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Year 2021, Volume: 11 Issue: 2, 191 - 198, 30.06.2021
https://doi.org/10.33808/clinexphealthsci.741916

Abstract

Project Number

This study was supported by the Research Fund of Mersin University in Turkey with Project Number 2016-2-AP3-1906.

References

  • Ponte ML, Flores Lazdin C, Fernandez Acuña JM, Noferi LN, Tosi EJ, Manzano DC, et al. Drug-Induced Hepatotoxicity. ECGDS 2017;2:440-443.
  • David S, Hamilton JP. Drug-induced Liver Injury. US Gastroenterol Hepatol Rev 2010; 6:73-80.
  • 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.
  • Bruniera FR, Ferreira FM, Savioli LR, Bacci MR, Feder D, Pereira EC, et al. Endothelial, renal and hepatic variables in wistar rats treated with vancomycin. An Acad Bras Cienc 2014;86:1963-1972.
  • Uckun Z, Guzel S, Canacankatan N, Yalaza C, Kibar D, Coskun Yilmaz B. Potential protective effects of naringenin against vancomycin-induced nephrotoxicity via reduction on apoptotic and oxidative stress markers in rats. Drug Chem Toxicol 2020;43(1):104-111.
  • Sahin M, Cam H, Olgar S, Tunc SE, Arslan C, Uz E, et al. Protective role of erdosteine on vancomycin-induced oxidative stress in rat liver. Mol Cell Biochem 2006;291:155-160.
  • Cano A, Cifuentes L, Amariles P. Structured Literature Review of Hepatic Toxicity Caused by Medicines. Rev Colomb Gastroenterol 2017;32(4):337-348.
  • Li S, Tan HY, Wang N, Zhang ZJ, Lao L, Wong CW, et al. The Role of Oxidative Stress and Antioxidants in Liver Diseases. Int J Mol Sci 2015;16:26087-26124.
  • Wang C, Fan RQ, Zhang YX, Nie H, Li K. Naringenin protects against isoniazid-and rifampicin-induced apoptosis in hepatic injury. World J Gastroenterol 2016;22:9775-9783.
  • Renugadevi J, Prabu SM. Cadmium-induced hepatotoxicity in rats and the protective effect of naringenin. Exp Toxicol Pathol 2010;62:171-181.
  • Jayaraman J, Namasivayam N. Naringenin modulates circulatory lipid peroxidation, anti-oxidant status and hepatic alcohol metabolizing enzymes in rats with ethanol induced liver injury. Fundam Clin Pharmacol 2011;25:682-689.
  • Hernández-Aquino E, Muriel P. Beneficial effects of naringenin in liver diseases: Molecular mechanisms. World J Gastroenterol 2018; 24:1679-1707.
  • Esmaeili MA, Alilou M. Naringenin attenuates CCl4 -induced hepatic inflammation by the activation of an Nrf2-mediated pathway in rats. Clin Exp Pharmacol Physiol 2014; 41:416-422.
  • Mershiba SD, Dassprakash MV, Saraswathy SD. Protective effect of naringenin on hepatic and renal dysfunction and oxidative stress in arsenic intoxicated rats. Mol Biol Rep 2013; 40:3681-3691.
  • Wang J, Yang Z, Lin L, Zhao Z, Liu Z, Liu X. Protective effect of naringenin against lead-induced oxidative stress in rats. Biol Trace Elem Res 2012;146:354-359.
  • Lv Y, Zhang B, Xing G, Wang F, Hu Z. Protective effect of naringenin against acetaminophen-induced acute liver injury in metallothionein (MT)-null mice. Food Funct 2013;4:297-302.
  • Fouad AA, Albuali WH, Zahran A, Gomaa W. Protective effect of naringenin against gentamicin-induced nephrotoxicity in rats. Environ Toxicol Pharmacol 2014;38:420-429.
  • Gnanasoundari M, Pari L. Impact of naringenin on oxytetracycline-mediated oxidative damage in kidney of rats. Ren Fail 2006;28:599-605.
  • 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.
  • Nishino Y, Takemura S, Minamiyama Y, Hirohashi K, Tanaka H, Inoue M, et al. Inhibition of vancomycin-induced nephrotoxicity by targeting superoxide dismutase to renal proximal tubule cells in the rat. Redox Rep 2002;7:317-319.
  • Sahu BD, Tatireddy S, Koneru M, Borkar RM, Kumar JM, Kuncha M, et al. Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction, apoptosis and inflammation in rats: Possible mechanism of nephroprotection. Toxicol Appl Pharmacol 2014;277:8-20.
