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Effects of bufadıenolıdes from Bufo vırıdıs toad venom on blood biochemical compositions and thromboelastographic parameters

Yıl 2023, Cilt: 27 Sayı: 3, 995 - 1003, 28.06.2025

Ziyoda Mirakhmetova Natalia Vypova Akmal M. Asrorov Ansor Yashinov Sharafitdin Mirzaakhmedov Mugrajitdin Tashmukhamedov Abulimiti Yili Haji Akber Aisa Shavkat Salikhov

Öz

Bufadienolides, cyclopentanophenantrene derivatives that possess similar structures to cardiac glycosides, have been established to reveal cytotoxicity. Their higher concentrations as anticancer means are expected to affect the normal function of the heart, liver, and kidney. In this work, we established the mass ratio of bufadienolides isolated from the venom of Bufo viridis. Arenobufagin, gamabufotalin, telocinobufagin, and marinobufagin were found as the major compounds in the sum. Their effects on biological parameters, used as indicators of the normal functioning of organs, were determined in rabbits. The blood samples, taken on the 10th and 30th days following the drug administration, showed these paramaters reaching the control levels for 30 days in all studied doses: 0.15, 0.45, and 0.6 mg/kg. The 0.15 and 0.6 mg/kg doses were established not to cause significant changes in the activities of alanine aminotransferase and aspartate aminotransferase, and the quantities of cholesterol and fasting blood sugar in blood samples. Significant changes were found in quantities of glucose (a reduction) and urea (an increase) on the 10th day of the administration. But their levels reached the control level for the next 20 days. We observed significant differences in thromboelastographic parameters in mice on the 10th day after the drug administration in a 0.15 mg/kg dose. In mice, LD50 levels of intravenous, subcutaneous, and oral administrations made 14.5, 110, and 215 mg/kg, respectively. These results enable the suggestion of optimum concentration that does not cause severe damage to the functions of organs.

Anahtar Kelimeler

Toad venom bufadienolides acute toxicity chronic toxicity glucose urea.

