Bioactive metabolites from endophytic Fusarium equiseti isolated from Hyoscyamus muticus mitigate cadmium toxicity in biological models.

Cadmium is a hazardous metal that induces oxidative stress, hepato-renal dysfunction, and metabolic disturbances. This study investigated the protective potential of bioactive secondary metabolites extracted from endophytic Fusarium equiseti (FE) against cadmium-induced toxicity. Gas chromatography- Mass Spectrometry (GC-MS) profiling revealed 17 compounds dominated by esters (67%) and fatty acids (26%). The major constituents were 9,12-Octadecadienoic acid (Z,Z) (10.21%), and Oleic acid (8.13%). In vitro-FE exhibited dose dependent antioxidant activity (IC50 = 145.91µ g/ml in DPPH assay) and broad-spectrum antimicrobial efficacy, producing inhibition zones up to 46 mm against E. coli. Anti- inflammatory evaluation showed hemolysis inhibition rising from 3.1% (100 µg/mL) to 55.9% (1000 µg/ml). Furthermore, the MTT assay revealed that the FE exhibited moderate cytotoxicity against HeLa and PC3 (IC50 values of 194.15 µg/ml and 162.88 µg/ml, respectively) cancer cell lines, while showing a lower toxicity toward normal WI38 cells (IC50 of 237.26 µg/ml; Selectivity Index up to 1.46). These metabolites are suggested to be the key contributors to the extract's antioxidant and antimicrobial activities. In vivo, twenty Wistar rats were randomly assigned to four sets (n = 5 per set): (1) Control; (2) CdCl2, receiving a single IP dose of 3 mg/kg; (3) FE (100 mg/ kg; OP; for 14 constitutive days; and (4) FE + CdCl2. CdCl2 significantly elevated WBCs, lymphocyte, MDA, ALT, AST, ALP, creatinine, uric acid, total lipids, TG, CH, and LDL- C while reducing bilirubin, albumin, HDL-C, SOD, and GSH. Pretreatment with FE markedly restored antioxidant markers (SOD and GSH), reduced MDA, normalized lipid and liver profiles, and improved hepato-renal histopathology. These findings show that FE metabolites exert antioxidant, antimicrobial, anti-inflammatory, and cytoprotective effects, mitigating cadmium- induced oxidative damage. FE represents a promising natural source for developing hepato-renal protective agents against heavy metal toxicity.