  • Guzel S, Uckun Sahinogullari Z, Canacankatan N, Antmen SE, Kibar D, Bayrak G. The ameliorating effect of silymarin against vancomycin-induced apoptosis and inflammation in rat liver. J Res Pharm 2019;23:719-728.
  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem 1951;193:265-275.
  • Guicciardi ME, Malhi H, Mott JL, Gores GJ. Apoptosis and necrosis in the liver. Compr Physiol 2013;3:977-1010.
  • Sak K. Cytotoxicity of dietary flavonoids on different human cancer types. Pharmacogn Rev 2014;8:122-146.
  • Brenner C, Galluzzi L, Kepp O, Kroemer G. Decoding cell death signals in liver inflammation. J Hepatol 2013;59:583-594.
  • Chtourou Y, Fetoui H, Jemai R, Ben Slima A, Makni M, Gdoura R. Naringenin reduces cholesterol-induced hepatic inflammation in rats by modulating matrix metalloproteinases-2, 9 via inhibition of nuclear factor κB pathway. Eur J Pharmacol 2015;746:96-105.
  • Dou W, Zhang J, Sun A, Zhang E, Ding L, Mukherjee S, et al. Protective effect of naringenin against experimental colitis via suppression of Toll-like receptor 4/NF-κB signalling. Br J Nutr 2013;110: 599–608.
  • Aristatile B, Al-Assaf AH, Pugalendi KV. Carvacrol suppresses the expression of inflammatory marker genes in D-galactosamine-hepatotoxic rats. Asian Pac J Trop Med 2013;6(3):205-211.
  • Martín-Sanz P, Casado M, Boscá L. Cyclooxygenase 2 in liver dysfunction and carcinogenesis: Facts and perspectives. World J Gastroenterol 2017;23:3572-3580.
  • Jayaraman J, Jesudoss VA, Menon VP, Namasivayam N. Anti-inflammatory role of naringenin in rats with ethanol induced liver injury. Toxicol Mech Methods 2012; 22:568–576.
  • Dong D, Xu L, Yin L, Qi Y, Peng J. Naringin prevents carbon tetrachloride-induced acute liver injury in mice. J Funct Foods 2015;12:179-191.
  • Reinders ME, Sho M, Izawa A, Wang P, Mukhopadhyay D, Koss KE, et al. Proinflammatory functions of vascular endothelial growth factor in alloimmunity. J Clin Invest 2003; 112:1655-1665.
  • Chen HJ, Hu MH, Xu FG, Xu HJ, She JJ, Xia HP. Understanding the inflammation-cancer transformation in the development of primary liver cancer. Hepatoma Res 2018;4:29.
  • Cao L, Quan XB, Zeng WJ, Yang XO, Wang MJ. Mechanism of Hepatocyte Apoptosis. J Cell Death 2016;9:19-29.
  • Subramanian P, Arul D. Attenuation of NDEA-induced hepatocarcinogenesis by naringenin in rats. Cell Biochem Funct 2013;31:511-517.
  • Hernández-Aquino E, Zarco N, Casas-Grajales S, Ramos-Tovar E, Flores-Beltrán RE, Arauz J, et al. Naringenin prevents experimental liver fibrosis by blocking TGFβ-Smad3 and JNK-Smad3 pathways. World J Gastroenterol 2017;23:4354-4368.
  • Yilma AN, Singh SR, Morici L, Dennis VA. Flavonoid naringenin: a potential immunomodulatory for Chlamydia trachomatis inflammation. Mediators Inflamm 2013; 2013:102457.
  • Del Campo JA, Gallego P, Grande L. Role of inflammatory response in liver diseases: Therapeutic strategies. World J Hepatol 2018;10:1-7.
  • Azam S, Jakaria M, Kim IS, Kim IS, Kim J, Haque ME, et al. Regulation of Toll-Like Receptor (TLR) Signaling Pathway by Polyphenols inthe Treatment of Age-Linked Neurodege- nerative Diseases: Focus on TLR4 Signaling. Front Immunol 2019;10:1000.
  • Humanes B, Jado JC, Camaño S, López-Parra V, Torres AM, Álvarez-Sala LA, et al. Protective effects of cilastatin against vancomycin-induced nephrotoxicity. Biomed Res Int 2015;704382.
  • Gupta A, Biyani M, Khaira A. Vancomycin nephrotoxicity: myths and facts. Neth J Med 2011;69:379-383.
  • Chen Y, Yang XY, Zeckel M, Killian C, Hornbuckle K, Regev A, Voss S. Risk of hepatic events in patients treated with vancomycin in clinical studies: a systematic review and meta-analysis. Drug Saf 2011;34:73-82.

