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The ameliorating effect of silymarin against vancomycin induced apoptosis and inflammation in rat liver

Yıl 2019, Cilt: 23 Sayı: 4, 719 - 728, 27.06.2025

Sevda Güzel Kara , Zuhal Uçkun Şahinoğulları , Necmiye Canacankatan , Şerife Efsun Antmen Deniz Kibar , Gulsen Bayrak

Öz

Silymarin (SL), a flavonolignan complex isolated from seeds of Silybum marianum (Asteraceae), is known for its hepatoprotective, anti-apoptotic, anti-inflammatory, and antioxidant activities. A glycopeptide antibiotic, Vancomycin (VA) which is used for the treatment of serious infections caused by multi-resistant Gram-positive microorganisms has been clinically used for a long time. The aim of the present study was to evaluate potential therapeutic efficiency of SL against VA-induced apoptosis and inflammation using apoptotic (caspase-3, -8, and, -9 enzyme activities) and inflammatory (Tumor necrosis factor-alpha (TNF-α)) markers, and histopathological examinations in rat liver. A total of 49 male Wistar albino rats was divided into 7 groups including control (saline, intraperitoneally (i.p.)), Dimethyl sulfoxide (i.p.), VA (400 mg/kg/day, i.p.), SL100 (100 mg/kg/day, i.p.), VA+SL50 (50 mg/kg/day, i.p.), VA+SL100 (100 mg/kg/day, i.p.), and VA+SL200 (200 mg/kg/day, i.p.). SL was administered once a daily for 8 days. One day after the first treatment of SL, VA administration was started and continued for 7 days. Hepatic TNF-α levels were evaluated by ELISA and hepatic caspase activities were evaluated according to the colorimetric method. Significantly increased caspase activities were determined in VA group compared to control group (P<0.05). However, significantly reduced caspase activities were determined in VA+SL200 group when compared to VA group (P<0.05). TNF-α level in VA group was found to be statistically higher than control group (P<0.05). TNF-α levels of SL100, VA+SL (50, 100, and 200) groups were significantly lower than VA group (P<0.05). VA+SL200 group was found to be the most effective group according to reducing caspase activities and TNF-α level.

