Renal Fibrosis and Oxidative Stress Induced by Silica Nanoparticles in Male Rats and Its Molecular Mechanisms.

Background: The utilization of amorphous silica nanoparticles (SiNPs) is gaining popularity in various applications, but it poses a potential risk to human and environmental health. However, the underlying causes and mechanisms of SiNPs-induced kidney damage are still largely unknown.

Objectives: This study aimed to investigate the SiNPs-induced damage in the kidney and further explore the possible mechanisms of SiNPs-induced nephrotoxicity.

Methods: Thirty adult male rats were divided into 3 different groups. Rats in groups 2 and 3 were administered SiNPs at 2 dosage levels (25 and 100 mg/kg of body weight), while the rats in the control group received no treatment for 28 days. Reactive oxygen species (ROS), antioxidant enzyme activities (glutathione peroxidase [GPx], superoxide dismutase [SOD], and catalase [CAT]), glutathione (GSH) levels, and oxidation markers (such as lipid peroxidation [malondialdehyde (MDA)] and protein oxidation [protein carbonyl (PCO)]) were analyzed in the kidney tissue. Additionally, renal fibrogenesis was studied through histopathological examination and the expression levels of fibrotic biomarkers.

Results: The findings revealed that in vivo treatment with SiNPs significantly triggered oxidative stress in kidney tissues in a dose-dependent manner. This was characterized by increased production of ROS, elevated levels of MDA, PCO, and nitric oxide (NO), along with a significant decline in the activities of SOD, CAT, GPx, and reduced GSH. These changes were consistent with the histopathological analysis, which indicated interstitial fibrosis with mononuclear inflammatory cell aggregation, tubular degeneration, glomerulonephritis, and glomerular atrophy. The fibrosis index was confirmed using Masson's trichrome staining. Additionally, there was a significant upregulation of fibrosis-related genes, including transforming growth factor-beta 1 (TGF-β1), matrix metalloproteinases 2 and 9 (MMP-2/9), whereas the expression of tissue inhibitor of metalloproteinase 2 (TIMP2) was downregulated.

Conclusions: This study provided a new research clue for the role of ROS and deregulated TGF-β signaling pathway in SiNPs nephrotoxicity.