STUDY OF THE EFFECT OF TREATMENT WITH THE RENIN-ANGIOTENSIN SYSTEM INHIBITOR LOSARTAN AND THE LIPID-LOWERING DRUG ATORVASTATIN AND THEIR INTERACTIONS IN DIABETIC RATS
Main Article Content
Keywords
renin-angiotensin, lipid-lowering drug, diabetic, rats.
Abstract
Background:Diabetes mellitus (DM) is a chronic metabolic disorder distinguished by high levels of blood sugar and disruptions in lipid, carbohydrate & protein metabolism due to insulin insufficiencies.
Aim:This study evaluated the effectiveness of Renin-Angiotensin-Aldosterone System antagonist losartan&its combination with atorvastatin in preventing diabetes mellitus accumulations.
Methods:The animal utilized in this study consisted of80 adult male albino ratsweighed between 200 and 250gfed a well-balanced diet and provided with clean water in containers. Before starting the experiment, they were housed for one week to acclimate to the laboratory environment.In this study, rats were divided into 8 groups and diabetes was induced by a single dosage of fifty mg/kgof an intraperitoneal injection of streptozotocin.
Isolated aortic rings were performed. Blood samples were collected for measuring of tumor necrosis factor-alpha level,lipid profile,serum insulin, blood glucose level, andrenal function tests:Serum creatinine measurements &Serum uric acid measurementsat the end of experimental period.
Results:The contractile response of the aorta induced by norepinephrine is significantly diminished in diabetic rats receiving glimepiride or losartan compared to diabetic rats untreated.The same treatment caused a significant (P<0.001) decrease in tumor necrosis factor-alpha (TNF-α) level, blood glucose level in addition to a significant increase in serum insulin level.Furthermore, there has been an improvement in oxidative stress parameters and renal function.Conclusion: RAAS blocker losartan and atorvastatin ameliorated SZT-induced diabetic nephropathy, impairment of lipid profile, and endothelial dysfunction through antihypertensive, antioxidant, and anti-inflammatory activities, and can protect against diabetic-induced renal and cardiovascular complications.
References
2. Molehin, O. R., Adefegha, S. A., &Adeyanju, A. A. (2020). Role of oxidative stress in the pathophysiology of type 2 diabetes and cardiovascular diseases. Role of oxidative stress in pathophysiology of diseases, 277-297.
3. Zhang, Y., Murugesan, P., Huang, K. et al. (2020)NADPH oxidases and oxidase crosstalk in cardiovascular diseases: novel therapeutic targets. Nat Rev Cardiol 17, 170–194.
4. Yun, J.S. and Ko, S.H. (2021).Current trends in epidemiology of cardiovascular disease and cardiovascular risk management in type 2 diabetes. Metabolism.;123:154838.
5. Paget GE and Barnes JM. (1964): Toxicity tests in Evaluation of drug activities and pharmacometrics. Ed, Laurance, D.R. and Bacharch, A.L. Acad press Massachusetts;135-166.
6. Wszola, M., Klak, M., Kosowska, A., Tymicki, G., Berman, A., Adamiok-Ostrowska, A., ... & Kaminski, A. (2021). Streptozotocin-induced diabetes in a mouse model (BALB/c) is not an effective model for research on transplantation procedures in the treatment of type 1 diabetes. Biomedicines, 9(12), 1790.
7. Elankani P., Reddy, G. D., Kabilan, N., Kumar, P., Ganesan, R.. Kumar, G. V. N. and Pitchaiah, D. (2020).EVALUATION OF THE ANTI-DIABETIC ACTIVITY OF THE TRAN VIDHAI KUDINEER ON FRUCTOSE AND STREPTOZOTOCIN INDUCED DIABETIC RATS.INTERNATIONAL JOURNAL OF Pharmaceutical Sciences and Research.
8. Biswas, S. K., Chatterjee, S., Laha, S., Pakira, V., Som, N. K., Saha, S., & Chakraborty, S. (2022). Instrument-free single-step direct estimation of the plasma glucose level from one drop of blood using smartphone-interfaced analytics on a paper strip. Lab on a Chip, 22(23), 4666-4679.
