EXPERIMENTAL RESEARCH
A study to reveal the effectiveness of taxifolin in sunitinib-induced oxidative muscle damage in rats
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1
Department of Neurology, Medicine Faculty, Erzincan Binali Yıldırım University, Erzincan, Turkey
2
Department of Biochemistry, Erzurum Atatürk University, Turkey
3
Department of Pharmacology, Erzincan Binali Yıldırım University, Erzincan, Turkey
4
Department of Histology, Erzincan Binali Yıldırım University, Erzincan, Turkey
5
Department of Biostatistics, Erzincan Binali Yıldırım University, Erzincan, Turkey
Submission date: 2021-05-04
Final revision date: 2021-07-28
Acceptance date: 2021-07-28
Publication date: 2021-09-20
Arch Med Sci Civil Dis 2021;6(1):103-108
KEYWORDS
TOPICS
ABSTRACT
Introduction:
The aim of this study is to examine the oxidative damage caused by sunitinib on skeletal muscle and whether taxifolin is effective against that oxidative damage.
Material and methods:
Thirty albino Wistar male rats were used in the experiment. The rats were divided into 3 equal-sized groups: a sunitinib-only administered group (SUN), a sunitinib + taxifolin administered group (SUT), and a control group (CG) without treatment. Taxifolin and sunitinib were administered by oral gavage at a dose of 50 mg/kg for taxifolin and a dose of 25 mg/kg for sunitinib. Striated hind limb muscle tissue of rats was removed; malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD) levels were measured in muscle tissue; muscle tissue was examined histopathologically; creatine kinase (CK) levels were determined in the blood samples of rats; and the results were compared between the groups.
Results:
In the SUN group, MDA and CK values were statistically significantly higher than in the SUT and CG groups, but SOD and GSH values were statistically significantly lower. The SUT and CG groups were similar when compared. Histopathologically, congested blood vessels, oedema, degeneration, inflammation, and rupture of muscle fibres in muscle tissue were detected in the SUN group. However, in the SUT group it was observed that blood vessels were normal, there were no degenerative findings, and inflammation was resolved.
Conclusions:
Sunitinib causes oxidative damage to skeletal muscle tissue. Taxifolin prevents the toxic effect of sunitinib on skeletal muscle due to its antioxidant effects.
REFERENCES (29)
1.
Krause DS, Van Etten RA. Tyrosine kinases as targets for cancer therapy. N Engl J Med 2005; 353: 172-87.
2.
Motzer RJ, Hutson TE, Tomczak P, et al. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol 2009; 27: 3584-90.
3.
Faivre S, Demetri G, Sargent W, Raymond E. Molecular basis for sunitinib efficacy and future clinical development. Nat Rev Drug Discov 2007; 6: 734-45.
4.
Bello CL, Sherman L, Zhou J, et al. Effect of food on the pharmacokinetics of sunitinib malate (su11248), a multi-targeted receptor tyrosine kinase inhibitor: results from a phase i study in healthy subjects. Anticancer Drugs 2006; 17: 353-8.
5.
Gorini S, De Angelis A, Berrino L, Malara N, Rosano G, Ferraro E. Chemotherapeutic drugs and mitochondrial dysfunction: focus on doxorubicin, trastuzumab, and sunitinib. Oxid Med Cell Longev 2018; 2018: 7582730.
6.
Huillard O, Mir O, Peyromaure M, et al. Sarcopenia and body mass index predict sunitinib-induced early dose-limiting toxicities in renal cancer patients. Br J Cancer 2013; 108: 1034-41.
7.
Sorensen JC, Cheregi BD, Timpani CA, Nurgali K, Hayes A, Rybalka E. Mitochondria: inadvertent targets in chemotherapy-induced skeletal muscle toxicity and wasting? Cancer Chemother Pharmacol 2016; 78: 673-83.
8.
Scheede-Bergdahl C, Jagoe RT. After the chemotherapy: potential mechanisms for chemotherapy-induced delayed skeletal muscle dysfunction in survivors of acute lymphoblastic leukaemia in childhood. Front Pharmacol 2013; 4: 49.
