ANKAFERD BLOOD STOPPER'IN KADMİYUMA BAĞLI GELİŞEN AKUT BÖBREK HASARINA ETKİSİ

Amaç Kadmiyum (Kd) insan sağlığı üzerinde zararlı etkilere neden olabilen çok toksik ve kanserojen bir ağır metaldir. Kd maruziyetine bağlı olarak özellikle böbreklerde toksisite gelişebilir. Ankaferd blood stopper (ABS), cerrahide hemostatik özelliği nedeniyle kullanılan bitkisel bir karışımdır. Ayrıca ABS’nin yara ve doku iyileşmesini artırdığı gösterilmiştir. Bu çalışmada, ABS'nin Kd kaynaklı böbrek hasarına karşı olası koruyucu etkilerini değerlendirmeyi amaçladık. Gereç ve Yöntem Otuz iki erkek sıçan rastgele 4 gruba ayrıldı: kontrol, Kd (kadmiyum klorür, 2,5 mg/kg tek doz ip), ABS (ABS, 1,5 ml/kg tek doz ip) ve Kd+ABS (kadmiyum klorür, 2,5 mg/kg tek doz ip-ABS, 1,5 ml/kg tek doz ip). Deney sonunda sıçanların serumlarından üre ve kreatinin seviyeleri ölçüldü. Ayrıca böbrek dokularından spektrofotometrik olarak total oksidan status (TOS), total antioksidan status (TAS) seviyeleri, süperoksit dismutaz (SOD) ve glutatyon peroksidaz (GPx) enzim aktiviteleri ölçüldü. TOS ve TAS düzeylerinden oksidatif stres indeksi (OSI) hesaplandı. Ayrıca sıçanların böbrek dokusunda Bcl-2-associated X protein (Bax), B-cell-lymphoma-2 (Bcl-2), silenced information regulator 1 (SIRT1) ve p53'ün mRNA ekspresyonundaki değişiklikler qRT-PCR yöntemi ile değerlendirildi. Bulgular Kadmiyum grubunda serum üre, kreatinin düzeyleri ve doku oksidatif stres belirteçleri, TOS ve OSI değerleri kontrol grubuna göre anlamlı olarak yüksek (p<0.05), Gpx aktivitesi anlamlı olarak düşüktü (p<0.05). Ayrıca p53 ekspresyonu ve Bax/Bcl2 oranı Kd grubunda anlamlı artış göstermiştir (p<0.05). Ancak ABS tedavisi, Kd uygulanan grupta üre, kreatinin, TOS, OSI düzeylerini ve Bax/Bcl2 oranı ile p53 ekspresyonunu anlamlı düzeyde azaltmıştır (p<0.05). Sonuç Ankaferd blood stopper akut Kd maruziyetinde oksidatif stresi ve mitokondri aracılı apoptozu azaltarak koruyucu etkiler göstermiştir.

Anahtar Kelimeler:

Urtica dioica, resveratrol, meyan, kekik, oksidatif stress

PROTECTIVE ROLE OF ANKAFERD BLOOD STOPPER ON CADMIUM-INDUCED ACUTE NEPHROTOXICITY

Objective Cadmium (Cd) is a very toxic and carcinogenic heavy metal that can cause harmful effects on human health. Toxicity may develop due to Cd exposure, especially in the kidneys. Ankaferd blood stopper (ABS) is a herbal mix that is used for its hemostatic properties in surgery. Also, ABS enhances wound and tissue healing. In this study, we aimed to evaluate the possible ameliorative effects of ABS in Cd-induced renal damage. Material and Method Thirty-two male rats were randomly divided into 4 groups: control, Cd (cadmium chloride, 2.5 mg/kg single dose, ip), ABS (ABS, 1.5 ml/kg single dose ip), and Cd+ABS (cadmium chloride, 2.5 mg/kg single dose ip- ABS, 1.5 ml/kg single dose ip). At the end of the experiment, urea and creatinine levels were analyzed from the rats’ serum. In addition, total oxidant status (TOS), total antioxidant status (TAS) levels, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activity were measured spectrophotometrically from renal tissues. The oxidative stress index (OSI) was calculated from TOS and TAS levels. Also, we evaluated alterations in the mRNA expression of Bcl- 2-associated X protein (Bax), B-cell-lymphoma-2 (Bcl- 2), silenced information regulator 1 (SIRT1), and p53 in kidney tissue of rats by using the qRT-PCR method. Results In the Cd group, serum urea, creatinine levels, and tissue oxidative stress markers, TOS and OSI were significantly higher while Gpx activity was significantly lower than in the control group (p<0.05). Also, the expression of p53 and in Bax/Bcl2 ratio significantly increased in the Cd group (p<0.05). But, ABS treatment significantly decreased urea, creatinine, TOS, OSI levels, and Bax/Bcl2 ratio, p53 expression in Cd applied group (p<0.05). Conclusion Ankaferd blood stopper showed protective effects by reducing oxidative stress and mitochondria-mediated apoptosis in acute Cd exposure.

