Effect of Atorvastatin and Lactobacillus acidophilus on cholesterol metabolism in experimental hypercholesterolemia
Abstract
Hypercholesterolemia is a very common health problem in the world. In this study, it was aimed to investigate the effects of atorvastatin and Lactobacillus acidophilus probiotic on cholesterol metabolism, and formation of neurosterides and myelin. Five groups were formed in the study. Group-1 was fed with standard rat chow as a control group. Group-2 was designated as hypercholosterolemi group and fed with cholesterol added rat chow. Group-3 was fed with cholesterol and atorvastatin. L.acidophilus probiotic was given in the last four weeks of the experiment to Group-4. L.acidophilus and atorvastatin were given together for the last four weeks to the Group-5. At the end of the trial, some biochemical parameters were determined by autoanalyzer device and ELISA. LDL receptor (LDL-R), HMG-CoA reductase, GAPDH genes were determined by RT-PCR. In the case of adding cholesterol to the diet, total cholesterol in the serum, LDL-cholesterol level increased, HDL-cholesterol level decreased, liver enzyme activity increased, Ox-LDL level increased significantly in the brain, testosterone, progesterone, MBP level, nNOS activity were significantly increased. GAPDH gene gave bands at the same intensities in brain and liver of in all groups. When compared with GAPDH, band intensities of the LDL-R and HMG-CoA reductase genes were decreased. It was determined that the hypocholesteric effect of the combination of statin and probiotic is better and neurosterides have a positive contribution to the level of serotonin hormone. As a result, it was concluded that L. acidophilus probiotic supplementation with atorvastatin can be recommended as supportive product in the treatment of hypercholesterolemia.
Ethical Statement
The study was approved by the Animal Experiments Local Ethics Committee of Ondokuz Mayis University (Approval no: 2016/08).
Supporting Institution
This research was supported by the Scientific Research Projects Commission of TUBITAK (Contract Grand Number: 115O908).
Project Number
115O908
References
- Agerbaek M, Gerdes LU, Richelsen B (1995). Hypocholesterolaemic effect of a new fermented milk product in healthy middle-aged men. Eur J Clin Nut, 49, 346-352.
- Albokhadaim, I (2015): Influence of dietary supplementation of propolis on hematology, biochemistry and lipid profile of rats fed high cholesterol diet. Adv Vet Anim Res, 2(1), 56-63.
- Anderson JW, Spencer DO, Riddel-Mason S, et al (1995): Postprandial serum glucose, insulin, and lipoprotein responses to high- and low-fiber diets. Metabol, 44, 848-854.
- Aydin S, Uzun H, Sozer V, Altuğ T (2009): Effects of atorvastatin therapy on protein oxidation and oxidative DNA damage in hypercholesterolemic rabbits. Pharmacol Res, 59(4), 242-247.
- Baba H, Suzuki T, Arai H, Emson PC (2004): Expression of nNOS and soluble guanylate cyclase in schizophrenic brain. Neurol Report, 15(4), 677-680.
- Block RC, Dorsey ER, Beck CA, et al (2010): Altered cholesterol and fatty acid metabolism in Huntington disease. Clin Lipidol, 4(1), 17-23.
- Brinton RD (2008): The healthy cell bias of estrogen action: mitochondrial bioenergetics and neurological implications. Trend Neurosci, 31, 529-537.
- Brookes ZL, McGown CC, Reilly CS (2009): Statins for all: the new premed? British J Anaesthiol, 103, 99-107.
- Dawson VL, Dawson TM, London ED, et al (1991): Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures. Proc Nat Acad Sci USA, 88, 6368-6371.
- DeChaves EI, Rusinol AE, Vance DE, et al (1997): Role of lipoproteins in the delivery of lipids to axons during axonal regeneration, J Biol Chem, 272(49), 30766-30768.
- Dhingra S, Bansal MP (2006): Attenuation of LDL receptor gene expression by selenium deficiency during hypercholesterolemia. Mol Cell Biochem, 282(1-2), 75-82.
- Dietschy JM, Turley SD (2001): Cholesterol metabolism in the brain. Curr Opin Lipidol, 12(2), 105-112.
