Abstract

Diclofenac sodium (DIC) is a widely used non-steroidal anti-inflammatory drug. Unfortunately, its prolonged use is associated with nephrotoxicity due to oxidative stress, inflammation, and fibrosis. We aimed to investigate the nephroprotective effects of vitamin B complex (B1, B6, B12) against DIC-induced nephrotoxicity and its impact on NOX4/RhoA/ROCK, a pathway that plays a vital role in renal pathophysiology. Thirty-two Wistar rats were divided into four groups: (1) normal control; (2) vitamin B complex (16 mg/kg B1, 16 mg/kg B6, 0.16 mg/kg B12, intraperitoneal); (3) DIC (10 mg/kg, intramuscular); and (4) DIC plus vitamin B complex group. After 14 days, the following were assayed: serum renal biomarkers (creatinine, blood urea nitrogen, kidney injury molecule-1), oxidative stress, inflammatory (tumor necrosis factor-α, interleukin-6), and fibrotic (transforming growth factor-β) markers as well as the protein levels of NOX4, RhoA, and ROCK. Structural changes, inflammatory cell infiltration, and fibrosis were detected using hematoxylin and eosin and Masson trichrome stains. Compared to DIC, vitamin B complex significantly decreased the renal function biomarkers, markers of oxidative stress and inflammation, and fibrotic cytokines. Glomerular and tubular damage, inflammatory infiltration, and excessive collagen accumulation were also reduced. Protein levels of NOX4, RhoA, and ROCK were significantly elevated by DIC, and this elevation was ameliorated by vitamin B complex. In conclusion, vitamin B complex administration could be a renoprotective approach during treatment with DIC via, at least in part, suppressing the NOX4/RhoA/ROCK pathway.

中文翻译：

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复合维生素 B 对双氯芬酸钠引起的肾毒性的保护作用：NOX4/RhoA/ROCK 的作用

摘要

双氯芬酸钠（DIC）是一种广泛使用的非甾体抗炎药。不幸的是，长期使用它会因氧化应激、炎症和纤维化而导致肾毒性。我们的目的是研究维生素 B 复合物（B1、B6、B12）对 DIC 诱导的肾毒性的肾保护作用及其对 NOX4/RhoA/ROCK 的影响，这一通路在肾脏病理生理学中发挥着至关重要的作用。将32只Wistar大鼠分为四组：（1）正常对照组；(2)复合维生素B(16mg/kg B1、16mg/kg B6、0.16mg/kg B12，腹腔注射)；(3)DIC(10mg/kg，肌肉注射)；(4)DIC加维生素B复合物组。14天后，检测以下指标：血清肾脏生物标志物（肌酐、血尿素氮、肾损伤分子-1）、氧化应激、炎症（肿瘤坏死因子-α、白细胞介素-6）和纤维化（转化生长因子-β） ) 标记物以及 NOX4、RhoA 和 ROCK 的蛋白质水平。使用苏木精和伊红以及马森三色染色检测结构变化、炎症细胞浸润和纤维化。与 DIC 相比，复合维生素 B 显着降低肾功能生物标志物、氧化应激和炎症标志物以及纤维化细胞因子。肾小球和肾小管损伤、炎症浸润和过度胶原蛋白积累也减少。DIC 显着升高 NOX4、RhoA 和 ROCK 的蛋白质水平，并且复合维生素 B 可以改善这种升高。总之，维生素 B 复合物给药可能是 DIC 治疗期间的一种肾脏保护方法，至少部分通过抑制 NOX4/RhoA/ROCK 通路。