Keywords:

Urtica dioica, oxidative stress, resveratrol, licorice, thyme,

PDF

___

1. Kubier A, Wilkin RT, Pichler T. Cadmium in soils and groundwater: a review. Applied Geochemistry. 2019;108:104388.
2. Ruoyu W, Panting S, Yahui G, Ping J, Yuliang C, Hang Y, et al. Cadmium in food: Source, distribution and removal. Food Chemistry. 2023;405:134666.
3. Zhao D, Wang P, Zhao F-J. Dietary cadmium exposure, risks to human health and mitigation strategies. Critical Reviews in Environmental Science and Technology. 2022:1-25.
4. Guo AH, Kumar S, Lombard DB. Epigenetic mechanisms of cadmium-induced nephrotoxicity. Current Opinion in Toxicology. 2022:100372.
5. Yan L-J, Allen DC. Cadmium-induced kidney injury: Oxidative damage as a unifying mechanism. Biomolecules. 2021;11(11):1575.
6. Liu J, Qu W, Kadiiska MB. Role of oxidative stress in cadmium toxicity and carcinogenesis. Toxicology and Applied Pharmacology. 2009;238(3):209-14.
7. Ma Y, Su Q, Yue C, Zou H, Zhu J, Zhao H, et al. The effect of oxidative stress-induced autophagy by cadmium exposure in kidney, liver, and bone damage, and neurotoxicity. International Journal of Molecular Sciences. 2022;23(21):13491.
8. Souza-Arroyo V, Fabián JJ, Bucio-Ortiz L, Miranda-Labra RU, Gomez-Quiroz LE, Gutiérrez-Ruiz MC. The mechanism of the cadmium-induced toxicity and cellular response in the liver. Toxicology. 2022:153339.
9. Gao M, Dong Z, Sun J, Liu W, Xu M, Li C, et al. Liver-derived exosome-laden lncRNA MT1DP aggravates cadmium-induced nephrotoxicity. Environmental Pollution. 2020;258:113717.
10. Ryter SW, Kim HP, Hoetzel A, Park JW, Nakahira K, Wang X, et al. Mechanisms of cell death in oxidative stress. Antioxidants & Redox Signaling. 2007;9(1):49-89.
11. Dong Y-j, Liu N, Xiao Z, Sun T, Wu S-h, Sun W-x, et al. Renal protective effect of sirtuin 1. Journal of Diabetes Research. 2014;2014.
12. Ogura Y, Kitada M, Koya D. Sirtuins and renal oxidative stress. Antioxidants. 2021;10(8):1198.
13. Alshammari GM, Al-Qahtani WH, AlFaris NA, Albekairi NA, Alqahtani S, Eid R, et al. Quercetin alleviates cadmium chloride- induced renal damage in rats by suppressing endoplasmic reticulum stress through SIRT1-dependent deacetylation of Xbp-1s and eIF2α. Biomedicine & Pharmacotherapy. 2021;141:111862.
14. Arab HH, Ashour AM, Eid AH, Arafa E-SA, Al Khabbaz HJ, Abd El-Aal SA. Targeting oxidative stress, apoptosis, and autophagy by galangin mitigates cadmium-induced renal damage: Role of SIRT1/Nrf2 and AMPK/mTOR pathways. Life Sciences. 2022;291:120300.
15. Dong W, Yan L, Tan Y, Chen S, Zhang K, Gong Z, et al. Melatonin improves mitochondrial function by preventing mitochondrial fission in cadmium-induced rat proximal tubular cell injury via SIRT1–PGC-1α pathway activation. Ecotoxicology and Environmental Safety. 2022;242:113879.
16. Kim J-Y, Jo J, Kim K, An H-J, Gwon M-G, Gu H, et al. Pharmacological activation of Sirt1 ameliorates cisplatin-induced acute kidney injury by suppressing apoptosis, oxidative stress, and inflammation in mice. Antioxidants. 2019;8(8):322.
17. Susnow N, Zeng L, Margineantu D, Hockenbery DM. Bcl-2 family proteins as regulators of oxidative stress. Seminars in Cancer Biology. 2009;19(1):42-9.
18. Alsawaf S, Alnuaimi F, Afzal S, Thomas RM, Chelakkot AL, Ramadan WS, et al. Plant flavonoids on oxidative stress-mediated kidney inflammation. Biology. 2022;11(12):1717.
19. Güneş E. Antioxidant effects of ankaferd blood stopper doped polyvinyl pyrolidon in an experimental model created in insect. Food and Chemical Toxicology. 2021;148:111935.
20. Uğur A, Sarac N, Cankal DA, Özle M. The antioxidant and antimutagenic activities of Ankaferd blood stopper, a natural hemostatic agent used in dentistry. Turkish Journal of Medical Sciences. 2016;46(3):657-63.
21. Koluman A, Akar N, Malkan UY, Haznedaroglu IC. Qualitative/ chemical analyses of Ankaferd hemostat and its antioxidant content in synthetic gastric fluids. BioMed Research International. 2016;2016.
22. Koçak E, Akbal E, Taş A, Köklü S, Karaca G, Can M, et al. Anti-inflammatory efficiency of Ankaferd blood stopper in experimental distal colitis model. Saudi Journal of Gastroenterology: Official Journal of the Saudi Gastroenterology Association. 2013;19(3):126.
