The Investigation Protective Effect of Tarantula Cubensis Extract in Rats Induced Experimental Gentamicin Nephrotoxicity

Abstract

Gentamicin (GM), which is used in the treatment of infections caused by gram-negative bacteria, has limited clinical use due to its serious nephrotoxic side effects. Tarantula cubensis extract (TCE) is a homeopathic product that is widely used and proven to be effective in veterinary medicine to benefit from its regeneration, demarcation, antiphlogistic and resorptive effects. The aim of the study was to investigate the possible protective effects of TCE against these negative effects of Gentamicin, which is one of the drugs that trigger the formation of free radicals in the body, in terms of oxidative stress, apoptosis and antioxidant parameters. In this study, rats were divided into four equal groups. Groups; Control, GM, TCE, GM+TCE. Blood and kidney tissue samples were taken 24 hours after the last injection. Urea and creatinine analysis were performed in serum, MDA, SOD and TAS analysis were performed in kidney and serum samples. Bcl-2 and Bax analyzes and histopathological evaluations were performed in the kidney tissue. An increase in MDA, creatinine and urea levels, and a decrease in TAS and SOD levels were observed in the GM group compared to the control group. On the other hand, in the GM+TCE group, a decrease was observed in increasing parameters compared to the GM group, and an increase in TAS and SOD levels was observed. In the histopathological and immunohistochemical examination of kidney tissue, it was determined that pathological disorders and increased apoptosis (decrease in Bcl-2, increase in Bax) in the GM group decreased with TCE application. In conclusion, in the light of the data in this study, we believe that high-dose gentamicin causes side effects in the kidneys, while TCE may have antioxidant, antiapoptotic, protective and curative effects. However, additional studies are needed to confirm this assumption.

Keywords

• Antioxidant
• apoptosis
• gentamicin
• nephrotoxicity
• Tarantula cubensis extract.

References

1. Abdelzaher, W.Y., El-Tahawy, N.F. G., Ali A.H.S.A.B., Mohamed H.A., Welson N.N. & Labib D.A. A. (2023) Rivastigmine ameliorates gentamicin experimentally induced acute renal toxicity. International Immunopharmacology, 114, 109492. 10.1016/j.intimp.2022.109492
2. Agena, R., Cortes-Sanchez, A.J., Hernandez-Sanchez, H. & Jaramillo-Flores M.E. (2023) Pro-apoptotic activity of bioactive compounds from seaweeds: promising sources for developing novel anticancer drugs. Marine Drugs, 21(3), 182, 10.3390/md21030182
3. Akbari, B., Baghaei-Yazdi, N., Bahmaie, M. & Abhari F.M. (2022) The role of plant-derived natural antioxidants in reduction of oxidative stress. BioFactors, 48, 611-633. 10.1002/biof.1831
4. Aksit, H., & Bildik, A. (2008). Apoptosis. Van Veterinary Journal, 19(1), 55-63.
5. Aldahmash, B.A., El-Nagar, D.M., & Ibrahim, K.E. (2016). Reno-protective effects of propolis on gentamicin-induced acute renal toxicity in swiss albino mice. Nefrologia, 36(6), 643-652. 10.1016/j.nefro.2016.06.004
6. Bai, R., Fan J., Wang Y., Wang Y., Li X., & Hu F. (2023) Protective effect of Cistanche deserticola on gentamicin-induced nephrotoxicity in rats. Chinese Herbal Medicines, 15 (1), 102-109. 10.1016/j.chmed.2022.03.008
7. Basar, G. (2014). Homeopati: Doğal, yan etkisiz ve bütünsel bir tedavi yöntemi. Turkiye Klinikleri Family Medicine - Special Topics, 5(4), 41-45.
8. Bratton, S.B., MacFarlane, M., Cain, K., & Cohen, G.M. (2000). Protein complexes activate distinct caspase cascades in death receptor and stress induced apoptosis. Experimental Cell Research, 256(1), 27–33. 10.1006/excr.2000.4835