9. Silva-Reis, R., Faustino-Rocha, A. I., Silva, J., Valada, A., Azevedo, T., Anjos, L., & Oliveira, P. A. (2021). Studying and Analyzing Humane Endpoints in the Fructose-Fed and Streptozotocin-Injected Rat Model of Diabetes. Animals, 13(8), 1397.
10. Wszola, M., Klak, M., Kosowska, A., Tymicki, G., Berman, A., Adamiok-Ostrowska, A., & Kaminski, A. (2021). Streptozotocin-induced diabetes in a mouse model (BALB/c) is not an effective model for research on transplantation procedures in the treatment of type 1 diabetes. Biomedicines, 9(12), 1790.
11. Nicosia, R. F. and Ottinetti, A. (1990). Growth of microvessels in serum-free matrix culture of rat aorta: a quantitative assay of angiogenesis in vitro. Lab. Invest. 63, 115–122.
12. Desoky N, EL-Bassossy HM, Fahmy A. and Azhar A. (2014): Apigenin restores normal vascular reactivity in diabetic rats via protein kinase C inhibition.Z.U.M.J.Vol.20:N.1:1-5.
13. Roghani M, Jalali-Nadoushan MR, Baluchnejadmojarad T, Vaezmahdavi MR, Naderi G, Dehkordi FR. And Joghataei MT. (2013): Endothelium –dependent Effect of Sesame Seed feeding on Vascular Reactivity of Streptozotocin-diabetic Rats: Underlying Mechanisms. Iranian journal of pharmaceutical Research,12(3):377-385.
14. Fabiano E. Xavier, Ana Paula C. Davel, Luciana V. Rossoni, Dalton V. Vassallo (2003): Time-dependent hyperreactivity to phenylephrine in aorta from untreated diabetic rats: role of prostanoids and calcium mobilization Vascular Pharmacology 40 : 67– 76.
15. Vandana S. Nade, L. A. Kawale And K. M. Patel (2015):Protective Effect of Sitagliptin and Rosuvastatin Combination on Vascular Endothelial Dysfunction in Type 2 Diabetes Indian Journal of Pharmaceutical Sciences 77(1):96-102.
16. Mostafa Sleem, Ashraf Taye, Mohamed A. El-Moselhy, Safwat A. Mangoura (2014): Combination therapy with losartan and L -carnitine protects againstendothelial dysfunction of streptozotocin-induced diabetic ratsEuropean Journal of Pharmacology -744-10-17.
17. Xiang Kong, Ming-zhe Ma, Li Qin, Yan Zhang, Xiao-yong Li1, Guo-dong Wang, Qing Su1 and Dao-you Zhang (2014): Pioglitazone enhances the blood pressure-lowering effect of losartan via synergistic attenuation of angiotensin II-induced vasoconstriction. Journal of the Renin- Angiotensin-Aldosterone System. 15(3):259-70.
18. Manpreet Kaur, Shilpi Sachdeva, Onkar Bedi, Tavleen Kaur, and Puneet Kumar (2015):Combined effect of hydrogen sulphide donor and losartan in experimental diabetic nephropathy in ratsJ Diabetes MetabDisord; 14: 63.
19. Mohamed I Saad, Maher A Kamel, Mervat Y Hanafi, Madiha H Helmy, Rowaida R Shehata(2014): Effect of Sitagliptin and Glimepiride on Glucose Homeostasis and cAMP Levels in Peripheral Tissues of HFD/STZ Diabetic Rats American Journal of Biomedical Research, , Vol. 2, No. 3, 52-60.
20. Marwa M.A. Khalaf, Gamal A. El Sherbiny, Hekma A. AbdEllatif, Afaf A. Ain-shoka, Mostafa E. El Sayed. (2012): Comparative Effects of Glimepiride, Vanadyl Sulfate and Their Combination on Hypoglycemic Parameters and Oxidative Stress British Journal of Pharmacology and Toxicology 3(6): 278-288.
21. Saleh N. Mwafy and Maged M. Yassin, (2011): Antidiabetic Activity Evaluation of Glimepiride and Nerium oleander Extract on Insulin, Glucose Levels and Some Liver Enzymes Activities in Experimental Diabetic Rat Model. Pakistan Journal of Biological Sciences, 14: 984-990.
