Effects of Dietary Flaxseed and Atorvastatin on Blood Hematology and Renal Health Metrics in Rats Fed High-Fat Diet
Abstract
Flaxseed is rich in omega-3 fatty acids and dietary fiber, both of which contribute to reduced inflammation and oxidative stress in the kidneys. Moreover, atorvastatin appears to enhance the activity of important antioxidant enzymes, potentially reducing the risk of chronic kidney disease and hematological disorders. Eighty male Wistar rats were divided randomly into ten groups: 1) ND (normal diet) 2) HFD (high-fat diet), 3) HFD+ ATO 10, 4) HFD+ ATO 20, 5) HFD+ FO (flaxseed oil), 6) HFD+ F (flaxseed), 7) HFD + ATO 10 + FO, 8) HFD + ATO 20 + FO, 9) HFD + ATO 10 + F, and 10) HFD + ATO 10 + F. Atorvastatin 10 and 20 mg/kg, FO 40 mg/kg, and flaxseed 40 g/kg were administrated for 8 weeks. After 23 weeks, serum level of kidney markers and CBC parameters were evaluated. ATO 20 led to reduce WBC, RBC, and HCT. Furthermore, ATO 20 + FO decreased WBC and ATO 20 + F reduced PLT, RBC and HCT. Administration of ATO 10 cause to increase creatinine (Cr) levels but other interventions had better effect on Cr, however these effects weren’t notable. There weren’t significant differences in Hb, MCV, MCH, MCHC, and urea between groups. F/FO therapies with ATO seems to have synergistic effects to improved dyslipidemia-associated kidney injuries and hematological indices. Although high dose of ATO can be more efficient than low dose.
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2. Muhamad NA, Maamor NH, Leman FN, Mohamad ZA, Bakon SK, Abdul Mutalip MH, et al. The Global Prevalence of Nonalcoholic Fatty Liver Disease and its Association With Cancers: Systematic Review and Meta-Analysis. Interact J Med Res. 2023;12:e40653.
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5. Paternostro R, Trauner M. Current treatment of non-alcoholic fatty liver disease. J Intern Med. 2022;292(2):190-204.
6. Ebrahimi B, Nazmara Z, Hassanzadeh N, Yarahmadi A, Ghaffari N, Hassani F, et al. Biomedical features of flaxseed against different pathologic situations: A narrative review. Iran J Basic Med Sci. 2021;24(5):551-60.
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8. Ghadge A, Harsulkar A, Karandikar M, Pandit V, Kuvalekar A. Comparative anti-inflammatory and lipid-normalizing effects of metformin and omega-3 fatty acids through modulation of transcription factors in diabetic rats. Genes Nutr. 2016;11:10.
9. Liu H, Wang F, Xia H, Pan D, Yang L, Wang S, et al. Comparison of the effects of 3 kinds of oils rich in omega-3 polyunsaturated fatty acids on glycolipid metabolism and lipoprotein subfractions. Food Science and Human Wellness. 2023;12(6):2221-31.
10. Al-Bishri W. Favorable Effects of Flaxseed Supplemented Diet on Liver and Kidney Functions in Hypertensive Wistar Rats. Journal of oleo science. 2013;62:709-15.
11. Chechi K, Yasui N, Ikeda K, Yamori Y, Cheema S. Flax oil-mediated activation of PPAR-correlates with reduction of hepatic lipid accumulation in obese spontaneously hypertensive/NDmcr-cp rats, a model of the metabolic syndrome. The British journal of nutrition. 2010;104:1313-21.
12. Al-Madhagy S, Ashmawy NS, Mamdouh A, Eldahshan OA, Farag MA. A comprehensive review of the health benefits of flaxseed oil in relation to its chemical composition and comparison with other omega-3-rich oils. European Journal of Medical Research. 2023;28(1):240.
13. Zhang S, Ren X, Zhang B, Lan T, Liu B. A Systematic Review of Statins for the Treatment of Nonalcoholic Steatohepatitis: Safety, Efficacy, and Mechanism of Action. Molecules. 2024;29(8):1859.