Kaynakça

  • [1] Filho ES, Pio YPF, Chaves MH, Ferreira PMP, Fonseca MG, Pessoa C, Lima DJB, Araújo BQ, Vieira GM Jr. Chemical constituents and cytotoxic activity of Rhinella jimi (Anura: Bufonidae). J Braz Chem Soc. 2021; 32(5): 1060–1069. http://doi.org/10.21577/0103-5053.20210009.4
  • [2] Fujii E, Isnada Y, Kakoki M, Nishimura N, Endo S, Fujiwara S, Wada N, Kawano Y, Okuno Y, Sugimoto T, Hata H. Bufalin induces DNA damage response under hypoxic condition in myeloma cells. Oncol Lett. 2018; 15(5): 6443–6449. http://doi.org/10.3892/ol.2018.8091
  • [3] Hashimoto S, Jing Y, Kawazoe N, Masuda Y, Nakajo S, Yoshida T, Kuroiwa Y, Nakaya K. Bufalin reduces the level of topoisomerase II in human leukemia cells and affects the cytotoxicity of anticancer drugs. Leuk Res. 1997; 21(9): 875–83. https://doi.org/10.1016/S0145-2126(97)00061-1
  • [4] LingHu HR, Luo H, Gang L. Bufalin induces glioma cell death by apoptosis or necroptosis. OncoTargets Ther. 2020; 13: 4767–4778. https://doi.org/10.2147/OTT.S242567
  • [5] Yuan J, Zhou X, Cao W, Bi L, Zhang Y, Yang Q, Wang S. Improved antitumor efficacy and pharmacokinetics of bufalin via PEGylated liposomes. Nanoscale Res Lett. 2017; 12: 585. https://doi.org/10.1186/s11671-017-2346-8
  • [6] Yue Q, Zhen H, Huang M, Zheng X, Feng L, Jiang B, Yang M, Wu W, Liu X, Guo D. Proteasome inhibition contributed to the cytotoxicity of arenobufagin after its binding with Na⁺, K⁺-ATPase in human cervical carcinoma HeLa cells. PLoS ONE. 2016; 7: e0159034. http://doi.org/10.1371/journal.pone.0159034
  • [7] Zhang Y, Yuan B, Bian B, Zhao H, Kiyomi A, Hayashi H, Iwatani Y, Sugiura M, Takagi N. Cytotoxic effects of hellebrigenin and arenobufagin against human breast cancer cells. Front Oncol. 2021; 11: 711220. https://doi.org/10.3389/fonc.2021.711220
  • [8] Han L, Yuan B, Shimada R, Hayashi H, Si N, Zhao HY, Bian B, Takagi N. Cytocidal effects of arenobufagin and hellebrigenin, two active bufadienolide compounds, against human glioblastoma cell line U-87. Int J Oncol. 2018; 53(6): 2488–2502. https://doi.org/10.3892/ijo.2018.4567
  • [9] Zhang DM, Liu JS, Deng LJ, Chen MF, Yiu A, Cao HH, Tian HY, Fung KP, Kurihara H, Pan JX, Ye WC. Arenobufagin, a natural bufadienolide from toad venom, induces apoptosis and autophagy in human hepatocellular carcinoma cells through inhibition of PI3K/Akt/mTOR pathway. Carcinogenesis. 2013; 34(6): 1331–1342. https://doi.org/10.1093/carcin/bgt060
  • [10] Yuan B, Xu K, Shimada R, Li J, Hayashi H, Okazaki M, Takagi N. Cytotoxic effects of arsenite in combination with gamabufotalin against human glioblastoma cell lines. Front Oncol. 2021; 11: 628914. https://doi.org/10.3389/fonc.2021.628914
  • [11] Yuan B, Shimada R, Xu K, Han L, Si N, Zhao H, Bian B, Hayashi H, Okazaki M, Takagi N. Multiple cytotoxic effects of gamabufotalin against human glioblastoma cell line U-87. Chem Biol Interact. 2019; 314: 108849. https://doi.org/10.1016/j.cbi.2019.108849
  • [12] Yuan B, He J, Kisoh K, Hayashi H, Tanaka S, Si N, Zhao HY, Hirano T, Bian B, Takagi N. Effects of active bufadienolide compounds on human cancer cells and CD4⁺CD25⁺Foxp3⁺ regulatory T cells in mitogen-activated human peripheral blood mononuclear cells. Oncol Rep. 2016; 36: 1377–1384. http://doi.org/10.3892/or.2016.4946
