Protective Effect of Bifidobacterium longum and Streptococcus thermophilus against Simvastatin-Induced Rhabdomyolysis in Hypercholesteraemic Rats
Authors
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Department of Pharmacology, Acharya Nagarjuna University College of Pharmaceutical Sciences, Guntur - 522510 ,IN
K. Dilip Raja -
Department of Pharmaceutical Analysis, Rajarshi Shahu College of Pharmacy, Nanded - 431718, Maharashtra ,INA. Shanta Kumari
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Department of Pharmaceutics, Acharya Nagarjuna University College of Pharmaceutical Sciences, Guntur - 522510, Andhra Pradesh ,INA. Prameela Rani
DOI:
https://doi.org/10.18311/ti/2024/v31i2/42123Keywords:
Bifidobacterium longum, Probiotics, Rhabdomyolysis, Streptococcus thermophilus, SimvastatinAbstract
Simvastatin (SMV), a commonly prescribed drug for lowering lipid levels, is linked to the serious side effect of rhabdomyolysis. This study explores the potential of probiotics, specifically Bifidobacterium longum (BL) and Streptococcus thermophilus (ST), as supplementary treatments to alleviate simvastatin-induced rhabdomyolysis in rats with high cholesterol levels. This study assesses the effects of combining simvastatin with probiotics on parameters such as lipid profiles, renal function, skeletal muscle markers, inflammatory cytokines, and histological characteristics. Rats with elevated cholesterol levels were exposed to SMV treatment alone and in conjunction with probiotics. This study compared the effects of combining simvastatin with BL and ST, focusing on their potential to ameliorate SMV-induced rhabdomyolysis. Combining simvastatin with BL and ST yielded notable outcomes. The supplementation significantly improved lipid profiles by reducing atherogenic lipids and increasing cardioprotective HDL-C levels. Additionally, the probiotics, particularly ST and BL, showed indications of preserving renal function and mitigating the adverse effects of simvastatin on muscle health. Analysis of inflammatory cytokines suggested that probiotics may modulate inflammation. Histological assessments confirmed the protective effects of probiotics by maintaining tissue integrity and normal cell appearance. While BL exhibited a slight advantage over ST, both probiotics demonstrated similar potential as adjunction therapies. This study’s findings highlight the promising role of probiotics, specifically BL and ST, in ameliorating simvastatin-induced rhabdomyolysis. These probiotics show the potential to improve lipid profiles, safeguard renal function, preserve muscle health, modulate inflammation, and maintain tissue integrity. These results provide a hopeful basis for potential therapeutic interventions in individuals experiencing adverse effects associated with SMV treatment.
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Copyright (c) 2024 K. Dilip Raja, A. Shantha Kumari, A. Prameela Rani
This work is licensed under a Creative Commons Attribution 4.0 International License.
Accepted 2024-04-12
Published 2024-04-25
References
Tsao CW, Aday AW, Almarzooq ZI, Anderson CAM, Arora P, Avery CL, et al. Heart disease and stroke statistics-2023 Update: A Report From the American Heart Association. Circ. 2023; 147(8). https://doi.org/10.1161/ CIR.0000000000001137 DOI: https://doi.org/10.1161/CIR.0000000000001137
Feingold KR. Cholesterol Lowering Drugs. In: Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, et al., editors. Endotext. South Dartmouth (MA): MDText. com, Inc.; 2000.
Schaiff RAB, Moe RM, Krichbaum DW. An overview of cholesterol management. Am Health Drug Benefits. 2008; 1(9):39-48.