Naringenin Reduces Hepatic Inflammation and Apoptosis Induced by Vancomycin in Rats

Year 2021, Volume: 11 Issue: 2, 191 - 198, 30.06.2021
https://doi.org/10.33808/clinexphealthsci.741916

Abstract

Objective: This investigation aimed to detect the possible protective impacts of naringenin (NAR) on vancomycin (VCM)-induced liver toxicity through measuring caspase-3, -8 and -9 activities as markers of apoptosis and the levels of tumor necrosis factor-alpha, cyclooxygenase-2 and vascular endothelial growth factor as inflammation markers and assessing the histopathological alterations in rats.



Methods:
The rats were allocated into seven groups as, the control group (saline, intraperitoneally (i.p.)), VCM group (400 mg/kg/day, i.p.), Carboxymethyl cellulose group (0.5% CMC, orally), NAR100 group (100 mg/kg/day, orally), VCM+NAR25 group (25 mg/kg/day, orally), VCM+NAR50 group (50 mg/kg/day, orally), VCM+NAR100 group (100 mg/kg/day, orally). The caspase enzyme activities and inflammation markers were measured using colorimetric methods and ELISA, respectively. Histopathological examinations were performed.



Results:
The caspase activities and levels of inflammation markers were significantly higher in the VCM group as opposed to the other groups. The caspase activities were significantly ameliorated in the VCM+NAR25 group compared to the VCM+NAR50 and VCM+NAR100 groups, but the levels of inflammation markers were significantly attenuated in VCM+NAR50 group and, especially, VCM+NAR100 group compared to VCM+NAR25 group.



Conclusion:
NAR has potential protective impact on liver injury caused by VCM, and the protective impacts of NAR at distinct doses may occur via different molecular mechanisms.

Project Number

This study was supported by the Research Fund of Mersin University in Turkey with Project Number 2016-2-AP3-1906.