9.
Damaraju VL, Kuzma M, Cass CE, Putman CT, Sawyer MB. Multitargeted kinase inhibitors imatinib, sorafenib and sunitinib perturb energy metabolism and cause cytotoxicity to cultured c2c12 skeletal muscle derived myotubes. Biochem Pharmacol 2018; 155: 162-71.
10.
Rice-Evans CA, Miller NJ, Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med 1996; 20: 933-56.
11.
Cotelle N. Role of flavonoids in oxidative stress. Curr Top Med Chem 2001; 1: 569-90.
12.
Asmi KS, Lakshmi T, Balusamy SR, Parameswari R. Therapeutic aspects of taxifolin – an update. J Adv Pharm Education Res 2017; 7: 187-9.
13.
Tang Z, Yang C, Zuo B, et al. Taxifolin protects rat against myocardial ischemia/reperfusion injury by modulating the mitochondrial apoptosis pathway. Peer J 2019; 7: e6383.
14.
Zu Y, Wu W, Zhao X, et al. Enhancement of solubility, antioxidant ability and bioavailability of taxifolin nanoparticles by liquid antisolvent precipitation technique. Int J Pharm 2014; 471: 366-76.
15.
Lim AY, Segarra I, Chakravarthi S, Akram S, Judson JP. Histopathology and biochemistry analysis of the interaction between sunitinib and paracetamol in mice. BMC Pharmacol 2010; 10: 14.
16.
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95: 351-8.
17.
Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with ellman’s reagent. Anal Biochem 1968; 25: 192-205.
18.
Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem 1988; 34: 497-500.
19.
Schulz JB, Lindenau J, Seyfried J, Dichgans J. Glutathione, oxidative stress and neurodegeneration. Eur J Biochem 2000; 267: 4904-11.
20.
Islam MS, Yu H, Miao L, Liu Z, He Y, Sun H. Hepatoprotective effect of the ethanol extract of illicium henryi against acute liver injury in mice induced by lipopolysaccharide. Antioxidants 2019; 8: 446.
21.
Gabryel B, Bontor K, Jarząbek K, et al. Sulodexide up-regulates glutathione s-transferase p1 by enhancing nrf2 expression and translocation in human umbilical vein endothelial cells injured by oxygen glucose deprivation. Arch Med Sci 2020; 16: 957-63.
22.
Imam F, Al-Harbi NO, Khan MR, et al. Protective effect of riva against sunitinib-induced cardiotoxicity by inhibiting oxidative stress-mediated inflammation: probable role of tgf- and smad signaling. Cardiovasc Toxicol 2020; 20: 281-90.
23.
Del Rio D, Stewart AJ, Pellegrini N. A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Nutr Metab Cardiovasc Dis 2005; 15: 316-28.
24.
Abreu IA, Cabelli DE. Superoxide dismutases-a review of the metal-associated mechanistic variations. Biochim Biophys Acta 2010; 1804: 263-74.
25.
Paech F, Abegg VF, Duthaler U, Terracciano L, Bouitbir J, Krähenbühl S. Sunitinib induces hepatocyte mitochondrial damage and apoptosis in mice. Toxicology 2018; 409: 13-23.
26.
Sumien N, Shetty RA, Gonzales EB. Creatine, creatine kinase, and aging. Subcell Biochem 2018; 90: 145-68.
27.
Adenis A, Bouché O, Bertucci F, et al. Serum creatine kinase increase in patients treated with tyrosine kinase inhibitors for solid tumors. Med Oncol 2012; 29: 3003-8.
28.
Maayah ZH, Ansari MA, El Gendy MA, Al-Arifi MN, Korashy HM. Development of cardiac hypertrophy by sunitinib in vivo and in vitro rat cardiomyocytes is influenced by the aryl hydrocarbon receptor signaling pathway. Arch Toxicol 2014; 88: 725-38.
29.
Sunil C, Xu B. An insight into the health-promoting effects of taxifolin (dihydroquercetin). Phytochemistry 2019; 166: 112066.