The protective effect of Ambrosia maritima versus vitamin D3 against gentamicin-induced acute cortical kidney injury in adult male albino rats: Histological and immunohistochemical study.

Gentamicin (GM) is a broad-spectrum antibiotic widely used for severe bacterial infections, but itis associated with acute nephrotoxicity. Ambrosia maritima L. is an annual herbaceous plant that has avariety of medicinal and antioxidant activities. Vitamin D3 is involved in a multitude of biological functions and essential antioxidant pathways. This study aims to investigate the protective effects of Damsissa (Ambrosia maritima) versus vitamin D3 against GM-induced nephrotoxicity using 72 male rats that were randomly divided into six groups: control, Damsissa (100 mg/kg/day), vitamin D3 (1000 IU/kg/day), GM(100 mg/kg/day for 7 days), GM + Damsissa, and GM + vitamin D3. Renal function, oxidative stress biomarkers (MDA, CAT, SOD, GSH), cytokine levels (IL-1β, IL-6, TNF-α, IL-4), and gene expression (Caspase-3, Keap1, PPARγ, Nrf2) were assessed. Histopathological and ultrastructural kidney analyses were conducted using H&E, Masson's trichrome, PCNA staining, and transmission electron microscopy. Blood samples were tested for renal and liver markers (creatinine, BUN, AST, ALT). Damsissa enhanced survival rates, returned the renal indices to near normal, and ameliorated pathological changes based on immunohistopathological and ultrastructural results. They further reduced pro-inflammatory cytokine production, optimized oxidative stress markers, and normalized gene expression levels. Both treatments exhibited abundant antioxidant and anti-inflammatory effects, which remarkably reduced GM-induced acute kidney injury. These results suggest that both Damsissa and vitamin D3 may exert protective effects against drug-induced nephrotoxicity.