Defesche JC, Gidding SS, Harada-Shiba M, Hegele RA, Santos RD, Wierzbicki AS. Familial hypercholesterolaemia. Nat Rev Dis Primers. 2017; 3. https://doi.org/10.1038/ nrdp.2017.93 PMid:29219151 DOI: https://doi.org/10.1038/nrdp.2017.93
Stancu C, Sima A. Statins: Mechanism of action and effects. J Cell Mol Med. 2001; 5(4):378-87. https://doi. org/10.1111/j.1582-4934.2001.tb00172.x PMid:12067471 PMCid:PMC6740083 DOI: https://doi.org/10.1111/j.1582-4934.2001.tb00172.x
Ward NC, Watts GF, Eckel RH. Statin toxicity. Circ Res. 2019; 124(2):328-50. https://doi.org/10.1161/ CIRCRESAHA.118.312782 PMid:30653440 DOI: https://doi.org/10.1161/CIRCRESAHA.118.312782
Ko A, Song J, Golovko G, El Ayadi A, Ozhathil DK, Wermine K, et al. Higher risk of acute kidney injury and death with rhabdomyolysis in severely burned patients. Surgery. 2022; 171(5):1412-6. https://doi.org/10.1016/j.surg.2021.09.029 PMid:35078633 PMCid:PMC9241979 DOI: https://doi.org/10.1016/j.surg.2021.09.029
Bin Dayel FF, Alfirevic A, Chadwick AE. Developing in vitro models to define the role of direct mitochondrial toxicity in frequently reported drug-induced rhabdomyolysis. Biomedicines. 2023; 11(5). https://doi. org/10.3390/biomedicines11051485 PMid:37239154 PMCid:PMC10216605 DOI: https://doi.org/10.3390/biomedicines11051485
Patel BR, Choudhury M. Rhabdomyolysis with simvastatin. Case Rep. 2011; 2011. https://doi.org/10.1136/ bcr.12.2009.2552 PMid:22715232 PMCid:PMC3028252
Weber W. Drug firm withdraws statin from the market. The Lancet. 2001; 358(9281). https://doi.org/10.1016/S0140- 6736(01)05756-7 DOI: https://doi.org/10.1016/S0140-6736(01)05756-7
Research C for DE and. FDA Adverse Event Reporting System (FAERS) public dashboard. FDA [Internet]. 2021. [cited 2023 Aug 29]; Available from: https://www.fda.gov/drugs/questions-andanswers- fdas-adverse-event-reporting-system-faers/ fda-adverse-event-reporting-system-faers-publicdashboard
Reid G, Jass J, Sebulsky MT, McCormick JK. Potential uses of probiotics in clinical practice. Clin Microbiol Rev. 2003; 16(4):658-72. https://doi.org/10.1128/CMR.16.4.658- 672.2003 PMid:14557292 PMCid:PMC207122 DOI: https://doi.org/10.1128/CMR.16.4.658-672.2003
Kim SJ, Park SH, Sin HS, Jang SH, Lee SW, Kim SY, et al. Hypocholesterolemic effects of probiotic mixture on diet-induced hypercholesterolemic rats. Nutrients. 2017; 9(3). https://doi.org/10.3390/nu9030293 PMid:28300786 PMCid:PMC5372956 DOI: https://doi.org/10.3390/nu9030293
Ruscica M, Pavanello C, Gandini S, Macchi C, Botta M, Dall’Orto D, et al. Nutraceutical approach for the management of cardiovascular risk - A combination containing the probiotic Bifidobacterium longum BB536 and red yeast rice extract: Results from a randomized, double-blind, placebo-controlled study. Nutr J. 2019; 18(1):13. https://doi.org/10.1186/s12937-019-0438-2 PMid:30795775 PMCid:PMC6387491 DOI: https://doi.org/10.1186/s12937-019-0438-2
Chen L, Chang S, Chang H, Wu C, Pan C, Chang C, et al. Probiotic supplementation attenuates age‐related sarcopenia via the gut-muscle axis in SAMP8 mice. J Cachexia Sarcopenia Muscle. 2022; 13(1):515-31. https://doi.org/10.1002/jcsm.12849 PMid:34766473 PMCid:PMC8818665 DOI: https://doi.org/10.1002/jcsm.12849
Chen J, Chen X, Ho CL. Recent development of probiotic bifidobacteria for treating human diseases. Front Bioeng Biotechnol. 2021; 9. https://doi.org/10.3389/ fbioe.2021.770248 PMid:35004640 PMCid:PMC8727868 DOI: https://doi.org/10.3389/fbioe.2021.770248
Mihailović M, Živković M, Jovanović JA, Tolinački M, Sinadinović M, Rajić J, et al. Oral administration of probiotic Lactobacillus paraplantarum BGCG11 attenuates diabetesinduced liver and kidney damage in rats. J Funct Foods. 2017; 38:427-37. https://doi.org/10.1016/j.jff.2017.09.033 DOI: https://doi.org/10.1016/j.jff.2017.09.033
Öner Ö, Aslim B, Aydaş SB. Mechanisms of cholesterollowering effects of lactobacilli and bifidobacteria strains as potential probiotics with their bsh gene analysis. J Mol Microbiol Biotechnol. 2014; 24(1):12-18. https://doi. org/10.1159/000354316 PMid:24158048 DOI: https://doi.org/10.1159/000354316
