Evaluation of possible palliative role of tamarixetin against cisplatin-induced renal toxicity by modulation of oxidative stress, inflammation and apoptosis in rats

JOURNAL OF KING SAUD UNIVERSITY SCIENCE(2023)

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摘要
Cisplatin (CP) is a top-notch anti-cancerous agent that is used during the treatments of various types of tumors. Tamarixetin (TM) is a naturally occurring polyphenolic compound with versatile therapeutic and pharmacological abilities. The current investigation was purposed to elucidate the antagonistic effects of TM against CP-prompted renal intoxication. Sprague Dawley rats (n = 48) were separated into 4 equal groups i.e., Group 1st was designated as control group while the 2nd group was treated with CP (10 mg/kg) only, group 3rd received CP (10 mg/kg) + TM (50 mg/kg) and designated as a co-treated group while group 4th was administered with TM (50 mg/kg) only. Our results revealed that treatment of CP reduced the activity of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione-disulfide reductase (GSR), glutathione S-transferase (GST) as well as glutathione (GSH) while elevate ROS and MDA levels. CP administration raised the level of urea, creatinine, KIM1 along with NGAL while significant reduction in creatinine clearance. Whereas, CP treatment substantially elevated the level of caspase-3, caspase- 9 and Bcl-2 associated X protein (Bax) while reducing the level of B cell lymphoma protein 2 (Bcl-2). CP administration significantly elevated the concentration of nuclear factor kappa-B (NF-kB), interleukin 6 (IL-6), interleukin 1 beta (IL-1b) as well as tumor necrosis factor a (TNF-a), and instigated histopathological damages in renal tissues. However, Co-treatment of CP + TM showed palliative effects against CP-induced impairments. The current study manifested that TM is a potential flavonoid that could be used as a therapeutic drug to ameliorate renal damages instigated by CP. (c) 2023 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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关键词
Cisplatin,Tarmarixetin,Renal damages,Inflammation,Oxidative stress
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