Local Effect of Intramuscular Injection of Meloxicam.. Ahmed Hisham Qassim Local Effect of Intramuscular Injection of Meloxicam and Diclofenac: An Experimental, Comparative and Histological Study Ahmed Hisham Qassim* , Omar Riadh Hamdi* , Ashraf Abdulraheem Ayoob* , Mohammed Taib Taher* *Department of Anatomy, Histology and Embryology, College of Medicine, University of Mosul, Mosul, Iraq. Correspondence:[email protected] (Ann Coll Med Mosul 2019; 41 (2):163-169). Received:17th Oct. 2019; Accepted: 15th Dec. 2019. ABSTRACT Objectives: To compare the local effect of therapeutic doses of meloxicam and diclofenac on the muscle of rats at different periods by intramuscular injection. Materials and methods: Thirty six adult albino rats were divided equally into 6 groups. The 1st and 2nd groups were injected intramuscularly with normal saline for 2 and 4 weeks respectively, the 3rd and 4th groups were injected intramuscularly with meloxicam for 2 and 4 weeks respectively, the last 2 groups were injected intramuscularly with diclofenac sodium also for 2 and 4 weeks respectively. The drugs were injected into the quadriceps femoris muscle of the right femur once each day till the end of the period stated. The specimens were histologically processed, stained with hematoxylin and eosin and examined with light microscope. Results: No changes were seen in quadriceps femoris muscles of groups 1, 2, 3 and 4, whereas group 5 showed congested blood vessels within normal muscle tissue. In Group 6 mononuclear inflammatory cells infiltration, vascular congestion, fibrosis, degenerative changes and muscle tissue necrosis were seen. Conclusion: Meloxicam is safer than diclofenac sodium on muscular tissue after a long-term daily intramuscular injection. Keyword: meloxicam, diclofenac, intramuscular injection, muscle tissue. التأثير الموضعي للحقن العضلي لعقاري الميلوكسيكام والدكلوفيناك: دراسة تجريبية, مقارنة و نسيجية . احوذ هشام قاسن* ، عور رياض حوذي* ، اشرف عبذ الرحين ايىب* ، هحوذ طية طاهر جرجيس* *فرع التشريح واﻻنسجة واﻻجنة، كلية الطة ، جاهعة الوىصل، الوىصل ، العراق الخﻻصة الهذف هن الذراسة: دساست هقاسًت الخأثٍش الوىضعً للدشع العﻻخٍت لعقاسي الوٍلىكسٍكام والذكلىفٌٍاك صىدٌىم على عضلت الدشراى بعذ فخشاث هخخلفت هي الحقي العضلً. اﻷدوات والطرق: سخت وثﻻثىى هي ركىس الدشراى البٍضاء قسوىا الى سج هداهٍع هخساوٌت. الوداهٍع حقٌج عضلٍاً باﻷدوٌت الخالٍت وبالخشحٍب, هحلىل هلحً عٍاسي لوذة أسبىعٍي وأسبعت أسابٍع؛ عقاس الوٍلىكسٍكام )2,00 هلغ/كغن( لوذة أسبىعٍي وأسبعت أسابٍع؛ عقاس الذكلىفٌٍاك صىدٌىم )0,0 هلغ/كغن( لوذة أسبىعٍي وأسبعت أسابٍع. اﻷدوٌت حن حقٌها فً العضلت سباعٍت الشأس للفخز اﻷٌوي هشة فً الٍىم إلى ًهاٌت الفخشة الوحذدة. حن ححضٍش الٌوارج ًسٍدٍاً وصبغج بالهٍواحىكسلٍي واﻻٌىسٍي وفحصج بالودهش الضىئً. النتائج: لن ٌﻻحظ أي حغٍش ًسٍدً فً العضﻻث للوداهٍع 1, 0, 3 و 4 ولكي الودوىعت 5 أظهشث احخقاى لﻷوعٍت الذهىٌت فً ًسٍح العضلت. أها الودوىعت 6 فأظهشث اًسﻻل خﻻٌا الخهابٍت احادٌت الٌىاة, احخقاى وعائً دهىي , حلٍف, إضافت إلى حغٍشاث ححللٍت وًخش فً الٌسٍح العضلً. اﻻستنتاج: عقاس الوٍلىكسٍكام أكثش أهاًاً هي عقاس الذكلىفٌٍاك صىدٌىم على الٌسٍح العضلً بعذ فخشة طىٌلت هي الحقي العضلً الٍىهً. Ann Coll Med Mosul December 2019 Vol. 41 No. 2 163 Ahmed Hisham Qassim Local Effect of Intramuscular Injection of Meloxicam.. الكلوات الوفتاحية: هٍلىكسٍكام, الذكلىفٌٍاك صىدٌىم, الحقي العضلً, الٌسٍح العضلً. INTRODUCTION ystemic and topical nonsteroidal anti- special plastic cages under ideal conditions. The S inflammatory drugs(NSAIDs) are the most number of animals in each cage was three. Food commonly prescribed drugs in the treatment of and water were available ad libitum throughout the inflammation and pain associated with chronic study. inflammatory conditions like rheumatoid arthritis and osteoarthritis1-5. They reduce inflammation by Drugs ® reducing prostaglandin synthesis through inhibition Meloxicam (Mobic , Boehringer Ingelheim, ® of cyclooxygenase enzyme(COX)6. COX-1 and Germany) and diclofenac sodium (Refen , COX-2 are isoforms of the enzyme, suppression of Hemofarm, Serbia) in the form of ampoules were COX-2 is responsible for the therapeutic gain of purchased from a common commercial supply NSAIDs, while their adverse effects result from (Alradwan drug store). The drugs were inhibition of COX-17. administered in therapeutic doses similar to that 23 The route of administration of NSAIDs is given to human . Which were calculated by (24) considered to be an important field for diluting the drugs with normal saline. The drugs investigation, because these drugs can be given were injected intramuscularly into the quadriceps orally, intramuscularly, rectally and intra-articularly femoris muscle of the right femur of the rat every in addition, they can be applied locally on mucosa day till the end of the stated period according to and skin8-10. Thus a lot of researches had been the