- Fukushima M, Nakano M, Morii Y, Ohashi T, et al (2000): Hepatic LDL receptor mRNA in rats is increased by dietary mushroom (Agaricus bisporus) fiber and sugar beet fiber. J Nut, 130, 2151-2156.
- Gilliland SE, Walker DK (1990): Factors to consider when selecting a culture of Lactobacillus acidophilus as a dietary adjunct to produce a hypocholesterolemic effect in humans. J Dairy Sci, 73(4), 905-911.
- Goldstein JL, Brown MS (1990): Regulation of mevalonate pathway. Nature, 343, 425-431.
- Han KH, Iijuka M, Shimada KI, et al (2005): Adzuki resistant starch lowered serum cholesterol and hepatic 3- hydroxy-3- methylglutaryl-CoA mRNA levels and increased hepatic LDL-receptor and cholesterol 7a-hydroxylase mRNA levels in rats fed a cholesterol diet. Brit J Nutr, 94, 902-908.
- Harini M, Astirin OP (2009): Blood cholesterol levels of hypercholesterolemic rat (Rattus norvegicus) after VCO treatment, Biosci, 1(2), 53-58.
- Harisa IEG (2011): L-Arginine Ameliorates Arylesterase/Paraoxonase Activity of Paraoxonase-1 in Hypercholesterolemic Rats. Asian J Biochem, 6(3), 263-272.
- Harrison VC, Peat G (1975): Serum cholesterol and bowel flora in the newborn. Amer J Clin Nut, 28, 1351-1355.
- Honing MLH, Morrison PJ, Banga JD, et al. (1998): Nitric oxide availability in diabetes mellitus. Diabet Metabol Rev, 14, 241-249.
- Horton JD, Cuthbert JA, Spady DK (1993): Dietary fatty acids regulate hepatic low density lipoprotein (LDL) transport by altering LDL receptor protein and mRNA levels. J Clin Invest, 92, 743-749.
- Huang X, Tang J, Zhou Q, Lu H, et al (2010): Polysaccharide from Fuzi (FPS) Prevents Hypercholesterolemia in Rats. Lipid Health Dis, 9, 9.
- Jeun J, Kim S, Cho SY, et al (2010): Hypocholesterolemic effects of Lactobacillus plantarum KCTC3928 by increased bile acidexcretion in C57BL/6 mice. Nutrition, 26(3), 321-330.
- Korade Z, Kenworth AK (2008): Lipid rafts, cholesterol, and the brain. Neuropharmacol, 55(8), 1265-1273.
- Liong MT, Shah NP (2005): Bile salt deconjugation and BSH activity of five bifidobacterial strains and their cholesterol co-precipitating properties. Food Res Intern, 38, 135-142.
- Liu J, Zhang YL, Spence MJ, et al. (1997): Liver LDL receptor mRNA expression is decreased in human ApoB/CETP double transgenic mice and is regulated by diet as well as the cytokine oncostatin M. Arterioscler Thromb, 17, 2948-2954.
- Ludka FK, Constantino LC, Kuminek G, et al (2014): Atorvastatin evokes a serotonergic system-dependent antidepressant-like effect in mice. Pharmacol Biochem Behav, 122, 253-260.
- Moor AN, Gottipati S, Mallet RT, et al. (2004): A putative mitochondrial mechanism for antioxidative cytoprotection by 17 beta-estradiol. Exper Eye Res, 78, 933-944.
- Mugge A, Brandes RP, Boger RH, et al (1994): Vascular release of superoxide radicals is enhanced in hypercholesterolemic rabbits. J Card Pharmacol, 24(6), 994-998.
- Ness GC, Eales S, Lopez D, Zao Z (1994): Regulation of 3-hydroxy-3 methylglutaryl coenzyme A reductase gene expression by sterols and nonsterols in rat liver. Arch Biochem Biophysiol, 308(2), 420-425.
- Nguyen TH, Splechtna B, Krasteva S, et al. (2007): Characterization and molecular cloning of a heterodimeric beta-galactosidase from the probiotic strain Lactobacillus acidophilus R22. FEMS Microbiol Lett, 269(1), 136-144.
- Onody A, Csonka C, Giricz Z, Ferdinandy P (2003): Hyperlipidemia Hinduced by a cholesterol-rich diet leads to enhanced peroxynitrite formation in rat hearts. Cardiovas Res, 58, 663-670.
