Comparative pre- and post-treatment effects of aqueous Zingiber officinale Lsfunction in wistar rats: insights into...

Cadmium (Cd) is a highly toxic heavy metal that accumulates in the kidney, causing oxidative stress, inflammation, apoptosis, and renal dysfunction. Ginger (Zingiber officinale) possesses antioxidant and anti-inflammatory properties, but comparative studies evaluating pre-treatment versus post-treatment regimens against cadmium nephrotoxicity remain limited. This study investigated the nephroprotective effects of aqueous Z. officinale rhizome extract in a comparative pre- and post-treatment design using histopathological, immunohistochemical, and molecular approaches. Thirty adult male Wistar rats were divided into five groups (n = 6): Control, CdCl₂ (5 mg/kg), Ginger alone (300 mg/kg), CdCl₂ + Ginger post-treatment, and Ginger pre-treatment + CdCl₂. Treatments were administered orally for six weeks after two weeks of acclimatization. Acute toxicity of the extract was evaluated using the Lorke method. Assessments included body weight, kidney morphometry, serum kidney function parameters, serum cadmium levels, relative gene expression of NF-κB and Nrf2, quantitative histopathology (H&E), and caspase-3 immunohistochemistry. Phytochemical profiling of the extract was performed using GC-MS and HPLC-DAD. The aqueous ginger extract showed high safety (LD₅₀ > 5000 mg/kg). Cadmium exposure significantly reduced body weight gain, elevated serum creatinine and cadmium levels, upregulated NF-κB and Nrf2 expression, induced glomerular collapse and tubular damage, and increased caspase-3 expression (p < 0.05). Both pre- and post-treatment with ginger significantly improved body weight gain, reduced serum cadmium concentration, attenuated histopathological lesions, lowered caspase-3 immunoexpression, and modulated NF-κB and Nrf2 gene expression toward control levels. Notably, pre-treatment showed superior histological protection, unlike in other parameters. Aqueous Z. officinale rhizome extract effectively ameliorates cadmium-induced renal dysfunction through antioxidant, anti-inflammatory, anti-apoptotic, and metal-chelating mechanisms. Pre-treatment offered better structural protection, while both regimens provided significant functional and molecular benefits. These findings support ginger as a promising natural agent for mitigating heavy metal nephrotoxicity.