Generic placeholder image

Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Research Article

Favorable Aspects of Silymarin in Linezolid Treatment Against Diabetic Methicillin-Resistant Staphylococcus aureus (MRSA) Infected Rats

Author(s): Lalitha Vivekanandan*, Sengottuvelu Singaravel and Sivakumar Thangavel

Volume 19, Issue 10, 2022

Published on: 09 June, 2022

Page: [938 - 949] Pages: 12

DOI: 10.2174/1570180819666220411080831

Price: $65

Abstract

Background: Linezolid used for diabetic methicillin-resistant Staphylococcus aureus (MRSA) infections is limited due to hepatotoxicity, lactic acidosis, anemia, and oxidative stress induced by diabetes and linezolid therapy. Silymarin is a hepatoprotective, antioxidant, antibacterial, and antidiabetic.

Objective: The research investigated the role of silymarin in linezolid treatment against MRSA-infected diabetic rats.

Methods: Type 2 diabetes mellitus (T2DM) was induced by a high-fat diet (58% calories fat) for 2 weeks, followed by a single intraperitoneal injection of streptozotocin (STZ) 35 mg/kg into Wistar rats. The diabetic rats were rendered neutropenic and subcutaneously injected with 106 CFU/ml of MRSA. Linezolid and silymarin were administered orally at a dose of 50 mg/kg twice daily for 14 days. The bacterial load/abscess, hematological, biochemical, enzymatic parameters, antioxidants, and histopathological studies were performed on the 42nd day.

Results: The MRSA was confirmed by PCR assay. The minimum inhibitory concentration of linezolid was found to be 0.5-2 μg/ml. The linezolid treated MRSA infected diabetic rats showed 9.69 x 103 CFU / abscess bacterial count, decreased intestinal alkaline phosphatase (IAP), RBC, antioxidants, elevated lactate, and liver markers than diabetic rats. The silymarin treatment showed a decrease in the bacterial count (2.98 x 103CFU / abscess), serum lactate, liver markers, increased IAP levels, and antioxidants in linezolid treated diabetic infected rats.

Conclusion: The research concluded that silymarin could be a better herbal therapeutic agent that attenuated diabetic and linezolid induced complications in MRSA-infected diabetic rats.

Keywords: High-fat diet, streptozotocin, linezolid, silymarin, IAP, MRSA.