22. Nesren Shaban Mohammed ,Esam Noori Al-Karwi, Ahmed Tariq Numan and Saad Abdul-Rehman Hussain(2010): Effects of Low Doses of Captopril or Losartan in Improving Glycemic Control by Oral Hypoglycemic Agents in Type 2 DM Patients AJPS, Vol. 8, No.2.
23. Jin H., Pan Y. (2007): Angiotensin type-1 receptor blockade with losartan increases insulin sensitivity and improves glucose homeostasis in subjects with type2 diabetes and nephropathy. Nephrol Dial Transplant 22: 1943–1949.
24. Yadav, N., Palkhede, J. D., & Kim, S. Y. (2021). Anti-Glucotoxicity Effect of Phytoconstituents via Inhibiting MGO-AGEs Formation and Breaking MGO-AGEs. International Journal of Molecular Sciences, 24(8), 7672.
25. Reghunath, S. R., Rashid, M., Chandran, V. P., Thunga, G., Shivashankar, K. N., & Acharya, L. D. (2021). Factors contributing to the adverse drug reactions associated with the dipeptidyl peptidase-4 (DPP-4) inhibitors: A scoping review. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 102790.
26. Goyal BR, Shraddha V. Bhadada and Mayur M. Patel. (2011): Comparative evaluation of spironolactone, atenolol, metoprolol, ramipril and perindopril on diabetes-induced cardiovascular complications in type 1 diabetes in rats. Institute of Pharmacy, vol. 19 no.1
27. Oyedepo, T. A., &Palai, S. (2021). Herbal remedies, toxicity, and regulations. In Preparation of Phytopharmaceuticals for the Management of Disorders (pp. 89-127). Academic Press.
28. Hassanin A, Malek HA (2014). Effect of renin inhibition on adipokines in diabetic rats. Pak J Pharm Sci.;27(4):767–72.
29. Xu D, Liu J, Ji C, Zhou L, Hong Guo (2007): Effects of telmisartan on hypertensive patients with dyslipidemia and insulin resistance. Journal of Geriatric Cardiology Vol 4 No 3 149-152.
30. Roberto I. Mota, Samuel E. Morgan & Edward M. Bahnson. (2020). Diabetic Vasculopathy: Macro and Microvascular Injury. Current Pathobiology Reports 8:1–14.
31. Nagy M.A.(2015): Antidiabetic, antihyperlipidemic and histopathological analysis of Panax quinquefolium extract on alloxan induced diabetic rats An Indian Journal BCAIJ, 9(2), [041-050].
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Ahmed El-Sayed Nour El-Deen
Department of Physiology, Faculty of Medicine, Al-Azhar University, Assiut, Egypt.
Ahmad Taha
Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University, Zarqa, Jordan.
Ahmed F. Abdel Ghany
Department of Physiology, Faculty of Medicine, Al-Azhar University, Assiut, Egypt.
Muhammad Abdelbaeth Elfiky
Department of Physiology, Faculty of Medicine, Al-Azhar University, Assiut, Egypt.
Ahmed A. Abd El-Rhman
Department of Physiology, Faculty of Medicine, Al-Azhar University, Assiut, Egypt.
Ahmed Gad Allah
Department of Physiology, Faculty of Medicine, Al-Azhar University, Assiut, Egypt.
Mohamed R. Elnady
Department of Physiology, Faculty of Medicine, Al-Azhar university, Damietta, Egypt
Ramadan Hassan Ibrahim Thabet
Department of Pharmacology, Faculty of Medicine, Al-Azhar University, Assiut, Egypt.
Sherif M. A. Mansour
Department of Pharmacology, Faculty of Medicine, Al-Azhar University, Assiut, Egypt.
Heba K. Badawy
Department of Biochemistry, Faculty of Pharmacy, Sinai University, Arish Branch, North Sinai, Egypt.
Ali Abd El-salam Ahmed
Department of Pharmacology, Faculty of Medicine, Al-Azhar University, Assiut, Egypt.
Eman Wahsh
Department of Pharmacology & Toxicology, Faculty of Pharmacy, Sinai university, Arish branch, Egypt
Sahar Badr El-Din
Department of Pharmacology, Faculty of Medicine for girls, Al-Azhar University Cairo Egypt.