Enhancement in antioxidant-based hepatoprotective activity of trolox by its conjugation to lactosylphenylpyranoside

Abstract

When Trolox (a polar analog of vitamin E) is conjugated to p-aminophenyl-beta-D-lactopyranoside, the resulting lactosylphenyl Trolox becomes a markedly more stable and effective hepatoprotector than Trolox. In primary rat hepatocytes exposed to xanthine oxidase-hypoxanthine, lactosylphenyl Trolox prolonged cell survival better than did Trolox, mannitol or ascorbate. In rats that underwent 80-min partial hepatic ischemia, infusion of lactosylphenyl Trolox at 2.9 to 5.7 mumol/kg body wt just before reoxygenation salvaged the organ more extensively than did Trolox. Mechanistically, we showed (a) that lactosylphenyl Trolox does not inhibit xanthine oxidase; (b) that lactosylphenyl Trolox effectively scavenges oxyradicals generated with xanthine oxidase and the peroxyl radicals produced with 2,2'-azo-bis(2-amidinopropane) HCl; (c) that both in hepatocytes and in vivo, lactosylphenyl Trolox is distinctly more cytoprotective than either or both of its precursors; and (d) that lactosylphenyl Trolox is amphipathic (i.e., it has both hydrophilic and hydrophobic properties), which enable it to better access and protect the lipid and aqueous milieus of the cell than the lipophile vitamin E and the moderately polar Trolox. Thus there are strong fundamental reasons for lactosylphenyl Trolox being an effective antioxidant-based hepatoprotector.

Enhancing Enzyme Stability Against TiO2-UV Induced Inactivation

“…Trolox was our choice of antioxidant because of its well-known ability to absorb free radicals and the availability of the carboxyl group in its structure for covalent modifications. 17 We synthesized polymerizable Trolox-HEMA by a condensation reaction between the hydroxyl group in HEMA and the carboxyl group in Trolox. Then, ACV-initiated co-oligomerization of HBMA and Trolox-HEMA was used to obtain an enzyme-reactive low molecular weight product, which was soluble in waterdioxane binary solvent mixtures.…”

“…To assess the impact of co-localization of a UV absorber and an antioxidant on the stability of the enzyme, first we need a reactive copolymer that comprises the two stabilizers within a single chain. Trolox was our choice of antioxidant because of its well-known ability to absorb free radicals and the availability of the carboxyl group in its structure for covalent modifications . We synthesized polymerizable Trolox-HEMA by a condensation reaction between the hydroxyl group in HEMA and the carboxyl group in Trolox.…”

Potent neuroprotectants linked to bifunctional inhibition

“…1). Trolox-or vitamin E-related compounds have been modified in the past to increase their solubility and bioavailability with subsequent increased efficacy (26,27), and attempts have been made to develop relatively selective nNOS and iNOS inhibitors. The work by Chabrier et al (4) takes a clever approach.…”