  • [13] Yu Z, Guo W, Ma X, Zhang B, Dong P, Huang L, Wang X, Wang C, Huo X, Yu W, Yi C, Xiao Y, Yang W, Qin Y, Yuan Y, Meng S, Liu Q, Deng W. Gamabufotalin, a bufadienolide compound from toad venom, suppresses COX-2 expression through targeting IKKβ/NF-κB signaling pathway in lung cancer cells. Mol Cancer. 2014; 13: 203. https://doi.org/10.1186/1476-4598-13-203
  • [14] Tang N, Shi L, Yu Z, Dong P, Wang C, Huo X, Zhang B, Huang S, Deng S, Liu K, Ma T, Wang X, Wu L, Ma XC. Gamabufotalin, a major derivative of bufadienolide, inhibits VEGF-induced angiogenesis by suppressing VEGFR-2 signaling pathway. Oncotarget. 2016; 7(3): 3533–3547. https://doi.org/10.18632/oncotarget.6514
  • [15] Filho EDSM, Chaves MH, Ferreira PMP, Pessoa C, Lima DJB, Maranhão SSA, de Jesus Rodrigues D, Vieira Júnior GM. Cytotoxicity potential of chemical constituents isolated and derivatised from Rhinella marina venom. Toxicon. 2021; 194: 37–43. https://doi.org/10.1016/j.toxicon.2021.02.006
  • [16] Machado KDC, Sousa LQ, Lima DJB, Soares BM, Cavalcanti BC, Maranhão SS, Noronha JDC, Rodrigues DJ, Militão GCG, Chaves MH, Vieira-Júnior GM, Pessoa C, Moraes MO, Sousa JMCE, Melo-Cavalcante AAC, Ferreira PMP. Marinobufagin, a molecule from poisonous frogs, causes biochemical, morphological and cell cycle changes in human neoplasms and vegetal cells. Toxicol Lett. 2018; 285: 121–131. https://doi.org/10.1016/j.toxlet.2017.12.018.
  • [17] Banfi FF, Guedes K, Andrighetti CR, Aguiar AC, Debiasi BW, Noronha J, Rodrigues D, Júnior GM, Sanchez BA. Antiplasmodial and cytotoxic activities of toad venoms from Southern Amazon, Brazil. Korean J Parasitol. 2016; 54(4): 415-421. https://doi.org/10.3347/kjp.2016.54.4.415.
  • [18] Amaral LS, Martins Ferreira J, Predes D, Abreu JG, Noël F, Quintas LEM. Telocinobufagin and Marinobufagin produce different effects in LLC-PK1 Cells: A case of functional selectivity of Bufadienolides. Int J Mol Sci. 2018; 19(9): 2769. https://doi.org/10.3390/ijms19092769.
  • [19] Soliev AB, Mirzaakhmedov ShYa, Tashmukhamedov MS, Kamaev FG, Salikhov ShI, Zakirova NI, Abramov AYu, Usanova IV, Syrov VN, Khushbaktova ZA. Chemical composition and biological activity of total bufadienolides from the Central Asian Bufo viridis toad venom. Pharm Chem J. 2007; 41: 600-604. https://doi.org/10.1007/s11094-008-0024-y.
  • [20] Agzamkhujaeva KhT, Mirzaakhmedov ShYa, Yakubova RA, Tashmukhamedov MS. Study of embryotoxic, teratogen actions of the drug “Bakagin” from the parotid secretes central asian green toad Bufo Viridis Laur and its effect to the reproductive function of rats. Eur J Biomed Life Sci. 2019; 3: 23–29.
  • [21] Usanova IV, Khushbaktova ZA, Syrov VN, Azizov DE, Mirzaakhmedov ShIa, Soliev AB, Tashmukhamedov MS, Salikhov ShI. Kardiotropnaia aktivnost' summy bufadienolidov iz iada sredneaziatskoĭ zhaby Bufo viridis [Cardiotropic activity of total bufadienolides from the poison of Central Asian toad Bufo viridis]. Eksp Klin Farmakol. 2002; 65(4): 23-27.