9. Dimova, M., Tugai, A., Tugai, T., Iutynska, G., Dordevic, D., & Kushkevych, I. (2022). Molecular research of lipid peroxidation and antioxidant enzyme activity of comamonas testosteroni bacterial cells under the hexachlorobenzene impact. International Journal of Molecular Sciences, 23(19), 1-11. 10.3390/ijms231911415
10. Dirican, E., Ozcan, H., Uzunçakmak S.K. & Takim U. (2023) Evaluation expression of the caspase-3 and caspase-9 apoptotic genes in schizophrenia patients. Clinical Psychopharmacology and Neuroscience, 21(1): 171-178. 10.9758/cpn.2023.21.1.171
11. Elkhoely, A. (2023) Liraglutide ameliorates gentamicin-induced acute kidney injury in rats via PGC-1α- mediated mitochondrial biogenesis: Involvement of PKA/CREB and Notch/Hes-1 signaling pathways. International Immunopharmacology, 114, 109578. 10.1016/j.intimp.2022.109578
12. Elmore, S. (2007). Apoptosis: A review of programmed cell death. Toxicologic Pathology, 35(4), 495–516. 10.1080/01926230701320337
13. Geshnigani, S.S.H., Mahdavinia, M., Kalantar, M., Goudarzi, M., Khorsandi, L., & Kalantar H. (2023) Diosmin prophylaxis reduces gentamicin-induced kidney damage in rats. Naunyn-Schmiedeberg's Archives of Pharmacology, 396, 63–71.10.1007/s00210-022-02295-3
14. Hodiamont, C.J., van den Broek, A.K., de Vroom, S.L., Prins J.M., Mathot R.A.A. & van Hest R.M. (2022). Clinical Pharmacokinetics of gentamicin in various patient populations and consequences for optimal dosing for gram-negative infections: an updated review. Clinical Pharmacokinetics, 61, 1075–1094. 10.1007/s40262-022-01143-0
15. Ilhan, F. (2018). Homeopatiyle sağlıklı kalmak. Journal of Traditional and Complementary Medicine, 1(1), 29-34. 10.5336/jtracom.2017-56452
16. Kacar, C., Zonturlu, A.K., Oral, H., Yildiz, S., & Ari, U.C. (2007). İneklerde erken puerperal dönemde theranekron® uygulamalarının uterus involusyonu ve vajinal akıntı üzerine etkisi. Kafkas Universitesi Veteriner Fakültesi Dergisi, 13(1), 11-15. 10.9775/kvfd.2006.36-A
17. Kader, C., Sünbül, M., Daş, Y.K., Yarım, M., Bedir, A., Karaca, E., Celikbilek, M., & Özaras, R. (2017). Telbivudine attenuates gentamicin-induced kidney injury in rats. International Journal of Antimicrobial Agents, 49(5), 595-602. 10.1016/j.ijantimicag.2017.01.015
18. Kalkan, Y., Asena, K., Kapakin, T., Kara, A., Atabay, T., Karadeniz, A., Simsek, N., Karakus, E., Can, I., Yildirim, S., Ozkanlar, S., & Sengul, E. (2012). Protective effect of Panax ginseng against serum biochemical changes and apoptosis in kidney of rats treated with gentamicin sulphate. Journal of Molecular Histology, 43(5), 603–613. 10.1007/s10735-012-9412-4
19. Karabacak, M., Eraslan, G., Kanbur, M., & Sarıca, Z.S. (2015). Effects of Tarantula cubensis D6 on aflatoxin induced injury in biochemical parameters in rats. Homeopathy, 104(3), 205-210. 10.1016/j.homp.2015.02.005
20. Karabulut, E. (2016). Gentamisinle nefrotoksisite sıçanlarda l-argininin koruyucu etkisinde antioksidan mekanizmaların rolü [Doctoral dissertation University of Çukurova]. https://acikbilim.yok.gov.tr/handle/20.500.12812/124726.
21. Khaksari, M., Esmaili, S., Abedloo, R., & Khastar, H. (2021). Palmatine ameliorates nephrotoxicity and hepatotoxicity induced by gentamicin in rats. Archives of Physiology and Biochemistry, 127(3), 273–278. 10.1080/13813455.2019.1633354
22. Leonard, D.F., Mahamadou, B., Albert, S., Basile, T., Sekou, B. & Bale, B. (2023) Effects of fruits of aqueous extract of Sarcocephalus latifolius b. on gentamicin-induced nephrotoxicity in rats. Journal of Pharmacy and Pharmacology Research, 7(1), 12-19. 10.26502/fjppr.066
