Effects of adenosine and dipyridamole on serum levels of some biochemical markers in rabbits: Running title: Biochemical effects of adenosine and dipyridamole
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Abstract
Adenosine is a nucleoside which occurs naturally in a diverse forms in all cells of the body and in most biological fluids. Under basal conditions, the extracellular adenosine concentration is maintained within certain limits. Dipyridamol inhibits adenosine reuptake by erythrocytes, endothelial cells and platelet increasing plasma levels of adenosine Aims: study the effects of adenosine and dipyridamole on serum levels of serum urea, creatinine, alkaline phosphatase(ALP), lactate dehydrogenase (LDH), Aspartate Aminotransferase (GOT), and Alanine Aminotransferase (GPT). Material and methods: Thirty-five male rabbits were included in the study. The animals were divided into 3 groups: Group one(5 animals): injected intraperitoneal (i.p) with 2 ml of distilled water/day (control group). Group two (15 animals): were treated by i.p injection of adenosine, they were divided into 3 sub groups (5 animals) according to adenosine dose:1 mg/kg, 2mg/kg and 4 mg/kg.Group 3 (15 animals): were treated by dipyridamole orally, they were divided into 3 sub-groups (5 animals) according to dipyridamole dose:4 mg/kg, 8 mg/kg and 12 mg/kg. Result: Significant differences among 3 groups were found in blood urea, LDH, GOT levels, and in GPT levels. While statistical analysis of serum levels of S. creatinine and ALP showed no significant differences among 3 study groups. Conclusion: both adenosine, dipyridamole cause Significant differences among 3 groups were found in blood urea, LDH, GOT levels, and in GPT levels in rabbit
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References
[1] Belardinelli R, Belardinelli L, Shryock, JC. (2001). Effects of dipyridamole on coronary collateralization and myocardial perfusion in patients with is chaemic cardio myopathly. Eur. Heart. J. 22: 1205- 1213.
[2] Bjarnason NH, Henriksen, Alexan- dersen P, Chroistiansen C. (2002). Mechanism of circadian variation in bone resorption. Bone. 30 (1): 307- 313.
[3] Borea PA, Gessi S, Merighi S, et al. (2017). Pathological overproduction: the bad side of adenosine. Br. J. Pharmacol. 174 (13): 1945- 1960.
[4] Born GVR, Mills DCB. (1969). Potentiation of the inhibitory effect of adenosine on platelet aggregation by drugs that prevent its uptake. J. Physiol. 202: 4P.
[5] Brows DJ, Mathei RT, Benjamin IS, Alexander B. (2003). The role of ATP and adenosine in the control of hepatic blood flow in the rabbit liver in vivo. Bio. Med. Central. 2: 1-10.
[6] Chakrabarti S, Freedman JE. (2008). Dipyridamole, cerebrovascular disease, and the vasculature. Vascular pharmacology. 48: 143- 149.
[7] Chakrabarti S, Vitseva O. lyu D, varghes S, Freedman JE. (2005). the effect of dipyridamole on vascular cell- derived reactive oxygen species. J. Pharmal col. Exp. Ther. 315: 494- 500.
[8] Chen JF, Cunha R. (2020). The belated US FDA approval of the adenosine A2 A receptor antagonist is tradefylline for treatment of parkinson's disease. Purinergic Signalling. 16: 167- 164.
[9] Dasegowda SM et al. Int. J. Res. Med. Sci. 2015 May; 3 (5): 1195- 1198.
[10] De caen AR, Kleinman ME, Chameides L, Atkins DL, Berg RA, Berg MD, Bhanji F, et al (2010). Part 10: paediatric basic and advanced life support 2010 International consensus on Cardiopulmonary resuscitation and emergency cardiovascular care Science with treatment recommendations. Resuscitation. 81: 213- 259.
[11] Di Perri T, Pasini FL; Frigerio C, et al. (1991). Pharamcodynamics of ticlopidine in man in relation to plasma and blood cell concentration. Eur. J- Clinic. Pharmacol. 41: 429- 434.
[12] Effendi WI, Nagano T, Koba yashi K, et al. (2020). Focusing on Adenosine Receptors as a potential Targeted Therapy in Human Diseases. Ceus. 9: 785.
[13] Halkes PHA et al. (2006). Aspirine plus dipyridamole versus aspirin alone after cerebral is chaemia of arterial origin (ESPRT): randomized controlled trial. Lancet. 367: 1665- 73.