  • [22] Ladefoged LK, Schiøtt B, Fedosova NU. Beneficent and maleficent effects of cations on Bufadienolide binding to Na+,K+-ATPase. J Chem Inf Model. 2021; 61(2): 976-986. https://doi.org/10.1021/acs.jcim.0c01396.
  • [23] Silva E, Soares-da-Silva P. New Insights into the Regulation of Na+,K+-ATPase by Ouabain, In Ed: Jeon KW, International Review of Cell and Molecular Biology. Academic Press, 2012; 294: 99-132. https://doi.org/10.1093/carcin/bgt060.
  • [24] Liu Z, Que S, Xu J, Peng T. Alanine aminotransferase-old biomarker and new concept: a review. Int J Med Sci. 2014; 11(9): 925-935. https://doi.org/10.7150/ijms.8951.
  • [25] Toney MD. Reaction specificity in pyridoxal phosphate enzymes. Arch Biochem Biophys. 2005; 433(1): 279-287. https://doi.org/10.1016/j.abb.2004.09.037.
  • [26] Kim W, Flamm SL, Di Bisceglie AM, Bodenheimer HC. Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease. Hepatology. 2008; 47(4): 1363-1370. https://doi.org/10.1002/hep.22109.
  • [27] Washington IM, Hoosier GV. Clinical Biochemistry and Hematology. In: Suckow MA, Stevens KA, Wilson RP. (Eds). The Laboratory Rabbit, Guinea Pig, Hamster, and Other Rodents. Academic Press, Elsevier Inc., 2012, pp. 57-116. https://doi.org/10.1016/B978-0-12-380920-9.00003-1.
  • [28] Evans GO. Animal Clinical Chemistry: A Practical Handbook for Toxicologists and Biomedical Researchers, second ed., CRC Press, USA, 2009. https://doi.org/10.1201/9781420080124.
  • [29] Sookoian S, Pirola CJ. Alanine and aspartate aminotransferase and glutamine-cycling pathway: their roles in pathogenesis of metabolic syndrome. World J Gastroenterol. 2012; 18(29): 3775-3781. https://doi.org/10.3748/wjg.v18.i29.3775.
  • [30] Csonka C, Kupai K, Bencsik P, Görbe A, Pálóczi J, Zvara A, Puskás LG, Csont T, Ferdinandy P. Cholesterol-enriched diet inhibits cardioprotection by ATP-sensitive K+ channel activators cromakalim and diazoxide. Am J Physiol Heart Circ Physiol. 2014; 306: H405–413. https://doi.org/10.1152/ajpheart.00257.2013.
  • [31] Campia I, Sala V, Kopecka J, Leo C, Mitro N, Costamagna C, Caruso D, Pescarmona G, Crepaldi T, Ghigo D, Bosia A, Riganti C. Digoxin and ouabain induce the efflux of cholesterol via liver X receptor signalling and the synthesis of ATP in cardiomyocytes. Biochem J. 2012; 447(2): 301–311. https://doi.org/10.1042/BJ20120200.
  • [32] Seki M, Nakayama M, Sakoh T, Yoshitomi R, Fukui A, Katafuchi E, Tsuda S, Nakano T, Tsuruya K, Kitazono T. Blood urea nitrogen is independently associated with renal outcomes in Japanese patients with stage 3-5 chronic kidney disease: a prospective observational study. BMC Nephrol. 2019; 20(1): 115. https://doi.org/10.1186/s12882-019-1306-1.
  • [33] Lan Q, Zheng L, Zhou X, Wu H, Buys N, Liu Z, Sun J, Fan H. The value of blood urea nitrogen in the prediction of risks of cardiovascular disease in an older population. Front Cardiovasc Med. 2021; 8: 614117. https://doi.org/10.3389/fcvm.2021.614117.
  • [34] Robinson WF, Robinson NA. Cardiovascular System. In: Maxie GM. (Ed.). Jubb, Kennedy & Palmer's Pathology of Domestic Animals. 6th ed. Saunders LTD, USA, 2016, pp. 1–101.e1. https://doi.org/10.1016/B978-0-7020-5319-1.00012-8.

