Vysokoškolská učebnice, která obsahuje úlohy a příklady, které se zaměřují na biochemii a lékařskou chemii.

• MeSH
• biochemie MeSH
• klinická chemie MeSH

• Konspekt
• Lékařské vědy. Lékařství
• Učební osnovy. Vyučovací předměty. Učebnice
• NLK Obory
• biochemie
• NLK Publikační typ
• učebnice vysokých škol
• pracovní sešity

A cost-effective method for separation of sanguinarine and chelerythrine from commercial Macleaya cordata extract (sanguiritrin) is described. In the first step, the alkaloids are reduced with NaBH4 to dihydro derivatives, which are easily separated by column chromatography on silica gel with chloroform and chloroform-methanol elution. In the second step, the dihydro derivatives are photochemically oxidized to the title alkaloids.

• MeSH
• alkaloidy chemie   izolace a purifikace   MeSH
• benzofenantridiny chemie   izolace a purifikace   MeSH
• financování organizované MeSH

The benzo[c]phenanthridine alkaloid sanguinarine has been studied for its antiproliferative activity in many cell types. Almost nothing however, is known about the cytotoxic effects of dihydrosanguinarine, a metabolite of sanguinarine. We compared the cytotoxicity of sanguinarine and dihydrosanguinarine in human leukemia HL-60 cells. Sanguinarine produced a dose-dependent decline in cell viability with IC(50) (inhibitor concentration required for 50% inhibition of cell viability) of 0.9 microM as determined by MTT assay after 4h exposure. Dihydrosanguinarine showed much less cytotoxicity than sanguinarine: at the highest concentration tested (20 microM) and 24h exposure, dihydrosanguinarine decreased viability only to 52%. Cytotoxic effects of both alkaloids were accompanied by activation of the intrinsic apoptotic pathway since we observed the dissipation of mitochondrial membrane potential, induction of caspase-9 and -3 activities, the appearance of sub-G(1) DNA and loss of plasma membrane asymmetry. This aside, sanguinarine also increased the activity of caspase-8. As shown by flow cytometry using annexin V/propidium iodide staining, 0.5 microM sanguinarine induced apoptosis while 1-4 microM sanguinarine caused necrotic cell death. In contrast, dihydrosanguinarine at concentrations from 5 microM induced primarily necrosis, whereas apoptosis occurred at 10 microM and above. We conclude that both alkaloids may cause, depending on the alkaloid concentration, both necrosis and apoptosis of HL-60 cells.

• MeSH
• apoptóza účinky léků   MeSH
• benzofenantridiny farmakologie   MeSH
• buněčný cyklus účinky léků   MeSH
• HL-60 buňky MeSH
• isochinoliny farmakologie   MeSH
• kaspasy metabolismus   MeSH
• lidé MeSH
• membránový potenciál mitochondrií účinky léků   MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

Macleaya cordata (Willd.) (Papaveraceae) is used as an active component in the natural feed additive Sangrovit. Sangrovit contains mixture of the intact aerial parts and the fraction of quaternary benzo[c]phenanthridine alkaloids from M. cordata (FQBA). In a 90-day pilot toxicity trial, Sangrovit and the FQBA were tested for safety. Male Wistar rats were fed for 90 days with 100, 7000 or 14000mg of Sangrovit or 600mg of FQBA in 1kg of feed. Body and organ weights, clinical chemistry and hematology markers, oxidative stress parameters, morphological structure of tongue, liver, ileum, kidney and heart samples, and total cytochrome P450 in liver were monitored. The results showed no statistically significant alterations in any parameter between control and treated animals, except for the group treated with 14000ppm Sangrovit that resulted in elevation of reduced glutathione level and superoxide dismutase activity in liver.

• MeSH
• benzofenantridiny analýza   MeSH
• dieta MeSH
• feces chemie   MeSH
• isochinoliny analýza   MeSH
• játra enzymologie   účinky léků   MeSH
• krevní obraz MeSH
• krmivo pro zvířata analýza   toxicita   MeSH
• krysa rodu rattus MeSH
• léky rostlinné čínské analýza   toxicita   MeSH
• oxidační stres účinky léků   MeSH
• Papaveraceae chemie   MeSH
• pilotní projekty MeSH
• potkani Wistar MeSH
• potravinářské přísady analýza   toxicita   MeSH
• přijímání potravy MeSH
• systém (enzymů) cytochromů P-450 analýza   metabolismus   MeSH
• tělesná hmotnost účinky léků   MeSH
• tkáňová distribuce MeSH
• velikost orgánu účinky léků   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

