Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P. O. Box: 2454, Riyadh, 11495, Saudi Arabia.
College of Pharmacy, King Saud University, Riyadh, 11495, Saudi Arabia.
Inflammation. 2024 Oct;47(5):1600-1615. doi: 10.1007/s10753-024-01996-6. Epub 2024 Feb 28.
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.
双氯芬酸钠（DIC）是一种广泛使用的非甾体抗炎药。不幸的是，由于氧化应激、炎症和纤维化，其长期使用与肾毒性有关。我们旨在研究维生素 B 复合物（B1、B6、B12）对 DIC 诱导的肾毒性的保护作用及其对 NOX4/RhoA/ROCK 的影响，该途径在肾脏病理生理学中起着至关重要的作用。32 只 Wistar 大鼠分为四组：（1）正常对照组；（2）维生素 B 复合物组（16mg/kg B1、16mg/kg B6、0.16mg/kg B12，腹腔内）；（3）DIC（10mg/kg，肌肉注射）；（4）DIC 加维生素 B 复合物组。14 天后，测定以下指标：血清肾生物标志物（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）标志物以及 NOX4、RhoA 和 ROCK 的蛋白水平。苏木精和伊红及 Masson 三色染色检测结构变化、炎症细胞浸润和纤维化。与 DIC 相比，维生素 B 复合物显著降低了肾功能生物标志物、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、炎症浸润和胶原过度积累也减少。DIC 显著升高了 NOX4、RhoA 和 ROCK 的蛋白水平，而维生素 B 复合物则改善了这种升高。总之，维生素 B 复合物的给药可能是通过至少部分抑制 NOX4/RhoA/ROCK 途径在 DIC 治疗期间的一种肾保护方法。
