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Year 2020, Volume: 24 Issue: 5, 640 - 647, 27.06.2025

Tarık Şener , Selin Çadirci Ozge Cevik , Şerif Ercan , Mustafa Kutay Koroglu , Selin Şakarcan Göksel Şener

https://doi.org/10.35333/jrp.2020.219

Abstract

References

  • [1] Rosenberg B. Fundamental studies with cisplatin. Cancer. 1985; 55(10): 2303-23l6. [CrossRef]
  • [2] Florea AM, Büsselberg D. Cisplatin as an anti-tumor drug: cellular mechanisms of activity, drug resistance and induced side effects. Cancers (Basel). 2011; 3(1): 1351–1371. [CrossRef]
  • [3] Dos Santos NA, Carvalho Rodrigues MA, Martins NM, dos Santos AC. Cisplatin-induced nephrotoxicity and targets of nephroprotection: an update. Arch Toxicol. 2012; 86: 1233-1250. [CrossRef]
  • [4] Deavall DG, Martin EA, Horner JM, Roberts R. Drug-induced oxidative stress and toxicity. J Toxicol. 2012; 2012: 645460. [CrossRef]
  • [5] Marullo R, Werner E, Degtyareva N, Moore B, Altavilla G, Ramalingam SS, Doetsch PW. Cisplatin induces a mitochondrial-ROS response that contributes to cytotoxicity depending on mitochondrial redox status and bioenergetic functions. PLoS ONE. 2013; 8(11): e81162. [CrossRef]
  • [6] Yu W, Chen Y, Dubrulle J, Stossi F, Putluri V, Sreekumar A, Putluri N, Baluya D, Lai SY, Sandulache VC. Cisplatin generates oxidative stress which is accompanied by rapid shifts in central carbon metabolism. Sci Rep. 2018; 8(1): 4306. [CrossRef]
  • [7] Chirino YI, Pedraza-Chaverri J. Role of oxidative and nitrosative stress in cisplatin-induced nephrotoxicity. Exp Toxicol Pathol. 2009; 61(3): 223-42. [CrossRef]
  • [8] Erlund I. Review of the flavonoids quercetin, hesperetin, and naringenin. Dietary sources, bioactivities, bioavailability, and epidemiology. Nutrition Res. 2004; 24: 851-874. [CrossRef]
  • [9] Anand David AV, Arulmoli R, Parasuraman S. Overviews of biological importance of quercetin: A bioactive flavonoid. Pharmacogn Rev. 2016; 10(20): 84-89. [CrossRef]
  • [10] Materska M. Quercetin and its derivatives: chemical structure and bioactivity. Pol J Food Nutr Sci. 2008; 58(4): 407- 13.
  • [11] Kuhlmann MK, Burkhardt G, Köhler H. Insights into potential cellular mechanisms of cisplatin nephrotoxicity and their clinical application. Nephrol Dial Transplant. 1997; 12(12): 2478-80. [CrossRef]
  • [12] Peres LA, da Cunha AD. Acute nephrotoxicity of cisplatin molecular mechanisms. Jr. J Bras Nefrol. 2013; 35(4): 332- 40. [CrossRef]
  • [13] Hanigan MH, Devarajan P. Cisplatin nephrotoxicity: molecular mechanisms. Cancer Ther. 2003; 1: 47-61.
  • [14] Sánchez-González PD, López-Hernández FJ, López-Novoa JM, Morales AI. An integrative view of the pathophysiological events leading to cisplatin nephrotoxicity. Crit Rev Toxicol. 2011; 41: 803-821. [CrossRef]
  • [15] Lien Ai Pham-Huy, Hua He, Chuong Pham-Huy. Free Radicals, Antioxidants in Disease and Health. Int J Biomed Sci. 2008; 4(2): 89–96.
  • [16] Knight JA. Review: Free radicals, antioxidants, and the immune system. Ann Clin Lab Sci. 2000; 30(2): 145-158.
  • [17] Sener G, Satiroglu H, Kabasakal L, Arbak S, Oner S, Ercan F, Keyer-Uysal M. The protective effect of melatonin on cisplatin nephrotoxicity. Fundam Clin Pharmacol. 2000; 14(6): 553-560. [CrossRef]
