The Effects of Viburnum Opulus L. on Kidneys of Rats with Ethylene Glycol-induced Nephrolithiasis

Year 2023, Volume: 18 Issue: 3, 216 - 229, 25.10.2023

Emre Şam , Mithat Ekşi , Fatih Akkaş , Halil Baytekin , Eray Metin Güler , Abdülmüttalip Şimşek , Feyzi Arda Atar , Abdurrahim Koçyiğit , Ali İhsan Taşçı

https://doi.org/10.33719/yud.2023-18-3-1345876

Abstract

Objective: Recent research has centered on the role of oxidative stress and free oxygen radicals in the formation of stones. Viburnum opulus L. (VO) is a fruit species known for its antioxidant activity, and its juice preparation is used in Turkish traditional medicine for stone removal. This study aimed to investigate the effects of VO on calcium oxalate (CaOx) crystallization and oxidative stress in rats with ethylene glycol (EG)-induced nephrolithiasis.
Material and Methods: Fifty adult male Wistar Hannover rats were divided into five groups: control (Group 1), EG (Group 2), EG + 50 mg/kg VO (Group 3), EG + 100 mg/kg VO (Group 4), and EG + 200 mg/kg VO (Group 5). On days 7, 14, and 28, 24-hour urine was collected, and blood samples were taken. On day 28, the rats were sacrificed, and inflammation, oxidative stress, and CaOx crystallization in kidney tissue were evaluated under polarized light microscopy.
Results: A statistically significant difference was found between Group 1 and Group 2 in terms of serum inflammation parameters, acute kidney injury, and oxidative stress evaluated on days 7, 14, and 28, and tissue inflammation and oxidative stress parameters evaluated on day 28. It was observed that these parameters improved in Groups 3-5 compared to Group 2, and the level of statistical significance increased as the dose increased. In the histopathological evaluation of the tissues on day 28, the mean number of crystals was statistically significantly higher in Group 2 than in Group 1. These parameters improved in Groups 3-5 compared to Group 2, and there was a statistically significant difference when Groups 4 and 5 were compared to Group 2.
Conclusion: It was found that VO improved inflammation, oxidative stress, acute kidney injury, and CaOx crystallization in rats with EG-induced nephrolithiasis in direct proportion to the increase in dose.

Keywords

Viburnum opulus L. , Kidney stone , Nephrolithiasis , Calcium oxalate , Ethylene glycol , Inflammation , Oxidative stress , Acute kidney injury , Crystallization

Etilen Glikolla İndüklenmiş Nefrolitiyazisli Sıçan Böbrekleri Üzerinde Viburnum Opulus L’nin Etkileri

Abstract

Amaç: Son yıllarda yapılan çalışmalarda taş oluşumunda oksidatif stres ve serbest oksijen radikallerinin rolü olduğu üzerinde durulmaktadır. Viburnum Opulus L. (VO), antioksidan etkinliğiyle bilinen ve Türk geleneksel tıbbında taş düşürmek için suyu hazırlanarak kullanılan bir meyvedir. Bu çalışmanın amacı, etilen glikol (EG) ile indüklenmiş nefrolitiyazisli sıçanlarda VO’nun kalsiyum okzalat (CaOx) kristalizasyonu ve oksidatif stres üzerindeki etkinliğini araştırmaktır.
Gereç ve Yöntemler : 50 adet yetişkin erkek Wistar Hannover türü sıçanlar 5 gruba ayrıldı: Kontrol (Grup 1), EG (Grup 2), EG + 50 mg/kg VO (Grup 3), EG + 100 mg/kg VO (Grup 4), EG + 200 mg/kg VO (Grup 5). 7., 14. ve 28. günlerde 24 saatlik idrar toplandı ve kan örnekleri alındı. 28. günde sıçanlar sakrifiye edildi ve böbrek dokusunda inflamasyon, oksidatif stres ve polarize ışık mikroskobu altında CaOx kristalizasyonu değerlendirildi.
Bulgular: 7., 14. ve 28. günde serumda inflamasyon, akut böbrek hasarı ve oksidatif stres, 28.günde dokuda inflamasyon ve oksidatif stres parametrelerinde Grup 2 (EG) ile Grup 1 (Kontrol) arasında istatistiksel olarak anlamlı farklılık saptandı. Bu parametrelerin Grup 3-5’te Grup 2 (EG)’ye göre iyileşme gösterdiği ve doz arttıkça istatistiksel olarak anlamlılığın arttığı görüldü. 28. günde dokuların histopatolojik değerlendirilmesinde ortalama kristal sayısı Grup 2 (EG)’de Grup 1 (Kontrol)’e göre istatistiksel olarak anlamlı yüksek saptandı. Bu parametrelerin Grup 3-5’te Grup 2’ye göre iyileşme gösterdiği ve Grup 4-5’te istatistiksel olarak anlamlı farklılık olduğu görüldü.
Sonuç: VO’nun EG ile indüklenmiş nefrolitiyazisli sıçanlarda inflamasyon, oksidatif stres, akut böbrek hasarı ve CaOx kristalizasyonunu doz artışıyla doğru orantılı olarak iyileştirdiği saptanmıştır.