14. Zhang B, Zhang C, Zhang X, Li N, Dong Z, Sun G, et al. Atorvastatin promotes AMPK signaling to protect against high fat diet-induced non-alcoholic fatty liver in golden hamsters. Exp Ther Med. 2020;19(3):2133-42.
15. Dehnavi S, Kiani A, Sadeghi M, Biregani AF, Banach M, Atkin SL, et al. Targeting AMPK by Statins: A Potential Therapeutic Approach. Drugs. 2021;81(8):923-33.
16. Koushki K, Shahbaz SK, Mashayekhi K, Sadeghi M, Zayeri ZD, Taba MY, et al. Anti-inflammatory Action of Statins in Cardiovascular Disease: the Role of Inflammasome and Toll-Like Receptor Pathways. Clin Rev Allergy Immunol. 2021;60(2):175-99.
17. Morofuji Y, Nakagawa S, Ujifuku K, Fujimoto T, Otsuka K, Niwa M, et al. Beyond Lipid-Lowering: Effects of Statins on Cardiovascular and Cerebrovascular Diseases and Cancer. Pharmaceuticals (Basel). 2022;15(2).
18. Zhao L, Li S, Gao Y. Efficacy of statins on renal function in patients with chronic kidney disease: a systematic review and meta-analysis. Ren Fail. 2021;43(1):718-28.
19. Ghelani H, Razmovski-Naumovski V, Inampudi V, Chang D, Nammi S. Atorvastatin Improves Hepatic Lipid Metabolism and Protects Renal Damage in Adenine-Induced Chronic Kidney Disease in Sprague-Dawley Rats. Biomed Res Int. 2019;2019:8714363.
20. Han E, Kim G, Lee JY, Lee YH, Kim BS, Lee BW, et al. Comparison between Atorvastatin and Rosuvastatin in Renal Function Decline among Patients with Diabetes. Endocrinol Metab (Seoul). 2017;32(2):274-80.
21. Chamani S, Kooshkaki O, Moossavi M, Rastegar M, Soflaei SS, McCloskey AP, et al. The effects of statins on the function and differentiation of blood cells. Arch Med Sci. 2023;19(5):1314-26.
22. Z E, Y Mnpk, M G, Ar EM, Sh S, Gh B, et al. The effect of endurance training combined with adenosine on the gene expression of UCP-1 and MAPK p38 in subcutaneous adipose tissue of male Wistar rats fed a high -fat diet. Yafte. 2023;25(3):66-79.
23. Eslami Z, Mirghani SJ, Eghbal Moghanlou A, Norouzi A, Naseh H, Joshaghani H, et al. An Efficient Model of Non-alcoholic Fatty Liver Disease (NAFLD) Versus Current Experimental Models: Effects of Fructose, Fat, and Carbon Tetrachloride on NAFLD. Hepat Mon. 2021;21(8):e117696.
24. Eslami Z, Rezaei Ghomi M, Saidi A, Mousavi SV, Farhadi M, Sheikh Robati N, et al. Endurance Training and Exogenous Adenosine Infusion Mitigate Hippocampal Inflammation and Cell Death in a Rat Model of Cerebral Ischemia/Reperfusion Injury: A Randomized Controlled Trial. Arch Neurosci. 2022;9(1):e119236.
25. Mehany HA, Abo-youssef AM, Ahmed LA, Arafa E-SA, Abd El-Latif HA. Protective effect of vitamin E and atorvastatin against potassium dichromate-induced nephrotoxicity in rats. Beni-Suef University Journal of Basic and Applied Sciences. 2013;2(2):96-102.
26. Stuglin C, Prasad K. Effect of flaxseed consumption on blood pressure, serum lipids, hemopoietic system and liver and kidney enzymes in healthy humans. J Cardiovasc Pharmacol Ther. 2005;10(1):23-7.
27. Al-Madhagy S, Ashmawy NS, Mamdouh A, Eldahshan OA, Farag MA. A comprehensive review of the health benefits of flaxseed oil in relation to its chemical composition and comparison with other omega-3-rich oils. Eur J Med Res. 2023;28(1):240.