[14] Herman- de- Sousa C, Pinheiro AR, Paramos- de- Carvalno D, et al (2020). Opposing effects of Adenosine and Inosine in Human Subcutancous fibroblast may be regulated by third party ADA cell providers. Cells. 9: 651.
[15] Honour AJ, Hockaday TDR, Mann JI, (1976). The reversibility by dipyridamole of the increased sensitivity of in vivo platelet aggregation in rabbits after alloxan. Br. J. exp. Path. 57: 11.
[16] Katzung BG. (2017). Basic and clinical Pharmacology. 14 th ED.
[17] Kim H H, Liao J K. (2008). Translational therapeutics of dipyridamole. Arterioscler. Thromb. Vasc. Biol. 28: 539-542.
[18] Kleinman ME, Chameides L, Schexnayder SM, Samson RA, Hazinski MF, Atkins DL, et al (2010). Part 14: pediatric Advanced life support 2010 American heart association guide lines for cardio pulmonary resuscitation and emergency cardio vascular care. Circulation. 122: 876- 908.
[19] Kusmic C; Picano E, Buscetti CL, et al. (2000 a). The antioxidant drug dipyridamole spares the vitamin E and thiois in red blood cells after oxidative stress. Cardiovasc. Res. 47: 510- 514.
[20] Lewis J1, Arora G2, Tu dorascu Dl3, Hickey Rw1, Saladino PA1, Monole MD4. (2017). Acute management of refractory and unstable pediatric supraventricular tachycardia. J. Pediatr. 181: 177- 182.
[21] Luliano AR, Colavita C; Bello CV, et al., (1996). Protection of low density lipoprotein oxidation at chemical and cellular level by the antioxidant drug dipyridamole. British Journal Pharmacolagy. 119: 1438- 1446.
[22] Luliano L, Pedersen JZ. Rotilio G, et al. (1995). A potent chain- breaking activity of the cardiovascular dring dipyridamole. Free. Rad. Biol. Med. 18: (2): 239- 247.
[23] Mahler G S. (1998). Adenosine is an endogenous nucleoside occurring in all of the body, and is currently approved by the U. S. Food and Drug Administration for two uses. Analytical profiles of Drug substances and Excipients.
[24] Melani C, Jaffe ES., Wilson WH. (2020). Pathological and treatment of lymphomatoid granulomatosis, a rare EBV- driven disorder. Blood. 135: 1344- 1352.
[25] Merello S, Ito K, Yamamura S, et al. (2006). 1L- 1B and TNF- ∝ Regulation of the Adenosine Receptor (A2A) Expression: Differential Requirement for NF- KB Binding to the proximal promoter. J. Immunol. 177: 7173- 7183.
[26] Murday AJ, Gershlick AH, Synder combe- Court, YD, Mills PG, Lewis CT. (1984), Intimal thickening in autogenous vein grafts in rabbiuts: influence of spirin and dipyridamole. Thorax. 39: 457- 461.
[27] Nassar PM, Almeida LE, Tabak M. (1997). Binding of dipyridamole to phospholipid vesicles: a fluorescence study. Biochimica. Biophysica. Biomembrones. 1328 (4): 140- 150.
[28] Ozel I, Akkaya I, Oylumlu E, Uzel G, et al. (2020). Adenosine- Induced NLRPII in B Lymphoblasts Suppresses Human CD4+ T Helper Cell Responses. Journal of Immunology Research.
[29] Palmer TM, Trevethick MA. (2008). Suppression of inflammatory and immune responses by the A2A adenosine receptor: An in troduction. Brit. J. Pharmacol. 1 (1): 27- 34.
[30] Pedulli GF, Lucarini M, Marchesi, et al. (1999). Medium effects on the antioxidant activity of dipyridamole. Free. Rad. Biol. Med. 26: 295- 302.
[31] Pellegrini GG, Chaves MM, Maria AF, Ponce GM, Toyos GI, Lif shitz, F et al. (2012). Salivary bone turnover markers in healthy pre- and post menopausel women: daily and seasonal rhythm. Clin. Oral. Inves. 16 (2): 651- 657.
[32] Persantin (dipyridamole USP). (2019).