  • [18] El-Gizawy MM, Hosny EN, Mourad HH, Abd-El Razik AN. Curcumin nanoparticles ameliorate hepatotoxicity and nephrotoxicity induced by cisplatin in rats Naunyn Schmiedebergs Arch Pharmacol. 2020; 393(10): 1941-1953. [CrossRef]
  • [19] Malik S, Bhatia J, Suchal K, Gamad N, Dinda AK, Gupta YK, Arya DS. Nobiletin ameliorates cisplatin-induced acute kidney injury due to its anti-oxidant, anti-inflammatory and anti-apoptotic effects. Exp Toxicol Pathol. 2015; 67(7-8): 427-433. [CrossRef]
  • [20] Zhao YM, Gao LP, Zhang HL, Guo JX, Guo PP. Grape seed proanthocyanidin extract prevents DDP-induced testicular toxicity in rats. Food Funct. 2014; 5(3): 605-611. [CrossRef]
  • [21] Salem EA, Salem NA, Maarouf AM, Serefoglu EC, Hellstrom WJ. Selenium and lycopene attenuate cisplatin-induced testicular toxicity associated with oxidative stress in Wistar rats. Urology. 2012; 79(5): 1184.e1-6. [CrossRef]
  • [22] Almaghrabi OA. Molecular and biochemical investigations on the effect of quercetin on oxidative stress induced by cisplatin in rat kidney. Saudi J Biol Sci. 2015; 22(2): 227-231. [CrossRef]
  • [23] Elbe H, Esrefoglu M, Vardi N, Taslidere E, Ozerol E, Tanbek K. Melatonin, quercetin and resveratrol attenuates oxidative hepatocellular injury in streptozotocin-induced diabetic rats. Hum Exp Toxicol. 2015; 34(9): 859-868. [CrossRef]
  • [24] Cui L, Li Z, Chang X, Cong G, Hao L. Quercetin attenuates vascular calcification by inhibiting oxidative stress and mitochondrial fission. Vascul Pharmacol. 2017; 88: 21-29. [CrossRef]
  • [25] Park DJ, Jeon S-J, Kang J-B, Koh PO. Quercetin Reduces Ischemic Brain Injury by Preventing Ischemia-induced Decreases in the Neuronal Calcium Sensor Protein Hippocalcin. Neuroscience. 2020; 430: 47-62. [CrossRef]
  • [26] El-Far AH, Lebda MA, Noreldin AE, Atta MS, Elewa YHA, Elfeky M, Mousa SA. Quercetin Attenuates Pancreatic and Renal D-Galactose-Induced Aging-Related Oxidative Alterations in Rats. Int J Mol Sci. 2020; 21(12): 4348. [CrossRef]
  • [27] Chen X, Peng X, Luo Y, You J, Yin D, Xu Q, He H, He M. Quercetin protects cardiomyocytes against doxorubicininduced toxicity by suppressing oxidative stress and improving mitochondrial function via 14-3-3γ. Toxicol Mech Methods. 2019; 29(5): 344-354. [CrossRef]
  • [28] Tsuji T, Kato A, Yasuda H, Miyaji T, Luo J, Sakao Y, Ito H, Fujigaki Y, Hishida A.The dimethylthiourea-induced attenuation of cisplatin nephrotoxicity is associated with the augmented induction of heat shock proteins. Toxicol Appl Pharmacol. 2009; 234(2): 202-208. [CrossRef]
  • [29] Cevik O, Erşahin M, Sener TE, Tinay İ, Tarcan T, Çetinel Ş, Şener A, Toklu HZ, Şener G. Beneficial effects of quercetin on rat urinary bladder after spinal cord injury. J Surg Res. 2013; 183(2): 695-703. [CrossRef]
  • [30] Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol. 1978; 52: 302-310. [CrossRef]
  • [31] Beutler E. Glutathione in red blood cell metabolism. A manual of biochemical methods. New York: Grune and Stratton; 1975. pp. 112-114.
  • [32] Bradford, M., 1976. A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding. Analytical Biochem. 72(1-2), pp. 248-254. [CrossRef]

Protective effects of quercetin against cisplatin induced urogenital organ toxicity