28. Yoon SS, Dillon CF, Carroll M, Illoh K, Ostchega Y. Effects of statins on serum inflammatory markers: the U.S. National Health and Nutrition Examination Survey 1999-2004. J Atheroscler Thromb. 2010;17(11):1176-82.
29. Zivkovic S, Maric G, Cvetinovic N, Lepojevic-Stefanovic D, Bozic Cvijan B. Anti-Inflammatory Effects of Lipid-Lowering Drugs and Supplements—A Narrative Review. Nutrients. 2023;15(6):1517.
30. Chello M, Patti G, Candura D, Mastrobuoni S, Di Sciascio G, Agrò F, et al. Effects of atorvastatin on systemic inflammatory response after coronary bypass surgery. Crit Care Med. 2006;34(3):660-7.
31. Almukhtar HM, Faisal IM, Merkhan MM. Short-term treatment with Atorvastatin selectively decreases Lymphocyte count. Research J Pharmand Tech. 2022;15(2):689-94.
32. Bennett LF, Liao C, Quickel MD, Yeoh BS, Vijay-Kumar M, Hankey-Giblin P, et al. Inflammation induces stress erythropoiesis through heme-dependent activation of SPI-C. Sci Signal. 2019;12(598).
33. Campos JR, Severino P, Ferreira CS, Zielinska A, Santini A, Souto SB, et al. Linseed Essential Oil - Source of Lipids as Active Ingredients for Pharmaceuticals and Nutraceuticals. Curr Med Chem. 2019;26(24):4537-58.
34. Adili R, Hawley M, Holinstat M. Regulation of platelet function and thrombosis by omega-3 and omega-6 polyunsaturated fatty acids. Prostaglandins Other Lipid Mediat. 2018;139:10-8.
35. Simopoulos AP. An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity. Nutrients. 2016;8(3):128.
36. Haliga RE, Iancu RI, Butcovan D, Mocanu V. Flaxseed prevents leukocyte and platelet adhesion to endothelial cells in experimental atherosclerosis by reducing sVCAM-1 and vWF. ScientificWorldJournal. 2013;2013:303950.
37. Stokes KY, Granger DN. Platelets: a critical link between inflammation and microvascular dysfunction. J Physiol. 2012;590(5):1023-34.
38. Wang Q, Liang X, Wang L, Lu X, Huang J, Cao J, et al. Effect of omega-3 fatty acids supplementation on endothelial function: a meta-analysis of randomized controlled trials. Atherosclerosis. 2012;221(2):536-43.
39. Mocanu V, Haliga R, Paduraru O, Baran D, Badoi D, Iancu R, et al. A diet rich in whole grain flaxseeds has antithrombotic effects without increasing oxidative stress in experimental atherosclerosis. Journal of Biologically Active Products From Nature. 2011;1(3):144-59.
40. Lee JC, Bhora F, Sun J, Cheng G, Arguiri E, Solomides CC, et al. Dietary flaxseed enhances antioxidant defenses and is protective in a mouse model of lung ischemia-reperfusion injury. Am J Physiol Lung Cell Mol Physiol. 2008;294(2):L255-65.
41. Szuwart T, Brzoska T, Luger TA, Filler T, Peuker E, Dierichs R. Vitamin E reduces platelet adhesion to human endothelial cells in vitro. Am J Hematol. 2000;65(1):1-4.
42. Gorabi AM, Kiaie N, Hajighasemi S, Banach M, Penson PE, Jamialahmadi T, et al. Statin-Induced Nitric Oxide Signaling: Mechanisms and Therapeutic Implications. J Clin Med. 2019;8(12).
43. Chirkov YY, Nguyen TH, Horowitz JD. Impairment of Anti-Aggregatory Responses to Nitric Oxide and Prostacyclin: Mechanisms and Clinical Implications in Cardiovascular Disease. Int J Mol Sci. 2022;23(3).
44. Sikora J, Kostka B, Marczyk I, Krajewska U, Chałubiński M, Broncel M. Effect of statins on platelet function in patients with hyperlipidemia. Arch Med Sci. 2013;9(4):622-8.
