Widening and Elaboration of Consecutive Research into Therapeutic Antioxidant Enzyme Derivatives

Abstract

Undiminishing actuality of enzyme modification for therapeutic purposes has been confirmed by application of modified enzymes in clinical practice and numerous research data on them. Intravenous injection of the superoxide dismutase-chondroitin sulfate-catalase (SOD-CHS-CAT) conjugate in preventive and medicative regimes in rats with endotoxin shock induced with a lipopolysaccharide bolus has demonstrated that antioxidant agents not only effectively prevent damage caused by oxidative stress (as believed previously) but also can be used for antioxidative stress therapy. The results obtained emphasize the importance of investigation into the pathogenesis of vascular damage and the role of oxidative stress in it. The effects of intravenous medicative injection of SOD-CHS-CAT in a rat model of endotoxin shock have demonstrated a variety in the activity of this conjugate in addition to prevention of NO conversion in peroxynitrite upon interaction with O2 ∙− superoxide radical. Together with the literature data, these findings offer a prospect for the study of NO-independent therapeutic effects of SOD-CHS-CAT, implying the importance of a better insight into the mechanisms of the conjugate activity in modeled cardiovascular damage involving vasoactive agents other than NO.

Translational research into vascular wall function: regulatory effects of systemic and specific factors

“…This may account for the effectiveness of SOD-CHS-CAT conjugate at small doses [45,46]. It should be noted that in an animal model of endotoxic shock SOD-CHS-CAT significantly increases viability after preventive and therapeutic administration [56]. These results are interesting in comparison with modeled therapeutic effects of modular approaches [51] and for a better understanding of the mechanism underlying the conjugate activity involving NO-dependent and NO-independent pathways for its therapeutic effect.…”

“…Among three concentration intervals of reactive forms of oxygen and nitrogen species (physiological, enhanced and toxic), there is the favourable effect on toxic interval with such approaches as center-specific, nanocarrier-based therapy [52], 3D supramolecular ensembles with antioxidants or enzymes [53] and nanotherapeutics with an antioxidant nucleus for blocking atherogenic oxidative stress and an amphiphilic polysaccharide covering targeted at scavenger receptor to inhibit athero-inflammatory cycle [54]. It should be noted that the effectiveness of blocking all ROS requires cooperative action of antioxidants [55], including synergist combinations of antioxidant enzymes, as exemplified by the original bienzyme conjugate superoxide dismutase-chondroitin sulfate-catalase (SOD-CHS-CAT) [56].…”

“…The antithrombotic effect in vivo produced by the conjugate is higher than those of various combinations and mixtures of its components (native or modified) [46,56], is achieved at low doses (25-50 U SOD and 55-110 U CAT per rat), which is one or two orders of magnitude lower than those for native or modified enzymes [57]. Chondroitin sulfate content on the vascular surface over atherosclerotic lesions increases at the initial stages of atherogenesis [58].…”

The Phytochemical and Pharmacological Properties of Persicaria odorata: A Review

“…The effectiveness of antioxidant therapy depends on antioxidant usage at the early stages of pathology, suitable concentration use depending on the damaged area, sufficient retention time, safety, beneficial interactions with body systems and absence of toxic product accumulation [37]. Neutralisation of active oxygen species at the beginning stages of their production can effectively block the damage induced by oxidative stress [38]. The antioxidant activity commonly is determined by using half-maximal inhibitory concentration (IC 50 ) on reagents such as DPPH (1,1-diphenyl-2-picrylhydrazy) and ABTS (2,2'-azino-bis (3-ethylbenzothiazoline-6sulfonic acid)) [39].…”

Approximation of new generation pharmacological enzyme researches to clinical practice

“…Повышенная выживаемость животных при эндотоксическом шоке у А.В. Максименко Приближение исследований фармакологических ферментов нового поколения к клинической практике крыс (индуцированном внутривенным болюсом липополисахарида) наблюдалась при использовании биферментного конъюгата СОД-ХС-КАТ, причем не только при превентивном, но и при лечебном (введение терапевтика после введения липополисахарида) режиме его поступления в организм [40]. Эти результаты существенно расширяли границы потенциального медицинского применения ферментных производных, сходных с конъюгатом СОД-ХС-КАТ.…”