Yıl 2023, Cilt: 27 Sayı: 3, 995 - 1003, 28.06.2025

Ziyoda Mirakhmetova Natalia Vypova Akmal M. Asrorov Ansor Yashinov Sharafitdin Mirzaakhmedov Mugrajitdin Tashmukhamedov Abulimiti Yili Haji Akber Aisa Shavkat Salikhov

Öz

Kaynakça

  • [1] Filho ES, Pio YPF, Chaves MH, Ferreira PMP, Fonseca MG, Pessoa C, Lima DJB, Araújo BQ, Vieira GM Jr. Chemical constituents and cytotoxic activity of Rhinella jimi (Anura: Bufonidae). J Braz Chem Soc. 2021; 32(5): 1060–1069. http://doi.org/10.21577/0103-5053.20210009.4
  • [2] Fujii E, Isnada Y, Kakoki M, Nishimura N, Endo S, Fujiwara S, Wada N, Kawano Y, Okuno Y, Sugimoto T, Hata H. Bufalin induces DNA damage response under hypoxic condition in myeloma cells. Oncol Lett. 2018; 15(5): 6443–6449. http://doi.org/10.3892/ol.2018.8091
  • [3] Hashimoto S, Jing Y, Kawazoe N, Masuda Y, Nakajo S, Yoshida T, Kuroiwa Y, Nakaya K. Bufalin reduces the level of topoisomerase II in human leukemia cells and affects the cytotoxicity of anticancer drugs. Leuk Res. 1997; 21(9): 875–83. https://doi.org/10.1016/S0145-2126(97)00061-1
  • [4] LingHu HR, Luo H, Gang L. Bufalin induces glioma cell death by apoptosis or necroptosis. OncoTargets Ther. 2020; 13: 4767–4778. https://doi.org/10.2147/OTT.S242567
  • [5] Yuan J, Zhou X, Cao W, Bi L, Zhang Y, Yang Q, Wang S. Improved antitumor efficacy and pharmacokinetics of bufalin via PEGylated liposomes. Nanoscale Res Lett. 2017; 12: 585. https://doi.org/10.1186/s11671-017-2346-8
  • [6] Yue Q, Zhen H, Huang M, Zheng X, Feng L, Jiang B, Yang M, Wu W, Liu X, Guo D. Proteasome inhibition contributed to the cytotoxicity of arenobufagin after its binding with Na⁺, K⁺-ATPase in human cervical carcinoma HeLa cells. PLoS ONE. 2016; 7: e0159034. http://doi.org/10.1371/journal.pone.0159034
  • [7] Zhang Y, Yuan B, Bian B, Zhao H, Kiyomi A, Hayashi H, Iwatani Y, Sugiura M, Takagi N. Cytotoxic effects of hellebrigenin and arenobufagin against human breast cancer cells. Front Oncol. 2021; 11: 711220. https://doi.org/10.3389/fonc.2021.711220
  • [8] Han L, Yuan B, Shimada R, Hayashi H, Si N, Zhao HY, Bian B, Takagi N. Cytocidal effects of arenobufagin and hellebrigenin, two active bufadienolide compounds, against human glioblastoma cell line U-87. Int J Oncol. 2018; 53(6): 2488–2502. https://doi.org/10.3892/ijo.2018.4567
  • [9] Zhang DM, Liu JS, Deng LJ, Chen MF, Yiu A, Cao HH, Tian HY, Fung KP, Kurihara H, Pan JX, Ye WC. Arenobufagin, a natural bufadienolide from toad venom, induces apoptosis and autophagy in human hepatocellular carcinoma cells through inhibition of PI3K/Akt/mTOR pathway. Carcinogenesis. 2013; 34(6): 1331–1342. https://doi.org/10.1093/carcin/bgt060
  • [10] Yuan B, Xu K, Shimada R, Li J, Hayashi H, Okazaki M, Takagi N. Cytotoxic effects of arsenite in combination with gamabufotalin against human glioblastoma cell lines. Front Oncol. 2021; 11: 628914. https://doi.org/10.3389/fonc.2021.628914
  • [11] Yuan B, Shimada R, Xu K, Han L, Si N, Zhao H, Bian B, Hayashi H, Okazaki M, Takagi N. Multiple cytotoxic effects of gamabufotalin against human glioblastoma cell line U-87. Chem Biol Interact. 2019; 314: 108849. https://doi.org/10.1016/j.cbi.2019.108849
