Silver Nanoparticles‐Induced Liver and Kidney Toxicity: Importance of Longitudinal Monitoring in Mitigating Toxicological Impact in Albino Rats

Silver nanoparticles (Ag-NPs) are being increasingly integrated into biomedical and consumer products; however, their long-term safety is not fully understood. The liver and kidneys demonstrate an apparent susceptibility to the accumulation of Ag-NPs; however, the intensity and reversibility of the consequent toxicity necessitate further investigation. This study aimed to outline the hepatorenal toxic effects of orally administered Ag-NPs and to assess the potential for recovery through longitudinal biochemical, histopathological, and apoptotic assessments. Adult male albino rats were divided into control, Ag-NPs-treated, and recovery groups. Animals were administered oral Ag-NPs at a dosage of 1 mg/kg/day for a duration of 28 days. Biochemical assays of liver enzymes, renal function, and oxidative stress markers were assessed. Histopathological examination and immunohistochemical analysis for Bcl-2 and Bax expression were evaluated. Assessments were conducted immediately after treatment and at 2- and 8-week recovery intervals. Subchronic administration of Ag-NPs led to significant hepatorenal injury, as evidenced by elevated serum levels of ALT, AST, urea, and creatinine, increased malondialdehyde, and reduced antioxidant defenses. Histological analysis revealed hepatocellular degeneration, necrosis, vascular congestion, and renal tubular damage. Immunohistochemistry demonstrated a proapoptotic shift characterized by the downregulation of Bcl-2 and the upregulation of Bax. Longitudinal monitoring revealed significant recovery, with partial resolution of biochemical and structural changes at 2 weeks and near-complete restoration of hepatic function and morphology by 8 weeks. In contrast, renal recovery was relatively delayed. The oral administration of Ag-NPs results in significant, nevertheless predominantly reversible, hepatorenal toxicity, which is mediated through oxidative stress and apoptosis. Longitudinal monitoring has become essential for tracking the evolving patterns of injury and recovery, demonstrating its significance in nanoparticle toxicology and risk assessment. A key innovation of this study is the longitudinal recovery design, which allowed for dynamic evaluation of the progression and reversibility of hepatorenal injury following the cessation of Ag-NPs exposure.