Keywords

Viburnum Opulus L. , Böbrek taşı , Nefrolitiyazis , Kalsiyum okzalat , Etilen glikol , İnflamasyon , Oksidatif stres , Akut böbrek hasarı , Kristalizasyon

References

• 1. Sorokin I, Mamoulakis C, Miyazawa K, Rodgers A, Talati J, Lotan Y. Epidemiology of stone disease across the world. World J Urol. 2017;35:1301-1320. https://doi.org/10.1007/s00345-017-2008-6 Cited: in: PMID:28213860.
• 2. Akinci M, Esen T, Tellaloglu S. Urinary stone disease in Turkey: An updated epidemiological study. Eur Urol. 1991;20:200-203. https://doi.org/10.1159/000471700 Cited: in: PMID:1823043.
• 3. Muslumanoglu AY, Binbay M, Yuruk E, Akman T, Tepeler A, Esen T, Tefekli AH. Updated epidemiologic study of urolithiasis in Turkey. I: Changing characteristics of urolithiasis. Urol Res. 2011;39:309-314. https://doi.org/10.1007/s00240-010-0346-6 Cited: in: PMID:21161646.
• 4. Itoh Y, Yasui T, Okada A, Tozawa K, Hayashi Y, Kohri K. Preventive effects of green tea on renal stone formation and the role of oxidative stress in nephrolithiasis. J Urol. 2005;173:271-275. https://doi.org/10.1097/01.ju.0000141311.51003.87 Cited: in: PMID: 15592095.
• 5. Tugcu V, Kemahli E, Ozbek E, Arinci YV, Uhri M, Erturkuner P, Metin G, Seckin I, Karaca C, Ipekoglu N, et al. Protective effect of a potent antioxidant, pomegranate juice, in the kidney of rats with nephrolithiasis induced by ethylene glycol. J Endourol. 2008;22:2723-2731. https://doi.org/10.1089/end.2008.0357 Cited: in: PMID:19025399.
• 6. Amin B, Moghri Feriz H, Timcheh Hariri A, Tayyebi Meybodi N, Hosseinzadeh H. Protective effects of the aqueous extract of Crocus sativus against ethylene glycol induced nephrolithiasis in rats. EXCLI J. 2015;14:411-422. https://doi.org/10.17179/excli2014-510
• 7. Kraujalyte V, Venskutonis PR, Pukalskas A, Česoniene L, Daubaras R. Antioxidant properties and polyphenolic compositions of fruits from different European cranberrybush (Viburnum opulus L.) genotypes. Food Chem. 2013;141:3695-3702. https://doi.org/10.1016/j.foodchem.2013.06.054 Cited: in: PMID: 23993538.
• 8. Sezik E, Yeşilada E, Honda G, Takaishi Y, Takeda Y, Tanaka T. Traditional medicine in Turkey X. Folk medicine in Central Anatolia. J Ethnopharmacol. 2001;75:95-115. https://doi.org/10.1016/S0378-8741(00)00399-8 Cited: in: PMID:11297840.
• 9. Khan SR. Animal models of kidney stone formation: An analysis. World J Urol. 1997;15:236-243. https://doi.org/10.1007/BF01367661 Cited: in: PMID:9280052.
• 10. Altun ML, Sever Yilmaz B. HPLC method for the analysis of salicin and chlorogenic acid from Viburnum opulus and V. lantana. Chem Nat Compd. 2007;43:205-207. https://doi.org/10.1007/s10600-007-0079-0
• 11. Velioglu YS, Ekici L, Poyrazoglu ES. Phenolic composition of European cranberrybush (Viburnum opulus L.) berries and astringency removal of its commercial juice. Int J Food Sci Technol. 2006;41:1011-1015. https://doi.org/10.1111/j.1365-2621.2006.01142.x
• 12. Česoniene L, Daubaras R, Vencloviene J, Viškelis P. Biochemical and agro-biological diversity of Viburnum opulus genotypes. Cent Eur J Biol. 2010;5:864-871. https://doi.org/10.2478/s11535-010-0088-z
• 13. Česonienė L, Daubaras R, Viškelis P. Evaluation of productivity and biochemical components in the fruit of different Viburnum accessions. Biologija. 2008;54:93-96. https://doi.org/10.2478/v10054-008-0018-4
• 14. Tuglu D, Yılmaz E, Yuvanc E, Erguder I, Kisa U, Bal F, Batislam E. Viburnum opulus: could it be a new alternative, such as lemon juice, to pharmacological therapy in hypocitraturic stone patients? Arch Ital Urol Androl. 2014;86:297-299. https://doi.org/10.4081/aiua.2014.4.297. Cited: in: PMID:25641457
• 15. Kızılay F, Ülker V, Çelik O, Özdemir T, Çakmak Ö, Can E, Nazlı O. The evaluation of the effectiveness of gilaburu (Viburnum opulus l.) extract in the medical expulsive treatment of distal ureteral stones. Turkish J Urol. 2019;45:S63-S69. https://doi.org/10.5152/tud.2019.23463
