Abstract:
t is a common knowledge among organoselenium experts that diphenyldiselenide (DPDS) exhibit
glutathione peroxidase (GPx) mimetic property. However, reports have indicated that its toxicity
on thiol-enzymes may be associated with its classical GPx mimetic catalytic antioxidant
mechanism. However, the influence of pH on the activity of these thiol-enzymes vis-à-vis the GPx
mimicry of DPDS is yet to be clarified. In this study, the antioxidant effect of diphenyldiselenide
was tested in brain and liver homogenate previously assaulted with Fe 2+ in the presence and
absence of iodoacetamide (IA) both at physiological pH and under condition of acidosis (pH 7.4 -
4.4). Furthermore, the effect of either acidosis or DPDS or combination of both was tested on the
activity of the sulphydryl enzymes, cerebral sodium pump (Na + /K + -ATPase) and hepatic delta
aminolevulinatedehydratase (δ-ALAD) in the presence of mono- and dithiols. Finally, rats were
administered FeSO 4 (30mg/kg body weight) and DPDS (10 mg/kg body weight) for 20 days.
Thereafter, the redox status, as well as the activities of Na + /K + -ATPase and δ-ALAD was evaluated
in the absence and presence of the mono- and dithiols. The results indicated that irrespective of
the pH, IA reduced the inhibitory effect of DPDS against the formation of Fe 2+ -mediated aldehydic
product of lipid peroxidation. Also, while acidosis (pH < 7.0) has no marked effect on the activity
of Na + /K + -ATPase, it markedly inhibited the activity of δ-ALAD at pH < 6.4. However, DPDS
inhibited the activity of Na + /K + -ATPase irrespective of the pH, and inhibited the activity of δ-
ALAD at pH ≥ 6.4. Also, while Fe 2+ evoked increased oxidative stress markers in vivo, DPDS
markedly reversed this effect. Also, the activities of both Na + /K + -ATPase and δ-ALAD that were
previously inhibited in the Fe 2+ treated groups were restored in the presence of the exogenous
mono- and dithiols. Consequently, considering the fact that IA blocks the antioxidant action of
DPDS at all pH tested, and that DPDS inhibited the activities of sodium pump and δ-ALAD at physiological pH and acidic pH, it is therefore reasonable to partly conclude that DPDS may
depend on the thiols of sulphydryl enzymes to effect its GPx mimicry at physiologically relevant
pH and in cases of acidosis.