Jiang J, Wu C, Zhang C, Zhang Q, Yu L, Zhao J, et al. Strain-specific effects of Bifidobacterium longum on hypercholesterolemic rats and potential mechanisms. Int J Mol Sci. 2021; 22(3). https://doi.org/10.3390/ijms22031305 PMid:33525627 PMCid:PMC7866116 DOI: https://doi.org/10.3390/ijms22031305
Al-Sheraji SH, Ismail A, Manap MY, Mustafa S, Yusof RM, Hassan FA. Hypocholesterolaemic effect of yoghurt containing Bifidobacterium pseudocatenulatum G4 or Bifidobacterium longum BB536. Food Chem. 2012; 135(2):356-61. https://doi.org/10.1016/j. foodchem.2012.04.120 PMid:22868099 DOI: https://doi.org/10.1016/j.foodchem.2012.04.120
Al-Sheraji SH, Amin I, Azlan A, Manap MY, Hassan FA. Effects of Bifidobacterium longum BB536 on lipid profile and histopathological changes in hypercholesterolaemic rats. Benef Microbes. 2015; 6(5):661-8. https://doi.org/10.3920/ BM2014.0032 PMid:26065647 DOI: https://doi.org/10.3920/BM2014.0032
El-Zahar KM, Hassan MFY, Al-Qaba SF. Protective effect of fermented camel milk containing Bifidobacterium longum BB536 on blood lipid profile in hypercholesterolemic rats. J Nutr Metab. 2021; 2021. https://doi.org/10.1155/2021/1557945 PMid:34745660 PMCid:PMC8570886 DOI: https://doi.org/10.1155/2021/1557945
Ito M, Kusuhara S, Yokoi W, Sato T, Ishiki H, Miida S, et al. Streptococcus thermophilus fermented milk reduces serum MDA-LDL and blood pressure in healthy and mildly hypercholesterolaemic adults. Benef Microbes. 2017; 8(2):171-8. https://doi.org/10.3920/BM2016.0102 PMid:28299944 DOI: https://doi.org/10.3920/BM2016.0102
Zhao J, Luo Y, Li Y, Cheng R, Shen X, Chen J, et al. Heatinactivated Streptococcus thermophilus MN002 alleviate lipid metabolism of high fat diet-fed induced obese mice through modulating gut microbiota structure and bile acids. Wei Sheng Yan Jiu. 2023; 52(2):259-64.
Kang X, Liang H, Luo Y, Li Z, He F, Han X, et al. Streptococcus thermophilus MN-ZLW-002 Can inhibit pre-adipocyte differentiation through macrophage activation. Biol Pharm Bull. 2021; 44(3):316-24. https://doi.org/10.1248/bpb.b20- 00335 PMid:33390424 DOI: https://doi.org/10.1248/bpb.b20-00335
Luo Y, Cheng R, Liang H, Miao Z, Wang J, Zhou Q, et al. Influence of high-fat diet on host animal health via bile acid metabolism and benefits of oral-fed Streptococcus thermophilus MN-ZLW-002. Exp Anim. 2022; 71(4):468-80. https://doi.org/10.1538/expanim.21-0182 PMid:35793979 PMCid:PMC9671773 DOI: https://doi.org/10.1538/expanim.21-0182
Kusuhara S, Ito M, Sato T, Yokoi W, Yamamoto Y, Harada K, et al. Intracellular GSH of Streptococcus thermophilus shows anti-oxidative activity against low-density lipoprotein oxidation in vitro and in a hyperlipidaemic hamster model. Benef Microbes. 2018; 9(1):143-52. https://doi.org/10.3920/ BM2017.0065 PMid:29065708 DOI: https://doi.org/10.3920/BM2017.0065
Srinivasan K, Viswanad B, Asrat L, Kaul CL, Ramarao P. Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: A model for type 2 diabetes and pharmacological screening. Pharmacol Res. 2005; 52(4):313-20. https://doi.org/10.1016/j.phrs.2005.05.004 PMid:15979893 DOI: https://doi.org/10.1016/j.phrs.2005.05.004
Bertelli JA, Mira JC. The grasping test: A simple behavioral method for objective quantitative assessment of peripheral nerve regeneration in the rat. J Neurosci Methods. 1995; 58(1):151-5. https://doi.org/10.1016/0165- 0270(94)00169-H PMid:7475220 DOI: https://doi.org/10.1016/0165-0270(94)00169-H
Trinder P. The determination of cholesterol in serum. Analyst. 1952; 77(915):321-5. https://doi.org/10.1039/ an9527700321 DOI: https://doi.org/10.1039/an9527700321
McGowan MW, Artiss JD, Strandbergh DR, Zak B. A peroxidase-coupled method for the colorimetric determination of serum triglycerides. Clin Chem. 1983; 29(3):538-42. https://doi.org/10.1093/clinchem/29.3.538 PMid:6825269 DOI: https://doi.org/10.1093/clinchem/29.3.538
Fossati P, Prencipe L. Serum triglycerides determined colorimetrically with an enzyme that produces hydrogen peroxide. Clin Chem. 1982; 28(10):2077-80. https://doi. org/10.1093/clinchem/28.10.2077 PMid:6812986 DOI: https://doi.org/10.1093/clinchem/28.10.2077
Naito H, Kaplan A. High-Density Lipoprotein (HDL) cholesterol. Clin Chem Tor Princet. 1984; 1207-13.