« Previous
Graphical Abstract

[1]
Chahine, E.B.; Sucher, A.J.; Knutsen, S.D. Skin and soft tissue infections. Consult Pharm., 2015, 30(7), 386-394.
[http://dx.doi.org/10.4140/TCP.n.2015.386] [PMID: 26173190]
[2]
Sreeramoju, P.; Porbandarwalla, N.S.; Arango, J.; Latham, K.; Dent, D.L.; Stewart, R.M.; Patterson, J.E. Recurrent skin and soft tissue infections due to methicillin-resistant Staphylococcus aureus requiring operative debridement. Am. J. Surg., 2011, 201(2), 216-220.
[http://dx.doi.org/10.1016/j.amjsurg.2009.12.024] [PMID: 20832054]
[3]
Ki, V.; Rotstein, C. Bacterial skin and soft tissue infections in adults: A review of their epidemiology, pathogenesis, diagnosis, treatment and site of care. Can. J. Infect. Dis. Med. Microbiol., 2008, 19(2), 173-184.
[http://dx.doi.org/10.1155/2008/846453] [PMID: 19352449]
[4]
Vivekanandan, L.; Sheik, H.; Singaravel, S.; Thangavel, S. Assessment of efficacy and safety of clindamycin against methicillin-resistant Staphylococcus aureus (MRSA) infected subcutaneous abscess model. Antiinfect. Agents, 2020, 18(2), 144-151.
[http://dx.doi.org/10.2174/2211352517666190301142421]
[5]
Ciandrini, E.; Morroni, G.; Arzeni, D.; Kamysz, W.; Neubauer, D.; Kamysz, E.; Cirioni, O.; Brescini, L.; Baffone, W.; Campana, R. Anti-microbial activity of different antimicrobial peptides (AMPs) against clinical methicillin-resistant Staphylococcus aureus (MRSA). Curr. Top. Med. Chem., 2018, 18(24), 2116-2126.
[http://dx.doi.org/10.2174/1568026618666181022140348] [PMID: 30345920]
[6]
Casqueiro, J.; Casqueiro, J.; Alves, C. Infections in patients with diabetes mellitus: A review of pathogenesis. Indian J. Endocrinol. Metab., 2012, 16(Suppl. 1), S27-S36.
[http://dx.doi.org/10.4103/2230-8210.94253] [PMID: 22701840]
[7]
Eckmann, C.; Dryden, M. Treatment of complicated skin and soft-tissue infections caused by resistant bacteria: Value of linezolid, tigecy-cline, daptomycin and vancomycin. Eur. J. Med. Res., 2010, 15(12), 554-563.
[http://dx.doi.org/10.1186/2047-783X-15-12-554] [PMID: 21163730]
[8]
Leong, H.N.; Kurup, A.; Tan, M.Y.; Kwa, A.L.H.; Liau, K.H.; Wilcox, M.H. Management of complicated skin and soft tissue infections with a special focus on the role of newer antibiotics. Infect. Drug Resist., 2018, 11, 1959-1974.
[http://dx.doi.org/10.2147/IDR.S172366] [PMID: 30464538]
[9]
Li, M.; Xiaojuan, Z.; Xingin, Z.; Lujing, Z.; Yuanyuan, Q. Comparison of efficacy of linezolid and vancomycin for treatment of hospital-acquired pneumonia: A metaanalysis. Biomed. Res. (Aligarh), 2017, 28, 3420-3426.
[10]
Singh, B.; Cocker, D.; Ryan, H.; Sloan, D.J. Linezolid for drug-resistant pulmonary tuberculosis. Cochrane Database Syst. Rev, 2019, (3)
[http://dx.doi.org/10.1002/14651858.CD012836.pub2]
[11]
Kleiner, D.E. The histopathological evaluation of drug-induced liver injury. Histopathology, 2017, 70(1), 81-93.
[http://dx.doi.org/10.1111/his.13082] [PMID: 27960237]
[12]
Burkhardt, O.; Pletz, M.W.; Mertgen, C.P.; Welte, T. Linezolid - the first oxazolidinone in the treatment of nosocomial MRSA pneumonia. Recent Patents Anti-Infect. Drug Disc., 2007, 2(2), 123-130.
[http://dx.doi.org/10.2174/157489107780832659] [PMID: 18221168]
[13]
Vivekanandan, L.; Sheik, H.; Singaravel, S.; Thangavel, S. Ameliorative effect of silymarin against linezolid-induced hepatotoxicity in methicillin-resistant Staphylococcus aureus (MRSA) infected Wistar rats. Biomed. Pharmacother., 2018, 108, 1303-1312.
[http://dx.doi.org/10.1016/j.biopha.2018.09.133] [PMID: 30372832]
[14]
Mohamed, J.; Nazratun Nafizah, A.H.; Zariyantey, A.H.; Budin, S.B. Mechanisms of diabetes-induced liver damage: The role of oxidative stress and inflammation. Sultan Qaboos Univ. Med. J., 2016, 16(2), e132-e141.
