Comparative evaluation of renal, pleiotropic and myotropic effects of statins in rats
V.G. Zeleniuk, I.I. Zamorskii, O.V. Gerush, T.S. Shchudrova, O.M. Goroshko, A.R. Zeleniuk
Higher state educational establishment of Ukraine “Bukovinian state medical university”, Chernivtsi, Ukraine
DOI: https://doi.org/10.15407/fz65.02.076
Abstract
The effect of certain statins with different lipophilicity (atorvastatin (ATO), lovastatin (LOV), simvastatin
(SIM)) on renal function of apparently healthy rats at a conventionally effective dose of 20 mg/kg was
established. As it has been found in our experiments on the 7th day of statins administration there was
only a slight increase in urine output along with a moderate growth of glomerular filtration rate (GFR)
and decrease in excretion of sodium ions and protein while maintaining the mechanisms of intrarenal
autoregulation. Renotropic action of statins, among various mechanisms, was evoked by their pleiotropic
effects what was confirmed by the presence of correspondent correlations. Antioxidant effect of drugs was
evidenced by decreased malondialdehyde (MDA) content and increased catalase (CAT) activity, as well as
by reducing trend of blood plasma proinflammatory cytokines (interleukin-1β (IL-1β), interleukin-6 (IL-6)
and tumor necrosis factor alpha (TNF-α)). An absence of statins influence on blood plasma transaminase
levels, blood plasma creatine phosphokinase (CPK) activity and skeletal muscles histostructure was also
demonstrated. The most marked renal effect was demonstrated by SIM – the most lipophilic drug among
the studied ones.
Keywords:
statins; renal function; apparently healthy rats: prooxidant-antioxidant balance; interleukins
References
- Davies JT, Delfino SF, Feinberg CE, Johnson MF, Nappi VL, Olinger JT, et al. Current and emerging uses of statins in clinical therapeutics: a review. Lipid Insights. 2016;9:13-29.
CrossRef
PubMed PubMedCentral
- Kavalipati N, Shah N, Ramakrishan A, Vasnawala H. Pleiotropic effects of statins. Indian J Endocrinol Metab. 2015;19(5):554-62.
CrossRef
PubMed PubMedCentral
- Amann K, Benz K. Statins - beyond lipids in CKD. Nephrol Dial Transplant. 2011;26:407-10.
CrossRef
PubMed
Wu K, Lei W, Tian J, Li H. Atorvastatin treatment attenuates renal injury in an experimental model of ischemiareperfusion in rats. BMC Nephrology [Internet]. 2014 [cited Jun 29];15:14. Available from: http://www.biomedcentral. com/1471-2369/15/14 doi: 10.1186/1471-2369-15-14
CrossRef
PubMed PubMedCentral
- Burgazli KM, Bui KL, Mericliler M, Albayrak AT, Parahuleva M, Erdogan A. The effects of different types of statins on proliferation and migration of HGF-induced Human Umbilical Vein Endothelial Cells (HUVECs). Eur Rev Med Pharmacol Sci. 2013;17(21):2874-83.
- Antonopoulos AS, Margaritis M, Lee R, Channon K, Antoniades C. Statins as anti-inflammatory agents in atherogenesis: molecular mechanisms and lessons from the recent clinical trials. Curr Pharm Des. 2012;18(11):1519-30.
CrossRef
PubMed PubMedCentral
- Violi F, Calvieri C, Ferro D, Pignatelli P. Statins as antithrombotic drugs. Circulation. 2013;127:251-57.
CrossRef
PubMed
- Bonfrate L, Procino G, Wang DQH, Svelto M, Portincasa P. A novel therapeutic effect of statins on nephrogenic diabetes insipidus. J. Cell. Mol. Med. 2015;19(2):265-82.
CrossRef
PubMed PubMedCentral
- Drapala A, Sikora M, Ufnal M. Statins, the reninangiotensin-aldosterone system and hypertension - a tale of another beneficial effect of statins. J Renin-AngiotensinAldosterone Syst. 2014;15(3):250-58.
CrossRef
PubMed
- Paulsen L, Holm C, Bech JN, Starklint J, Pedersen EB. Effects of statins on renal sodium and water handling. Nephrol Dial Transplant. 2008;23:1556-61.
CrossRef
PubMed
- Maji D, Shaikh S, Solanki D, Gaurav K. Safety of statins. Indian J Endocrinol Metab. 2013;17(4):636-46.
CrossRef
PubMed PubMedCentral
- Zeleniuk VG, Zamorskii II, Goroshko OM. Renoprotective efficacy of different doses of statins in experimental acute renal failure. Fiziol Zh. 2014;60(2): 75-81.
CrossRef
PubMed
Clinical Methods: The History, Physical, and Laboratory Examinations. Editors: Walker H.K., Hall W.D., Hurst J.W. 3rd edition [Internet]. Boston: Butterworths; 1990 [cited 2017 Jun 29]. Available from: https://www.ncbi.nlm.nih. gov/books/NBK201/
- Szasz G. A kinetic photometric method for serum gammaglutamyl transpeptidase. Clin Chem. 1969;15(2):124-36.
- Lechleitner M. Non lipid related effects of statins. J Clin Basic Cardiol. 2002 5(3):205-8.
- Moon GJ, Kim SJ, Cho YH, Ryoo S, Bang OY. Antioxidant Effects of Statins in Patients with Atherosclerotic Cerebrovascular Disease. J Clin Neurol. 2014;10(2):140-7.
CrossRef
PubMed PubMedCentral
- Trevisan R, Dodesini AR, Lepore G. Lipids and Renal Disease. JASN. 2006;17(4,2):S145-7.
CrossRef
PubMed
- Ortega ML, Fornoni A. Role of cytokines in the pathogenesis of acute and chronic kidney disease, glomerulonephritis, and end-stage kidney disease. Int J Interferon, Cytokine and Mediat Res. 2010;2:49-62.
CrossRef
- Nakamura K, Hayashi H, Kubokawa M. Proinflammatory cytokines and potassium channels in the kidney. Mediators Inflamm [Internet]. 2015 [cited 2017 Jun 29]. Available from: https://www.hindawi.com/journals/mi/2015/362768/ DOI: 10.1155/2015/362768.
CrossRef
PubMed PubMedCentral
- Xiao-lei W, Tuo Z, Liu-hua H et al. Comparison of effects of different statins on contrast-induced acute kidney injury in rats: histopathological and biochemical findings. Oxid Med Cell Longev. 2017 2017:a6282486. doi: 10.1155/2017/6282486.
CrossRef
PubMed PubMedCentral
- Xiong B, Nie D, Cao Y, Zou Y, Yao Y, Qian J, et al. Preoperative statin treatment for the prevention of acute kidney injury in patients undergoing cardiac surgery: a meta-analysis of randomised controlled trials. Heart Lung Circ. 2017;26(11):1200-1207. doi: 10.1016/j. hlc.2016.11.024.
CrossRef
PubMed
- Yang Y, Song M, Liu Y, Liu H, Sun L, Peng Y et al. Renoprotective approaches and strategies in acute kidney injury. Pharmacol Ther. 2016;163:58-73.
CrossRef
PubMed PubMedCentral
|