Investigation of uroprotective effects of seed methanol extracts of Hypericum triquetrifolium Turra. on cyclophosphamide-induced bladder hemorrhagic cystitis and nephrotoxicity in Wistar albino rats

Year 2020, Volume: 45 Issue: 4, 1361 - 1371, 27.12.2020

Songül Çetik Yıldız Cumali Keskin Varol Şahintürk Adnan Ayhancı

https://doi.org/10.17826/cumj.730817

Cited By: 3

Abstract

Purpose: This study investigated the possible uroprotective effects of Hypericum triquetrifolium Turra. (HT) seed methanol extracts (25,50,100 mg/kg, i.p., for 6 days) against cyclophosphamide (CYP)-induced (150 mg/kg, single dose, i.p.) acute bladder hemorrhagic cystitis (HC) and nephrotoxicity in rats.
Materials and Methods: Wistar albino rats used in this study were divided into nine groups, each including seven rats. Group 1 (control) was treated with 0.5ml saline (SF) and Group 2 was treated with CYP (150 mg/kg). Groups 3, 4, 5 were treated with 25, 50, 100 mg/kg HT, respectively while groups 6, 7, 8 were treated with 25, 50, 100 mg/kg CYP + HT, respectively. Finally, Group 9 (control-2) was treated with 0.5ml-%0.2 dimethyl sulfoxide (DMSO). The serum creatinine, blood urea nitrogen (BUN), superoxide dismutase (SOD) and catalase (CAT) levels were measured in blood serum.
Results: The CYP-treated rats histopathologically had mild-moderate bladder and renal injuries. The serum creatinine and BUN levels, which are the biochemical markers of renal injury, significantly increased compared to the control group.
Conclusion: HT showed a protective effect on CYP-related bladder HC and nephrotoxicity in rats by inhibiting inflammation and apoptosis.

Keywords

cyclophosphamide

Supporting Institution

This study was supported by Mardin Artuklu University - Coordination Unit of Scientific Research Project (MAU-BAP-15-SHMYO-23).

Project Number

MAU-BAP-15-SHMYO-23

Wistar albino sıçanlarında Hypericum triquetrifolium Turra. tohum metanol ekstraktlarının siklofosfamid-nedenli mesane hemorajik sistiti ve nefrotoksisitesi üzerine üroprotektif etkilerinin incelenmesi

Abstract

Amaç: Bu çalışmada, Hypericum triquetrifolium Turra (HT) tohum metanol ekstraktlarının (25,50,100 mg/kg, i.p., 6 gün boyunca) siklofosfamid (CYP) nedenli (150 mg/kg, tek doz, i.p.) akut mesane hemorajik sistit (HC) ve nefrotoksisiteye karşı olası üroprotektif etkileri araştırıldı.
Gereç ve Yöntem: Bu çalışmada kullanılan Wistar albino sıçanlar, her biri yedi sıçan olmak üzere dokuz gruba ayrıldı. Grup 1 (kontrol) 0.5ml salin (SF) ile muamele edildi ve Grup 2, CYP (150 mg/kg) ile muamele edildi. Grup 3, 4, 5 sırasıyla 25, 50, 100 mg/kg HT ile tedavi edilirken, grup 6, 7, 8 sırasıyla 25, 50, 100 mg/kg HT + CYP ile tedavi edildi. Son olarak, Grup 9 (kontrol-2) 0.5ml-% 0.2 dimetil sülfoksit (DMSO) ile muamele edildi. Kan serumunda serum kreatinin, kan üre azotu (BUN), süperoksit dismutaz (SOD) ve katalaz (CAT) seviyeleri ölçüldü.
Bulgular: CYP ile tedavi edilen sıçanların histopatolojik olarak hafif-orta derecede mesane ve böbrek yaralanmaları vardı. Böbrek hasarının biyokimyasal belirteçleri olan serum kreatinin ve BUN düzeyleri, kontrol grubuna göre önemli ölçüde artmıştır.
Sonuç: HT, enflamasyonu ve apoptozu inhibe ederek sıçanlarda CYP ile ilişkili mesane HC'si ve nefrotoksisite üzerinde koruyucu bir etki göstermiştir.