[http://dx.doi.org/10.18295/squmj.2016.16.02.002] [PMID: 27226903]
[15]
Bal, A.M.; David, M.Z.; Garau, J.; Gottlieb, T.; Mazzei, T.; Scaglione, F.; Tattevin, P.; Gould, I.M. Future trends in the treatment of methi-cillin-resistant Staphylococcus aureus (MRSA) infection: An in-depth review of newer antibiotics active against an enduring pathogen. J. Glob. Antimicrob. Resist., 2017, 10, 295-303.
[http://dx.doi.org/10.1016/j.jgar.2017.05.019] [PMID: 28732783]
[16]
Kishor, K.; Dhasmana, N.; Kamble, S.S.; Sahu, R.K. Linezolid induced adverse drug reactions-an update. Curr. Drug Metab., 2015, 16(7), 553-559.
[http://dx.doi.org/10.2174/1389200216666151001121004] [PMID: 26424176]
[17]
Karimi, G.; Vahabzadeh, M.; Lari, P.; Rashedinia, M.; Moshiri, M.; Garbhapu, A.; Yalavarthi, P.; Koganti, P.; Bakhtiary, M.; Marzban, M.; Mehdizadeh, M. Silymarin, a promising pharmacological agent for treatment of diseases; J. Archives, 2020, p. 23.
[18]
Suh, H.J.; Cho, S.Y.; Kim, E.Y.; Choi, H.S. Blockade of lipid accumulation by silibinin in adipocytes and zebrafish. Chemico-biological Inter., 2015, 227, 53-62.
[http://dx.doi.org/10.1016/j.cbi.2014.12.027] [PMID: 25559859]
[19]
Lee, Y.S.; Jang, K.A.; Cha, J.D. Synergistic antibacterial effect between silibinin and antibiotics in oral bacteria. J. Biomed. Biotechnol., 2012, 2012, 618081.
[http://dx.doi.org/10.1155/2012/618081] [PMID: 21941436]
[20]
McClure, J.A.; Conly, J.M.; Lau, V.; Elsayed, S.; Louie, T.; Hutchins, W.; Zhang, K. Novel multiplex PCR assay for detection of the staphylococcal virulence marker Panton-Valentine leukocidin genes and simultaneous discrimination of methicillin-susceptible from -resistant Staphylococci. J. Clin. Microbiol., 2006, 44(3), 1141-1144.
[http://dx.doi.org/10.1128/JCM.44.3.1141-1144.2006] [PMID: 16517915]
[21]
Wayne, P.A. Clinical and Laboratory Standards Institute. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard, CLSI document M7-A7, 7th ed.; 2006.
[22]
Srinivasan, K.; Viswanad, B.; Asrat, L.; Kaul, C.L.; 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), 313-320.
[http://dx.doi.org/10.1016/j.phrs.2005.05.004] [PMID: 15979893]
[23]
Tsuji, M.; Takema, M.; Miwa, H.; Shimada, J.; Kuwahara, S. In vivo antibacterial activity of S-3578, a new broad-spectrum cephalosporin: Methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa experimental infection models. Antimicrob. Agents Chemother., 2003, 47(8), 2507-2512.
[http://dx.doi.org/10.1128/AAC.47.8.2507-2512.2003] [PMID: 12878512]
[24]
Sacar, M.; Sacar, S.; Kaleli, I.; Cevahir, N.; Teke, Z.; Kavas, S.T.; Asan, A.; Aytekin, F.O.; Baltalarli, A.; Turgut, H. Efficacy of linezolid in the treatment of mediastinitis due to methicillin-resistant Staphylococcus aureus: An experimental study. Int. J. Infect. Dis., 2008, 12(4), 396-401.
[http://dx.doi.org/10.1016/j.ijid.2007.09.017] [PMID: 18162429]
[25]
Lowry, O.H.; Rosebrough, N.J.; Farr, A.L.; Randall, R.J. Protein measurement with the Folin phenol reagent. J. Biol. Chem., 1951, 193(1), 265-275.
[http://dx.doi.org/10.1016/S0021-9258(19)52451-6] [PMID: 14907713]
[26]
Nieshus, W.G.; Samuelsson, B. Formation of MDA from phospholipids arachidonate during microsomal lipid peroxidation. Eur. J. Biochem., 1986, 6, 126-130.
[27]
Kakkar, P.; Das, B.; Viswanathan, P.N. A modified spectrophotometric assay of superoxide dismutase. Indian J. Biochem. Biophys., 1984, 21(2), 130-132.
[PMID: 6490072]
[28]
Aebi, H. Methods in enzymatic analysis, 2nd ed; Academic Press: New York, 1974, pp. 673-684.
[http://dx.doi.org/10.1016/B978-0-12-091302-2.50032-3]
[29]
Racker, E. Glutathione reductase from bakers’ yeast and beef liver. J. Biol. Chem., 1955, 217(2), 855-865.