subdivided groups. carried out with results showing that intramuscular Groups And Experimental Design administration had some advantages over oral After one week of acclimatization, the animals route in that it has faster onset of action, avoids were divided into six groups, each consisted of six first pass metabolism, besides, it prevents direct rats. contact of the drug with gastric mucosa8,11-14. On the contrary, intramuscular route can cause tissue Control Groups necrosis at the site of injection even after a short Groups 1 and 2: received a single daily 15,16 term use . intramuscular injection of normal saline (1ml/ Kg) Since meloxicam is a preferentially selective for 2 and 4 weeks respectively. COX-2 inhibitor, whereas diclofenac sodium is a 17,18 nonselective COX inhibitor . several Treated Groups researchers had studied the efficacy, tolerability, -Group 3: animals received a single daily as well as the safety of meloxicam and compared it intramuscular injection of 0.22mg/ kg of meloxicam with diclofenac after a short period of intramuscular for 2 weeks. injection or after a long period of oral -Group 4: is similar to that of group 3, but the drug administration in both experimental animals and is given for 4 weeks. humans19-22. -Group 5: rats were daily intramuscularly injected The aim of the present study is to compare the with a single dose of diclofenac sodium (2.2 mg/ local effect of therapeutic doses of meloxicam and kg) for 2 weeks. diclofenac on rats’ muscle given for the same -Group 6: is similar to that of group 5, but the drug periods as an intramuscular injection. is given for 4 weeks. Twenty four hours after the last injection, rats MATERIALS AND METHODS were killed by inhaling overdose of Ether. Animals Dissection of the right hind limbs was done and the Thirty six male adult albino rats were obtained quadriceps femoris muscle was removed from from the animal house of Experimental Research each animal and prepared for histological Unit, College of Medicine, University of Mosul, processing. Iraq. The animals were kept in the laboratory in 164 Ann Coll Med Mosul December 2019 Vol. 41 No. 2 Local Effect of Intramuscular Injection of Meloxicam.. Ahmed Hisham Qassim Histological Study The quadriceps femoris muscle tissue samples were fixed in 10% neutral buffered formalin for 24 hours, then they were dehydrated, cleared, embedded in paraffin and sectioned by the microtome into sections of 5µm thickness, thereafter the sections were mounted on glass slides and stained with hematoxylin and eosin. The histological slides were examined through Olympus light microscope, and several sections were chosen to obtain their photographs using a digital camera. Figure 2: Photomicrograph of quadriceps femoris muscle of group 4 showing normal morphology. RESULTS (H&E X 100). Control (Untreated) Groups: In groups 1 and 2, the histological changes in the muscular biopsy were unremarkable (Figure 1). Treated Groups In groups 3 and 4, microscopic examination was similar to that of control groups (Figure 2). In animals of group 5, the histological finding was only congested skeletal muscle fibers(Figure 3). However, in group 6, the histological sections revealed mononuclear inflammatory cells infiltration, vascular congestion, fibrosis, degenerative changes and muscle tissue necrosis. Moreover, several areas showed hemorrhage which could be of traumatic origin (Figures 4 and Figure 3: Photomicrograph of quadriceps femoris muscle of group 5 showing congested blood vessels 5, Table 1). within normal muscle tissue (arrows). (H&E X 100). Figure 1: Photomicrograph of quadriceps femoris muscle of control groups showing normal Figure 4: Photomicrograph of quadriceps femoris morphology. (H&E X 100). muscle of group 6 showing mononuclear inflammatory cells infiltration (black arrow), vascular congestion (v), fibrosis (white arrow) and degenerative changes of muscle tissue (arrowhead). (H&E X 100). Ann Coll Med Mosul December 2019 Vol. 41 No. 2 165 Ahmed Hisham Qassim Local Effect of Intramuscular Injection of Meloxicam.. Figure 5: Photomicrograph of quadriceps femoris muscle of group 6 showing muscle tissue necrosis (black arrow) and hemorrhage (white arrow). (H&E X 100). Table 1: Showing drugs administered with their doses and duration of administration, as well as, histological changes of quadriceps femoris muscle obtained in different groups. Duration of Drug Dose of the Groups administrati Histological changes of muscle administered drug on Group 1 Normal saline 1 ml / kg 2 weeks Normal muscle tissue Group 2 Normal saline 1 ml / kg 4 weeks Normal muscle tissue Group 3 Meloxicam 0.22 mg / kg 2 weeks Normal muscle tissue Group 4 Meloxicam 0.22 mg / kg 4 weeks Normal muscle tissue Congestion of blood vessels within normal