Depletion and resynthesis of tissue thiols by helenalin and tenulin

The depletion of tissue thiols by two anti-leukemic agents helenalin and tenulin was studied in mice. Helenalin (100 mg/kg) and tenulin (213 mg/kg) in dimethyl sulfoxide (DMSO) were administered orally, and the acid-soluble total thiol concentrations in the liver, kidney, stomach and small intestine were determined at 0.5, 1.0, 3.0, 6.0, 12.0 and 24.0 hr post-treatment. The lowest tissue thiol levels (42-84% of pretrial values) were observed within 0.5 - 1.0 hr following helenalin treatment. The tenulin treated mice exhibited the lowest values (46-80% of pretrial control values) at 3.0 hr post-treatment in all tissues except in the stomach, which reached its lowest value at 1.0 hr. The most dramatic effects were found in the stomach and small intestine where the mean thiol concentrations varied from 43% to 141% (at 1.0 and 24.0 hr) and from 76% to 169% (at 0.5 and 24.0 hr) of pretrial values, respectively, among helenalin treated mice. The tissue thiol levels in DMSO- and physiological saline (PSS)-treated mice fluctuated probably due to fasting and/or diurnal changes.