[http://dx.doi.org/10.1016/S0021-9258(18)65950-2] [PMID: 13271446]
[30]
Paglia, D.E.; Valentine, W.N. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J. Lab. Clin. Med., 1967, 70(1), 158-169.
[PMID: 6066618]
[31]
Lobarzewski, J.; Ginalska, G. Industrial use of soluble or immobilized plant peroxidases. Plant Peroxidase News Letter, 1995, 6, 3-7.
[32]
Ellman, G.L. Tissue sulfhydryl groups. Arch. Biochem. Biophys., 1959, 82(1), 70-77.
[http://dx.doi.org/10.1016/0003-9861(59)90090-6] [PMID: 13650640]
[33]
Dugan, R.E.; Frigerio, A.; Siebert, J.M. Colorimetric determination of vitamin A and its derivatives with trifluoroacetic acid. Anal. Chem., 1964, 36, 114-117.
[http://dx.doi.org/10.1021/ac60207a035]
[34]
Omaye, S.T.; Turnbull, J.D.; Sauberlich, H.E. Selected methods for the determination of ascorbic acid in animal cells, tissues, and fluids. Methods Enzymol., 1979, 62, 3-11.
[http://dx.doi.org/10.1016/0076-6879(79)62181-X] [PMID: 440112]
[35]
Palan, P.R.; Mikhail, M.S.; Basu, J.; Romney, S.L. Plasma levels of antioxidant beta-carotene and alpha-tocopherol in uterine cervix dys-plasias and cancer. Nutr. Cancer, 1991, 15(1), 13-20.
[http://dx.doi.org/10.1080/01635589109514106] [PMID: 2017395]
[36]
Kasai, T.; Tanaka, T.; Kiriyama, S.; Sonoyama, K. Facile preparation of rat intestinal mucosa for assay of mucosal enzyme activity. J. Nutr. Sci. Vitaminol. (Tokyo), 1993, 39(4), 399-403.
[http://dx.doi.org/10.3177/jnsv.39.399] [PMID: 8283318]
[37]
Kao, L.S.; Knight, M.T.; Lally, K.P.; Mercer, D.W. The impact of diabetes in patients with necrotizing soft tissue infections. Surg. Infect. (Larchmt.), 2005, 6(4), 427-438.
[http://dx.doi.org/10.1089/sur.2005.6.427] [PMID: 16433607]
[38]
Bodnar, T.; Starr, K.; Halter, J.B. Linezolid-associated hypoglycemia in a 64-year-old man with type 2 diabetes. Am. J. Geriatr. Pharmacother., 2011, 9(1), 88-92.
[http://dx.doi.org/10.1016/j.amjopharm.2011.02.002] [PMID: 21459312]
[39]
French, G. Safety and tolerability of linezolid. J. Antimicrob. Chemother., 2003, 51(2)(Suppl. 2), ii45-ii53.
[PMID: 12730142]
[40]
Ashrafizadeh, M.; Ahmadi, Z.; Mohammadinejad, R.; Farkhondeh, T.; Samarghandian, S. Nano-soldiers ameliorate silibinin delivery: A review study. Curr. Drug Deliv., 2020, 17(1), 15-22.
[http://dx.doi.org/10.2174/1567201816666191112113031] [PMID: 31721702]
[41]
Angelousi, A.; Larger, E. Anaemia, a common but often unrecognized risk in diabetic patients: A review. Diabetes Metab., 2015, 41(1), 18-27.
[http://dx.doi.org/10.1016/j.diabet.2014.06.001] [PMID: 25043174]
[42]
Barbieri, J.; Fontela, P.C.; Winkelmann, E.R.; Zimmermann, C.E.; Sandri, Y.P.; Mallet, E.K.; Frizzo, M.N. Anemia in patients with type 2 diabetes mellitus. Anemia, 2015, 2015, 354737.
[http://dx.doi.org/10.1155/2015/354737] [PMID: 26640706]
[43]
Oguntibeju, O.O. Type 2 diabetes mellitus, oxidative stress and inflammation: Examining the links. Int. J. Physiol. Pathophysiol. Pharmacol., 2019, 11(3), 45-63.
[PMID: 31333808]
[44]
Voroneanu, l.; Nistor, I.; Dumea, R.; Apetrii, M.; Covic, A. Silymarin in type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials. J. Diabetes Res., 2016.
[45]
Narisawa, S.; Huang, L.; Iwasaki, A.; Hasegawa, H.; Alpers, D.H.; Millán, J.L. Accelerated fat absorption in intestinal alkaline phosphatase knockout mice. Mol. Cell. Biol., 2003, 23(21), 7525-7530.
[http://dx.doi.org/10.1128/MCB.23.21.7525-7530.2003] [PMID: 14560000]
[46]
Federico, A.; Dallio, M.; Loguercio, C. Silymarin/silybin and chronic liver disease: A marriage of many years. Molecules, 2017, 22(2), 191.
[http://dx.doi.org/10.3390/molecules22020191] [PMID: 28125040]
[47]