Keywords

Siklofosfamid, Hypericum triquetrifolium, Nefrotoksiste, Hemorajik Sistit, Üroprotektif

Project Number

MAU-BAP-15-SHMYO-23

References

• 1. Jurado-Garcia JM, Sanchez A, Pajaras B. Combined oral cyclophosphamide and bevacizumab in heavily pretreated ovarian cancer. Clin Transl Oncol. 2008;10(9):583-86.
• 2. Caglar K, Kinalp C, Arpaci F, Turan M, Saglam K, Ozturk B et al. Cumulative prior dose of cisplatin as a cause of the nephrotoxicity of high-dose chemotherapy followed by autologous stem-cell transplantation. Nephrol Dial Transplant. 2002;17(11):1931-35.
• 3. Abraham P, Rabi S. Nitrosative stress, protein tyrosine nitration, PARP activation and NAD depletion in the kidneys of rats after single dose of cyclophosphamide. Clin Exp Nephrol. 2009;13(4):281–87.
• 4. Chuang YC, Yoshimura N, Huang CC, Wu M, Tyagi P, Chancellor MB. Expression of E-series prostaglandin (EP) receptors and urodynamic effects of an EP4 receptor antagonist on cyclophosphamide-induced overactive bladder in rats. BJU Int. 2010;106(11):1782-87.
• 5. Korkmaz A, Topal T, Oter S. Pathophysiological aspects of cyclophosphamide and ifosfamide induced hemorrhagic cystitis. Cell Biol Toxicol. 2007;23(5):303-12.
• 6. Liu Q, Lin X, Li H, Yuan J, Peng Y, Dong L, Dai S. Paeoniflorin ameliorates renal function in cyclophosphamide-induced mice via AMPK suppressed inflammation and apoptosis. Biomed Pharmacother. 2016a;84:1899-905.
• 7. Sinanoglu O, Yener AN, Ekici S, Midi A, Aksungar FB. The protective effects of spirulina in cyclophosphamide induced nephrotoxicity and urotoxicity in rats. Urology. 2012;80(6):1392–98.
• 8. Topal T, Oztas Y, Korkmaz A, Sadir S, Oter S, Omer C, Bilgic H. Melatonin ameliorates bladder damage induced by cyclophosphamide in rats. J Pineal Res. 2005;38(4):272-77.
• 9. Bhatia K, Kaur M, Atif F, Ali M, Rehman H, Rahman S, Raisuddin S. Aqueous extract of Trigonella foenum-graecum L. ameliorates additive urotoxicity of buthionine sulfoximine and cyclophosphamide in mice. Food Chem Toxicol. 2006;44(10):1744-50.
• 10. Tripathi DN, Jena GB. Effect of melatonin on the expression of Nrf2 and NF-kappaB during cyclophosphamide-induced urinary bladder injury in rat. J Pineal Res. 2010;48(4):324–31.
• 11. Ribeiro RA, Lima RCP, Leite CAVG, Mota JMSC, Macedo FYB, Lima MVA, Brito GAC. Chemotherapy-induced hemorrhagic cystitis: pathogenesis, pharmacological approaches and new insights. J Exp Integr Med. 2012;2(2):95-112.
• 12. Yoshida T, Kawashima A, Ujike T, Uemura M, Nishimura K, Miyoshi S. Hyperbaric oxygen therapy for radiation-induced hemorrhagic cystitis. Int J Urol. 2008;15(7):639–41.
• 13. Ebrahimi B, Eirin A, Li Z, Zhu XY, Zhang X, Lerman A et al. Mesenchymal stem cells improve medullary inflammation and fibrosis after revascularization of swine atherosclerotic renal artery stenosis. PLoS One. 2013;8(7):e67474.
• 14. Park S, Kim CS, Lee J, Suk-Kim J. Effect of regular exercise on the histochemical changes of d-galactose-induced oxidative renal injury in high-fat diet-fed rats. Acta Histochem Cytochem. 2013;46(4):111-19.
• 15. Dhodi DK, Bhagat SB, Pathak D, Patel SB. Drug-induced nephrotoxicity. Int J Basic Clin Pharmacol. 2014;3(4):591-97.