• 16. Ilhan M, Ergene B, Süntar I, Özbilgin S, Saltan Çitoʇlu G, Demirel MA, Keleş H, Altun L, Küpeli Akkol E. Preclinical evaluation of antiurolithiatic activity of viburnum opulus L. on sodium oxalate-induced urolithiasis rat model. Evidence-based Complement Altern Med. 2014;2014:578103. https://doi.org/10.1155/2014/578103
• 17. Evan AP. Physiopathology and etiology of stone formation in the kidney and the urinary tract. Pediatr Nephrol. 2010;25:831-841. https://doi.org/10.1007/s00467-009-1116-y Cited: in: PMID:19198886.
• 18. Khan SR. Renal tubular damage/dysfunction: Key to the formation of kidney stones. Urol Res. 2006;34:86-91. https://doi.org/10.1007/s00240-005-0016-2 Cited: in: PMID:16404622.
• 19. Basavaraj DR, Biyani CS, Browning AJ, Cartledge JJ. The Role of Urinary Kidney Stone Inhibitors and Promoters in the Pathogenesis of Calcium Containing Renal Stones. EAU-EBU Updat Ser. 2007;5:126-136. https://doi.org/10.1016/j.eeus.2007.03.002
• 20. Khan SR. Calcium oxalate crystal interaction with renal tubular epithelium, mechanism of crystal adhesion and its impact on stone development. Urol Res. 1995;23:71-79. https://doi.org/10.1007/BF00307936 Cited: in: PMID:7676537.
• 21. Baggio B, Gambaro G, Ossi E, Favaro S, Borsatti A. Increased urinary excretion of renal enzymes in idiopathic calcium oxalate nephrolithiasis. J Urol. 1983;129:1161-1162. https://doi.org/10.1016/S0022-5347(17)52619-1 Cited: in: PMID:6133962.
• 22. Boonla C, Wunsuwan R, Tungsanga K, Tosukhowong P. Urinary 8-hydroxydeoxyguanosine is elevated in patients with nephrolithiasis. Urol Res. 2007;35:185-191. https://doi.org/10.1007/s00240-007-0098-0 Cited: in: PMID:17541572.
• 23. Zuo J, Khan A, Glenton PA, Khan SR. Effect of NADPH oxidase inhibition on the expression of kidney injury molecule and calcium oxalate crystal deposition in hydroxy-L-proline-induced hyperoxaluria in the male Sprague-Dawley rats. Nephrol Dial Transplant. 2011;26:1785-1796. https://doi.org/10.1093/ndt/gfr035 Cited: in: PMID:21378157.
• 24. Parikh CR, Devarajan P. New biomarkers of acute kidney injury. Crit Care Med. 2008;36:S159-S165. https://doi.org/10.1097/CCM.0b013e318168c652 Cited: in: PMID:18382188.
• 25. Khan SR. Crystal-induced inflammation of the kidneys: Results from human studies, animal models, and tissue-culture studies. Clin Exp Nephrol. 2004;8:75-88. https://doi.org/10.1007/s10157-004-0292-0 Cited: in: PMID: 15235923.
• 26. Boonla C, Hunapathed C, Bovornpadungkitti S, Poonpirome K, Tungsanga K, Sampatanukul P, Tosukhowong P. Messenger RNA expression of monocyte chemoattractant protein-1 and interleukin-6 in stone-containing kidneys. BJU Int. 2008;101:1170-1177. https://doi.org/10.1111/j.1464-410X.2008.07461.x Cited: in: PMID:18241247.
• 27. Mushtaq S, Siddiqui AA, Naqvi ZA, Rattani A, Talati J, Palmberg C, Shafqat J. Identification of myeloperoxidase, α-defensin and calgranulin in calcium oxalate renal stones. Clin Chim Acta. 2007;384:41-47. https://doi.org/10.1016/j.cca.2007.05.015 Cited:in: PMID:17610860.
• 28. Altun ML, Saltan Çitoǧlu G, Sever Yilmaz B, Özbek H. Antinociceptive and anti-inflammatory activities of Viburnum opulus. Pharm Biol. 2009;47:653-658. https://doi.org/10.1080/13880200902918345
• 29. Miller NL, Gillen DL, Williams JC, Evan AP, Bledsoe SB, Coe FL, Worcester EM, Matlaga BR, Munch LC, Lingeman JE. A formal test of the hypothesis that idiopathic calcium oxalate stones grow on Randall’s plaque. BJU Int. 2009;103:966-971. https://doi.org/10.1111/j.1464-410X.2008.08193.x Cited: in: PMID:19021625.
• 30. Khan SR. Reactive oxygen species, inflammation and calcium oxalate nephrolithiasis. Transl Androl Urol. 2014;3:256-276. https://doi.org/10.3978/j.issn.2223-4683.2014.06.04