45. Nenna A, Nappi F, Lusini M, Satriano UM, Schilirò D, Spadaccio C, et al. Effect of Statins on Platelet Activation and Function: From Molecular Pathways to Clinical Effects. Biomed Res Int. 2021;2021:6661847.
2. Muhamad NA, Maamor NH, Leman FN, Mohamad ZA, Bakon SK, Abdul Mutalip MH, et al. The Global Prevalence of Nonalcoholic Fatty Liver Disease and its Association With Cancers: Systematic Review and Meta-Analysis. Interact J Med Res. 2023;12:e40653.
3. Pan Q, Fan JG, Yilmaz Y. Pathogenetic Pathways in Nonalcoholic Fatty Liver Disease: An Incomplete Jigsaw Puzzle. Clin Liver Dis. 2023;27(2):317-32.
4. Dong XC, Chowdhury K, Huang M, Kim HG. Signal Transduction and Molecular Regulation in Fatty Liver Disease. Antioxid Redox Signal. 2021;35(9):689-717.
5. Paternostro R, Trauner M. Current treatment of non-alcoholic fatty liver disease. J Intern Med. 2022;292(2):190-204.
6. Ebrahimi B, Nazmara Z, Hassanzadeh N, Yarahmadi A, Ghaffari N, Hassani F, et al. Biomedical features of flaxseed against different pathologic situations: A narrative review. Iran J Basic Med Sci. 2021;24(5):551-60.
7. Han H, Qiu F, Zhao H, Tang H, Li X, Shi D. Dietary Flaxseed Oil Prevents Western-Type Diet-Induced Nonalcoholic Fatty Liver Disease in Apolipoprotein-E Knockout Mice. Oxidative Medicine and Cellular Longevity. 2017;2017(1):3256241.
8. Ghadge A, Harsulkar A, Karandikar M, Pandit V, Kuvalekar A. Comparative anti-inflammatory and lipid-normalizing effects of metformin and omega-3 fatty acids through modulation of transcription factors in diabetic rats. Genes Nutr. 2016;11:10.
9. Liu H, Wang F, Xia H, Pan D, Yang L, Wang S, et al. Comparison of the effects of 3 kinds of oils rich in omega-3 polyunsaturated fatty acids on glycolipid metabolism and lipoprotein subfractions. Food Science and Human Wellness. 2023;12(6):2221-31.
10. Al-Bishri W. Favorable Effects of Flaxseed Supplemented Diet on Liver and Kidney Functions in Hypertensive Wistar Rats. Journal of oleo science. 2013;62:709-15.
11. Chechi K, Yasui N, Ikeda K, Yamori Y, Cheema S. Flax oil-mediated activation of PPAR-correlates with reduction of hepatic lipid accumulation in obese spontaneously hypertensive/NDmcr-cp rats, a model of the metabolic syndrome. The British journal of nutrition. 2010;104:1313-21.
12. Al-Madhagy S, Ashmawy NS, Mamdouh A, Eldahshan OA, Farag MA. A comprehensive review of the health benefits of flaxseed oil in relation to its chemical composition and comparison with other omega-3-rich oils. European Journal of Medical Research. 2023;28(1):240.
13. Zhang S, Ren X, Zhang B, Lan T, Liu B. A Systematic Review of Statins for the Treatment of Nonalcoholic Steatohepatitis: Safety, Efficacy, and Mechanism of Action. Molecules. 2024;29(8):1859.
14. Zhang B, Zhang C, Zhang X, Li N, Dong Z, Sun G, et al. Atorvastatin promotes AMPK signaling to protect against high fat diet-induced non-alcoholic fatty liver in golden hamsters. Exp Ther Med. 2020;19(3):2133-42.
15. Dehnavi S, Kiani A, Sadeghi M, Biregani AF, Banach M, Atkin SL, et al. Targeting AMPK by Statins: A Potential Therapeutic Approach. Drugs. 2021;81(8):923-33.
16. Koushki K, Shahbaz SK, Mashayekhi K, Sadeghi M, Zayeri ZD, Taba MY, et al. Anti-inflammatory Action of Statins in Cardiovascular Disease: the Role of Inflammasome and Toll-Like Receptor Pathways. Clin Rev Allergy Immunol. 2021;60(2):175-99.