• 16. Fillastre JP, Godin M. Drug-induced nephropathies. In Davison, A. M.; Cameron, J. S.; Grünfeld, J. P. et al. Oxford Textbook of Clinical Nephrology. New York: Oxford University Press. 1998;2645-57.
• 17. Ikarashi Y, Kakihara Y, Imai C, Tanaka A, Watanabe A, Uchiyama M. Glomerular dysfunction, independent of tubular dysfunction, indu- ced by antineoplastic chemotherapy in children. Pediatr Int. 2004;46(5):570-75.
• 18. Taha NR, Amin HA, Sultan AA. The protective effect of Moringa oleifera leaves against cyclophosphamide-induced urinary bladder toxicity in rats. Tissue Cell. 2015;47(1):94–104.
• 19. Hamsa TP, Kuttan G. Protective role of Ipomoea obscura (L.) on cyclophosphamide-induced uro and nephrotoxicities by modulating antioxidant status and proinflammatory cytokine levels. Inflammopharmacology. 2011;19(3):155-67.
• 20. Moraes JP, Pereira DS, Matos AS, Santana DG, Santos CA, Estevam CS et al. The ethanol extract of the inner bark of Caesalpinia pyramidalis (Tul.) reduces urinary bladder damage during cyclophosphamide-induced cystitis in rats. Sci World J. 2013;694010:1–8.
• 21. Farshid AA, Tamaddonfard E, Ranjbar S. Oral administration of vitamin C and histidine attenuate cyclophosphamide-induced hemorrhagic cystitis in rats. Indian J Pharmacol. 2013;45(2):126-29.
• 22. Ozguven A, Yılmaz O, Taneli F, Ulman C, Vatansever S, Onag A. Protective effect of ketamine against hemorrhagic cystitis in rats receiving ifosfamide. Indian J Pharmacol. 2014;46(2):147–51.
• 23. Conforti F, Loizzo MR, Statti AC, Menichini F. Cytotoxic activity of antioxidant constituents from Hypericum triquetrifolium Turra. Nat Prod Res. 2007;21(1):42-6.
• 24. Keskin C, Aktepe N, Yukselten Y, Sunguroglu A, Boga M. In vitro antioxidant, cytotoxic, cholinesterase inhibitory activities and anti-genotoxic effects of Hypericum retusum Aucher flowers, fruits and seeds methanol extracts in human mononuclear leukocytes. Iran J Pharm Res. 2017;16(1):210-20.
• 25. Yildiz SC, Keskin C, Sahinturk V, Ayhanci A. Cardioprotective effects of Hypericum triquetrifolium Turra. against cyclophosphamide related cardiotoxicity in rats. J Res Pharm. 2018;22(3):374-85.
• 26. Yildiz SC, Keskin C, Sahinturk V, Ayhanci A. A histopathological, immunohistochemical and biochemical investigation on the in vitro antioxidant, myeloprotective, hematoprotective and hepatoprotective effects of Hypericum triquetrifolium seed extract against cyclophosphamide-induced toxicity. Braz Arch Biol Techn. 2019;62:e19180345.
• 27. Liu N, Shimizu S, Shimizu T, Nakamura K, Yamamoto M, Higashi Y, Saito M. Protective effects of the selective alpha1A-adrenoceptor antagonist silodosin against cyclophosphamide-induced cystitis in rats. J Pharmacol Sci. 2016b ;132(1):71-7.
• 28. McEvoy GK. editor, Bethesda, Maryland: AHFS, Drug Information. American Society of Health-System. Pharmacists. 2004;929-52.
• 29. Repchinsky C. Compendium of Pharmaceuticals and Specialties. 2004;1610-13.
• 30. Cohen M, Lippman M, Chabner B. Role of pineal gland in aetiology and treatment of breast cancer. Lancet. 1978;2(8094):814-16.
