-
Nihon Rinsho. Japanese Journal of... Aug 1999
-
Archives of Internal Medicine May 1973
Topics: Acute Kidney Injury; Animals; Anuria; Creatinine; Dogs; Guanidines; Humans; Uremia
PubMed: 4701382
DOI: No ID Found -
Nihon Rinsho. Japanese Journal of... Nov 2004
Topics: Humans; Kidney Function Tests; Methylguanidine; Uremia
PubMed: 15628489
DOI: No ID Found -
Kidney International Sep 1974
Topics: Animals; Creatinine; Dogs; Guanidines; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Peritoneal Dialysis; Protein Binding; Renal Dialysis; Urea; Uremia
PubMed: 4425483
DOI: 10.1038/ki.1974.96 -
Lancet (London, England) Nov 1976
Topics: Blood Glucose; Glucose Tolerance Test; Guanidines; Humans; Insulin; Methylguanidine; Renal Dialysis; Uremia
PubMed: 62253
DOI: 10.1016/s0140-6736(76)90875-8 -
Nephron 1998A state of peroxidation is one of the factors contributing to uremia. For example, we have reported that certain species of reactive oxygen, particularly the hydroxyl...
A state of peroxidation is one of the factors contributing to uremia. For example, we have reported that certain species of reactive oxygen, particularly the hydroxyl radical, play an important role in the biosynthesis of methylguanidine which contributes to toxicity in patients with uremia. However, it is uncertain which enzymes are involved in the synthesis of methylguanidine from creatinine. In this study, we attempt to show methylguanidine synthesis in the presence of peroxisomal enzymes that catalyze the beta-oxidation of fatty acids. In addition, we investigate the effect of clofibrate, which induces peroxisomal enzymes or glutathione peroxidase activity, on methylguanidine synthesis in the peroxisomal fraction. Male Wistar rats were fed with the chow containing 0.5% clofibrate to induce peroxisomal enzymes and control rats were fed with ordinary laboratory chow. Peroxisomal fractions were obtained from liver homogenates by centrifugation, and incubated with creatinine in 0.1 M potassium phosphate buffer pH 7.4 at 37 degrees C. Results show that methylguanidine is synthesized from creatinine concomitant with the synthesis of hydrogen peroxide from endogenous substrates in the peroxisomal fraction. This methylguanidine synthesis is inhibited by the addition of dimethylsulfoxide, glutathione, or sodium azide (p < 0.01). The rate of methylguanidine synthesis in clofibrate-treated rats was significantly less than that in control rats (p < 0.02). These results suggest that methylguanidine is synthesized in the peroxisomal fraction, and reactive oxygen species which are generated through this enzymatic reaction, participate in methylguanidine synthesis. Moreover, the induction of a scavenger system, especially glutathione peroxidase takes precedent over the generation of reactive oxygen species in peroxisomes treated with clofibrate.
Topics: Animals; Anticholesteremic Agents; Clofibrate; Creatinine; Enzyme Induction; Hydrogen Peroxide; In Vitro Techniques; Liver; Male; Methylguanidine; Microbodies; Palmitoyl Coenzyme A; Rats; Rats, Wistar; Reactive Oxygen Species
PubMed: 9453408
DOI: 10.1159/000044886 -
Life Sciences Aug 2004In the present study we evaluate the effect of methylguanidine (MG), a product of protein catabolism, in a model of acute inflammation (zymosan induced inflammation) in... (Comparative Study)
Comparative Study
In the present study we evaluate the effect of methylguanidine (MG), a product of protein catabolism, in a model of acute inflammation (zymosan induced inflammation) in mice where oxyradical and nitric oxide (NO) play a crucial role. Our data show that MG, given intraperitoneally at the dose of 30 mg/Kg, inhibits the inflammatory response reducing significantly (P < 0.05) peritoneal exudates formation, mononuclear cell infiltration and histological injury in mice. Furthermore, our data suggests that there is a significant (P < 0.05) reduction in kidney, liver and pancreas injury as demonstrated by the reduction in amylase, lipase, creatinine, AST, ALT, bilirubine and alkaline phosfatase levels. MG is also able to reduce the appearance of nitrotyrosine and of the nuclear enzyme poly (adenosine diphosphate [ADP]-ribose) synthase (PARS) immunoreactivity in the inflamed intestinal and lung tissues. The histological examination revealed a significant reduction in zymosan-induced intestinal and lung damage in MG-treated mice. Taken together, the present results demonstrate that MG exerts potent anti-inflammatory effects on zymosan-induced shock.
Topics: Analysis of Variance; Animals; Disease Models, Animal; Exudates and Transudates; Immunohistochemistry; Intestinal Mucosa; Intestines; Kidney; Lipid Peroxidation; Lung; Male; Methylguanidine; Mice; Neutrophils; Pancreas; Peritonitis; Peroxidase; Peroxynitrous Acid; Poly(ADP-ribose) Polymerases; Shock; Tyrosine; Zymosan
PubMed: 15240178
DOI: 10.1016/j.lfs.2004.02.031 -
Nucleic Acids Research Aug 2023Antisense oligonucleotides (ASOs) are becoming a promising class of drugs for treating various diseases. Over the past few decades, many modified nucleic acids have been...
Antisense oligonucleotides (ASOs) are becoming a promising class of drugs for treating various diseases. Over the past few decades, many modified nucleic acids have been developed for application to ASOs, aiming to enhance their duplex-forming ability toward cognate mRNA and improve their stability against enzymatic degradations. Modulating the sugar conformation of nucleic acids by substituting an electron-withdrawing group at the 2'-position or incorporating a 2',4'-bridging structure is a common approach for enhancing duplex-forming ability. Here, we report on incorporating an N-tert-butylguanidinium group at the 2',4'-bridging structure, which greatly enhances duplex-forming ability because of its interactions with the minor groove. Our results indicated that hydrophobic substituents fitting the grooves of duplexes also have great potential to increase duplex-forming ability.
Topics: Methylguanidine; Nucleic Acid Conformation; Oligonucleotides; Oligonucleotides, Antisense; RNA, Messenger; Guanidines
PubMed: 37462081
DOI: 10.1093/nar/gkad608 -
The Biochemical Journal Mar 1916
PubMed: 16742617
DOI: 10.1042/bj0100103 -
Beilstein Journal of Organic Chemistry 2021Chemical modifications have been extensively used for therapeutic oligonucleotides because they strongly enhance the stability against nucleases, binding affinity to the...
Chemical modifications have been extensively used for therapeutic oligonucleotides because they strongly enhance the stability against nucleases, binding affinity to the targets, and efficacy. We previously reported that oligonucleotides modified with an -methylguanidine-bridged nucleic acid (GuNA[Me]) bearing the thymine (T) nucleobase show excellent biophysical properties for applications in antisense technology. In this paper, we describe the synthesis of GuNA[Me] phosphoramidites bearing other typical nucleobases including adenine (A), guanine (G), and 5-methylcytosine (C). The phosphoramidites were successfully incorporated into oligonucleotides following the method previously developed for the GuNA[Me]-T-modified oligonucleotides. The binding affinity of the oligonucleotides modified with GuNA[Me]-A, -G, or -C toward the complementary single-stranded DNAs or RNAs was systematically evaluated. All of the GuNA[Me]-modified oligonucleotides were found to have a strong affinity for RNAs. These data indicate that GuNA[Me] could be a useful modification for therapeutic antisense oligonucleotides.
PubMed: 33747234
DOI: 10.3762/bjoc.17.54