0000000000276486
AUTHOR
Kristīne Ošiņa
Effects of an Antimutagenic 1,4-Dihydropyridine AV-153 on Expression of Nitric Oxide Synthases and DNA Repair-related Enzymes and Genes in Kidneys of Rats with a Streptozotocin Model of Diabetes Mellitus.
Development of complications of diabetes mellitus (DM), including diabetic nephropathy, is a complex multi-stage process, dependent on many factors including the modification of nitric oxide (NO) production and an impaired DNA repair. The goal of this work was to study in vivo effects of 1,4-dihydropyridine AV-153, known as antimutagen and DNA binder, on the expression of several genes and proteins involved in NO metabolism and DNA repair in the kidneys of rats with a streptozotocin (STZ)-induced model of DM. Transcription intensity was monitored by means of real-time RT-PCR and the expression of proteins by immunohistochemistry. Development of DM significantly induced PARP1 protein express…
Metal ions modify DNA-protecting and mutagen-scavenging capacities of the AV-153 1,4-dihydropyridine.
Abstract 1,4-Dihydropyridines (1,4-DHP) possess important biochemical and pharmacological properties, including antioxidant and antimutagenic activities. AV-153-Na, an antimutagenic and DNA-repair enhancing compound was shown to interact with DNA by intercalation. Here we studied DNA binding of several AV-153 salts to evaluate the impact of AV-153 modifications on its DNA binding capacity, the ability to scavenge the peroxynitrite, to protect HeLa and B-cells cells against DNA damage. Affinity of the AV-153 salts to DNA measured by a fluorescence assay was dependent on the metal ion forming a salt in position 4 of the 1,4-DHP, and it decreased as follows: Mg > Na > Ca > Li > Rb > K. AV-153-…
1,4-Dihydropyridine derivatives without Ca2+-antagonist activity up-regulatePsma6mRNA expression in kidneys of intact and diabetic rats
Impaired degradation of proteins by the ubiquitin-proteasome system (UPS) is observed in numerous pathologies including diabetes mellitus (DM) and its complications. Dysregulation of proteasomal degradation might be because of altered expression of genes and proteins involved in the UPS. The search for novel compounds able to normalize expression of the UPS appears to be a topical problem. A novel group of 1,4-dihydropyridine (1,4-DHP) derivatives lacking Ca2+-antagonists activities, but capable to produce antidiabetic, antioxidant and DNA repair enhancing effects, were tested for ability to modify Psma6 mRNA expression levels in rat kidneys and blood in healthy animals and in rats with str…
Modifications of expression of genes and proteins involved in DNA repair and nitric oxide metabolism by carbatonides [disodium-2,6-dimethyl-1,4-dihydropyridine- 3,5-bis(carbonyloxyacetate) derivatives] in intact and diabetic rats
Abstract Studies on the pathogenesis of diabetes mellitus complications indicate that the compounds reducing free radicals and enhancing DNA repair could be prospective as possible remedies. Carbatonides, the disodium-2,6-dimethyl-1,4- dihydropyridine-3,5-bis(carbonyloxyacetate) derivatives, were tested for these properties. EPR spectroscopy showed that metcarbatone was an effective scavenger of hydroxyl radicals produced in the Fenton reaction, etcarbatone, and propcarbatone were less effective, styrylcarbatone was ineffective. UV/VIS spectroscopy revealed that styrylcarbatone manifested a hyperchromic effect when interacting with DNA, while all other carbatonides showeda hypochromic effec…
Changes in glucose transporter expression and nitric oxide production are associated with liver injury in diabetes
In diabetes mellitus (DM), both hyperglycaemia and hyperlipidaemia can initiate accumulation of fat in the liver, which might be further mediated by inducible nitric oxide synthase. We have studied changes in GLUT1, nitric oxide (NO(·)) concentration and liver damage in two rat DM models. STZ model was induced by strepozotocin 50 mg/kg. HS model was induced by high-fat diet and 30 mg/kg streptozotocin. GLUT1 expression was studied by means of real-time RT-PCR and immunohistochemistry. Production of NO(·) was monitored by means of erythrocyte sedimentation rate spectroscopy of Fe-DETC-NO complex. Liver damage was assessed using histological activity index (HAI). NO(·) concentration was incre…
CD105, CD29, CD54, CD4 un CD8 antigēnus ekspresējošo šūnu skaita izmaiņas kaulu smadzenēs osteorefleksoterapijas laikā
Daudzas ar novecošanos saistītas slimības ir iespējams ārstēt, izmantojot osteorefleksoterapiju, kuras pamatā ir ar centrālo nervu sistēmu cieši saistīto osteoreceptoru kairināšana. Maģistra darba mērķis bija noskaidrot, kā osteorefleksoterapija ietekmē mezenhimālo cilmes šūnu un T-limfocītu skaitu kaulu smadzenēs un kaula blīvumu. Izmantojot imunocitoķīmijas metodes un gaismas mikroskopiju, tika konstatēts, ka pēc terapijas palielinās CD105, CD29 un CD54 antigēnus ekspresējošo šūnu skaits, kas varētu būt attiecināms uz mezenhimālo cilmes šūnu skaitu, samazinās CD4 un CD8 antigēnus ekspresējošo šūnu un limfocītu skaits, kas liecina par iespējumu iekaisuma reakciju samazināšanos, kā arī piea…