Anahtar Kelimeler

Caspase hepatoprotective histopathology silymarin TNF-α

Kaynakça

  • [1] Vargas-Mendoza N, Madrigal-Santillán E, Morales-González Á, Esquivel-Soto J, Esquivel-Chirino C, García-Luna González-Rubio M, Gayosso-de-Lucio JA, Morales-González JA. Hepatoprotective effect of silymarin. World J Hepatol. 2014; 6(3): 144-149. [CrossRef]
  • [2] Cengiz M, Kutlu HM, Burukoğlu DD, Ayhancı A. A comparative study on the therapeutic effects of silymarin and silymarin-loaded solid lipid nanoparticles on D-GaIN/TNF-α-induced liver damage in Balb/c mice. Food Chem Toxicol. 2015; 77: 93-100. [CrossRef]
  • [3] Domitrović R, Jakovac H, Blagojević G. Hepatoprotective activity of berberine is mediated by inhibition of TNF-α, COX-2, and iNOS expression in CCl4-intoxicated mice. Toxicology. 2011; 280: 33-43. [CrossRef]
  • [4] Anadozie SO, Akinyemi JA, Agunbiade S, Ajiboye BO, Adewale OB. Bryophyllum pinnatum inhibits arginase II activity and prevents oxidative damage occasioned by carbon tetrachloride (CCl4) in rats. Biomed Pharmacother. 2018; 101: 8-13. [CrossRef]
  • [5] Ozay Y, Guzel S, Erdogdu I, Yildirim Z, Pehlivanoglu B, Turk B, Darcan S. Evaluation of the wound healing properties of luteolin ointments on excision and incision wound models in diabetic and non-diabetic rats. Rec Nat Prod. 2018; 12(4): 350-366. [CrossRef]
  • [6] Fan L, Ma Y, Liu Y, Zheng D, Huang G. Silymarin induces cell cycle arrest and apoptosis in ovarian cancer cells. Eur J Pharmacol. 2014; 743: 79-88. [CrossRef]
  • [7] Fehér J, Lengyel G. Silymarin in the prevention and treatment of liver diseases and primary liver cancer. Curr Pharm Biotechnol. 2012; 13: 210-217. [CrossRef]
  • [8] Ghaznavi H, Mehrzadi S, Dormanesh B, Tabatabaei SMTH, Vahedi H, Hosseinzadeh A, Pazoki-Toroudi H, Rashidian A. Comparison of the protective effects of melatonin and silymarin against gentamicin-induced nephrotoxicity in rats. J Evid Based Complementary Altern Med. 2016; 21(4): 49-55. [CrossRef]
  • [9] Dabak DO, Kocaman N. Effects of silymarin on methotrexate-induced nephrotoxicity in rats. Ren Fail. 2015; 37(4): 734-739. [CrossRef]
  • [10] Chang JC, Wu YT, Lee WC, Lin LC, Tsai TH. Herb–drug interaction of silymarin or silibinin on the pharmacokinetics of trazodone in rats. Chem Biol Interact. 2009; 182: 227-232. [CrossRef]
  • [11] Elyasi S, Khalili H, Dashti-Khavidaki S, Mohammadpour A. Vancomycin-induced nephrotoxicity: mechanism, incidence, risk factors and special populations: a literature review. Eur J Clin Pharmacol. 2012; 68(9): 1243-1255. [CrossRef]
  • [12] Patel N, Joseph C, Corcoran GB, Ray SD. Silymarin modulates doxorubicin-induced oxidative stress, Bcl-xL and p53 expression while preventing apoptotic and necrotic cell death in the liver. Toxicol Appl Pharmacol. 2010; 245: 143-152. [CrossRef]
  • [13] Sozmen M, Devrim AK, Tunca R, Bayezit M, Dag S, Essiz D. Protective effects of silymarin on fumonisin B1-induced hepatotoxicity in mice. J Vet Sci. 2014; 15(1): 51-60. [CrossRef]
  • [14] Sajedianfard J, Nazifi S, Izadi A, Chahardahcherik M, Honarmad M. Effect of various doses of silymarin on the oxidative stress induced by busulfan administration in the different organs of rats. Turk J Pharm Sci. 2016; 13(2): 233-240. [CrossRef]
  • [15] Kim SH, Lee IC, Baek HS, Shin IS, Moon C, Bae CS, Kim SH, Kim JC, Kim HC. Mechanism for the protective effect of diallyl disulfide against cyclophosphamide acute urotoxicity in rats. Food Chem Toxicol. 2014; 64: 110-118. [CrossRef]
  • [16] Aghazadeh S, Amini R, Yazdanparast R, Ghaffari SH. Anti-apoptotic and anti-inflammatory effects of Silybum marianum in treatment of experimental steatohepatitis. Exp Toxicol Pathol. 2011; 63: 569-574. [CrossRef]
  • [17] Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007; 35(4): 495-516. [CrossRef]