References

  • Ponte ML, Flores Lazdin C, Fernandez Acuña JM, Noferi LN, Tosi EJ, Manzano DC, et al. Drug-Induced Hepatotoxicity. ECGDS 2017;2:440-443.
  • David S, Hamilton JP. Drug-induced Liver Injury. US Gastroenterol Hepatol Rev 2010; 6:73-80.
  • 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.
  • Bruniera FR, Ferreira FM, Savioli LR, Bacci MR, Feder D, Pereira EC, et al. Endothelial, renal and hepatic variables in wistar rats treated with vancomycin. An Acad Bras Cienc 2014;86:1963-1972.
  • Uckun Z, Guzel S, Canacankatan N, Yalaza C, Kibar D, Coskun Yilmaz B. Potential protective effects of naringenin against vancomycin-induced nephrotoxicity via reduction on apoptotic and oxidative stress markers in rats. Drug Chem Toxicol 2020;43(1):104-111.
  • Sahin M, Cam H, Olgar S, Tunc SE, Arslan C, Uz E, et al. Protective role of erdosteine on vancomycin-induced oxidative stress in rat liver. Mol Cell Biochem 2006;291:155-160.
  • Cano A, Cifuentes L, Amariles P. Structured Literature Review of Hepatic Toxicity Caused by Medicines. Rev Colomb Gastroenterol 2017;32(4):337-348.
  • Li S, Tan HY, Wang N, Zhang ZJ, Lao L, Wong CW, et al. The Role of Oxidative Stress and Antioxidants in Liver Diseases. Int J Mol Sci 2015;16:26087-26124.
  • Wang C, Fan RQ, Zhang YX, Nie H, Li K. Naringenin protects against isoniazid-and rifampicin-induced apoptosis in hepatic injury. World J Gastroenterol 2016;22:9775-9783.
  • Renugadevi J, Prabu SM. Cadmium-induced hepatotoxicity in rats and the protective effect of naringenin. Exp Toxicol Pathol 2010;62:171-181.
  • Jayaraman J, Namasivayam N. Naringenin modulates circulatory lipid peroxidation, anti-oxidant status and hepatic alcohol metabolizing enzymes in rats with ethanol induced liver injury. Fundam Clin Pharmacol 2011;25:682-689.
  • Hernández-Aquino E, Muriel P. Beneficial effects of naringenin in liver diseases: Molecular mechanisms. World J Gastroenterol 2018; 24:1679-1707.
  • Esmaeili MA, Alilou M. Naringenin attenuates CCl4 -induced hepatic inflammation by the activation of an Nrf2-mediated pathway in rats. Clin Exp Pharmacol Physiol 2014; 41:416-422.
  • Mershiba SD, Dassprakash MV, Saraswathy SD. Protective effect of naringenin on hepatic and renal dysfunction and oxidative stress in arsenic intoxicated rats. Mol Biol Rep 2013; 40:3681-3691.
  • Wang J, Yang Z, Lin L, Zhao Z, Liu Z, Liu X. Protective effect of naringenin against lead-induced oxidative stress in rats. Biol Trace Elem Res 2012;146:354-359.
  • Lv Y, Zhang B, Xing G, Wang F, Hu Z. Protective effect of naringenin against acetaminophen-induced acute liver injury in metallothionein (MT)-null mice. Food Funct 2013;4:297-302.
  • Fouad AA, Albuali WH, Zahran A, Gomaa W. Protective effect of naringenin against gentamicin-induced nephrotoxicity in rats. Environ Toxicol Pharmacol 2014;38:420-429.
  • Gnanasoundari M, Pari L. Impact of naringenin on oxytetracycline-mediated oxidative damage in kidney of rats. Ren Fail 2006;28:599-605.
  • 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.
  • Nishino Y, Takemura S, Minamiyama Y, Hirohashi K, Tanaka H, Inoue M, et al. Inhibition of vancomycin-induced nephrotoxicity by targeting superoxide dismutase to renal proximal tubule cells in the rat. Redox Rep 2002;7:317-319.
  • Sahu BD, Tatireddy S, Koneru M, Borkar RM, Kumar JM, Kuncha M, et al. Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction, apoptosis and inflammation in rats: Possible mechanism of nephroprotection. Toxicol Appl Pharmacol 2014;277:8-20.
  • Guzel S, Uckun Sahinogullari Z, Canacankatan N, Antmen SE, Kibar D, Bayrak G. The ameliorating effect of silymarin against vancomycin-induced apoptosis and inflammation in rat liver. J Res Pharm 2019;23:719-728.