- Park SC, Hwang MH, Kim YH, et al (2006): Comparison of pH and Bile Resistance of Lactobacillus acidophilus Strains Isolated from Rat, Pig, Chicken, and Human Sources. World J Microbiol Biotechnol, 22(1), 35-37.
- Peterson AL (2014): A review of vitamin D and Parkinson's disease. Maturit, 78(1), 40-44.
- Prasad K, Kalra J (1989): Experimental atherosclerosis and oxygen free radicals. Angiol, 40(9), 835-843.
- Rena L, Yong S, Li-Bang Y, et al. (2000): Estrogen enhances uptake of amyloid ß-protein by microglia derived from the human cortex. J Neurochem, 75, 14-47.
- Robel P, Corpe´chot C, Baulieu EE (1973): Testosterone and androstanolone in rat plasma and tissues. FEBS Lett, 33, 218-220.
- Samout N, Bouzenna H, Ettaya A (2015): Antihypercholesterolemic effect of Cleome arabica L. on high cholesterol diet induced damage in rats. Excli, 14, 791-800.
- Schaafsma G (1996): State of art concerning probiotic strains in milk products. IDF Nutr New Lett, 5, 23-24.
- Shepardson NE, Shankar GM, Selkoe DJ (2011): Cholesterol level and statin use in Alzheimer disease: II. review of human trials and recommendations. Archiv Neurol, 68(11), 1385-1392.
- Smet ID, Hoorde LV, Woestyne MV, et al (1995): Significance of bile salt hydrolytic activities of lactobacilli. J Appl Bacteriol, 79, 292-301.
Deneysel hiperkolesterolemide Atorvastatin ve Lactobacillus acidophilus'un kolesterol metabolizmasına etkisi
Abstract
Hiperkolesterolemi dünyada çok yaygın bir sağlık sorunudur. Bu çalışmada atorvastatin ve Lactobacillus acidophilus probiyotik uygulamasının beyindeki kolesterol metabolizması ve nörosterid ve miyelin oluşumu üzerine etkilerinin araştırılması amaçlandı. Çalışmada beş grup oluşturulmuştur. Grup-1, kontrol grubu olarak standart rat yemi ile beslendi. Grup-2 hiperkolesterolemi grubu olarak belirlendi ve 8 hafta boyunca kolesterol katkılı sıçan yemi ile beslendi. Grup-3 kolesterol ve atorvastatin ile beslendi. Grup-4'e deneyin son dört haftasında L. acidophilus probiyotik verildi. Grup 5'e L. acidophilus ve atorvastatin son dört hafta birlikte verildi. Deneme sonunda bazı biyokimyasal parametre düzeyleri otoanalizör cihazı ve ELISA ile belirlendi. LDL reseptörü, HMG-CoA redüktaz, GAPDH genleri RT-PCR yöntemi ile araştırıldı. Diyete kolesterol eklenmesi durumunda, serumdaki toplam kolesterol, LDL-kolesterol düzeyi arttı, HDL-kolesterol düzeyi azaldı, karaciğer enzim aktivitesi arttı, Ox-LDL düzeyi beyinde anlamlı düzeyde arttı, testosteron, progesteron, MBP düzeyinde, nNOS aktivitesi önemli ölçüde arttı. RT-PCR sonucunda GAPDH geni tüm gruplarda beyin ve karaciğerde aynı yoğunlukta bantlar verdi. GAPDH geni ile karşılaştırıldığında, LDL reseptörü ve HMG-CoA redüktaz genlerinin bant yoğunlukları azalmıştır. Statin ve probiyotik kombinasyonunun hipokolesterik etkisinin daha iyi olduğu ve nörosteridlerin serotonin hormonu düzeyine olumlu katkısı olduğu belirlendi. Sonuç olarak L. acidophilus probiyotik hiperkolesterolemi tedavisinde atorvastatin ile alternatif tedavi olarak önerilebilir.
Keywords
Atorvastatin Atorvastatin Atorvastatin Atorvastatin Lactobacillus acidophilus Lactobacillus acidophilus Lactobacillus acidophilus Lactobacillus acidophilus hiperkolesterolemi
Project Number
115O908
References
- Agerbaek M, Gerdes LU, Richelsen B (1995). Hypocholesterolaemic effect of a new fermented milk product in healthy middle-aged men. Eur J Clin Nut, 49, 346-352.
