Cationization of catalase, peroxidase, and superoxide dismutase. Effect of improved intraarticular retention on experimental arthritis in mice.

Abstract

Several enzymes and other proteins were made cationic either by coupling to polylysine or by shielding of anionic sites. These cationic proteins, all having an isoelectric point >8.5 exhibited excellent retention in articular structures when injected in mouse knee joints. Autoradiography and histochemistry showed that cationic forms of catalase, superoxide dismutase, and horseradish peroxidase were firmly retained by synovial and cartilaginous tissues. The half-life of these enzymes in the joint is thus significantly extended compared with native enzymes. The native enzymes and their cationic derivatives were tested for antiinflammatory properties in mice, using antigeninduced arthritis and zymosan-induced arthritis. It was found that injection of cationic catalase or peroxidase induced a marked suppression of some parameters of the inflammatory response in both types of arthritis, as measured by ""'technetium pertechnetate uptake and leakage of I251-labeled albumin. Native catalase and peroxidase were less, or not at all effective. Cationic superoxide dismutase or cationic nonenzyme proteins did not suppress inflammation. The observed suppression of two different types of inflammation (an immune and a nonimmune arthritis) by catalase and peroxidase suggests that elimination of peroxides contributes to the suppression of an inflammatory response.We would hypothesize that cationic enzymes offer the possibility for investigating the mechanisms of inflammation and, in addition, might be interesting from a therapeutical point of view.

Amelioration of antigen-induced arthritis in rats by transfer of extracellular superoxide dismutase and catalase genes

“…13,21 In rat adjuvant-induced foot pad oedema, administration of human recombinant MnSOD resulted in a reduction of paw swelling. 21 In a different model, antigen-induced arthritis in the mouse, amidated catalase suppressed the inflammatory response, whereas SOD had no effect.…”

“…21 In a different model, antigen-induced arthritis in the mouse, amidated catalase suppressed the inflammatory response, whereas SOD had no effect. 13 It appears that superoxide radicals and hydrogen peroxide might exert different effects on the different animal models. 4 for each cell type, ( ) were injected into right knee joints of animals (n¼5).…”

Soft Tissue Repair Capacity after Oxygen-Derived Free Radical-Induced Damage in One Hindlimb of the Rat

“…Oxygen-derived free radicals are involved in various diseases affecting the extremities [1][2][3][4][5]. In free radicalrelated processes, lipid peroxidation occurs followed by cellular damage.…”

“…thritis [1], diabetic neuropathy [2], compartment syn drome [3], interm ittent claudication [4], and athero sclerosis [5]. However, next to free radicals, other in flammatory mediators [6,7] and alterations in cellular energy metabolism [8] contribute to the tissue damage in these processes.…”

Blood-brain barrier transport of cationized immunoglobulin G: enhanced delivery compared to native protein.

“…Similarly, cationization of catalase or peroxidase causes enhanced delivery of protein to the synovial fluid (34). The use of cationized IgG molecules as a vehicle for enhanced delivery through the BBB should consider the following.…”