  • [18] Kandemir FM, Yildirim S, Kucukler S, Caglayan C, Mahamadu A, Dortbudak MB. Therapeutic efficacy of zingerone against vancomycin-induced oxidative stress, inflammation, apoptosis and aquaporin 1 permeability in rat kidney. Biomed Pharmacother. 2018; 105: 981-991. [CrossRef]
  • [19] Wu Y, Zhao D, Zhuang J, Zhang F, Xu C. Caspase-8 and caspase-9 functioned differently at different stages of the cyclic stretch-induced apoptosis in human periodontal ligament cells. PLoS One. 2016; 11(12): e0168268. [CrossRef]
  • [20] Filippone E, Kraft WK, Farber JL. The nephrotoxicity of vancomycin. Clin Pharmacol Ther. 2017; 102(3): 459-469. [CrossRef]
  • [21] Gupta A, Biyani M, Khaira A. Vancomycin nephrotoxicity: myths and facts. Neth J Med. 2011; 69(9): 379-383.
  • [22] Sahin M, Cam H, Olgar S, Tunc SE, Arslan C, Uz E, Yilmaz HR. Protective role of erdosteine on vancomycin-induced oxidative stress in rat liver. Mol Cell Biochem. 2006; 291: 155-160. [CrossRef]
  • [23] El-Adawi H, El-Azhary D, Abd El-Wahab A, El-Shafeey M, Abdel-Mohsen M. Protective effect of milk thistle and grape seed extracts on fumonisin B1 induced hepato- and nephro-toxicity in rats. J Med Plants Res. 2011; 5(27): 6316-6327. [CrossRef]
  • [24] Karimi G, Vahabzadeh M, Lari P, Rashedinia M, Moshiri M. Silymarin, a promising pharmacological agent for treatment of diseases. Iran J Basic Med Sci. 2011; 14(4): 308-317.
  • [25] Chiu FL, Lin JK. Down-regulation of androgen receptor expression by luteolin causes inhibition of cell proliferation and induction of apoptosis in human prostate cancer cells and xenografts. Prostate. 2008; 68: 61-71. [CrossRef]
  • [26] Bektur NE, Sahin E, Baycu C, Unver G. Protective effects of silymarin against acetaminophen-induced hepatotoxicity and nephrotoxicity in mice. Toxicol Ind Health. 2016; 32: 589-600. [CrossRef]
  • [27] Choi YH, Cho SS, Simkhada JR, Rahman MS, Choi YS, Kim CS, Yoo JC. A novel multifunctional peptide oligomer of bacitracin with possible bioindustrial and therapeutic applications from a Korean food-source Bacillus strain. PLoS One. 2017; 12(5): e0176971. [CrossRef]
  • [28] Manna SK, Mukhopadhyay A, Van NT, Aggarwal BB. Silymarin suppresses TNF-induced activation of NF-kB, c-Jun N-terminal kinase, and apoptosis. J Immunol. 1999; 163: 6800-6809.
  • [29] Zhang W, Hong R, Tian T. Silymarin’s protective effects and possible mechanisms on alcoholic fatty liver for rats. Biomol Ther (Seoul). 2013; 21(4): 264-269. [CrossRef]
  • [30] Kumas M, Esrefoglu M, Guler EM. Protective effects of silymarin against isotretinoin induced liver and kidney injury in mice. Indian J Exp Biol. 2018; 56: 158-163.
  • [31] Navidi-Shishaone M, Mohhebi S, Nematbakhsh M, Roozbehani S, Talebi A, Pezeshki Z, Eshraghi-Jazi F, Mazaheri S, Shirdavani S, Gharagozloo M, Moaeidi BA. Co-administration of silymarin and deferoxamine against kidney, liver and heart iron deposition in male iron overload rat model. Int J Prev Med. 2014; 5(1): 110-116.
  • [32] Nishino Y, Takemura S, Minamiyama Y, Hirohashi K, Tanaka H, Inoue M, Okada S, Kinoshita H. Inhibition of vancomycin-induced nephrotoxicity by targeting superoxide dismutase to renal proximal tubule cells in the rat. Redox Rep. 2002; 7: 317-319. [CrossRef]
  • [33] Konishi H, Morita Y, Mizumura M, Iga I, Nagai K. Difference in nephrotoxicity of vancomycin administered once daily and twice daily in rats. J Chemother. 2013; 25: 273-278. [CrossRef]
  • [34] Burukoglu D, Ozer MC, Celik M, Baycu C. The role of satellite cells in crush injury of rat skeleton muscle. Eskişehir Technical University J Sci Technol C-Life Sci Biotechnol. 2013; 3(1): 1-7.
  • [35] Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem. 1951; 193: 265-275.

