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Calcium Enhances Antiinflammatory Activity of Aspirin in Albino Rats

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Calcium Enhances Antiinflammatory Activity of Aspirin in Albino Rats Research Paper Calcium enhances antiinflammatory activity of aspirinaspirin in albino ratsrats A.S. Karnad, P.A. Patil, S.I. Majagi ABSTRACT Objective: To evaluate the effects of calcium carbonate and calcium gluconate on acute and subacute inflammation, and to study their possible interactions with aspirin, verapamil and magnesium sulphate. Materials and Methods: Calcium carbonate in the dose of 10, 25, 50 mg/kg, calcium Department of Pharmacology and gluconate in the dose of 5, 10, 25, 50 mg/kg, and aspirin in the dose of 54, 200 mg/kg Pharmacotherapeutics, were administered orally in different groups of albino rats, to study their effect on J.N. Medical College, inflammation induced by carrageenan or a foreign body. Aspirin (54 mg/kg) was Nehru Nagar, administered either with calcium carbonate (10 mg/kg) or calcium gluconate (5 mg/kg) Belgaum-590 010. India to separate groups in order to study their interaction, especially with reference to gastric Received: 19.10.2005 ulceration. Similarly, possible interactions of verapamil (4 mg/kg) with calcium carbonate Revised: 2.3.2006 (10 mg/kg) and magnesium sulfate (500 mg/kg) with calcium carbonate (50 mg/kg) were Accepted: 24.4.2006 also studied. Results: Both calcium carbonate and calcium gluconate produced significant Correspondence to: antiinflammatory activity in acute as.com). well as subacute inflammation models and was Suneel Ishwar Majagi comparable to that of aspirin. Sub-antiinflammatory dose of calcium salts potentiated E-mail: [email protected] the antiinflammatory activity of aspirin. Verapamil also potentiated the anti-inflammatory activity of calcium carbonate while magnesium sulfate antagonized the antiinflammatory activity of calcium carbonate in both the models of inflammation. Conclusion: Co-administration of calcium salt potentiated the antiinflammatory response and minimized the.medknow gastro-toxicity of aspirin. KEY WORDS: Acetylsalicylic acid, antiinflammatory agent, calcium channel blocker, calcium salt, magnesium salt. (www Introduction On the contrary, in another study[10] locally applied calcium This PDFa site is hosted available by forMedknow freeneither download inhibited Publications oedema forfrommation nor reduced inflammatory Inflammation continues to be an area of great interest for signs. Similarly, calcium salts failed to prevent effusion across research, probably due to the nonavailability of a safer and capillary endothelial membrane.[11] Moreover, calcium more effective antiinflammatory agent. In recent years gluconate has been reported to produce pancreatitis in cats.[12] increased understanding of the inflammatory mechanism and All these indicate that calcium salts are not only devoid of the mediators involved has led to the development of newer antiinflammatory activity but may be pro-inflammatory. antiinflammatory agents like monoclonal antibodies and antagonists of inflammogens. Interestingly, several other drugs Calcium channel blockers have also been reported to [13] like minocycline,[1] ascorbic acid[2] and calcium salts possess antiinflammatory property and a calcium-channel (calcium dobesilate, calcium hydroxide, calcium pentosan antagonist, verapamil, has been shown to potentiate the [14] polysulfate)[3-5] have also been reported to possess antiinflammatory activity of aspirin. These studies probably antiinflammatory property. Earlier, calcium chloride was support the pro-inflammatory activity of calcium salts. advocated for the treatment of urticaria, acute oedema, In view of these controversies, the present study was pruritus and erythema,[6] calcium carbonate and calcium planned to investigate the effect of calcium carbonate and gluconate for the treatment of insect stings[7] and calcium calcium gluconate on acute and subacute inflammation in hydroxide to suppress periapical inflammation in dental Wistar rats. The other objective was to investigate the practice.[8, 9] These reports indicate that calcium salts possess interaction of calcium salts with aspirin, as well as with antiinflammatory property. verapamil. Indian J Pharmacol | December 2006 | Vol 38 | Issue 6 | 397-402 397 Karnad et al. Materials and methods lens. The severity of the ulcers was determined by an arbitrary scoring system.