Year 2020, Volume: 24 Issue: 5, 640 - 647, 27.06.2025

Tarık Şener , Selin Çadirci Ozge Cevik , Şerif Ercan , Mustafa Kutay Koroglu , Selin Şakarcan Göksel Şener

https://doi.org/10.35333/jrp.2020.219

Abstract

Cisplatin is a chemotherapeutic agent that is the first to enter treatment from organic platinum-derived drugs. Nephrotoxicity and cytotoxicity are major factors that limit its use. The aim of the study is to investigate the possible protective effects of quercetin against cisplatin-induced urogenital organ toxicity. In our study, Sprague Dawley four month old male rats were divided into 4 groups; control + saline (SF), control + quercetin (20 mg/kg for 21 days), cisplatin (7 mg/kg as a single dose) + SF and cisplatin + quercetin groups. After decapitation, the kidney, bladder, testis and corpus cavernosum tissue samples were taken to analyze caspase-3, an index of apoptosis, and oxidative stress parameters such as malondialdehyde (MDA), gluta-thione (GSH), and 8-hydroxy-2' -deoxyguanosine (8-OHdG). Furthermore, tissues were also examined histologically. Cisplatin caused significant increases in MDA and 8-OHdG levels, demonstrating increases in lipid peroxidation and oxidative DNA damage, respectively, in all tissues. In parallel with the oxidant stress increase, the endogenous strong antioxidant GSH levels were decreased. Caspase activity and caspase 3 expressions, which we measured as an indicator of apoptosis, increased significantly with cisplatin treatment. On the other hand, treatment with quercetin, a powerful antioxidant flavonoid, reversed these changes. Histological findings also demonstrated well-preserved tissues due to quercetin treatment. In conclusion, our results suggested that quercetin, when given with cisplatin, can be protective against the chemotherapeutic induced toxicity and thus provide therapeutic benefit.