23. Hortu I, Ozceltik G, Karadadas E, Erbas O, Yigitturk G, Ulukus M. The role of ankaferd blood stopper and oxytocin as potential therapeutic agents in endometriosis: a rat model. Current Medical Science. 2020;40(3):556-62.
24. Abdel-Moneim AM, Said KM. Acute effect of cadmium treatment on the kidney of rats: biochemical and ultrastructural studies. Pakistan Journal of Biological Sciences: PJBS. 2007;10(20):3497-506.
25. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clinical Biochemistry. 2004;37(4):277-85.
26. Erel O. A new automated colorimetric method for measuring total oxidant status. Clinical Biochemistry. 2005;38(12):1103-11.
27. Altindag O, Erel O, Soran N, Celik H, Selek S. Total oxidative/ anti-oxidative status and relation to bone mineral density in osteoporosis. Rheumatology International. 2008;28(4):317-21.
28. Embuscado ME. Spices and herbs: Natural sources of antioxidants– a mini review. Journal of Functional Foods. 2015;18:811-9.
29. Siouda W, Abdennour C. Can Urtica dioica supplementation attenuate mercury intoxication in Wistar rats? Veterinary World.2015;8(12):1458.
30. Aldulaimi AMA, Al Jumaily A-AIH, Husain FF. The effect of aqueous Urtica dioica extract in male rats exposed to copper sulfate poisoning. IOP Conference Series: Earth and Environmental Science. 2021;735:012008.
31. Katalinic V, Mozina SS, Generalic I, Skroza D, Ljubenkov I, Klancnik A. Phenolic profile, antioxidant capacity, and antimicrobial activity of leaf extracts from six Vitis vinifera L. varieties. International Journal of Food Properties. 2013;16(1):45-60.
32. Fu B, Zhao J, Peng W, Wu H, Zhang Y. Resveratrol rescues cadmium-induced mitochondrial injury by enhancing transcriptional regulation of PGC-1α and SOD2 via the Sirt3/FoxO3a pathway in TCMK-1 cells. Biochemical and Biophysical Research Communications. 2017;486(1):198-204.
33. Cirmi S, Maugeri A, Micali A, Marini HR, Puzzolo D, Santoro G, et al. Cadmium-induced kidney injury in mice is counteracted by a flavonoid-rich extract of bergamot juice, alone or in association with curcumin and resveratrol, via the enhancement of different defense mechanisms. Biomedicines. 2021;9(12):1797.
34. Dirican E, Turkez H. In vitro studies on protective effect of Glycyrrhiza glabra root extracts against cadmium-induced genetic and oxidative damage in human lymphocytes. Cytotechnology. 2014;66(1):9-16.
35. Mohamed NE-S. Effect of aqueous extract of glycyrrhiza glabra on the biochemical changes induced by cadmium chloride in rats. Biological Trace Element Research. 2019;190(1):87-94.
36. Mohammed E, Kamel M, El Iraqi K, Tawfik AM, Khattab MS, Elsabagh M. Zingiber officinale and Glycyrrhiza glabra, individually or in combination, reduce heavy metal accumulation and improve growth performance and immune status in Nile tilapia, Oreochromis niloticus. Aquaculture Research. 2020;51(5):1933-41.
37. Onoja RI, Chukwudi CU, Emejuo NT, Ugwuanyi HE, Ugwueze EU. Possible ameliorative effects of hydromethanol extract of Thymus vulgaris on cadmium induced hepatorenal toxicity in rats. Notulae Scientia Biologicae. 2020;12(3):568-77.
38. Abou Asa S, El-Nahass E-S, Abdelhady D. Protective effect of thymus vulgaris extract against cadmium induced nephrotoxicity and testicular damage in albino rats. Assiut Veterinary Medical Journal. 2018;64(156):142-53.
39. Sarı H, Çelik S, Çağlar F, Aktaş S, Bozkurt O, Yörükoğlu K, et al. A candidate antineoplastic herbal agent for bladder cancer: Ankaferd blood stopper. International Journal of Clinical Practice. 2021;75(11):e14789.
40. Durhan A, Koşmaz K, Süleyman M, Tez M, Şenlikci A, Ersak C, et al. Assessment of Ankaferd Blood Stopper in experimental liver ischemia reperfusion injury. Turkish Journal of Medical Sciences. 2020;50(5):1421-7.
41. Buyuktiryaki M, Tayman C, Koyuncu I, Cakir U, Turkmenoglu TT, Cakir E, et al. Therapeutic and preventative effects of ankaferd blood stopper in an experimental necrotizing enterocolitis model. Biomedicine & Pharmacotherapy. 2019;110:105-10.
42. Huri E, Haznedaroglu IC, Akgul T, Astarci M, Ustun H, Germiyanoulu C. Biphasic effects of ankaferd blood stopper on renal tubular apoptosis in the rat partial nephrectomy model representing distinct levels of hemorrhage. Saudi Medical Journal. 2010;31(8):864-8.