Quantification of the therapeutic dosage of validamycin A. (A) The half-lethal dose (LD50) was evaluated by determining the survival rate following oral administration of VA to zebrafish at doses of 0, 7000, and 14,000 mg/kg (mpk); (B) Half-effective dose (ED50) was determined after administering varying concentrations of VA—0, 0.75, 7.5, 75, 150, 300, 600, and 1200 mpk—alongside 220 mpk of PTZ to the fish. The ED50 was measured based on the presence or absence of epileptiform discharges. The therapeutic index was calculated by dividing the LD50 by the ED50. For VA, the therapeutic index was determined to be above 34.2, indicating a high safety margin for the drug. Each experimental group comprised 8–10 fish.
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