The Protective Effects of Vitamin B Complex on Diclofenac Sodium-Induced Nephrotoxicity: The Role of NOX4/RhoA/ROCK.

Autor: Attia H; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P. O. Box: 2454, Riyadh, 11495, Saudi Arabia. hsalem@ksu.edu.sa., Badr A; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P. O. Box: 2454, Riyadh, 11495, Saudi Arabia., Alshehri O; College of Pharmacy, King Saud University, Riyadh, 11495, Saudi Arabia., Alsulaiman W; College of Pharmacy, King Saud University, Riyadh, 11495, Saudi Arabia., Alshanwani A; Department of Physiology, College of Medicine, King Saud University, Riyadh, 11495, Saudi Arabia., Alshehri S; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P. O. Box: 2454, Riyadh, 11495, Saudi Arabia., Arafa M; Pathology Department, College of Medicine, King Saud University, Riyadh, 11495, Saudi Arabia., Hasan I; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P. O. Box: 2454, Riyadh, 11495, Saudi Arabia., Ali R; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P. O. Box: 2454, Riyadh, 11495, Saudi Arabia.
Jazyk: angličtina
Zdroj: Inflammation [Inflammation] 2024 Oct; Vol. 47 (5), pp. 1600-1615. Date of Electronic Publication: 2024 Feb 28.
DOI: 10.1007/s10753-024-01996-6
Abstrakt: 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.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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