Yıl 2019, Cilt: 23 Sayı: 4, 719 - 728, 27.06.2025

Sevda Güzel Kara , Zuhal Uçkun Şahinoğulları , Necmiye Canacankatan , Şerife Efsun Antmen Deniz Kibar , Gulsen Bayrak

Öz

Kaynakça

  • [1] Vargas-Mendoza N, Madrigal-Santillán E, Morales-González Á, Esquivel-Soto J, Esquivel-Chirino C, García-Luna González-Rubio M, Gayosso-de-Lucio JA, Morales-González JA. Hepatoprotective effect of silymarin. World J Hepatol. 2014; 6(3): 144-149. [CrossRef]
  • [2] Cengiz M, Kutlu HM, Burukoğlu DD, Ayhancı A. A comparative study on the therapeutic effects of silymarin and silymarin-loaded solid lipid nanoparticles on D-GaIN/TNF-α-induced liver damage in Balb/c mice. Food Chem Toxicol. 2015; 77: 93-100. [CrossRef]
  • [3] Domitrović R, Jakovac H, Blagojević G. Hepatoprotective activity of berberine is mediated by inhibition of TNF-α, COX-2, and iNOS expression in CCl4-intoxicated mice. Toxicology. 2011; 280: 33-43. [CrossRef]
  • [4] Anadozie SO, Akinyemi JA, Agunbiade S, Ajiboye BO, Adewale OB. Bryophyllum pinnatum inhibits arginase II activity and prevents oxidative damage occasioned by carbon tetrachloride (CCl4) in rats. Biomed Pharmacother. 2018; 101: 8-13. [CrossRef]
  • [5] Ozay Y, Guzel S, Erdogdu I, Yildirim Z, Pehlivanoglu B, Turk B, Darcan S. Evaluation of the wound healing properties of luteolin ointments on excision and incision wound models in diabetic and non-diabetic rats. Rec Nat Prod. 2018; 12(4): 350-366. [CrossRef]
  • [6] Fan L, Ma Y, Liu Y, Zheng D, Huang G. Silymarin induces cell cycle arrest and apoptosis in ovarian cancer cells. Eur J Pharmacol. 2014; 743: 79-88. [CrossRef]
  • [7] Fehér J, Lengyel G. Silymarin in the prevention and treatment of liver diseases and primary liver cancer. Curr Pharm Biotechnol. 2012; 13: 210-217. [CrossRef]
  • [8] Ghaznavi H, Mehrzadi S, Dormanesh B, Tabatabaei SMTH, Vahedi H, Hosseinzadeh A, Pazoki-Toroudi H, Rashidian A. Comparison of the protective effects of melatonin and silymarin against gentamicin-induced nephrotoxicity in rats. J Evid Based Complementary Altern Med. 2016; 21(4): 49-55. [CrossRef]
  • [9] Dabak DO, Kocaman N. Effects of silymarin on methotrexate-induced nephrotoxicity in rats. Ren Fail. 2015; 37(4): 734-739. [CrossRef]
  • [10] Chang JC, Wu YT, Lee WC, Lin LC, Tsai TH. Herb–drug interaction of silymarin or silibinin on the pharmacokinetics of trazodone in rats. Chem Biol Interact. 2009; 182: 227-232. [CrossRef]
  • [11] Elyasi S, Khalili H, Dashti-Khavidaki S, Mohammadpour A. Vancomycin-induced nephrotoxicity: mechanism, incidence, risk factors and special populations: a literature review. Eur J Clin Pharmacol. 2012; 68(9): 1243-1255. [CrossRef]
  • [12] Patel N, Joseph C, Corcoran GB, Ray SD. Silymarin modulates doxorubicin-induced oxidative stress, Bcl-xL and p53 expression while preventing apoptotic and necrotic cell death in the liver. Toxicol Appl Pharmacol. 2010; 245: 143-152. [CrossRef]
  • [13] Sozmen M, Devrim AK, Tunca R, Bayezit M, Dag S, Essiz D. Protective effects of silymarin on fumonisin B1-induced hepatotoxicity in mice. J Vet Sci. 2014; 15(1): 51-60. [CrossRef]
  • [14] Sajedianfard J, Nazifi S, Izadi A, Chahardahcherik M, Honarmad M. Effect of various doses of silymarin on the oxidative stress induced by busulfan administration in the different organs of rats. Turk J Pharm Sci. 2016; 13(2): 233-240. [CrossRef]
  • [15] Kim SH, Lee IC, Baek HS, Shin IS, Moon C, Bae CS, Kim SH, Kim JC, Kim HC. Mechanism for the protective effect of diallyl disulfide against cyclophosphamide acute urotoxicity in rats. Food Chem Toxicol. 2014; 64: 110-118. [CrossRef]
  • [16] Aghazadeh S, Amini R, Yazdanparast R, Ghaffari SH. Anti-apoptotic and anti-inflammatory effects of Silybum marianum in treatment of experimental steatohepatitis. Exp Toxicol Pathol. 2011; 63: 569-574. [CrossRef]
  • [17] Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007; 35(4): 495-516. [CrossRef]