• 31. Jayaraman T, Kannappan S, Ravichandran MK, Anuradha CV. Impact of essentiale L on ethanol-induced changes in rat brain and erythrocytes. Singapore Med J. 2008;49(4):320–27.
• 32. Amien AI, Fahmy SR, Abd-Elgleel FM, Elaskalany SM. Renoprotective effect of Mangifera indica polysaccharides and silymarin against cyclophosphamide toxicity in rats. J Basic Appl Zool. 2015;72:154–62.
• 33. Abraham P, Rabi S. Protective effect of aminoguanidine against cyclophosphamide-induced oxidative stress and renal damage in rats. Redox Rep. 2011;16(1); 8–14.
• 34. Shapiro CL, Recht A. Side effects of adjuvant treatment of breast cancer. N Engl J Med. 2001;344(26):1997-2008.
• 35. Dobrek L, Baranowska A, Skowron B, Thor P. Biochemical and histological evaluation of kidney function in rats after a single administration of cyclophosphamide and ifosfamide. J Nephrol Kidney Dis. 2017;1(1):1002.
• 36. Kurniawan LB, Bahrun U, Mangarengi F, Darmawaty ER, Mansyur A. Blood urea nitrogen as a predictor of mortality in myocardial infarction. Univ Med. 2013;32(3):172–78.
• 37. Sharma A, Hirulkar NB, Wadel P, Das P. Influence of hyperglycemia on renal function parameters in patients with diabetes mellitus. Intern. J Pharm Biol Arch. 2011;2(2):734-39.
• 38. Deng Z, Gu Y, Hou X, Zhang L, Bao Y, Hu C, Jia W. Association between uric acid, cancer incidence and mortality in patients with type 2 diabetes: Shanghai diabetes registry study. Diabetes Metab Res Rev. 2016;32(3):325–32.
• 39. Rehman M, Tahir M, Ali F, Qamar W, Lateef A, Khan R et al. Cyclophosphamide- induced nephrotoxicity, genotoxicity, and damage in kidney genomic DNA of Swiss albino mice: the protective effect of Ellagic acid. Mol Cell Biochem. 2012;365(1-2):119–27.
• 40. Haylen BT, de Ridder D, Freeman RM, Swift SE, Berghmans B, Lee J et al. An international urogynecological association (IUGA)/international continence society (ICS) joint report on the terminology for female pelvic floor dysfunction. Neurourol Urodyn. 2010;29:4-20.
• 41. Lee WC, Chiang PH, Tain YL, Wu CC, Chuang YC. Sensory dysfunction of bladder mucosa and bladder oversensitivity in a rat model of metabolic syndrome. PloS One. 2012;7(9):e45578.
• 42. Yamaguchi O, Nishizawa O, Takeda M, Yokoyama O, Homma Y, Kakizaki H et al. Clinical guidelines for overactive bladder. Int J Urol 2009;16(2):126-42.
• 43. Kim SH, Lee IC, Baek HS, Shin IS, Moon C, Bae CS et al. Mechanism for the protective effect of diallyl disulfide against cyclophosphamide acute urotoxicity in rats. Food Chem Toxicol. 2014;64:110-18.
• 44. Ogoda M, Ito Y, Fuchihata Y, Onoue S, Yamada S. Characterization of muscarinic and P2X receptors in the urothelium and detrusor muscle of the rat bladder. J Pharmacol Sci. 2016;131(1):58-63.
• 45. Sugumar E, Indirani K, Abraham P. Normal plasma creatinine levels despite histological evidence of renal damage in cyclophosphamide treated rats. Clin Chim Acta. 2007;376(1-2):244-45.
• 46. Cook SA, Sugden PH, Clerk A. Regulation of bcl-2 family proteins during development and in response to oxidative stress in cardiac myocytes: association with changes in mitochondrial membrane potential. Circ Res. 1999;85(10):940-49.