Srivastava LM, Das N, Sinha S. Essentials of practical biochemistry. CBS Publishers; 2002.
Börner U, Szász G, Bablok W, Busch EW. A specific fully enzymatic method for creatinine: reference values in serum (author’s transl). J Clin Chem Clin Biochem Z Klin Chem Klin Biochem. 1979; 17(11):679-82. https://doi. org/10.1515/cclm.1979.17.11.683 DOI: https://doi.org/10.1515/cclm.1979.17.11.683
Tiffany TO, Jansen JM, Burtis CA, Overton JB, Scott CD. Enzymatic kinetic rate and end-point analyses of substrate, by use of a GeMSAEC fast analyzer. Clin Chem. 1972; 18(8):829-40. https://doi.org/10.1093/clinchem/18.8.829 PMid:5043271 DOI: https://doi.org/10.1093/clinchem/18.8.829
Saka W, Akhigbe R, Popoola O, Oyekunle O. Changes in serum electrolytes, urea, and creatinine in aloe veratreated rats. J Young Pharm JYP. 2012; 4(2):78-81. https:// doi.org/10.4103/0975-1483.96620 PMid:22754258 PMCid:PMC3385221 DOI: https://doi.org/10.4103/0975-1483.96620
Young DS. Effects of preanalytical variables on clinical laboratory tests. Washington, DC: AACC Press; 1997. 39. Drury RAB, Wallington EA, Cameron SR. Carleton’s histological technique. London; 1967.
Safitri N, Alaina MF, Pitaloka DAE, Abdulah R. A narrative review of statin-induced rhabdomyolysis: Molecular mechanism, risk factors, and management. Drug Health Patient Saf. 2021; 13:211-9. https://doi.org/10.2147/DHPS. S333738 PMid:34795533 PMCid:PMC8593596 DOI: https://doi.org/10.2147/DHPS.S333738
Thompson PD, Clarkson PM, Rosenson RS. National lipid association statin safety task force muscle safety expert panel. An assessment of statin safety by muscle experts. Am J Cardiol. 2006; 97(8A):69C-76C. https://doi.org/10.1016/j. amjcard.2005.12.013 PMid:16581332 DOI: https://doi.org/10.1016/j.amjcard.2005.12.013
Pasternak RC, Smith SC, Bairey-Merz CN, Grundy SM, Cleeman JI, Lenfant C, et al. ACC/AHA/NHLBI clinical advisory on the use and safety of statins. J Am Coll Cardiol. 2002; 40(3):567-72. https://doi.org/10.1016/S0735- 1097(02)02030-2 PMid:12142128 DOI: https://doi.org/10.1016/S0735-1097(02)02030-2
Plaza-Diaz J, Ruiz-Ojeda FJ, Gil-Campos M, Gil A. Mechanisms of action of probiotics. Adv Nutr Bethesda Md. 2019; 10(suppl_1):S49-66. https://doi.org/10.1093/ advances/nmy063 PMid:30721959 PMCid:PMC6363529 DOI: https://doi.org/10.1093/advances/nmy063
Liong MT. Roles of probiotics and prebiotics in colon cancer prevention: Postulated mechanisms and in-vivo evidence. Int J Mol Sci. 2008; 9(5):854-63. https://doi.org/10.3390/ ijms9050854 PMid:19325789 PMCid:PMC2635701 DOI: https://doi.org/10.3390/ijms9050854
Jäger R, Purpura M, Stone JD, Turner SM, Anzalone AJ, Eimerbrink MJ, et al. Probiotic Streptococcus thermophilus FP4 and Bifidobacterium breve BR03 supplementation attenuates performance and range-of-motion decrements following muscle damaging exercise. Nutrients. 2016; 8(10). https://doi.org/10.3390/nu8100642 PMid:27754427 PMCid:PMC5084029 DOI: https://doi.org/10.3390/nu8100642
Chen YM, Wei L, Chiu YS, Hsu YJ, Tsai TY, Wang MF, et al. Lactobacillus plantarum TWK10 supplementation improves exercise performance and increases muscle mass in mice. Nutrients. 2016; 8(4). https://doi.org/10.3390/ nu8040205 PMid:27070637 PMCid:PMC4848674 DOI: https://doi.org/10.3390/nu8040205