Antal, E.J.; Hendershot, P.E.; Batts, D.H.; Sheu, W.P.; Hopkins, N.K.; Donaldson, K.M. Linezolid, a novel oxazolidinone antibiotic: As-sessment of monoamine oxidase inhibition using pressor response to oral tyramine. J. Clin. Pharmacol., 2001, 41(5), 552-562.
[http://dx.doi.org/10.1177/00912700122010294] [PMID: 11361052]
[48]
Malo, M.S. A high level of intestinal alkaline phosphatase is protective against type 2 diabetes mellitus irrespective of obesity. EBioMedicine, 2015, 2(12), 2016-2023.
[http://dx.doi.org/10.1016/j.ebiom.2015.11.027] [PMID: 26844282]
[49]
Ghosh, S.S.; Gehr, T.W.; Ghosh, S. Curcumin and chronic kidney disease (CKD): Major mode of action through stimulating endogenous intestinal alkaline phosphatase. Molecules, 2014, 19(12), 20139-20156.
[http://dx.doi.org/10.3390/molecules191220139] [PMID: 25474287]
[50]
Kaliannan, K.; Wang, B.; Li, X.Y.; Kim, K.J.; Kang, J.X. A host-microbiome interaction mediates the opposing effects of omega-6 and omega-3 fatty acids on metabolic endotoxemia. Sci. Rep., 2015, 5, 11276.
[http://dx.doi.org/10.1038/srep11276] [PMID: 26062993]
[51]
Mahmood, A.; Shao, J.S.; Alpers, D.H. Rat enterocytes secrete SLPs containing alkaline phosphatase and cubilin in response to corn oil feeding. Am. J. Physiol. Gastrointest. Liver Physiol., 2003, 285(2), G433-G441.
[http://dx.doi.org/10.1152/ajpgi.00466.2002] [PMID: 12660142]
[52]
Kaliannan, K.; Hamarneh, S.R.; Economopoulos, K.P.; Nasrin Alam, S.; Moaven, O.; Patel, P.; Malo, N.S.; Ray, M.; Abtahi, S.M.; Mu-hammad, N.; Raychowdhury, A.; Teshager, A.; Mohamed, M.M.; Moss, A.K.; Ahmed, R.; Hakimian, S.; Narisawa, S.; Millán, J.L.; Hohmann, E.; Warren, H.S.; Bhan, A.K.; Malo, M.S.; Hodin, R.A. Intestinal alkaline phosphatase prevents metabolic syndrome in mice. Proc. Natl. Acad. Sci. USA, 2013, 110(17), 7003-7008.
[http://dx.doi.org/10.1073/pnas.1220180110] [PMID: 23569246]
[53]
Ebrahimpour-Koujan, S.; Gargari, B.P.; Mobasseri, M.; Valizadeh, H.; Asghari-Jafarabadi, M. Lower glycemic indices and lipid profile among type 2 diabetes mellitus patients who received novel dose of Silybum marianum (L.) Gaertn. (silymarin) extract supplement: A Tri-ple-blinded randomized controlled clinical trial. Phytomedicine, 2018, 44, 39-44.
[http://dx.doi.org/10.1016/j.phymed.2018.03.050] [PMID: 29895491]
[54]
Carson, J.; Cerda, J.; Chae, J.H.; Hirano, M.; Maggiore, P. Severe lactic acidosis associated with linezolid use in a patient with the mito-chondrial DNA A2706G polymorphism. Pharmacotherapy, 2007, 27(5), 771-774.
[http://dx.doi.org/10.1592/phco.27.5.771] [PMID: 17461714]
[55]
Asmat, U.; Abad, K.; Ismail, K. Diabetes mellitus and oxidative stress-A concise review. Saudi Pharm. J., 2016, 24(5), 547-553.
[http://dx.doi.org/10.1016/j.jsps.2015.03.013] [PMID: 27752226]
[56]
Gaschler, M.M.; Stockwell, B.R. Lipid peroxidation in cell death. Biochem. Biophys. Res. Commun., 2017, 482(3), 419-425.
[http://dx.doi.org/10.1016/j.bbrc.2016.10.086] [PMID: 28212725]
[57]
Tiwari, B.K.; Pandey, K.B.; Abidi, A.B.; Rizvi, S.I. Markers of oxidative stress during diabetes mellitus. J. Biomark., 2013, 2013, 378790.
[http://dx.doi.org/10.1155/2013/378790] [PMID: 26317014]
[58]
Maritim, A.C.; Sanders, R.A.; Watkins, J.B. III Diabetes, oxidative stress, and antioxidants: A review. J. Biochem. Mol. Toxicol., 2003, 17(1), 24-38.
[http://dx.doi.org/10.1002/jbt.10058] [PMID: 12616644]
[59]
George, J. Ascorbic acid concentrations in dimethylnitrosamine-induced hepatic fibrosis in rats. Clin. Chim. Acta, 2003, 335(1-2), 39-47.
[http://dx.doi.org/10.1016/S0009-8981(03)00285-7] [PMID: 12927683]
[60]
Exner, R.; Wessner, B.; Manhart, N.; Roth, E. Therapeutic potential of glutathione. Wien. Klin. Wochenschr., 2000, 112(14), 610-616.
[PMID: 11008322]

© 2024 Bentham Science Publishers | Privacy Policy