Effects of single or combined administration of salmon calcitonin and omega-3 fatty acids vs. diclofenac sodium in sodium monoiodoacetate-induced knee osteoarthritis in male Wistar rats

Abstract

Background: There is a continuous search for a better therapy in osteoarthritis (OA) management. Therefore, this study investigated the effects of salmon calcitonin (Sct) and/or omega-3 fatty acids (N-3) relative to diclofenac sodium (DF) in induced knee osteoarthritic male Wistar rats. Methods:The 40 rats that were used in this study were divided into 8 groups (n = 5 rats), viz: Normal control; OA control; OA + N-3; OA + Low dose of Sct (Sct.Lw); OA + High dose of Sct (Sct.Hi); OA + N-3 + SCt.Lw; OA + N-3 + Sct.Hi; and, OA + DF. OA was induced with 4 mg of sodium monoiodoacetate in 40 μL of saline. The solution was injected into the left knee joint space of anaesthetised rats. Sct was administered at 2.5 and 5.0 IU/kg b.w. (im), whereas N-3 and DF were administered at 200 and 1 mg/kg b.w. (p.o.), respectively. Treatments commenced 9 days after the induction of OA, and they lasted for 28 days. Results: Sct and/or N-3 significantly reduced c-telopeptide of type 1 collagen (CTX-1), collagen type 2 α-1 (C2M), malondialdehyde (MDA), uric acid (UA), and interleukin-6 (IL-6), but, significantly increased superoxide dismutase (SOD) after OA induction. Both therapies had additive effects on C2M, MDA, SOD, and catalase (CAT), but, nonadditive actions on UA, IL-6, and CTX-1. Like the Sct and N-3, DF significantly reduced CTX-1, C2M, UA, and IL-6. However, it had no significant effect on SOD and MDA, even though it significantly reduced CAT activity. None of the therapies had significant effect on total alkaline phosphatase activity, except N-3 + Sct.Lw. Conclusions:The combined, and sometimes the single administration of Sct and N-3 proved to be better therapies in OA management than DF.

Diclofenac – induced hepatotoxicity: Low dose of omega-3 fatty acids have more protective effects

“…It has been documented that supplementation with N-3 at a high dose could be accompanied with some unfavorable events [ 35 ]. The noted anti-inflammatory effects of N-3 [ 36 ] in this study could be attributed to their metabolites, such as, resolvins [ 37 ], neuroprotectin-D1 and docosatrienes [ 38 , 39 ]. Resolvin D1, resolvin E1, and protectin D1 inhibits transendothelial migration of neutrophils into sites of inflammation.…”

The GLP-1 agonist, liraglutide, ameliorates inflammation through the activation of the PKA/CREB pathway in a rat model of knee osteoarthritis

“…Knee OA was induced according to previous protocols [5, 14]. Briefly, 4 mg of MIA were dissolved in 40 μL of sterile saline and this volume of solution was injected intraarticularly through the patellar ligament of the left knee joint of each rat that had been anesthetized using 50 mg/kg sodium pentobarbital by intraperitoneal injection.…”

“…OA can affect the hand, spine, hip, wrist and ankle. However, knee OA represents the most widespread form of this disease [5]. Although, there are various therapeutic methods for OA, such as surgery, drug and adjuvant therapy, it is difficult to completely stop the development of OA, which results in continuous pain and even long-term disability [6].…”

“…For example, Hwang et al, indicated that Zanthoxylum piperitum ethanol extract could decrease the levels of reactive oxygen species (ROS) and the expression of hypoxanthine phosphoribosyl transferase 1 (HPRT1), thereby suppressing inflammation. This suggests that this extract might be a potential therapeutic agent to modulate OA [5]. Therefore, molecules involved in inflammation are attractive therapeutic targets for the treatment of OA.…”

Knee osteoarthritis in young growing rats is associated with widespread osteopenia and impaired bone mineralization

“…For example, Ferrándiz et al demonstrated that IL-1β level in 2-month-old ACLT rats was significant higher than that of sham-operated rats from ~ 110 to ~ 200 pg/mL 11 . Measurements of bone turnover markers revealed that knee OA was associated with increased c-telopeptide of type 1 collagen (CTX-1) and alkaline phosphatase levels 26 . We thus hypothesized that OA from ACLT would lead to bone loss in both local sites (i.e., tibiae) and distant sites (i.e., vertebrae).…”