{"title":"Interaction of PUFAs and Doxorubicin: the Enhanced Toxicity in Breast Cancer Cells","authors":"A. Zajdel, A. Wilczok","doi":"10.32383/appdr/171546","DOIUrl":"https://doi.org/10.32383/appdr/171546","url":null,"abstract":"Doxorubicin (DOX) still remains one the most effective a clinical drug for breast cancer treatment. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the n-3 polyunsaturated fatty acids (PUFAs), exert pronounced toxicity against many types of cancers including breast cancer. That is why it was decided to investigate the mechanism of DOX and PUFAs toxicity on SK-BR-3 and MDA-MB-231 cells. The influence of DOX on the PUFAs oxidation and effect of DOX and EPA or DHA on cellular metabolic activity, viability, cytotoxicity, apoptosis and oxidative DNA damage in these cells were measured. DOX induced oxidation of the EPA and DHA. Toxicity of DOX and PUFAs towards breast cancer cells was associated with oxidative damage. These PUFAs reduced growth of the tested cells and caused their death. EPA and DHA potentiated DOX toxic effects through induction of oxidative DNA damage. The antitumor effect of PUFAs alone and combined with DOX strongly depended on induction of the oxidative stress that facilitated cell death. The observed changes of DOX toxicity induced by PUFAs suggest the possibility of their application in developing therapeutic anticancer strategies.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139253776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Agnieszka Zakrzeska, P. Kitlas, A. Shlyahtun, Natalia Szymańska, Ryszard Jabłoński, M. Tomulewicz
{"title":"Hypoglycemic Effect of Betulin in Rats With Experimental Diabetes","authors":"Agnieszka Zakrzeska, P. Kitlas, A. Shlyahtun, Natalia Szymańska, Ryszard Jabłoński, M. Tomulewicz","doi":"10.32383/appdr/172620","DOIUrl":"https://doi.org/10.32383/appdr/172620","url":null,"abstract":"Betulin is natural pentacyclic triterpenoids lupane-structure, which shows a wide range of biological activity, including possibly hypoglycemic effects. Diabetes mellitus is a metabolic disease, accompanied by chronic hyperglycemia caused by absolute or relative insulin deficiency. The main effective drug in the treatment of type 1 diabetes is insulin injections. In the case of type 2 diabetes, it is an adjuvant therapy. To purpose of this study was to show hypoglycemic action of betulin in a model of experimentally induced diabetes in rats. For the induction of diabetes, alloxan at a dose of 170 mg/kg, i.p. was used. The hypoglycemic effect of betulin was evaluated using doses of 50 and 100 mg/kg/day for 30 days. The activity of glucose metabolism enzymes: liver glycogen phosphorylase, hexokinase and liver and skeletal muscle phosphofructokinase in rats, glucose-6-phosphate dehydrogenase (DG-6-P) of the liver was also evaluated. Betulin in a dose-dependent manner normalized of glycemia, increased the basal insulin concentration in the blood serum, increased the activity of carbohydrate metabolizing enzymes and on the gene expression profile of enzymes involved in carbohydrate metabolism. Betulin also significant improved the morphology of the pancreas. In particular, there was an increase in the area of the islands, their diameter, an increase in the number of β cells in the composition of the islands. We conclude that betulin has hypoglycemic properties, improving glycemia and carbohydrate metabolizing enzymes and pancreatic morphology.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":"45 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139251045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Compatibility Study of Ketoprofen With Selected Excipients Used in Solid Dosage Forms: Experimental Design Approach","authors":"Joanna Ronowicz-Pilarczyk","doi":"10.32383/appdr/172622","DOIUrl":"https://doi.org/10.32383/appdr/172622","url":null,"abstract":"A good understanding of the physico-chemical characteristics of a drug substance and excipients is necessary to obtain a safe and effective drug dosage form. Based on the current recommendations of the regulatory agencies (EMA, FDA) regarding the implementation of the Quality by Design concept at the drug product development stage, this article is focused on the application of the experimental design approach at the preformulation studies. The purpose of this work was the implementation of experimental design methodology in a compatibility study between ketoprofen (non-steroidal anti-inflammatory drug) and selected solid dosage forms excipients. The fractional factorial design was used to generate a matrix of multi-component mixtures of ketoprofen and selected excipients. In order to accelerate any chemical incompatibilities, the received mixtures were exposed to elevated temperature and humidity (60°C/75% RH) in a climate chamber for 3 weeks. The ketoprofen-excipients compatibility was studied by means of the RP-HPLC method. It was confirmed that the type of disintegrant had a strong impact on ketoprofen degradation. The incompatibility in mixtures of ketoprofen with sodium starch glycolate was indicated. According to literature data, it may be the result of a decrease in crystallinity and thus a decrease in the stability of ketoprofen in the presence of sodium starch glycolate. The effects of the other types of excipients were statistically insignificant (p > 0.05). The applied experimental design methodology allowed for a rational selection of optimal excipients and thus, this approach may support significantly decision-making in the pharmaceutical industry.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":"47 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139252354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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