- Albokhadaim, I (2015): Influence of dietary supplementation of propolis on hematology, biochemistry and lipid profile of rats fed high cholesterol diet. Adv Vet Anim Res, 2(1), 56-63.
- Anderson JW, Spencer DO, Riddel-Mason S, et al (1995): Postprandial serum glucose, insulin, and lipoprotein responses to high- and low-fiber diets. Metabol, 44, 848-854.
- Aydin S, Uzun H, Sozer V, Altuğ T (2009): Effects of atorvastatin therapy on protein oxidation and oxidative DNA damage in hypercholesterolemic rabbits. Pharmacol Res, 59(4), 242-247.
- Baba H, Suzuki T, Arai H, Emson PC (2004): Expression of nNOS and soluble guanylate cyclase in schizophrenic brain. Neurol Report, 15(4), 677-680.
- Block RC, Dorsey ER, Beck CA, et al (2010): Altered cholesterol and fatty acid metabolism in Huntington disease. Clin Lipidol, 4(1), 17-23.
- Brinton RD (2008): The healthy cell bias of estrogen action: mitochondrial bioenergetics and neurological implications. Trend Neurosci, 31, 529-537.
- Brookes ZL, McGown CC, Reilly CS (2009): Statins for all: the new premed? British J Anaesthiol, 103, 99-107.
- Dawson VL, Dawson TM, London ED, et al (1991): Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures. Proc Nat Acad Sci USA, 88, 6368-6371.
- DeChaves EI, Rusinol AE, Vance DE, et al (1997): Role of lipoproteins in the delivery of lipids to axons during axonal regeneration, J Biol Chem, 272(49), 30766-30768.
- Dhingra S, Bansal MP (2006): Attenuation of LDL receptor gene expression by selenium deficiency during hypercholesterolemia. Mol Cell Biochem, 282(1-2), 75-82.
- Dietschy JM, Turley SD (2001): Cholesterol metabolism in the brain. Curr Opin Lipidol, 12(2), 105-112.
- Fukushima M, Nakano M, Morii Y, Ohashi T, et al (2000): Hepatic LDL receptor mRNA in rats is increased by dietary mushroom (Agaricus bisporus) fiber and sugar beet fiber. J Nut, 130, 2151-2156.
- Gilliland SE, Walker DK (1990): Factors to consider when selecting a culture of Lactobacillus acidophilus as a dietary adjunct to produce a hypocholesterolemic effect in humans. J Dairy Sci, 73(4), 905-911.
- Goldstein JL, Brown MS (1990): Regulation of mevalonate pathway. Nature, 343, 425-431.
- Han KH, Iijuka M, Shimada KI, et al (2005): Adzuki resistant starch lowered serum cholesterol and hepatic 3- hydroxy-3- methylglutaryl-CoA mRNA levels and increased hepatic LDL-receptor and cholesterol 7a-hydroxylase mRNA levels in rats fed a cholesterol diet. Brit J Nutr, 94, 902-908.
- Harini M, Astirin OP (2009): Blood cholesterol levels of hypercholesterolemic rat (Rattus norvegicus) after VCO treatment, Biosci, 1(2), 53-58.
- Harisa IEG (2011): L-Arginine Ameliorates Arylesterase/Paraoxonase Activity of Paraoxonase-1 in Hypercholesterolemic Rats. Asian J Biochem, 6(3), 263-272.
- Harrison VC, Peat G (1975): Serum cholesterol and bowel flora in the newborn. Amer J Clin Nut, 28, 1351-1355.
- Honing MLH, Morrison PJ, Banga JD, et al. (1998): Nitric oxide availability in diabetes mellitus. Diabet Metabol Rev, 14, 241-249.
- Horton JD, Cuthbert JA, Spady DK (1993): Dietary fatty acids regulate hepatic low density lipoprotein (LDL) transport by altering LDL receptor protein and mRNA levels. J Clin Invest, 92, 743-749.
- Huang X, Tang J, Zhou Q, Lu H, et al (2010): Polysaccharide from Fuzi (FPS) Prevents Hypercholesterolemia in Rats. Lipid Health Dis, 9, 9.
