Abrogation of cisplatin-induced nephrotoxicity in rats and HEK-293 cell lines by formononetin: in vivo and in vitro study

被引：9

作者：

Shinde S.D. ^{[1
]}

Jain P.G. ^{[2
]}

Cheke R.S. ^{[3
]}

Surana S.J. ^{[2
]}

Gunjegaonkar S.M. ^{[4
]}

机构：

[1] Department of Pharmacology, Shri. R.D. Bhakt College of Pharmacy, Jalna, 431203, Maharashtra

[2] Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research, Dist-Dhule, Shirpur, 425405, Maharashtra

[3] Department of Pharmaceutical Chemistry, Dr. Rajendra Gode College of Pharmacy Malkapur, Buldana, 443101, Maharashtra

[4] Department of Pharmacology, JSPM’s Charak College of Pharmacy and Research, Wagholi, Pune, 412207, Maharashtra

来源：

Comparative Clinical Pathology | 2021年 / 30卷 / 4期

关键词：

Cisplatin; Cytokine; Formononetin; HEK-293 cell line; Nitric oxide; Oxidative stress;

D O I：

10.1007/s00580-021-03252-x

中图分类号：

学科分类号：

摘要：

The present study was performed to investigate the underlying defensive mechanisms of formononetin in nephrotoxicity by using in vivo and in vitro models. MTT assay was carried out to test the toxic effect of formononetin in HEK-293 cells which were treated with formononetin (5, 10, 20 µM) and cisplatin (20 µM). The concentrations of TNF-α and nitric oxide (NO) were determined in the cell supernatant. Nephrotoxicity in rats was induced by a single intraperitoneal injection of cisplatin at a dose of 5 mg/kg, and formononetin at doses of 10 and 30 mg/kg was used to study protective activity. Blood urea nitrogen (BUN), serum creatinine, oxidative strain, a proinflammatory cytokine, NO, and histological alteration were measured to find the therapeutic activity of formononetin. Cells treated with cisplatin showed increased levels of TNF-α and NO. Formononetin-treated cell lines showed a decreased level of TNF-α and NO production. In vivo studies determine that in the disease control group, the levels of proinflammatory cytokines, oxidative stress, BUN, and creatinine were increased because of cisplatin-induced nephrotoxicity. After the treatment of formononetin for 14 days, the levels of cytokines and oxidative stress were reduced in the test control group as compared to the disease control group. The inhibitory action of formononetin on inflammatory responses was achieved by reducing the expressions of cytokines. Cisplatin-treated rats showed the altered structure of kidney tissue; meanwhile, formononetin normalizes the structure of kidney tissue. From our findings, we conclude that formononetin has therapeutic potential in renal complications like nephrotoxicity, by inhibiting the production of proinflammatory cytokines (i.e., TNF-α) and oxidative stress (i.e., NO) in HEK-293 cell lines as well as protecting the rats from nephrotoxicity. © 2021, The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.

引用

页码：617 / 625

页数：8

共 34 条

[1]

Achilli C., Ciana A., Minetti G., Immortalized HEK 293 kidney cell lines as models of renal cells: friends or foes?, J Controversies Biomed Res, 4, 1, pp. 6-9, (2018)

[2]

An Y., Et al., Amelioration of cisplatin-induced nephrotoxicity by pravastatin in mice, Exp Toxicol Pathol, 63, 3, pp. 215-219, (2011)

[3]

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, 49, 9, pp. 2013-2021, (2011)

[4]

Barrera-Chimal J., Bobadilla N.A., Are recently reported biomarkers helpful for early and accurate diagnosis of acute kidney injury?, Biomarkers, 17, 5, pp. 385-393, (2012)

[5]

Chen C.Y., Et al., Preparation and antioxidant activity of Radix Astragali residues extracts rich in calycosin and formononetin, Biochem Eng J, 56, 1-2, pp. 84-93, (2011)

[6]

Chirino Y.I., Hernandez-Pando R., Pedraza-Chaverri J., Peroxynitrite decomposition catalyst ameliorates renal damage and protein nitration in cisplatin-induced nephrotoxicity in rats, BMC Pharmacol, 4, 1, pp. 20-28, (2004)

[7]

El-Bakoush A., Olajide O.A., Formononetin inhibits neuroinflammation and increases estrogen receptor beta (ERβ) protein expression in BV2 microglia, Int Immunopharmacol, 61, pp. 325-337, (2018)

[8]

Fuchs T.C., Hewitt P., Biomarkers for drug-induced renal damage and nephrotoxicity-an overview for applied toxicology, AAPS J, 13, 4, pp. 615-631, (2011)

[9]

Gaona L., Et al., Protective effect of sulforaphane pretreatment against cisplatin-induced liver and mitochondrial oxidant damage in rats, Toxicol, 286, 1-3, pp. 20-27, (2011)

[10]

Hoitsma A.J., Wetzels J.F., Koene R.A., Drug-induced nephrotoxicity, Drug Saf, 6, 2, pp. 131-147, (1991)

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