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

Abstract 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) CdCl 2 , receiving a single IP dose of 3 mg/kg; (3) FE (100 mg/ kg; OP; for 14 constitutive days; and (4) FE + CdCl 2. CdCl 2 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.