- Jeun J, Kim S, Cho SY, et al (2010): Hypocholesterolemic effects of Lactobacillus plantarum KCTC3928 by increased bile acidexcretion in C57BL/6 mice. Nutrition, 26(3), 321-330.
- Korade Z, Kenworth AK (2008): Lipid rafts, cholesterol, and the brain. Neuropharmacol, 55(8), 1265-1273.
- Liong MT, Shah NP (2005): Bile salt deconjugation and BSH activity of five bifidobacterial strains and their cholesterol co-precipitating properties. Food Res Intern, 38, 135-142.
- Liu J, Zhang YL, Spence MJ, et al. (1997): Liver LDL receptor mRNA expression is decreased in human ApoB/CETP double transgenic mice and is regulated by diet as well as the cytokine oncostatin M. Arterioscler Thromb, 17, 2948-2954.
- Ludka FK, Constantino LC, Kuminek G, et al (2014): Atorvastatin evokes a serotonergic system-dependent antidepressant-like effect in mice. Pharmacol Biochem Behav, 122, 253-260.
- Moor AN, Gottipati S, Mallet RT, et al. (2004): A putative mitochondrial mechanism for antioxidative cytoprotection by 17 beta-estradiol. Exper Eye Res, 78, 933-944.
- Mugge A, Brandes RP, Boger RH, et al (1994): Vascular release of superoxide radicals is enhanced in hypercholesterolemic rabbits. J Card Pharmacol, 24(6), 994-998.
- Ness GC, Eales S, Lopez D, Zao Z (1994): Regulation of 3-hydroxy-3 methylglutaryl coenzyme A reductase gene expression by sterols and nonsterols in rat liver. Arch Biochem Biophysiol, 308(2), 420-425.
- Nguyen TH, Splechtna B, Krasteva S, et al. (2007): Characterization and molecular cloning of a heterodimeric beta-galactosidase from the probiotic strain Lactobacillus acidophilus R22. FEMS Microbiol Lett, 269(1), 136-144.
- Onody A, Csonka C, Giricz Z, Ferdinandy P (2003): Hyperlipidemia Hinduced by a cholesterol-rich diet leads to enhanced peroxynitrite formation in rat hearts. Cardiovas Res, 58, 663-670.
- Park SC, Hwang MH, Kim YH, et al (2006): Comparison of pH and Bile Resistance of Lactobacillus acidophilus Strains Isolated from Rat, Pig, Chicken, and Human Sources. World J Microbiol Biotechnol, 22(1), 35-37.
- Peterson AL (2014): A review of vitamin D and Parkinson's disease. Maturit, 78(1), 40-44.
- Prasad K, Kalra J (1989): Experimental atherosclerosis and oxygen free radicals. Angiol, 40(9), 835-843.
- Rena L, Yong S, Li-Bang Y, et al. (2000): Estrogen enhances uptake of amyloid ß-protein by microglia derived from the human cortex. J Neurochem, 75, 14-47.
- Robel P, Corpe´chot C, Baulieu EE (1973): Testosterone and androstanolone in rat plasma and tissues. FEBS Lett, 33, 218-220.
- Samout N, Bouzenna H, Ettaya A (2015): Antihypercholesterolemic effect of Cleome arabica L. on high cholesterol diet induced damage in rats. Excli, 14, 791-800.
- Schaafsma G (1996): State of art concerning probiotic strains in milk products. IDF Nutr New Lett, 5, 23-24.
- Shepardson NE, Shankar GM, Selkoe DJ (2011): Cholesterol level and statin use in Alzheimer disease: II. review of human trials and recommendations. Archiv Neurol, 68(11), 1385-1392.
- Smet ID, Hoorde LV, Woestyne MV, et al (1995): Significance of bile salt hydrolytic activities of lactobacilli. J Appl Bacteriol, 79, 292-301.
Details
| Primary Language | English |
|---|---|
| Subjects | Veterinary Anatomy and Physiology, Veterinary Biochemistry, Veterinary Microbiology |
| Journal Section | Research Article |
| Authors | |
| Project Number | 115O908 |
| Early Pub Date | September 21, 2023 |
| Publication Date | April 1, 2024 |
| Published in Issue | Year 2024Volume: 71 Issue: 2 |