17. Morofuji Y, Nakagawa S, Ujifuku K, Fujimoto T, Otsuka K, Niwa M, et al. Beyond Lipid-Lowering: Effects of Statins on Cardiovascular and Cerebrovascular Diseases and Cancer. Pharmaceuticals (Basel). 2022;15(2).
18. Zhao L, Li S, Gao Y. Efficacy of statins on renal function in patients with chronic kidney disease: a systematic review and meta-analysis. Ren Fail. 2021;43(1):718-28.
19. Ghelani H, Razmovski-Naumovski V, Inampudi V, Chang D, Nammi S. Atorvastatin Improves Hepatic Lipid Metabolism and Protects Renal Damage in Adenine-Induced Chronic Kidney Disease in Sprague-Dawley Rats. Biomed Res Int. 2019;2019:8714363.
20. Han E, Kim G, Lee JY, Lee YH, Kim BS, Lee BW, et al. Comparison between Atorvastatin and Rosuvastatin in Renal Function Decline among Patients with Diabetes. Endocrinol Metab (Seoul). 2017;32(2):274-80.
21. Chamani S, Kooshkaki O, Moossavi M, Rastegar M, Soflaei SS, McCloskey AP, et al. The effects of statins on the function and differentiation of blood cells. Arch Med Sci. 2023;19(5):1314-26.
22. Z E, Y Mnpk, M G, Ar EM, Sh S, Gh B, et al. The effect of endurance training combined with adenosine on the gene expression of UCP-1 and MAPK p38 in subcutaneous adipose tissue of male Wistar rats fed a high -fat diet. Yafte. 2023;25(3):66-79.
23. Eslami Z, Mirghani SJ, Eghbal Moghanlou A, Norouzi A, Naseh H, Joshaghani H, et al. An Efficient Model of Non-alcoholic Fatty Liver Disease (NAFLD) Versus Current Experimental Models: Effects of Fructose, Fat, and Carbon Tetrachloride on NAFLD. Hepat Mon. 2021;21(8):e117696.
24. Eslami Z, Rezaei Ghomi M, Saidi A, Mousavi SV, Farhadi M, Sheikh Robati N, et al. Endurance Training and Exogenous Adenosine Infusion Mitigate Hippocampal Inflammation and Cell Death in a Rat Model of Cerebral Ischemia/Reperfusion Injury: A Randomized Controlled Trial. Arch Neurosci. 2022;9(1):e119236.
25. Mehany HA, Abo-youssef AM, Ahmed LA, Arafa E-SA, Abd El-Latif HA. Protective effect of vitamin E and atorvastatin against potassium dichromate-induced nephrotoxicity in rats. Beni-Suef University Journal of Basic and Applied Sciences. 2013;2(2):96-102.
26. Stuglin C, Prasad K. Effect of flaxseed consumption on blood pressure, serum lipids, hemopoietic system and liver and kidney enzymes in healthy humans. J Cardiovasc Pharmacol Ther. 2005;10(1):23-7.
27. Al-Madhagy S, Ashmawy NS, Mamdouh A, Eldahshan OA, Farag MA. A comprehensive review of the health benefits of flaxseed oil in relation to its chemical composition and comparison with other omega-3-rich oils. Eur J Med Res. 2023;28(1):240.
28. Yoon SS, Dillon CF, Carroll M, Illoh K, Ostchega Y. Effects of statins on serum inflammatory markers: the U.S. National Health and Nutrition Examination Survey 1999-2004. J Atheroscler Thromb. 2010;17(11):1176-82.
29. Zivkovic S, Maric G, Cvetinovic N, Lepojevic-Stefanovic D, Bozic Cvijan B. Anti-Inflammatory Effects of Lipid-Lowering Drugs and Supplements—A Narrative Review. Nutrients. 2023;15(6):1517.
30. Chello M, Patti G, Candura D, Mastrobuoni S, Di Sciascio G, Agrò F, et al. Effects of atorvastatin on systemic inflammatory response after coronary bypass surgery. Crit Care Med. 2006;34(3):660-7.
