In vitro glutathione peroxidase mimicry of ebselen is linked to its oxidation of critical thiols on key cerebral suphydryl proteins – A novel component of its GPx-mimic antioxidant mechanism emerging from its thiol-modulated toxicology and pharmacology

AbstractThe antioxidant mechanism of ebselen in rats brain is largely linked with its glutathione peroxidase (GPx) rather than its peroxiredoxin mimicry ability. However, the precise molecular dynamics between the GPx-mimicry of ebselen and thiol utilization is yet to be fully clarified and thus still open. Herein, we investigated the influence of dithiothreitol (DTT) on the antioxidant action of ebselen against oxidant-induced cerebral lipid peroxidation and deoxyribose degradation. Furthermore, the critical inhibitory concentrations of ebselen on the activities of sulphydryl enzymes such as cerebral sodium pump, δ-aminolevulinic acid dehydratase (δ-ALAD) and lactate dehydrogenase (LDH) were also investigated. We observe that ebselen (at ⩾42μM) markedly inhibited lipid peroxidation in the presence and absence of DTT, whereas it inhibited deoxyribose degradation only in the presence of DTT. Furthermore, under in vitro conditions, ebselen inhibited the thiol containing enzymes; cerebral sodium pump (at ⩾40μM), δ-ALAD (⩾10μM) and LDH (⩾1μM) which were either prevented or reversed by DTT. However, the inhibition of the activities of these sulphydryl proteins in diabetic animals was prevented by ebselen. Summarily, it is apparent that the effective in vitro inhibitory doses of ebselen on the activity of the sulphydryl proteins are far less than its antioxidant doses. In addition, the presence of DTT is evidently a critical requirement for ebselen to effect its antioxidant action against deoxyribose degeradation and not lipid peroxidation. Consequently, we conclude that ebselen possibly utilizes available thiols on sulphydryl proteins to effect its GPx mimicry antioxidant action against lipid peroxidation in rat brain homogenate

Polymerization of gallic acid enhances its antioxidant capacity: Implications for plant defence mechanisms

Gallic acid (3, 4, 5-trihydroxybenzoic acid, GA) and its polymer, tannic acid (TA) are ubiquitous phytochemicals and are found to co-exist in plants. However, the rationale for the polymerisation of GA in plants is rather obscure. Hence, the present study compared the free radical scavenging ability, iron chelating potency, ferric reducing antioxidant power and inhibitory potential of both GA and TA against deoxyribose and lipid oxidative assaults in vitro. The results show that TA exhibited marked free radical scavenging ability as well as chelate Fe2+ and reduce Fe3+ more effectively than GA. Furthermore, this differential antioxidant capacity is also observed in the ability of both polyphenols to protect against hydroxyl radical induced deoxyribose degradation in the Fenton reaction. Similarly, in comparison with GA, TA also exerted marked inhibitory effect against mammalian cerebral and hepatic lipids assaulted with different prooxidants possessing diverse mechanisms of action. The present finding suggests that the polymerisation of GA to form a more efficient radical scavenger may have be associated with the need for increased antioxidant capacity required to cope with disturbed redox balance associated with pathological conditions in plants in which free radical induced oxidative stress may be implicated in their etiologies

Polymerization of gallic acid enhances its antioxidant capacity: Implications for plant defence mechanisms

Gallic acid (3, 4, 5-trihydroxybenzoic acid, GA) and its polymer, tannic acid (TA) are ubiquitous phytochemicals and are found to co-exist in plants. However, the rationale for the polymerisation of GA in plants is rather obscure. Hence, the present study compared the free radical scavenging ability, iron chelating potency, ferric reducing antioxidant power and inhibitory potential of both GA and TA against deoxyribose and lipid oxidative assaults in vitro. The results show that TA exhibited marked free radical scavenging ability as well as chelate Fe2+ and reduce Fe3+ more effectively than GA. Furthermore, this differential antioxidant capacity is also observed in the ability of both polyphenols to protect against hydroxyl radical induced deoxyribose degradation in the Fenton reaction. Similarly, in comparison with GA, TA also exerted marked inhibitory effect against mammalian cerebral and hepatic lipids assaulted with different prooxidants possessing diverse mechanisms of action. The present finding suggests that the polymerisation of GA to form a more efficient radical scavenger may have be associated with the need for increased antioxidant capacity required to cope with disturbed redox balance associated with pathological conditions in plants in which free radical induced oxidative stress may be implicated in their etiologies