23. Li, B., Li, N., Wang, N., Li, C., Liu, X., Cao, Z., Xing, C. & Wang, S. (2023) Targeting ROS-sensitive TRP ion channels for relieving oxidative stress-related diseases based on nanomaterials. Materials Today Advances, 17,1-19. 10.1016/j.mtadv.2022.100335
24. Li, M., Maderdrut, J.L., Lertora, J.J., Arimura, A., & Batuman, V. (2008). Renoprotection by pituitary adenylate cyclase activating polypeptide in multiple myeloma and other kidney diseases. Regulatory Peptides, 145(1-3), 24-32. 10.1016/j.regpep.2007.09.012
25. Lotfollahzadeh, S., Alizadeh, M.R., Mohri, M., & Mokhber-Dezfouli, M.R. (2012). The therapeutic effect of Tarantula cubensis Extract (Theranekron(R)) in foot and mouth disease in cattle: a randomised trial in an endemic setting. Homeopathy, 101(3), 159-164. 10.1016/j.homp.2012.05.008
26. Lowry, O.H., Rosebrough, N.J., Farr, A.L., & Randall, R.J. (1951). Protein Measurement with folin phenol reagent. Journal of Biological Chemistry, 193, 265-75.
27. Mak, T. (2003). The E. Donnall Thomas lecture apoptosis: "This death that makes life live". Biology of Blood and Marrow Transplantation, 9, 483-488. 10.1016/S1083-8791(03)00215-5
28. Memisogullari, R. (2005). The role of free radicals and the effect of antioxidants in diabetes. Düzce Tıp Fakültesi Dergisi, 3, 30-39.
29. Nadeem R.I., Aboutaleb A.S., Younis N.S., Ahmed H.I. (2023) Diosmin Mitigates Gentamicin-Induced Nephrotoxicity in Rats: Insights on miR-21 and -155 Expression, Nrf2/HO-1 and p38-MAPK/NF-κB Pathways. Toxics, 11, 48. 10.3390/toxics11010048
30. Ozbek, S.S. (2019). Sıçan böbrek iskemi reperfüzyon modelinde Tarantula cubensis ekstraktının etkileri. [Doctoral dissertation University of Atatürk]. https://acikbilim.yok.gov.tr/handle/20.500.12812/54332.
31. Ozsayin, G.H. (2019). Gentamisin ile sıçanlarda oluşturulan nefrotoksisite üzerinde Cyclotrichium niveum ekstresinin koruyucu etkisi. [Master dissertation University of Cukurova]. https://acikbilim.yok.gov.tr/handle/20.500.12812/123637.
32. Puppel, K., Kapusta, A., & Kuczynska, B. (2015). The etiology of oxidative stress in the various species of animals. Journal of the Science of Food and Agriculture, 95(11), 2179-2184. 10.1002/jsfa.7015
33. Rizwana, K., Mohammad, A., Shah, C.S., Fahamiya, N. & Shiffa, M. (2022). Nephroprotective activity of the hydro-alcoholic, ethanolic extract and its fractions of tukhme soya (Anethum sowa Roxb.) against gentamicin induced nephrotoxicity in albino rats. Journal of Young Pharmacists, 14(1), 50-55. 10.5530/jyp.2022.14.10
34. Said, M.M. (2011). The protective effect of eugenol against gentamicin induced nephrotoxicity and oxidative damage in rat kidney. Fundamental & Clinical Pharmacology, 25(6), 708-716. 10.1111/j.1472-8206.2010.00900.x
35. Sakr, S. & Kamel M.A. (2023) Effect of alogliptin and l-carnitine on nephrotoxicity-inducedby gentamicin in rats. Zagazig Veterinary Journal, 51(1), 45-58. 10.21608/zvjz.2023.176497.1194
36. Samy, M., Ahmed, R.S.I., Shanab, O., Maher, Z.M., Sedik, W.F., Mostafa, L., El-ghoneimy, A.A. (2023) Protective and ameliorative effects of Curcumin and/or Quercetin against gentamicin induced testicular damage in rats. SVU- International Journal of Veterinary Sciences, 6(1), 63-73. 10.21608/svu.2023.173096.1236
37. Secilmis, M.A., Karatas, Y., Yorulmaz, O., Buyukafsar, K., Singirik, E., Doran, F., Inal, C., & Dikmen, A. (2005). Protective effect of l-arginine intake on the impaired renal vascular responses in the gentamicin-treated rats. Nephron Physiology, 100(2), 13-20. 10.1159/000084657
38. Sharma, S.P. (2004). Nitric oxide and the kidney. Indian Journal of Nephrology, 14(3), 77-84.