  • [12] Yuan B, He J, Kisoh K, Hayashi H, Tanaka S, Si N, Zhao HY, Hirano T, Bian B, Takagi N. Effects of active bufadienolide compounds on human cancer cells and CD4⁺CD25⁺Foxp3⁺ regulatory T cells in mitogen-activated human peripheral blood mononuclear cells. Oncol Rep. 2016; 36: 1377–1384. http://doi.org/10.3892/or.2016.4946
  • [13] Yu Z, Guo W, Ma X, Zhang B, Dong P, Huang L, Wang X, Wang C, Huo X, Yu W, Yi C, Xiao Y, Yang W, Qin Y, Yuan Y, Meng S, Liu Q, Deng W. Gamabufotalin, a bufadienolide compound from toad venom, suppresses COX-2 expression through targeting IKKβ/NF-κB signaling pathway in lung cancer cells. Mol Cancer. 2014; 13: 203. https://doi.org/10.1186/1476-4598-13-203
  • [14] Tang N, Shi L, Yu Z, Dong P, Wang C, Huo X, Zhang B, Huang S, Deng S, Liu K, Ma T, Wang X, Wu L, Ma XC. Gamabufotalin, a major derivative of bufadienolide, inhibits VEGF-induced angiogenesis by suppressing VEGFR-2 signaling pathway. Oncotarget. 2016; 7(3): 3533–3547. https://doi.org/10.18632/oncotarget.6514
  • [15] Filho EDSM, Chaves MH, Ferreira PMP, Pessoa C, Lima DJB, Maranhão SSA, de Jesus Rodrigues D, Vieira Júnior GM. Cytotoxicity potential of chemical constituents isolated and derivatised from Rhinella marina venom. Toxicon. 2021; 194: 37–43. https://doi.org/10.1016/j.toxicon.2021.02.006
  • [16] Machado KDC, Sousa LQ, Lima DJB, Soares BM, Cavalcanti BC, Maranhão SS, Noronha JDC, Rodrigues DJ, Militão GCG, Chaves MH, Vieira-Júnior GM, Pessoa C, Moraes MO, Sousa JMCE, Melo-Cavalcante AAC, Ferreira PMP. Marinobufagin, a molecule from poisonous frogs, causes biochemical, morphological and cell cycle changes in human neoplasms and vegetal cells. Toxicol Lett. 2018; 285: 121–131. https://doi.org/10.1016/j.toxlet.2017.12.018.
  • [17] Banfi FF, Guedes K, Andrighetti CR, Aguiar AC, Debiasi BW, Noronha J, Rodrigues D, Júnior GM, Sanchez BA. Antiplasmodial and cytotoxic activities of toad venoms from Southern Amazon, Brazil. Korean J Parasitol. 2016; 54(4): 415-421. https://doi.org/10.3347/kjp.2016.54.4.415.
  • [18] Amaral LS, Martins Ferreira J, Predes D, Abreu JG, Noël F, Quintas LEM. Telocinobufagin and Marinobufagin produce different effects in LLC-PK1 Cells: A case of functional selectivity of Bufadienolides. Int J Mol Sci. 2018; 19(9): 2769. https://doi.org/10.3390/ijms19092769.
  • [19] Soliev AB, Mirzaakhmedov ShYa, Tashmukhamedov MS, Kamaev FG, Salikhov ShI, Zakirova NI, Abramov AYu, Usanova IV, Syrov VN, Khushbaktova ZA. Chemical composition and biological activity of total bufadienolides from the Central Asian Bufo viridis toad venom. Pharm Chem J. 2007; 41: 600-604. https://doi.org/10.1007/s11094-008-0024-y.
  • [20] Agzamkhujaeva KhT, Mirzaakhmedov ShYa, Yakubova RA, Tashmukhamedov MS. Study of embryotoxic, teratogen actions of the drug “Bakagin” from the parotid secretes central asian green toad Bufo Viridis Laur and its effect to the reproductive function of rats. Eur J Biomed Life Sci. 2019; 3: 23–29.
  • [21] Usanova IV, Khushbaktova ZA, Syrov VN, Azizov DE, Mirzaakhmedov ShIa, Soliev AB, Tashmukhamedov MS, Salikhov ShI. Kardiotropnaia aktivnost' summy bufadienolidov iz iada sredneaziatskoĭ zhaby Bufo viridis [Cardiotropic activity of total bufadienolides from the poison of Central Asian toad Bufo viridis]. Eksp Klin Farmakol. 2002; 65(4): 23-27.