  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem 1951;193:265-275.
  • Guicciardi ME, Malhi H, Mott JL, Gores GJ. Apoptosis and necrosis in the liver. Compr Physiol 2013;3:977-1010.
  • Sak K. Cytotoxicity of dietary flavonoids on different human cancer types. Pharmacogn Rev 2014;8:122-146.
  • Brenner C, Galluzzi L, Kepp O, Kroemer G. Decoding cell death signals in liver inflammation. J Hepatol 2013;59:583-594.
  • Chtourou Y, Fetoui H, Jemai R, Ben Slima A, Makni M, Gdoura R. Naringenin reduces cholesterol-induced hepatic inflammation in rats by modulating matrix metalloproteinases-2, 9 via inhibition of nuclear factor κB pathway. Eur J Pharmacol 2015;746:96-105.
  • Dou W, Zhang J, Sun A, Zhang E, Ding L, Mukherjee S, et al. Protective effect of naringenin against experimental colitis via suppression of Toll-like receptor 4/NF-κB signalling. Br J Nutr 2013;110: 599–608.
  • Aristatile B, Al-Assaf AH, Pugalendi KV. Carvacrol suppresses the expression of inflammatory marker genes in D-galactosamine-hepatotoxic rats. Asian Pac J Trop Med 2013;6(3):205-211.
  • Martín-Sanz P, Casado M, Boscá L. Cyclooxygenase 2 in liver dysfunction and carcinogenesis: Facts and perspectives. World J Gastroenterol 2017;23:3572-3580.
  • Jayaraman J, Jesudoss VA, Menon VP, Namasivayam N. Anti-inflammatory role of naringenin in rats with ethanol induced liver injury. Toxicol Mech Methods 2012; 22:568–576.
  • Dong D, Xu L, Yin L, Qi Y, Peng J. Naringin prevents carbon tetrachloride-induced acute liver injury in mice. J Funct Foods 2015;12:179-191.
  • Reinders ME, Sho M, Izawa A, Wang P, Mukhopadhyay D, Koss KE, et al. Proinflammatory functions of vascular endothelial growth factor in alloimmunity. J Clin Invest 2003; 112:1655-1665.
  • Chen HJ, Hu MH, Xu FG, Xu HJ, She JJ, Xia HP. Understanding the inflammation-cancer transformation in the development of primary liver cancer. Hepatoma Res 2018;4:29.
  • Cao L, Quan XB, Zeng WJ, Yang XO, Wang MJ. Mechanism of Hepatocyte Apoptosis. J Cell Death 2016;9:19-29.
  • Subramanian P, Arul D. Attenuation of NDEA-induced hepatocarcinogenesis by naringenin in rats. Cell Biochem Funct 2013;31:511-517.
  • Hernández-Aquino E, Zarco N, Casas-Grajales S, Ramos-Tovar E, Flores-Beltrán RE, Arauz J, et al. Naringenin prevents experimental liver fibrosis by blocking TGFβ-Smad3 and JNK-Smad3 pathways. World J Gastroenterol 2017;23:4354-4368.
  • Yilma AN, Singh SR, Morici L, Dennis VA. Flavonoid naringenin: a potential immunomodulatory for Chlamydia trachomatis inflammation. Mediators Inflamm 2013; 2013:102457.
  • Del Campo JA, Gallego P, Grande L. Role of inflammatory response in liver diseases: Therapeutic strategies. World J Hepatol 2018;10:1-7.
  • Azam S, Jakaria M, Kim IS, Kim IS, Kim J, Haque ME, et al. Regulation of Toll-Like Receptor (TLR) Signaling Pathway by Polyphenols inthe Treatment of Age-Linked Neurodege- nerative Diseases: Focus on TLR4 Signaling. Front Immunol 2019;10:1000.
  • Humanes B, Jado JC, Camaño S, López-Parra V, Torres AM, Álvarez-Sala LA, et al. Protective effects of cilastatin against vancomycin-induced nephrotoxicity. Biomed Res Int 2015;704382.
  • Gupta A, Biyani M, Khaira A. Vancomycin nephrotoxicity: myths and facts. Neth J Med 2011;69:379-383.
  • Chen Y, Yang XY, Zeckel M, Killian C, Hornbuckle K, Regev A, Voss S. Risk of hepatic events in patients treated with vancomycin in clinical studies: a systematic review and meta-analysis. Drug Saf 2011;34:73-82.
There are 43 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Articles
Authors