31. Almukhtar HM, Faisal IM, Merkhan MM. Short-term treatment with Atorvastatin selectively decreases Lymphocyte count. Research J Pharmand Tech. 2022;15(2):689-94.
32. Bennett LF, Liao C, Quickel MD, Yeoh BS, Vijay-Kumar M, Hankey-Giblin P, et al. Inflammation induces stress erythropoiesis through heme-dependent activation of SPI-C. Sci Signal. 2019;12(598).
33. Campos JR, Severino P, Ferreira CS, Zielinska A, Santini A, Souto SB, et al. Linseed Essential Oil - Source of Lipids as Active Ingredients for Pharmaceuticals and Nutraceuticals. Curr Med Chem. 2019;26(24):4537-58.
34. Adili R, Hawley M, Holinstat M. Regulation of platelet function and thrombosis by omega-3 and omega-6 polyunsaturated fatty acids. Prostaglandins Other Lipid Mediat. 2018;139:10-8.
35. Simopoulos AP. An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity. Nutrients. 2016;8(3):128.
36. Haliga RE, Iancu RI, Butcovan D, Mocanu V. Flaxseed prevents leukocyte and platelet adhesion to endothelial cells in experimental atherosclerosis by reducing sVCAM-1 and vWF. ScientificWorldJournal. 2013;2013:303950.
37. Stokes KY, Granger DN. Platelets: a critical link between inflammation and microvascular dysfunction. J Physiol. 2012;590(5):1023-34.
38. Wang Q, Liang X, Wang L, Lu X, Huang J, Cao J, et al. Effect of omega-3 fatty acids supplementation on endothelial function: a meta-analysis of randomized controlled trials. Atherosclerosis. 2012;221(2):536-43.
39. Mocanu V, Haliga R, Paduraru O, Baran D, Badoi D, Iancu R, et al. A diet rich in whole grain flaxseeds has antithrombotic effects without increasing oxidative stress in experimental atherosclerosis. Journal of Biologically Active Products From Nature. 2011;1(3):144-59.
40. Lee JC, Bhora F, Sun J, Cheng G, Arguiri E, Solomides CC, et al. Dietary flaxseed enhances antioxidant defenses and is protective in a mouse model of lung ischemia-reperfusion injury. Am J Physiol Lung Cell Mol Physiol. 2008;294(2):L255-65.
41. Szuwart T, Brzoska T, Luger TA, Filler T, Peuker E, Dierichs R. Vitamin E reduces platelet adhesion to human endothelial cells in vitro. Am J Hematol. 2000;65(1):1-4.
42. Gorabi AM, Kiaie N, Hajighasemi S, Banach M, Penson PE, Jamialahmadi T, et al. Statin-Induced Nitric Oxide Signaling: Mechanisms and Therapeutic Implications. J Clin Med. 2019;8(12).
43. Chirkov YY, Nguyen TH, Horowitz JD. Impairment of Anti-Aggregatory Responses to Nitric Oxide and Prostacyclin: Mechanisms and Clinical Implications in Cardiovascular Disease. Int J Mol Sci. 2022;23(3).
44. Sikora J, Kostka B, Marczyk I, Krajewska U, Chałubiński M, Broncel M. Effect of statins on platelet function in patients with hyperlipidemia. Arch Med Sci. 2013;9(4):622-8.
45. Nenna A, Nappi F, Lusini M, Satriano UM, Schilirò D, Spadaccio C, et al. Effect of Statins on Platelet Activation and Function: From Molecular Pathways to Clinical Effects. Biomed Res Int. 2021;2021:6661847.
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| Issue | Articles in Press: Vol 64 No 03 (2026) | |
| Section | Original Articles | |
| Keywords | ||
| Linseed oil Flax Statin Kidney High-fat diet Hematological indices | ||
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How to Cite
1.
Eslami Z, Sheikh Arabi M, Joshaghani H. Effects of Dietary Flaxseed and Atorvastatin on Blood Hematology and Renal Health Metrics in Rats Fed High-Fat Diet. Acta Med Iran. 2026;.
