Protective effects of certain pharmaceutical compounds against abrin induced cell death in Jurkat cell line

Abstract

Abrin is a plant glycoprotein toxin from the seeds of Abrus precatorius, and shares the structure and properties with ricin. Abrin is highly toxic, with an estimated human fatal dose of 0.1-1 μg/kg, causing death after accidental and intentional poisoning. It is a potent toxin warfare agent. There are no antidotes available for abrin intoxication. It is becoming increasingly important to develop countermeasures for abrin by developing pre- and post-exposure medical therapy. The present study involves the screening of certain pharmaceutical agents for their potential to counter abrin toxicity in Jurkat T lymphocytes and the probable mechanism of action of the compounds with protective effect. The compounds studied are: Prednisolone, Minocycline, Amifostine, DRDE-07 (amifostine analog), Melatonin, Ebselen, N-Acetyl-l-cysteine (NAC) and Trolox. Among them, only NAC and trolox were found to confer significant protection in Jurkat cells by restoring antioxidant enzymes depleted by abrin treatment. Abrin also shown to increase in stress factor associated proteins SAPK/JNK, c-fos and c-jun levels which were effectively suppressed by NAC and trolox. In addition to this, both compounds significantly inhibit abrin induced inflammation and caspase-3 activity. These data suggest that NAC and trolox may serve as potential candidates for management of abrin-induced poisoning.