  • [18] Kandemir FM, Yildirim S, Kucukler S, Caglayan C, Mahamadu A, Dortbudak MB. Therapeutic efficacy of zingerone against vancomycin-induced oxidative stress, inflammation, apoptosis and aquaporin 1 permeability in rat kidney. Biomed Pharmacother. 2018; 105: 981-991. [CrossRef]
  • [19] Wu Y, Zhao D, Zhuang J, Zhang F, Xu C. Caspase-8 and caspase-9 functioned differently at different stages of the cyclic stretch-induced apoptosis in human periodontal ligament cells. PLoS One. 2016; 11(12): e0168268. [CrossRef]
  • [20] Filippone E, Kraft WK, Farber JL. The nephrotoxicity of vancomycin. Clin Pharmacol Ther. 2017; 102(3): 459-469. [CrossRef]
  • [21] Gupta A, Biyani M, Khaira A. Vancomycin nephrotoxicity: myths and facts. Neth J Med. 2011; 69(9): 379-383.
  • [22] Sahin M, Cam H, Olgar S, Tunc SE, Arslan C, Uz E, Yilmaz HR. Protective role of erdosteine on vancomycin-induced oxidative stress in rat liver. Mol Cell Biochem. 2006; 291: 155-160. [CrossRef]
  • [23] El-Adawi H, El-Azhary D, Abd El-Wahab A, El-Shafeey M, Abdel-Mohsen M. Protective effect of milk thistle and grape seed extracts on fumonisin B1 induced hepato- and nephro-toxicity in rats. J Med Plants Res. 2011; 5(27): 6316-6327. [CrossRef]
  • [24] Karimi G, Vahabzadeh M, Lari P, Rashedinia M, Moshiri M. Silymarin, a promising pharmacological agent for treatment of diseases. Iran J Basic Med Sci. 2011; 14(4): 308-317.
  • [25] Chiu FL, Lin JK. Down-regulation of androgen receptor expression by luteolin causes inhibition of cell proliferation and induction of apoptosis in human prostate cancer cells and xenografts. Prostate. 2008; 68: 61-71. [CrossRef]
  • [26] Bektur NE, Sahin E, Baycu C, Unver G. Protective effects of silymarin against acetaminophen-induced hepatotoxicity and nephrotoxicity in mice. Toxicol Ind Health. 2016; 32: 589-600. [CrossRef]
  • [27] Choi YH, Cho SS, Simkhada JR, Rahman MS, Choi YS, Kim CS, Yoo JC. A novel multifunctional peptide oligomer of bacitracin with possible bioindustrial and therapeutic applications from a Korean food-source Bacillus strain. PLoS One. 2017; 12(5): e0176971. [CrossRef]
  • [28] Manna SK, Mukhopadhyay A, Van NT, Aggarwal BB. Silymarin suppresses TNF-induced activation of NF-kB, c-Jun N-terminal kinase, and apoptosis. J Immunol. 1999; 163: 6800-6809.
  • [29] Zhang W, Hong R, Tian T. Silymarin’s protective effects and possible mechanisms on alcoholic fatty liver for rats. Biomol Ther (Seoul). 2013; 21(4): 264-269. [CrossRef]
  • [30] Kumas M, Esrefoglu M, Guler EM. Protective effects of silymarin against isotretinoin induced liver and kidney injury in mice. Indian J Exp Biol. 2018; 56: 158-163.
  • [31] Navidi-Shishaone M, Mohhebi S, Nematbakhsh M, Roozbehani S, Talebi A, Pezeshki Z, Eshraghi-Jazi F, Mazaheri S, Shirdavani S, Gharagozloo M, Moaeidi BA. Co-administration of silymarin and deferoxamine against kidney, liver and heart iron deposition in male iron overload rat model. Int J Prev Med. 2014; 5(1): 110-116.
  • [32] Nishino Y, Takemura S, Minamiyama Y, Hirohashi K, Tanaka H, Inoue M, Okada S, Kinoshita H. Inhibition of vancomycin-induced nephrotoxicity by targeting superoxide dismutase to renal proximal tubule cells in the rat. Redox Rep. 2002; 7: 317-319. [CrossRef]
  • [33] Konishi H, Morita Y, Mizumura M, Iga I, Nagai K. Difference in nephrotoxicity of vancomycin administered once daily and twice daily in rats. J Chemother. 2013; 25: 273-278. [CrossRef]
  • [34] Burukoglu D, Ozer MC, Celik M, Baycu C. The role of satellite cells in crush injury of rat skeleton muscle. Eskişehir Technical University J Sci Technol C-Life Sci Biotechnol. 2013; 3(1): 1-7.
  • [35] Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem. 1951; 193: 265-275.
Toplam 35 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Eczacılık Biyokimyası, Farmakognozi, Farmasotik Toksikoloji
Bölüm Articles
Yazarlar

