:Interleukin-1beta / Q000097:blood; D007550:Isothiuronium / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008592:Menisci, Tibial / Q000601:surgery; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D009573:Nitrites / Q000097:blood; D010003:Osteoarthritis / Q000150:complications*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D053583:Interleukin-1beta; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D007550:Isothiuronium; D052247:Nitric Oxide Synthase Type II; C027744:S-methylisothiopseudouronium
keywords: Anterior cruciate ligament transection; S-methylisothiourea; mechanical hyperalgesia; osteoarthritis; thermal hyperalgesia