Zuhal Uçkun Şahinoğulları 0000-0002-3244-4103

Sevda Güzel 0000-0002-6642-5824

Necmiye Canacankatan 0000-0003-3863-962X

Cem Yalaza 0000-0002-9073-5611

Deniz Kibar This is me 0000-0001-7114-6021

Gulsen Bayrak This is me 0000-0002-1397-7203

Project Number This study was supported by the Research Fund of Mersin University in Turkey with Project Number 2016-2-AP3-1906.
Publication Date June 30, 2021
Submission Date May 31, 2020
Published in Issue Year 2021 Volume: 11 Issue: 2

Cite

APA Uçkun Şahinoğulları, Z., Güzel, S., Canacankatan, N., Yalaza, C., et al. (2021). Naringenin Reduces Hepatic Inflammation and Apoptosis Induced by Vancomycin in Rats. Clinical and Experimental Health Sciences, 11(2), 191-198. https://doi.org/10.33808/clinexphealthsci.741916
AMA Uçkun Şahinoğulları Z, Güzel S, Canacankatan N, Yalaza C, Kibar D, Bayrak G. Naringenin Reduces Hepatic Inflammation and Apoptosis Induced by Vancomycin in Rats. Clinical and Experimental Health Sciences. June 2021;11(2):191-198. doi:10.33808/clinexphealthsci.741916
Chicago Uçkun Şahinoğulları, Zuhal, Sevda Güzel, Necmiye Canacankatan, Cem Yalaza, Deniz Kibar, and Gulsen Bayrak. “Naringenin Reduces Hepatic Inflammation and Apoptosis Induced by Vancomycin in Rats”. Clinical and Experimental Health Sciences 11, no. 2 (June 2021): 191-98. https://doi.org/10.33808/clinexphealthsci.741916.
EndNote Uçkun Şahinoğulları Z, Güzel S, Canacankatan N, Yalaza C, Kibar D, Bayrak G (June 1, 2021) Naringenin Reduces Hepatic Inflammation and Apoptosis Induced by Vancomycin in Rats. Clinical and Experimental Health Sciences 11 2 191–198.
IEEE Z. Uçkun Şahinoğulları, S. Güzel, N. Canacankatan, C. Yalaza, D. Kibar, and G. Bayrak, “Naringenin Reduces Hepatic Inflammation and Apoptosis Induced by Vancomycin in Rats”, Clinical and Experimental Health Sciences, vol. 11, no. 2, pp. 191–198, 2021, doi: 10.33808/clinexphealthsci.741916.
ISNAD Uçkun Şahinoğulları, Zuhal et al. “Naringenin Reduces Hepatic Inflammation and Apoptosis Induced by Vancomycin in Rats”. Clinical and Experimental Health Sciences 11/2 (June 2021), 191-198. https://doi.org/10.33808/clinexphealthsci.741916.
JAMA Uçkun Şahinoğulları Z, Güzel S, Canacankatan N, Yalaza C, Kibar D, Bayrak G. Naringenin Reduces Hepatic Inflammation and Apoptosis Induced by Vancomycin in Rats. Clinical and Experimental Health Sciences. 2021;11:191–198.
MLA Uçkun Şahinoğulları, Zuhal et al. “Naringenin Reduces Hepatic Inflammation and Apoptosis Induced by Vancomycin in Rats”. Clinical and Experimental Health Sciences, vol. 11, no. 2, 2021, pp. 191-8, doi:10.33808/clinexphealthsci.741916.
Vancouver Uçkun Şahinoğulları Z, Güzel S, Canacankatan N, Yalaza C, Kibar D, Bayrak G. Naringenin Reduces Hepatic Inflammation and Apoptosis Induced by Vancomycin in Rats. Clinical and Experimental Health Sciences. 2021;11(2):191-8.

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