39. Sun, Y., Oberley, L.W., & Li, Y. (1988). A simple for clinical assay of superoxide dismutase. Clinical Chemistry, 34, 497-500.
40. Tanyeli, A., Eraslan, E., Guler, M.C., Sebin, S.O., Celebi, D., Ozgeris, F.B., Toktay, E. (2019) Investigation of biochemical and histopathological effects of tarantula cubensis D6 on lung tissue in cecal ligation and puncture-induced polymicrobial sepsis model in rats. Medicine Science 8: 644-650. 10.5455/medscience.2019.08.9045
41. Ulutas, B., Kiral, F., & Birincioglu, S. (2006). Unable to protect gentamicin induced nephrotoxicity with allopurinol in rats. Ankara Üniversitesi Veteriner Fakültesi Dergisi, 53, 65-68. 10.1501/Vetfak_0000000066
42. Vaux, D.L., & Flavell, R.A. (2000). Apoptosis genes and autoimmunity. Current Opinion in Immunology, 12(6), 719–724. 10.1016/s0952-7915(00)00168-0
43. Veljkovic, M., Pavlovic, D.R., Stojiljkovic, N., Ilic, S., Jovanovic, I., Ulrih, N.P., Rakic, V., Velickovic, L., & Sokolovic, D. (2016). Bilberry: Chemical profiling, in vitro and in vivo antioxidant activity and nephroprotective effect against gentamicin toxicity in rats. Phytotherapy Research, 31(1), 115-123. 10.1002/ptr.5738
44. Vervliet, T., Duelen, R., Pradhan, A., Rovere, R.L., Roderick, H.L. & Sampaolesi, M. (2023) Cardiomyocyte differentiation from human induced pluripotent stem cells is delayed following knockout of Bcl-2. Journal of Cell Science, 136 (2): jcs260216. 10.1242/jcs.260216
45. Volpini, R.A., Balbi, A.P., Costa, R.S., & Coimbra, T.M. (2006). Increased expression of p38 mitogen- activated protein kinase is related to the acute renal lesions induced by gentamicin. Brazilian Journal of Medical and Biological Research, 39(6), 817-23. 10.1590/s0100-879x2006000600016
46. Vural, H., Demir, C.V., Yılmaz, N., & Eren, D. (2007). Alzheimer hastalığında total antioksidan kapasitenin araştırılması. Tıp Araştırmaları Dergisi, 5(2), 63-66.
47. Wang, C., Wang R., Hu, L., Xi, M., Wang, M., Ma, Y., Chen, J., Liu, C., Song, Y., Ding, N. & Gao P. (2023) Metabolites and metabolic pathways associated with allelochemical effects of linoleic acid on Karenia mikimotoi. Journal of Hazardous Materials, 447, 130815. 10.1016/j.jhazmat.2023.130815
48. Wijayanti, H.N., Fadhilah, Y.N., Yuniarti, W.M., Lukiswanto, B.S., Arimbi, A., Suprihati, E. Kurnijasanti R. (2023) Protective effect of Moringa oleifera leaves extract against gentamicin induced hepatic and nephrotoxicity in rats. Iraqi Journal of Veterinary Sciences, 37 (1), 129-135. 10.33899/ijvs.2022.133276.2197
49. Yadav, N., Sharma, S., Sharma, S., & Sharma, K.P. (2017). Critical analysis of protective role of plants against gentamicin induced nephrotoxicity. Indian Journal of Environmental Sciences, 21(1), 1-34. 10.5281/zenodo.3964264
50. Yaman, I., Balikci, E. (2010) Protective effects of nigella sativa against gentamicin-induced nephrotoxicity in rats. Experimental and Toxicologic Pathology, 62, 183-190. 10.1016/j.etp.2009.03.006
51. Yarijani, Z.M., Najafi, H., & Madani, S.H. (2016). Protective effect of crocin on gentamicin-induced nephrotoxicity in rats. Iranian Journal of Basic Medical Sciences, 19(3), 337-343.
52. Yilmaz, M., Mert, H., Irak, K., Erten, R., & Mert, N. (2018) The effect of fucoidan on the gentamicin induced nephrotoxicity in rats. Fresenius Environmental Bulletin, 27(4), 2235-2241. 10.1501/vetfak_0000002821
53. Yoshioka, T., Kawada, K., & Shimada, T. (1979). Lipid peroxidation in maternal and cord blood and protective mechanism against active oxygen toxicity in the blood. American Journal of Obstetrics & Gynecology, 135, 372–376. 10.1016/0002-9378(79)90708-7