Keywords

Cisplatin oxidative stress quercetin bladder kidney testis corpus cavernosum

References

  • [1] Rosenberg B. Fundamental studies with cisplatin. Cancer. 1985; 55(10): 2303-23l6. [CrossRef]
  • [2] Florea AM, Büsselberg D. Cisplatin as an anti-tumor drug: cellular mechanisms of activity, drug resistance and induced side effects. Cancers (Basel). 2011; 3(1): 1351–1371. [CrossRef]
  • [3] Dos Santos NA, Carvalho Rodrigues MA, Martins NM, dos Santos AC. Cisplatin-induced nephrotoxicity and targets of nephroprotection: an update. Arch Toxicol. 2012; 86: 1233-1250. [CrossRef]
  • [4] Deavall DG, Martin EA, Horner JM, Roberts R. Drug-induced oxidative stress and toxicity. J Toxicol. 2012; 2012: 645460. [CrossRef]
  • [5] Marullo R, Werner E, Degtyareva N, Moore B, Altavilla G, Ramalingam SS, Doetsch PW. Cisplatin induces a mitochondrial-ROS response that contributes to cytotoxicity depending on mitochondrial redox status and bioenergetic functions. PLoS ONE. 2013; 8(11): e81162. [CrossRef]
  • [6] Yu W, Chen Y, Dubrulle J, Stossi F, Putluri V, Sreekumar A, Putluri N, Baluya D, Lai SY, Sandulache VC. Cisplatin generates oxidative stress which is accompanied by rapid shifts in central carbon metabolism. Sci Rep. 2018; 8(1): 4306. [CrossRef]
  • [7] Chirino YI, Pedraza-Chaverri J. Role of oxidative and nitrosative stress in cisplatin-induced nephrotoxicity. Exp Toxicol Pathol. 2009; 61(3): 223-42. [CrossRef]
  • [8] Erlund I. Review of the flavonoids quercetin, hesperetin, and naringenin. Dietary sources, bioactivities, bioavailability, and epidemiology. Nutrition Res. 2004; 24: 851-874. [CrossRef]
  • [9] Anand David AV, Arulmoli R, Parasuraman S. Overviews of biological importance of quercetin: A bioactive flavonoid. Pharmacogn Rev. 2016; 10(20): 84-89. [CrossRef]
  • [10] Materska M. Quercetin and its derivatives: chemical structure and bioactivity. Pol J Food Nutr Sci. 2008; 58(4): 407- 13.
  • [11] Kuhlmann MK, Burkhardt G, Köhler H. Insights into potential cellular mechanisms of cisplatin nephrotoxicity and their clinical application. Nephrol Dial Transplant. 1997; 12(12): 2478-80. [CrossRef]
  • [12] Peres LA, da Cunha AD. Acute nephrotoxicity of cisplatin molecular mechanisms. Jr. J Bras Nefrol. 2013; 35(4): 332- 40. [CrossRef]
  • [13] Hanigan MH, Devarajan P. Cisplatin nephrotoxicity: molecular mechanisms. Cancer Ther. 2003; 1: 47-61.
  • [14] Sánchez-González PD, López-Hernández FJ, López-Novoa JM, Morales AI. An integrative view of the pathophysiological events leading to cisplatin nephrotoxicity. Crit Rev Toxicol. 2011; 41: 803-821. [CrossRef]
  • [15] Lien Ai Pham-Huy, Hua He, Chuong Pham-Huy. Free Radicals, Antioxidants in Disease and Health. Int J Biomed Sci. 2008; 4(2): 89–96.
  • [16] Knight JA. Review: Free radicals, antioxidants, and the immune system. Ann Clin Lab Sci. 2000; 30(2): 145-158.
  • [17] Sener G, Satiroglu H, Kabasakal L, Arbak S, Oner S, Ercan F, Keyer-Uysal M. The protective effect of melatonin on cisplatin nephrotoxicity. Fundam Clin Pharmacol. 2000; 14(6): 553-560. [CrossRef]
  • [18] El-Gizawy MM, Hosny EN, Mourad HH, Abd-El Razik AN. Curcumin nanoparticles ameliorate hepatotoxicity and nephrotoxicity induced by cisplatin in rats Naunyn Schmiedebergs Arch Pharmacol. 2020; 393(10): 1941-1953. [CrossRef]
  • [19] Malik S, Bhatia J, Suchal K, Gamad N, Dinda AK, Gupta YK, Arya DS. Nobiletin ameliorates cisplatin-induced acute kidney injury due to its anti-oxidant, anti-inflammatory and anti-apoptotic effects. Exp Toxicol Pathol. 2015; 67(7-8): 427-433. [CrossRef]
  • [20] Zhao YM, Gao LP, Zhang HL, Guo JX, Guo PP. Grape seed proanthocyanidin extract prevents DDP-induced testicular toxicity in rats. Food Funct. 2014; 5(3): 605-611. [CrossRef]
  • [21] Salem EA, Salem NA, Maarouf AM, Serefoglu EC, Hellstrom WJ. Selenium and lycopene attenuate cisplatin-induced testicular toxicity associated with oxidative stress in Wistar rats. Urology. 2012; 79(5): 1184.e1-6. [CrossRef]
  • [22] Almaghrabi OA. Molecular and biochemical investigations on the effect of quercetin on oxidative stress induced by cisplatin in rat kidney. Saudi J Biol Sci. 2015; 22(2): 227-231. [CrossRef]
  • [23] Elbe H, Esrefoglu M, Vardi N, Taslidere E, Ozerol E, Tanbek K. Melatonin, quercetin and resveratrol attenuates oxidative hepatocellular injury in streptozotocin-induced diabetic rats. Hum Exp Toxicol. 2015; 34(9): 859-868. [CrossRef]
  • [24] Cui L, Li Z, Chang X, Cong G, Hao L. Quercetin attenuates vascular calcification by inhibiting oxidative stress and mitochondrial fission. Vascul Pharmacol. 2017; 88: 21-29. [CrossRef]
  • [25] Park DJ, Jeon S-J, Kang J-B, Koh PO. Quercetin Reduces Ischemic Brain Injury by Preventing Ischemia-induced Decreases in the Neuronal Calcium Sensor Protein Hippocalcin. Neuroscience. 2020; 430: 47-62. [CrossRef]
  • [26] El-Far AH, Lebda MA, Noreldin AE, Atta MS, Elewa YHA, Elfeky M, Mousa SA. Quercetin Attenuates Pancreatic and Renal D-Galactose-Induced Aging-Related Oxidative Alterations in Rats. Int J Mol Sci. 2020; 21(12): 4348. [CrossRef]
  • [27] Chen X, Peng X, Luo Y, You J, Yin D, Xu Q, He H, He M. Quercetin protects cardiomyocytes against doxorubicininduced toxicity by suppressing oxidative stress and improving mitochondrial function via 14-3-3γ. Toxicol Mech Methods. 2019; 29(5): 344-354. [CrossRef]
  • [28] Tsuji T, Kato A, Yasuda H, Miyaji T, Luo J, Sakao Y, Ito H, Fujigaki Y, Hishida A.The dimethylthiourea-induced attenuation of cisplatin nephrotoxicity is associated with the augmented induction of heat shock proteins. Toxicol Appl Pharmacol. 2009; 234(2): 202-208. [CrossRef]
  • [29] Cevik O, Erşahin M, Sener TE, Tinay İ, Tarcan T, Çetinel Ş, Şener A, Toklu HZ, Şener G. Beneficial effects of quercetin on rat urinary bladder after spinal cord injury. J Surg Res. 2013; 183(2): 695-703. [CrossRef]
  • [30] Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol. 1978; 52: 302-310. [CrossRef]
  • [31] Beutler E. Glutathione in red blood cell metabolism. A manual of biochemical methods. New York: Grune and Stratton; 1975. pp. 112-114.
  • [32] Bradford, M., 1976. A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding. Analytical Biochem. 72(1-2), pp. 248-254. [CrossRef]
There are 32 citations in total.

