The Protective Effect of New Carnosine-Hyaluronic Acid Conjugate on the Inflammation and Cartilage Degradation in the Experimental Model of Osteoarthritis

Abstract

Osteoarthritis (OA) is a disease that currently has no cure. There are numerous studies showing that carnosine and hyaluronic acid (HA) have a positive pharmacological action during joint inflammation. For this reason, the goal of this research was to discover the protective effect of a new carnosine conjugate with hyaluronic acid (FidHycarn) on the inflammatory response and on the cartilage degradation in an in vivo experimental model of OA. This model was induced by a single intra-articular (i.ar.) injection of 25 µL of normal saline with 1 mg of monosodium iodoacetate solution (MIA) in the knee joint of rats. MIA injection caused histological alterations and degradation of the cartilage, as well as behavioral changes. Oral treatment with FidHycarn ameliorated the macroscopic signs, improved thermal hyperalgesia and the weight distribution of the hind paw, and decreased histological and radiographic alterations. The oxidative damage was analyzed by evaluating the levels of nitrotyrosine and inducible nitric oxide synthase (iNOS) that were significantly reduced in FidHycarn rats. Moreover, the levels of pro-inflammatory cytokines and chemokines were also significantly reduced by FidHycarn. Therefore, for the first time, the effectiveness of oral administration of FidHycarn has been demonstrated in an osteoarthritis model. In conclusion, the new FidHycarn could represent an interesting therapeutic strategy to combat osteoarthritis. affects the joints that support most of the weight (such as the knees and feet) and the joints we use the most (e.g., hand joints). In a healthy joint, the cartilage shelters the surface of the bones and supports the bones to move liberally against each other. When a joint develops OA, part of the cartilage tapers and the surface becomes coarser. This means the articulation does not move as easily as it should. When the cartilage becomes worn out or damaged, all the tissues within the articulation become more active than usual as the body attempts to repair the damage. However, the reparation processes do not always operate well, and thus, modifications to the joint structure can occasionally cause or contribute to symptoms such as swelling, pain, and ultimately, disability.One of the leading characteristics of OA is collagen deterioration, as suggested by augmented tissue swelling and the loss of proteoglycans [1]. Both collagen destruction and the loss of proteoglycans unfavorably affect the mechanical properties of cartilage. Chondrocytes respond to tissue injury by increasing collagen and proteoglycan synthesis in an attempt to repair the tissue [2]. If repair fails, the damage will progress to articular cartilage degeneration. It is still not clear exactly what causes osteoarthritis. We do know that it is not simply 'wear and tear' and that the danger of developing OA depends on a number of factors.Furthermore, these degradation processes are thought to be largely elicited through excess production of pro-inflammatory and catabolic mediators. Among them, interleukin-1β (IL-1β) has...

Carnosine Alleviates Knee Osteoarthritis and Promotes Synoviocyte Protection via Activating the Nrf2/HO-1 Signaling Pathway: An In-Vivo and In-Vitro Study

“…Paola and colleagues investigated the protective effect of CA conjugated hyaluronic acid compound on monosodium iodoacetate (MIA)-induced OA in rats. CA conjugated with hyaluronic acid demonstrated good cartilage protection by lowering serum inflammatory cytokines and mechanical allodynia pain [ 72 ]. Chronic OA pain causes significant physiological distress and impairs physical and social functioning in patients [ 73 ].…”

Hyaluronic Acid: A Key Ingredient in the Therapy of Inflammation

“…The results show that the levels of cytokines and chemokines, as well as oxidative damage, were reduced in the presence of FidHycarn when compared to the administration of CARN, HA, or the mixture of CARN and HA. In this particular case, HA has the ability to protect CARN against enzymatic degradation (serum carnosinases), increasing the effectiveness of FidHycarn [86].…”

The Role of Cashew (Anacardium occidentale L.) Nuts on an Experimental Model of Painful Degenerative Joint Disease

“…On day 21 post-MIA administration, blood samples were collected and knee joints were inspected in detail to determine histopathological changes. Cartilage was stained to verify whether there was any presence of osteoarthritis [17,19].…”

“…Moreover, cashews are able to reduce lipid peroxidation and raise SOD and catalase (CAT) activity, reducing injuries to cell membranes [14]. The monosodium iodoacetate (MIA) animal model is an established model of osteoarthritis for both pain-related behaviors and histopathological changes [15][16][17][18]. Accordingly, our study was designed to evaluate the potential beneficial effect of the oral administration of cashew nuts on an experimental rat model of MIA-induced osteoarthritis.…”