关键词: Anti-inflammatory Antioxidant Chemotherapy nephrotoxicity Cytotoxicity Itaconyl chondroitin sulfate nanogel delivery system

Mesh : Rats Male Animals Cisplatin / pharmacology Kidney Chondroitin Sulfates / pharmacology Nanogels Rats, Sprague-Dawley Antioxidants / pharmacology Doxorubicin / pharmacology Oxidative Stress Creatinine / metabolism Polyethylene Glycols Polyethyleneimine

来  源:   DOI:10.1016/j.ijbiomac.2023.128839

Abstract:
In this study, we aim to unveil the potential of itaconyl chondroitin sulfate nanogel (ICSNG) in tackling chronic kidney diseases triggered by the administration of CDDP and doxorubicin (Adriamycin, ADR). To that end, the new drug delivery system (ICSNG) was initially prepared, characterized, and loaded with the target drugs. Thereafter, the in-vivo studies were performed using five equally divided groups of 100 male Sprague-Dawley (SD) rats. Biochemical evaluation and immunohistochemistry studies have revealed the renal toxicity and the ameliorative effects of ICSNG on renal function. When ICSNG-based treatments were contrasted with the CDDP and ADR infected groups, they significantly increased paraoxonase-1 (PON-1), superoxide dismutase (SOD), catalase (CAT) and albumin activity and significantly decreased nitric oxide (NO), tumor necrosis factor alpha (TNF-α), creatinine, urea, and cyclooxygenase-2 (COX-2) activity (p < 0.001). The findings of the current study imply that ICSNG may be able to lessen renal inflammation and damage in chronic kidney disorders brought on by the administration of CDDP and ADR. Interestingly, according to the estimated selectivity indices, the ICSNG-encapsulated drugs have demonstrated superior selectivity for cancer MCF-7 cells, over healthy HSF cells, in comparison to the bare drugs.
摘要:
在这项研究中,我们的目标是揭示衣康基硫酸软骨素纳米凝胶(ICSNG)在解决由CDDP和多柔比星(阿霉素,ADR)。为此,新的给药系统(ICSNG)最初是准备的,characterized,并装载了目标药物。此后,使用5组100只雄性Sprague-Dawley(SD)大鼠进行体内研究.生化评估和免疫组织化学研究揭示了肾毒性和ICSNG对肾功能的改善作用。当基于ICSNG的治疗与CDDP和ADR感染组进行对比时,它们显着增加对氧磷酶-1(PON-1),超氧化物歧化酶(SOD),过氧化氢酶(CAT)和白蛋白活性,并显着降低一氧化氮(NO),肿瘤坏死因子α(TNF-α),肌酐,尿素,和环氧合酶-2(COX-2)活性(p<0.001)。当前研究的结果表明,ICSNG可能能够减轻CDDP和ADR给药引起的慢性肾脏疾病的肾脏炎症和损害。有趣的是,根据估计的选择性指数,ICSNG封装的药物对癌症MCF-7细胞具有优异的选择性,超过健康的HSF细胞,与裸露的药物相比。
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