Advances in Clinical and Experimental Medicine
2019, vol. 28, nr 11, November, p. 1537–1543
doi: 10.17219/acem/111819
Publication type: original article
Language: English
Download citation:
Peripheral neurotoxic effects of cisplatin on rats and treatment with rutin
1 Department of Neurology, Erzincan University, Mengücek Gazi Research and Training Hospital, Turkey
2 Department of Pathology, Erzincan University, Mengücek Gazi Research and Training Hospital, Turkey
3 Department of Pharmacology, Faculty of Medicine, Erzincan University Hospital, Turkey
4 Department of Biochemistry, Faculty of Medicine, Erzurum University Hospital, Turkey
5 Department of Biostatistics, Faculty of Medicine, Erzincan University Hospital, Turkey
Abstract
Background. Cisplatin, used in cancer treatment, has toxic and apoptotic effects on the peripheral nervous system. Rutin, also known as vitamin P, has antioxidant and antiapoptotic activity.
Objectives. The purpose of this study was to investigate the biochemical and histopathologic efficacy of rutin on neurotoxic and apoptotic effects caused by cisplatin in the peripheral nervous system.
Material and Methods. Twenty-four albino Wistar male rats were divided into the following 4 groups: control group (CG), only cisplatin-injected group (CIS), cisplatin and rutin 50 mg/kg (RG-50)-injected group, and cisplatin and rutin 100 mg/kg (RG-100)-injected group. Analyses were performed on sciatic nerve tissue of experimental animals. Analyses of malondialdehyde (MDA), total glutathione (tGSH), glutathione reductase (GSHRd), glutathione-s-transferase (GST), and superoxide dismutase (SOD) were performed. Caspase-3 expression in nerve tissue was also investigated. The analyzed groups were compared with CG.
Results. Biochemical investigation shows that there is a statistically significant difference between CG and only CIS and RG-50. Control group and RG-100 were found to be similar. Cisplatin-induced changes were observed in histopathological analysis of the nerve tissue. The RG-100 and CG were found to be similar. The caspase-3 expression in the neural tissue was compared between groups. Control group and CIS were found to be different. Control group and RG-100 were found to be similar.
Conclusion. Antioxidant and antiapoptotic effectiveness of rutin was detected against the toxic effects caused by cisplatin in the peripheral nerve tissue.
Key words
apoptosis, antioxidants, cisplatin, rutin, caspase-3
References (27)
- Almutairi MM, Alanazi WA, Alshammari MA, et al. Neuro-protective effect of rutin against Cisplatin-induced neurotoxic rat model. BMC Complement Altern Med. 2017;17(1):472.
- Akman T, Akman L, Erbas O, Terek MC, Taskiran D, Ozsaran A. The preventive effect of oxytocin to cisplatin-induced neurotoxicity: An experimental rat model. Biomed Res Int. 2015;2015:167235.
- Chiorazzi A, Semperboni S, Marmiroli P. Current view in platinum drug mechanisms of peripheral neurotoxicity. Toxics. 2015;3(3):304–321.
- Singh Z, Karthigesu IP, Singh P, Kaur R. Use of malondialdehyde as a biomarker for assessing oxidative stress in different disease pathologies: A review. Iran J Public Health. 2014;43(3):7.
- Eslami S, Sahebkar A. Glutathione-S-transferase M1 and T1 null genotypes are associated with hypertension risk: A systematic review and meta-analysis of 12 studies. Curr Hypertens Rep. 2014;16(6):432.
- Couto N, Wood J, Barber J. The role of glutathione reductase and related enzymes on cellular redox homoeostasis network. Free Radic Biol Med. 2016;95:27–42.
- Pisoschi AM, Pop A. The role of antioxidants in the chemistry of oxidative stress: A review. Eur J Med Chem. 2015;97:55–74.
- Nagata S. Apoptosis and clearance of apoptotic cells. Annu Rev Immunol. 2018;36:489–517.
- Nassiri-Asl M, Hosseinzadeh H. Review of the protective effects of rutin on the metabolic function as an important dietary flavonoid. J Endocrinol Invest. 2014;37(9):783–788.
- Gullón B, Lú-Chau TA, Moreira MT, Lema JM, Eibes G. Rutin: A review on extraction, identification and purification methods, biological activities and approaches to enhance its bioavailability. Trends Food Sci Technol. 2017;67:220–235.
- Nkpaa KW, Onyeso GI. Rutin attenuates neurobehavioral deficits, oxidative stress, neuroinflammation and apoptosis in fluoride treated rats. Neurosci Lett. 2018;682:92–99.
- Karakurt Y, Ucak T, Tasli N, et al. The effects of lutein on cisplatin-induced retinal injury: An experimental study. Cutan Ocul Toxicol. 2018;37(4):374–379.
- Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95(2):351–358.
- Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem. 1968;25(1):192–205.
- Carlberg I, Mannervik B. Glutathione reductase. Methods Enzymol. 1985;113:484–490.
- Habig WH, Jakoby WB. Assays for differentiation of glutathione S-transferases. Methods Enzymol. 1981;77:398–405.
- Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem. 1988;34(3):497–500.
- Hashem RM, Safwar G, Rashed LA, Bakry S. Biochemical findings on cisplatin-induced oxidative neurotoxicity in rats. Int J Adv Res. 2015;3(10):1222–1234.
- Umarani V, Muvvala S, Ramesh A, Lakshmi B, Sravanthi N. Rutin potentially attenuates fluoride-induced oxidative stress-mediated cardiotoxicity, blood toxicity and dyslipidemia in rats. Toxicol Mech Methods. 2015;25(2):143–149.
- Abarikwu S, Olufemi P, Lawrence C, Wekere F, Ochulor A, Barikuma A. Rutin, an antioxidant flavonoid, induces glutathione and glutathione peroxidase activities to protect against ethanol effects in cadmium‐induced oxidative stress in the testis of adult rats. Andrologia. 2017;49(7). doi:10.1111/and.12696
- Niu C, Ma M, Han X, Wang Z, Li H. Hyperin protects against cisplatin-induced liver injury in mice. Acta Cir Bras. 2017;32(8):633–640.
- Osawe S, Farombi E. Quercetin and rutin ameliorates sulphasalazine‐induced spermiotoxicity, alterations in reproductive hormones and steroidogenic enzyme imbalance in rats. Andrologia. 2018;50(5):e12981.
- Oz M, Atalik KEN, Yerlikaya FH, Demir EA. Curcumin alleviates cisplatin-induced learning and memory impairments. Neurobiol Learn Mem. 2015;123:43–49.
- Patil SL, Somashekarappa H, Rajashekhar K. Radiomodulatory role of rutin and quercetin in Swiss Albino mice exposed to the whole body gamma radiation. Indian J Nucl Med. 2012;27(4):237–242.
- Uchino H, Matsumura Y, Negishi T, et al. Cisplatin-incorporating polymeric micelles (NC-6004) can reduce nephrotoxicity and neurotoxicity of cisplatin in rats. Br J Cancer. 2005;93(6):678–687.
- Ramalingayya GV, Cheruku SP, Nayak PG, et al. Rutin protects against neuronal damage in vitro and ameliorates doxorubicin-induced memory deficits in vivo in Wistar rats. Drug Des Devel Ther. 2017;11:1011–1026.
- Arjumand W, Seth A, Sultana S. Rutin attenuates cisplatin induced renal inflammation and apoptosis by reducing NFκB, TNF-α and caspase-3 expression in Wistar rats. Food Chem Toxicol. 2011;49(9):2013–2021.