  • [22] Ladefoged LK, Schiøtt B, Fedosova NU. Beneficent and maleficent effects of cations on Bufadienolide binding to Na+,K+-ATPase. J Chem Inf Model. 2021; 61(2): 976-986. https://doi.org/10.1021/acs.jcim.0c01396.
  • [23] Silva E, Soares-da-Silva P. New Insights into the Regulation of Na+,K+-ATPase by Ouabain, In Ed: Jeon KW, International Review of Cell and Molecular Biology. Academic Press, 2012; 294: 99-132. https://doi.org/10.1093/carcin/bgt060.
  • [24] Liu Z, Que S, Xu J, Peng T. Alanine aminotransferase-old biomarker and new concept: a review. Int J Med Sci. 2014; 11(9): 925-935. https://doi.org/10.7150/ijms.8951.
  • [25] Toney MD. Reaction specificity in pyridoxal phosphate enzymes. Arch Biochem Biophys. 2005; 433(1): 279-287. https://doi.org/10.1016/j.abb.2004.09.037.
  • [26] Kim W, Flamm SL, Di Bisceglie AM, Bodenheimer HC. Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease. Hepatology. 2008; 47(4): 1363-1370. https://doi.org/10.1002/hep.22109.
  • [27] Washington IM, Hoosier GV. Clinical Biochemistry and Hematology. In: Suckow MA, Stevens KA, Wilson RP. (Eds). The Laboratory Rabbit, Guinea Pig, Hamster, and Other Rodents. Academic Press, Elsevier Inc., 2012, pp. 57-116. https://doi.org/10.1016/B978-0-12-380920-9.00003-1.
  • [28] Evans GO. Animal Clinical Chemistry: A Practical Handbook for Toxicologists and Biomedical Researchers, second ed., CRC Press, USA, 2009. https://doi.org/10.1201/9781420080124.
  • [29] Sookoian S, Pirola CJ. Alanine and aspartate aminotransferase and glutamine-cycling pathway: their roles in pathogenesis of metabolic syndrome. World J Gastroenterol. 2012; 18(29): 3775-3781. https://doi.org/10.3748/wjg.v18.i29.3775.
  • [30] Csonka C, Kupai K, Bencsik P, Görbe A, Pálóczi J, Zvara A, Puskás LG, Csont T, Ferdinandy P. Cholesterol-enriched diet inhibits cardioprotection by ATP-sensitive K+ channel activators cromakalim and diazoxide. Am J Physiol Heart Circ Physiol. 2014; 306: H405–413. https://doi.org/10.1152/ajpheart.00257.2013.
  • [31] Campia I, Sala V, Kopecka J, Leo C, Mitro N, Costamagna C, Caruso D, Pescarmona G, Crepaldi T, Ghigo D, Bosia A, Riganti C. Digoxin and ouabain induce the efflux of cholesterol via liver X receptor signalling and the synthesis of ATP in cardiomyocytes. Biochem J. 2012; 447(2): 301–311. https://doi.org/10.1042/BJ20120200.
  • [32] Seki M, Nakayama M, Sakoh T, Yoshitomi R, Fukui A, Katafuchi E, Tsuda S, Nakano T, Tsuruya K, Kitazono T. Blood urea nitrogen is independently associated with renal outcomes in Japanese patients with stage 3-5 chronic kidney disease: a prospective observational study. BMC Nephrol. 2019; 20(1): 115. https://doi.org/10.1186/s12882-019-1306-1.
  • [33] Lan Q, Zheng L, Zhou X, Wu H, Buys N, Liu Z, Sun J, Fan H. The value of blood urea nitrogen in the prediction of risks of cardiovascular disease in an older population. Front Cardiovasc Med. 2021; 8: 614117. https://doi.org/10.3389/fcvm.2021.614117.
  • [34] Robinson WF, Robinson NA. Cardiovascular System. In: Maxie GM. (Ed.). Jubb, Kennedy & Palmer's Pathology of Domestic Animals. 6th ed. Saunders LTD, USA, 2016, pp. 1–101.e1. https://doi.org/10.1016/B978-0-7020-5319-1.00012-8.
Toplam 34 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Eczacılık ve İlaç Bilimleri (Diğer)
Bölüm Articles
Yazarlar