[16] The ulcer index was calculated as a mean Animals score of ulcer severity in all the treated groups and was Male albino Wistar rats (150–270 g) were used. The animals compared with that of control. were acclimatized to normal laboratory conditions with Serum calcium 12:12 h natural light:dark cycle and were fed with standard Serum calcium was estimated in a separate group of laboratory diet with free access to water. animals. Half millilitre of blood was collected from the heart Acute inflammation of the anaesthetized animals with the help of a 21 g hypodermic Rats were divided into several groups of six each. They needle inserted into the ventricle. The serum calcium was were starved overnight with water ad libitum prior to the day estimated by the 0-cresolphthalein complexone (0-cpc) of experiment. The control group received 0.5 ml of 1% gum method[17] using a kit (Accurex Biomedical private limited). acacia suspension orally, while the other groups received Drugs and doses different drug treatments as detailed below. The clinical doses for various drugs were converted to rat- Thirty minutes after drug administration, acute equivalent doses with the help of a converting table devised inflammation was induced by injecting 0.05 ml of 1% by Paget and Barnes cited by Ghosh.[18] Calcium carbonate (LR carrageenan (Sigma co., St Louis) in normal saline into the grade; BDH) in 1% gum acacia suspension was used in 10, 25 subplantar region of the left hind paw, as per the method of and 50 mg/kg doses. Winter et al.[15] A mark was applied on the leg at the malleolus 1. Calcium gluconate (generous gift by Korten to facilitate subsequent readings. The paw oedema volume Pharmaceuticals Pvt. Ltd., India) dissolved in water was measured by mercury displacement with the help of a was used in 5, 10, 25 and 50 mg/kg doses. plethysmograph at 0, 0.5, 1,3 and 5 h after injecting 2. Aspirin (I.P. grade, Vikas, Pharma, Mumbai) in 1% gum carrageenan. The difference between 0 h and subsequent acacia suspension was administered at 54 and readings was considered as oedema volume. The percentage 200 mg/kg doses. inhibition of oedema in various groups was calculated using 3. Verapamil hydrochloride (I.P. grade, Torrent the formula: laboratories, Ahmedabad) dissolved in water was % oedema inhibition =1 - Vt X 100 administered in the dose of 4 mg/kg. Vc 4. Magnesium sulfate (LR grade, S.D fine chemicals Ltd., Vt and Vc were oedema volume in the drug-treated and Boisar).com). dissolved in water was used in the dose of 500 control groups respectively. mg/kg i.p. Subacute inflammation In the interaction studies, aspirin, calcium carbonate and Subacute inflammation was induced by a slightly modified verapamil were used in their subeffective doses simultaneously, method of D’Arcy et al.[15] Seven groups of six rats each were whereas magnesium sulfate was administered i.p 15 min after used. Under light ether anaesthesia, hair in the axilla and the the oral administration of calcium carbonate. groin were clipped, and two sterile cotton pellets, weighing All the procedures were performed in accordance with the 10 mg each and two sterile grass piths (25 X 2 mm) were.medknow guidelines issued by the Institutional Animal Ethical implanted subcutaneously, through a small incision, either in Committee, constituted as per the directions of the Committee the axilla or the groin, at random. The wounds were then for the Purpose of Control and Supervision of Experiments on sutured and the animals were caged individually after(www recovery Animals, Ministry of Animals Welfare Division, Government from anaesthesia. Aseptic precautions were taken throughout of India. the experiment. The rats then received treatments as shown Statistical analysis below. The treatment was started on the day after the Data were expressed as mean±SEM and were analysed implantation and wasThis repeated PDFa site ever is yhosted 24available h, regularly by forforMedknow freeby the one-waydownload Publications ANOVA followed from by the Dunnett’s test. P<0.05 10 days. was considered significant. On the 11th day the rats were sacrificed with an overdose Results of ether anaesthesia, and the cotton pellets, grass piths and Acute studies the stomachs were removed. The pellets, freed from extraneous Carrageenan-induced paw edema in the control group did o tissue, were dried overnight at 60 C and their dry weight not differ from the corresponding values in the calcium measured. Net granuloma formation was calculated by carbonate (10 mg/kg)-treated group, indicating the ineffective subtracting the initial weights of cotton pellet from the final dose of calcium carbonate. On the contrary, calcium gluconate weights. Mean granuloma dry weight for the various groups in the dose of 5 mg/kg showed a significant (P<0.001) pro- was calculated and expressed as mg/100 g body weight. The inflammatory activity after 3 h. grass piths were preserved in 10% formalin for The mean paw volume at 1 h in the calcium carbonate (50 histopathological study after H&E staining. mg) and the calcium gluconate (50 mg) groups was comparable Ulcer index to the corresponding value of the aspirin (200 mg) group, The stomachs were cut open along the greater curvature indicating significant (P<0.001) inhibition of oedema as and gently
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