[33] Radojkovic M, Stojanovic M, Stanojeric G, Radojkovic D, Gilgorijevic J, Ilic I, Stojanovic N. (2017). Ischemic Preconditioning Vs adenosine Vs prostaglandin El for protection against liver ischemia/ reperfusion injury. Braz. J. Med. Biol. Res. 50 (8): e 6185.
[34] Rajah SM, Penny AF, Crow MJ, Ahmed R, Watson DA. (1997). The effect of dipyridamole on platelet function: correlation with blood levels in man. Br. J. Clin. Pharmac. 4: 129- 33.
[35] Rajah SM, Penny AF, Crow MJ, Pepper MD, Watson DA. (1979). The interaction of varying doses of dipyridamole and acetylsalicylic acid on the inhibition of platelet functions and their effects on bleeding time. Br. J. Clin. Pharmac. 7: 483- 9.
[36] Sailaja YR, Basker R; Saralakumari D- (2003). The antioxidant status during maturation of reticnloytes to erythrocytes in type 2 diabetics. Free. Rad. Biol, Med. 35 (2): 133- 139.
[37] Sedlak TW; Paw B; Parker GM; et al., (2019). The glutathione cycle shapes synaptic glutamate activity. PNAS. 116 (7): 2701- 2706.
[38] Shin Jw, Seol IC, Son CG. (2010). Interpretation of animal dose and human equivalent dose for drug development. The Journal of Korean Oriental Medicine. (31) 3: 1-7.
[39] Stelee P, Rain water J, Vogel R, (1981). Effects of platelet suprressant treatment with dipyridamole and aspirin on exercise performance and platelet survival time in coronary disease. Chest. 80: 557- 61.
[40] Verro P, Gorelick PB, Nguyen D. (2008). Aspirin plus dipyridamole versus aspirin for prevention of vascular events after stroke or TIA: ameta- analysis. Stroke. 39: 1358- 1363.
[41] Vicram R, Craig W, Sandeep P, et al. (2004). Noise induces A1 adenosine receptor expression in the chinchilla cochlea. Hear. Res. 188: 47- 56.
[42] Yip S, Benavente O. (2011). Antliplatelet agents for stroke prevention. Neuro therapeutics. 8: 475- 487.
[43] Klein R.; Nagy O.; Tothova C.; Chovanova F. (2020). Clinical and Diafnostic Singificance of Lactate Dehydrogenase and its Isoenzymes in Animals. Vet. Med. Int . 20(2): 191-196.
[44] Farhana A.; Lappin SL. (2020). Biochemistry, Lactate Dehudrogenase. 20 (6): 855-868.
[45] Martins NM.; Grinai NA.; Curti CM.; et al. (2008). Cisplatin indnces mitochondrial oxidative stress with resultant enerygetic metabolism impairment, membramce rigidification and apoptosis in rat liver. J. Appl. Toxical. 29(3): 337 – 44.
[46] Jarsiah P.; Nosrati A.; Alizadeh A.; et al. (2017). Hepatotoxicity and ALT/ AST Enzymes Activities change in therapeutic and toxic Doses. Consumption of Acetaminophen in Rats. Int. Biol. Biomed. J. 3(3).
[47] Woreta TA.; Alqahtani SA. (20214). Evaluation of Abnormal liver test . Med. Clin. North. Am. 98(1): 1-16.
[48] Karadeniz A.; Simsek N.; Karakus E.; et al (2011). Royal jeuy Modulates Oxidative stress and Apoptosis in liver and kidneys of Rats Treated with Cisplatin. Oxid. Med. Cell. Longev. 23 (4): 209-240.
[49] Attyah AM.; Ismail SH. (2012). Protective Effect of Ginger Extract Ageist Cisplatin – Induced Hepatotoxicity and Cradiotoxicity in Rats. Iraqi. H. Pharm. Sci . 21 (1).
[50] Kalender S.; Ogutcu A.; Uzunhisarcikli M.; et al . (2005). Diazinon – induced hepatotoxicity and protectice effect of vitamin E on some biochemical indices and ultra structural changes. Toxicology. 211(3): 197 – 206.
[51] Singh S.; Mckintosh R. (2020). Adenosine.
[52] Patinha D.; Dovale Afonso J. Sousa T.; et al. (2013). Activation of adenosine receptors improves renal antioxidant status in diabetic wister but not SHR rats. Upsala . J. Med. Scie. 119 (1).