Details

Primary Language English
Subjects Pharmacology and Pharmaceutical Sciences (Other)
Journal Section Articles
Authors

Tarık Şener

Selin Çadirci

Ozge Cevik

Şerif Ercan

Mustafa Kutay Koroglu

Selin Şakarcan

Göksel Şener

Publication Date June 27, 2025
Published in Issue Year 2020 Volume: 24 Issue: 5

Cite

APA Şener, T., Çadirci, S., Cevik, O., Ercan, Ş., et al. (2025). Protective effects of quercetin against cisplatin induced urogenital organ toxicity. Journal of Research in Pharmacy, 24(5), 640-647. https://doi.org/10.35333/jrp.2020.219
AMA Şener T, Çadirci S, Cevik O, Ercan Ş, Koroglu MK, Şakarcan S, Şener G. Protective effects of quercetin against cisplatin induced urogenital organ toxicity. J. Res. Pharm. June 2025;24(5):640-647. doi:10.35333/jrp.2020.219
Chicago Şener, Tarık, Selin Çadirci, Ozge Cevik, Şerif Ercan, Mustafa Kutay Koroglu, Selin Şakarcan, and Göksel Şener. “Protective Effects of Quercetin Against Cisplatin Induced Urogenital Organ Toxicity”. Journal of Research in Pharmacy 24, no. 5 (June 2025): 640-47. https://doi.org/10.35333/jrp.2020.219.
EndNote Şener T, Çadirci S, Cevik O, Ercan Ş, Koroglu MK, Şakarcan S, Şener G (June 1, 2025) Protective effects of quercetin against cisplatin induced urogenital organ toxicity. Journal of Research in Pharmacy 24 5 640–647.
IEEE T. Şener, S. Çadirci, O. Cevik, Ş. Ercan, M. K. Koroglu, S. Şakarcan, and G. Şener, “Protective effects of quercetin against cisplatin induced urogenital organ toxicity”, J. Res. Pharm., vol. 24, no. 5, pp. 640–647, 2025, doi: 10.35333/jrp.2020.219.
ISNAD Şener, Tarık et al. “Protective Effects of Quercetin Against Cisplatin Induced Urogenital Organ Toxicity”. Journal of Research in Pharmacy 24/5 (June 2025), 640-647. https://doi.org/10.35333/jrp.2020.219.
JAMA Şener T, Çadirci S, Cevik O, Ercan Ş, Koroglu MK, Şakarcan S, Şener G. Protective effects of quercetin against cisplatin induced urogenital organ toxicity. J. Res. Pharm. 2025;24:640–647.
MLA Şener, Tarık et al. “Protective Effects of Quercetin Against Cisplatin Induced Urogenital Organ Toxicity”. Journal of Research in Pharmacy, vol. 24, no. 5, 2025, pp. 640-7, doi:10.35333/jrp.2020.219.
Vancouver Şener T, Çadirci S, Cevik O, Ercan Ş, Koroglu MK, Şakarcan S, Şener G. Protective effects of quercetin against cisplatin induced urogenital organ toxicity. J. Res. Pharm. 2025;24(5):640-7.