The Topical Application of Rosuvastatin in Preventing Knee Intra-Articular Adhesion in Rats

Abstract

BackgroundIntra-articular adhesion is one of the common complications of post knee surgery and injury. The formation of joint adhesion can lead to serious dysfunction. Rosuvastatin (ROS) is a new 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, with multiple biological effects. In our study, the object was to evaluate the effectiveness of ROS in the prevention of post-operative knee adhesion in rats.Material/MethodsFemoral condyle exposing surgery was performed on 45 healthy Sprague Dawley rats. Gelatin sponges soaked with 20 mg/kg of ROS, 10 mg/kg of ROS, or saline were used to cover the surgical site. The post-operative knee joints were fixed in a flexed position with micro Kirschner wires for four weeks. ROS effectiveness for treating intra-articular adhesion was determined with visual score evaluation, hydroxyproline content, histological analyses, immunohistochemistry, and inflammatory and vascular endothelial growth factors expression.ResultsThe animals’ recovery was stable after surgery. The hydroxyproline content, visual score, and inflammatory vascular growth factors expression levels suggested that, compared with the control group, the ROS treatment groups showed better outcomes. ROS prevented joint adhesion formation, collagen deposition, and vascularization at the surgical site, and also inhibited inflammatory activity post-operatively. Compared with the 10 mg/kg ROS group, the 20 mg/kg ROS group showed significantly better outcomes.ConclusionsThe local application of ROS reduced intra-articular adhesion formation, collagen deposition, and vascularization at the surgical site, and inhibited inflammatory activity post-operatively. These results suggested optimal concentration of ROS to be 20 mg/kg.

E8002 Reduces Adhesion Formation and Improves Joint Mobility in a Rat Model of Knee Arthrofibrosis

“…Positive effects of hydrogel microspheres, TAP hydrogel, hyaluronic acid and carboxymethylcellulose, decorin, chitosan, lovastatin, rapamycin, and hydroxycaptotensin have been identified in animals, but most of these have yet to be tested in human patients [13][14][15][16][17][18][19][20], and to the best of our knowledge, there have no studies of the use of these agents in clinical practice for the prevention of arthrofibrosis following knee joint surgery in humans. The reasons for the delay in the trial of these substances in clinical practice is unknown, but this serves to emphasize the necessity for the development of new methods for the control of arthrofibrosis.…”

“…Haematoxylin and eosin (HE)-stained images of the fibrous scars are shown in Fig- ure 3A. Because no scarring developed in the No Adhesion group, we counted the numbers of haematoxylin-stained nuclei in the fibrous scars of the other two groups, which were considered to be the nuclei of fibroblasts [20]. There were significantly fewer nuclei in the E8002 group than in the Adhesion group (Adhesion group: 5495 ± 244 cells, E8002 group: 4540 ± 349 cells, Student's t-test: p = 0.04) (Figure 3A,B).…”

“…The approaches to the treatment of knee fibrosis include manipulation under anaesthesia, debridement, and physical therapy [12], but the ideal measure would be to prevent the development of arthrofibrosis. Hydrogel microspheres, temperature-sensitive anti-adhesive poloxamer (TAP) hydrogel, hyaluronic acid, carboxymethylcellulose, decorin, chitosan, lovastatin, rapamycin, and hydroxycaptotensin have been shown to have anti-adhesive effects [13][14][15][16][17][18][19][20], and chitosan and TAP hydrogel have been shown to be effective in clinical trials [14,17]. However, these agents have yet to be commercialized, and no surgical means of preventing adhesions following knee surgery have been established.…”

Prevention of Intra-Abdominal Adhesions Using the Combination of Mediclore® and a Statin

“…Furthermore, statins also reduce vascular endothelial growth factor and oxidative stress, which is known to be a very effective indicator of postoperative adhesion. Vas-cular endothelial growth factor is thought to lead to the proliferation of endothelial cells, fibroblasts, and vascularization, which is one of the most important mechanisms for healing processes and adhesion [25]. Free oxygen radicals, such as nitric oxide and malondialdehyde, affect cell membrane integrity and increase prostaglandin and thromboxane production, possibly contributing to adhesion formation [26].…”

“…Third, the amount of rosuvastatin administered in this study was relatively higher than that in the clinical setting. Although the amount of rosuvastatin administered (20 mg/kg) was chosen based on a previous preclinical study [25], too large an amount may induce myopathy, type 2 diabetes mellitus, and neurological, hepatic, and renal toxicity [27, 28]. Therefore, although no cases of systemic complications or mortality were observed before the rats were killed, the safety and toxicity of rosuvastatin require further investigation prior to its use in clinical trials.…”