Sevda Güzel Kara

Zuhal Uçkun Şahinoğulları

Necmiye Canacankatan

Şerife Efsun Antmen

Deniz Kibar

Gulsen Bayrak

Yayımlanma Tarihi 27 Haziran 2025
Yayımlandığı Sayı Yıl 2019 Cilt: 23 Sayı: 4

Kaynak Göster

APA Güzel Kara, S., Uçkun Şahinoğulları, Z., Canacankatan, N., Antmen, Ş. E., vd. (2025). The ameliorating effect of silymarin against vancomycin induced apoptosis and inflammation in rat liver. Journal of Research in Pharmacy, 23(4), 719-728.
AMA Güzel Kara S, Uçkun Şahinoğulları Z, Canacankatan N, Antmen ŞE, Kibar D, Bayrak G. The ameliorating effect of silymarin against vancomycin induced apoptosis and inflammation in rat liver. J. Res. Pharm. Haziran 2025;23(4):719-728.
Chicago Güzel Kara, Sevda, Zuhal Uçkun Şahinoğulları, Necmiye Canacankatan, Şerife Efsun Antmen, Deniz Kibar, ve Gulsen Bayrak. “The Ameliorating Effect of Silymarin Against Vancomycin Induced Apoptosis and Inflammation in Rat Liver”. Journal of Research in Pharmacy 23, sy. 4 (Haziran 2025): 719-28.
EndNote Güzel Kara S, Uçkun Şahinoğulları Z, Canacankatan N, Antmen ŞE, Kibar D, Bayrak G (01 Haziran 2025) The ameliorating effect of silymarin against vancomycin induced apoptosis and inflammation in rat liver. Journal of Research in Pharmacy 23 4 719–728.
IEEE S. Güzel Kara, Z. Uçkun Şahinoğulları, N. Canacankatan, Ş. E. Antmen, D. Kibar, ve G. Bayrak, “The ameliorating effect of silymarin against vancomycin induced apoptosis and inflammation in rat liver”, J. Res. Pharm., c. 23, sy. 4, ss. 719–728, 2025.
ISNAD Güzel Kara, Sevda vd. “The Ameliorating Effect of Silymarin Against Vancomycin Induced Apoptosis and Inflammation in Rat Liver”. Journal of Research in Pharmacy 23/4 (Haziran 2025), 719-728.
JAMA Güzel Kara S, Uçkun Şahinoğulları Z, Canacankatan N, Antmen ŞE, Kibar D, Bayrak G. The ameliorating effect of silymarin against vancomycin induced apoptosis and inflammation in rat liver. J. Res. Pharm. 2025;23:719–728.
MLA Güzel Kara, Sevda vd. “The Ameliorating Effect of Silymarin Against Vancomycin Induced Apoptosis and Inflammation in Rat Liver”. Journal of Research in Pharmacy, c. 23, sy. 4, 2025, ss. 719-28.
Vancouver Güzel Kara S, Uçkun Şahinoğulları Z, Canacankatan N, Antmen ŞE, Kibar D, Bayrak G. The ameliorating effect of silymarin against vancomycin induced apoptosis and inflammation in rat liver. J. Res. Pharm. 2025;23(4):719-28.