Ziyoda Mirakhmetova

Natalia Vypova

Akmal M. Asrorov

Ansor Yashinov

Sharafitdin Mirzaakhmedov

Mugrajitdin Tashmukhamedov

Abulimiti Yili

Haji Akber Aisa

Shavkat Salikhov

Yayımlanma Tarihi 28 Haziran 2025
Yayımlandığı Sayı Yıl 2023 Cilt: 27 Sayı: 3

Kaynak Göster

APA Mirakhmetova, Z., Vypova, N., Asrorov, A. M., Yashinov, A., vd. (2025). Effects of bufadıenolıdes from Bufo vırıdıs toad venom on blood biochemical compositions and thromboelastographic parameters. Journal of Research in Pharmacy, 27(3), 995-1003.
AMA Mirakhmetova Z, Vypova N, Asrorov AM, Yashinov A, Mirzaakhmedov S, Tashmukhamedov M, Yili A, Aisa HA, Salikhov S. Effects of bufadıenolıdes from Bufo vırıdıs toad venom on blood biochemical compositions and thromboelastographic parameters. J. Res. Pharm. Haziran 2025;27(3):995-1003.
Chicago Mirakhmetova, Ziyoda, Natalia Vypova, Akmal M. Asrorov, Ansor Yashinov, Sharafitdin Mirzaakhmedov, Mugrajitdin Tashmukhamedov, Abulimiti Yili, Haji Akber Aisa, ve Shavkat Salikhov. “Effects of bufadıenolıdes from Bufo vırıdıs Toad Venom on Blood Biochemical Compositions and Thromboelastographic Parameters”. Journal of Research in Pharmacy 27, sy. 3 (Haziran 2025): 995-1003.
EndNote Mirakhmetova Z, Vypova N, Asrorov AM, Yashinov A, Mirzaakhmedov S, Tashmukhamedov M, Yili A, Aisa HA, Salikhov S (01 Haziran 2025) Effects of bufadıenolıdes from Bufo vırıdıs toad venom on blood biochemical compositions and thromboelastographic parameters. Journal of Research in Pharmacy 27 3 995–1003.
IEEE Z. Mirakhmetova, N. Vypova, A. M. Asrorov, A. Yashinov, S. Mirzaakhmedov, M. Tashmukhamedov, A. Yili, H. A. Aisa, ve S. Salikhov, “Effects of bufadıenolıdes from Bufo vırıdıs toad venom on blood biochemical compositions and thromboelastographic parameters”, J. Res. Pharm., c. 27, sy. 3, ss. 995–1003, 2025.
ISNAD Mirakhmetova, Ziyoda vd. “Effects of bufadıenolıdes from Bufo vırıdıs Toad Venom on Blood Biochemical Compositions and Thromboelastographic Parameters”. Journal of Research in Pharmacy 27/3 (Haziran 2025), 995-1003.
JAMA Mirakhmetova Z, Vypova N, Asrorov AM, Yashinov A, Mirzaakhmedov S, Tashmukhamedov M, Yili A, Aisa HA, Salikhov S. Effects of bufadıenolıdes from Bufo vırıdıs toad venom on blood biochemical compositions and thromboelastographic parameters. J. Res. Pharm. 2025;27:995–1003.
MLA Mirakhmetova, Ziyoda vd. “Effects of bufadıenolıdes from Bufo vırıdıs Toad Venom on Blood Biochemical Compositions and Thromboelastographic Parameters”. Journal of Research in Pharmacy, c. 27, sy. 3, 2025, ss. 995-1003.
Vancouver Mirakhmetova Z, Vypova N, Asrorov AM, Yashinov A, Mirzaakhmedov S, Tashmukhamedov M, Yili A, Aisa HA, Salikhov S. Effects of bufadıenolıdes from Bufo vırıdıs toad venom on blood biochemical compositions and thromboelastographic parameters. J. Res. Pharm. 2025;27(3):995-1003.