Rajabian Fatemeh, Razavi BiBi Marjan, Mehri Soghra, Amouian Sakineh, Ghasemzadeh Rahbardar Mahboobeh, Khajavi Rad Abolfazl, Hosseinzadeh Hossein
Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Pharmaceutical Research Centre, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2025 May;398(5):5373-5387. doi: 10.1007/s00210-024-03600-y. Epub 2024 Nov 16.
Contrast-induced nephropathy (CIN) is the most important side effect following contrast media application. The purpose of this study was to investigate the nephroprotective effects of trans sodium crocetinate (TSC) against sodium amidotrizoate/meglumine amidotrizoate (SAMA). Wistar rats were classified into eight groups (n = 6, male, 220-250 g) including (1) sham, injection of solvents (intraperitoneally; i.p.), (2) premedication-control, N(ω)-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg, i.p.) + indomethacin (IND, 10 mg/kg, i.p.), (3) model (L-NAME + IND + SAMA (12.5 ml/kg, i.p.)), (4-6) TSC 10, 20, and 40 mg/kg/day, 7 days, i.p., and L-NAME + IND + SAMA, (7) N-acetylcysteine (NAC, 125 mg/kg/day, 7 days, i.p.) and L-NAME + IND + SAMA, (8) TSC alone (40 mg/kg/day, 7 days, i.p.). Rats were injected with L-NAME, IND, and SAMA 40 h after water deprivation. SAMA caused the enhancement of histopathological damage in kidney tissue, biochemical factors (serum blood urea nitrogen and creatinine), and oxidative stress. Moreover, SAMA increased inflammation (TNF-α), apoptosis proteins (Caspase 3-cleaved and Bax/Bcl-2 ratio), and autophagy markers (Beclin-1 and LC3 II/I ratio). TSC declined biochemical factors and oxidative stress. Also, TSC 40 mg/kg decreased histopathological damage, inflammation, apoptosis, and autophagy markers. This study demonstrated that TSC has nephroprotective effects through anti-oxidant, anti-inflammatory, and anti-apoptotic properties, as well as regulating autophagy.
对比剂肾病(CIN)是使用对比剂后最重要的副作用。本研究的目的是探讨反式藏红花酸钠(TSC)对泛影酸钠/葡甲胺泛影酸钠(SAMA)的肾保护作用。将Wistar大鼠分为八组(n = 6,雄性,220 - 250 g),包括:(1)假手术组,注射溶剂(腹腔注射;i.p.);(2)预处理对照组,N(ω)-硝基-L-精氨酸甲酯(L-NAME,10 mg/kg,i.p.)+吲哚美辛(IND,10 mg/kg,i.p.);(3)模型组(L-NAME + IND + SAMA(12.5 ml/kg,i.p.));(4 - 6)TSC 10、20和40 mg/kg/天,共7天,腹腔注射,以及L-NAME + IND + SAMA;(7)N-乙酰半胱氨酸(NAC,125 mg/kg/天,共7天,腹腔注射)和L-NAME + IND + SAMA;(8)单独使用TSC(40 mg/kg/天,共7天,腹腔注射)。大鼠在禁水40小时后注射L-NAME、IND和SAMA。SAMA导致肾组织的组织病理学损伤、生化指标(血清尿素氮和肌酐)以及氧化应激增强。此外,SAMA增加了炎症(TNF-α)、凋亡蛋白(裂解的Caspase 3和Bax/Bcl-2比值)以及自噬标志物(Beclin-1和LC3 II/I比值)。TSC降低了生化指标和氧化应激。此外,40 mg/kg的TSC降低了组织病理学损伤、炎症、凋亡和自噬标志物。本研究表明,TSC通过抗氧化、抗炎和抗凋亡特性以及调节自噬发挥肾保护作用。