Three of four natural compounds, which are caffeic acid, eupatilin and 4'-demethyleupatilin, isolated from Chinese plant, Artbmisia rubripes Nakai selectively inhibited 5lipoxygenase of cultured mastocytoma cells. Half-inhibition doses (1.50) for caffeic acid, eupatilin and 4' -demethyleupatilin were 3.7, 14 and 18 x 10e6 M, respectively. The inhibition by caffeic acid was non-competitive types. Prostaglandin synthase activities were little inhibited by eupatilin and 4'-demethyleupatilin, but rather stimulated by affeic acid. The formation of leukotriene C4 and D4 by mast tumor cells was almost completely suppressed by these compounds at 10m4 M.
J-Lipoxygenase Inhibitor leukotriene Caffeic acid Prostaglandin synthease Lipoxygenase
The anemia associated with chronic renal failure is one of the best target diseases for erythropoietin (Epo) gene transfer. We previously reported a short-term (1 month) study of continuous rat Epo delivery by muscle-targeted gene transfer of plasmid DNA expressing rat Epo (pCAGGS-Epo) using in vivo electroporation in normal rats. Here, we performed a long-term pharmacokinetic study of continuous Epo delivery by this method in normal rats and uremic five-sixths nephrectomized rats. In normal rats, Epo gene expression and sufficient erythropoiesis occurred with Epo gene transfer in a dose-dependent manner, and persisted for at least 11
Background: We previously demonstrated that erythropoietin (Epo) expression increases in five-sixths nephrectomized rats, after muscle-targeted gene transfer by in vivo electroporation, using plasmid DNA expressing rat Epo (pCAGGS-Epo). Here, we apply this method to a rat model with severe anemia associated with chronic renal failure; these rats have hematocrit levels in the 30–35% range, similar to those in humans with end-stage renal disease. Methods: Wistar rats were treated to produce adenine-induced uremia. The uremic rats were then treated with muscle-targeted gene transfer using pCAGGS-Epo. Some uremic rats died from chronic renal failure; one of these was dissected, and the kidneys were histologically examined. For the remaining rats, we measured body weight and blood pressure, and obtained blood samples regularly. Results: The uremic rats showed severe anemia, with hematocrit levels at 32.6 ± 3.3%. Epo-gene transfer increased Epo expression and serum Epo levels, and also increased the hematocrit levels to 64.5 ± 4.8%. The dose of pCAGGS-Epo used in this study did not induce severe hypertension. Conclusions: Continuous Epo-gene expression improves the anemia associated with chronic renal failure, and without severe side effects. Our results support the potential use of gene electrotransfer for human gene therapy applications.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.