Ranganathan N, Patel BG, Ranganathan P, Marczely J, Dheer R, Pechenyak B, et al. In vitro and in vivo assessment of intraintestinal bacteriotherapy in chronic kidney disease. Am Soc Artif Intern Organs. 2006; 52(1):70-9. https://doi. org/10.1097/01.mat.0000191345.45735.00 PMid:16436893 DOI: https://doi.org/10.1097/01.mat.0000191345.45735.00
Sugahara H, Odamaki T, Fukuda S, Kato T, Xiao J zhong, Abe F, et al. Probiotic Bifidobacterium longum alters gut luminal metabolism through modification of the gut microbial community. Sci Rep. 2015; 5. https://doi.org/10.1038/ srep13548 PMid:26315217 PMCid:PMC4552000 DOI: https://doi.org/10.1038/srep13548
Khalesi S, Sun J, Buys N, Jayasinghe R. Effect of probiotics on blood pressure. Hypertension. 2014; 64(4):897-903. https://doi.org/10.1161/HYPERTENSIONAHA.114.03469 PMid:25047574 DOI: https://doi.org/10.1161/HYPERTENSIONAHA.114.03469
Sadrzadeh-Yeganeh H, Elmadfa I, Djazayery A, Jalali M, Heshmat R, Chamary M. The effects of probiotic and conventional yoghurt on lipid profile in women. Br J Nutr. 2010; 103(12):1778-83. https://doi.org/10.1017/ S0007114509993801 PMid:20100374 DOI: https://doi.org/10.1017/S0007114509993801
Remuzzi G, Perico N, Macia M, Ruggenenti P. The role of renin-angiotensin-aldosterone system in the progression of chronic kidney disease. Kidney Int Suppl. 2005; (99):S57- 65. https://doi.org/10.1111/j.1523-1755.2005.09911.x PMid:16336578 DOI: https://doi.org/10.1111/j.1523-1755.2005.09911.x
Armitage J. The safety of statins in clinical practice. Lancet Lond Engl. 2007; 370(9601):1781-90. https://doi. org/10.1016/S0140-6736(07)60716-8 PMid:17559928 DOI: https://doi.org/10.1016/S0140-6736(07)60716-8
Dalbeth N, Wong S, Gamble GD, Horne A, Mason B, Pool B, et al. Acute effect of milk on serum urate concentrations: A randomised controlled crossover trial. Ann Rheum Dis. 2010; 69(9):1677-82. https://doi.org/10.1136/ ard.2009.124230 PMid:20472590 DOI: https://doi.org/10.1136/ard.2009.124230
Mahboobi S, Iraj B, Maghsoudi Z, Feizi A, Ghiasvand R, Askari G, et al. The effects of probiotic supplementation on markers of blood lipids, and blood pressure in patients with prediabetes: A randomized clinical trial. Int J Prev Med. 2014; 5(10):1239-46.
Faghih S, Abadi AR, Hedayati M, Kimiagar SM. Comparison of the effects of cows’ milk, fortified soy milk, and calcium supplement on weight and fat loss in premenopausal overweight and obese women. Nutr Metab Cardiovasc Dis. 2011; 21(7):499-503. https://doi.org/10.1016/j. numecd.2009.11.013 PMid:20227261 DOI: https://doi.org/10.1016/j.numecd.2009.11.013
Vincent HK, Bourguignon C, Vincent KR. Resistance training lowers exercise-induced oxidative stress and homocysteine levels in overweight and obese older adults. Obes Silver Spring Md. 2006; 14(11):1921-30. https://doi. org/10.1038/oby.2006.224 PMid:17135607 DOI: https://doi.org/10.1038/oby.2006.224
Thompson PD, Clarkson P, Karas RH. Statin-associated myopathy. JAMA. 2003; 289(13):1681-90. https://doi. org/10.1001/jama.289.13.1681 PMid:12672737 DOI: https://doi.org/10.1001/jama.289.13.1681