A quaternary benzo[c]phenanthridine alkaloid chelerythrine displays a wide range of biological activities including cytotoxicity to normal and cancer cells. In contrast, less is known about the biological activity of dihydrochelerythrine, a product of chelerythrine reduction. We examined the cytotoxicity of chelerythrine and dihydrochelerythrine in human promyelocytic leukemia HL-60 cells. After 4h of treatment, chelerythrine induced a dose-dependent decrease in the cell viability with IC50 of 2.6 microM as shown by MTT reduction assay. Dihydrochelerythrine appeared to be less cytotoxic since the viability of cells exposed to 20 microM dihydrochelerythrine for 24h was reduced only to 53%. Decrease in the viability induced by both alkaloids was accompanied by apoptotic events including the dissipation of mitochondrial membrane potential, activation of caspase-9 and -3, and appearance of cells with sub-G1 DNA. Moreover, chelerythrine, but not dihydrochelerythrine, elevated the activity of caspase-8. A dose-dependent induction of apoptosis and necrosis by chelerythrine and dihydrochelerythrine was confirmed by annexin V/propidium iodide dual staining flow cytometry. Besides, both alkaloids were found to induce accumulation of HL-60 cells in G1 phase of the cell cycle. We conclude that both chelerythrine and dihydrochelerythrine affect cell cycle distribution, activate mitochondrial apoptotic pathway, and induce apoptosis and necrosis in HL-60 cells.

• MeSH
• akutní promyelocytární leukemie farmakoterapie   patologie   MeSH
• alkaloidy aplikace a dávkování   farmakologie   MeSH
• antitumorózní látky aplikace a dávkování   farmakologie   MeSH
• apoptóza účinky léků   MeSH
• benzofenantridiny aplikace a dávkování   farmakologie   MeSH
• buněčná smrt účinky léků   MeSH
• časové faktory MeSH
• DNA nádorová metabolismus   účinky léků   MeSH
• financování organizované MeSH
• G1 fáze účinky léků   MeSH
• HL-60 buňky MeSH
• inhibiční koncentrace 50 MeSH
• kaspasy metabolismus   účinky léků   MeSH
• lidé MeSH
• membránový potenciál mitochondrií účinky léků   MeSH
• viabilita buněk účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• srovnávací studie MeSH

The quaternary benzo[c]phenanthridine alkaloid sanguinarine (SG) is the main component of Sangrovit, a natural livestock feed additive. Dihydrosanguinarine (DHSG) has recently been identified as a SG metabolite in rat. The conversion of SG to DHSG is a likely elimination pathway of SG in mammals. This study was conducted to evaluate the toxicity of DHSG in male Wistar rats at concentrations of 100 and 500 ppm DHSG in feed for 90 days (average doses of 14 and 58 mg DHSG/kg body weight/day). No significant alterations in body or organ weights, macroscopic details of organs, histopathology of liver, ileum, kidneys, tongue, heart or gingiva, clinical chemistry or hematology markers in blood in the DHSG-treated animals were found compared to controls. No lymphocyte DNA damage by Comet assay, formation of DNA adducts in liver by 32P-postlabeling, modulation of cytochrome P450 1A1/2 or changes in oxidative stress parameters were found. Thus, repeated dosing of DHSG for 90 days at up to 500 ppm in the diet (i.e. approximately 58 mg/kg/day) showed no evidence of toxicity in contrast to results published in the literature. In parallel, DHSG pharmacokinetics was studied in rat after oral doses 9.1 or 91 mg/kg body weight. The results showed that DHSG undergoes enterohepatic cycling with maximum concentration in plasma at the first or second hour following application. DHSG is cleared from the body relatively quickly (its plasma levels drop to zero after 12 or 18 h, respectively).

• MeSH
• adukty DNA MeSH
• benzofenantridiny farmakokinetika   krev   toxicita   MeSH
• biochemická analýza krve MeSH
• časové faktory MeSH
• financování organizované MeSH
• ileum patologie   účinky léků   MeSH
• isochinoliny farmakokinetika   krev   toxicita   MeSH
• játra patologie   účinky léků   MeSH
• kometový test MeSH
• krmivo pro zvířata MeSH
• krysa rodu rattus MeSH
• náhodné rozdělení MeSH
• orgánová specificita MeSH
• oxidační stres účinky léků   MeSH
• pilotní projekty MeSH
• plocha pod křivkou MeSH
• poškození DNA účinky léků   MeSH
• potkani Wistar MeSH
• systém (enzymů) cytochromů P-450 účinky léků   MeSH
• testy genotoxicity MeSH
• tkáňová distribuce MeSH
• velikost orgánu účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH

• MeSH
• financování organizované MeSH
• Publikační typ
• abstrakty MeSH

• MeSH
• klinická chemie MeSH
• matematika MeSH

• Konspekt
• Chemie. Mineralogické vědy
• Učební osnovy. Vyučovací předměty. Učebnice
• NLK Obory
• chemie, klinická chemie
• chemie, klinická chemie
• přírodní vědy
• NLK Publikační typ
• učebnice vysokých škol

Sanguinarine is an alkaloid with known antibiotic and anti-inflammatory activity and its pharmacokinetics have been studied in the rat after a single oral dose (10 mg kg(-1) body weight). Alkaloid determination in the plasma and liver was carried out by high-performance liquid chromatography-electrospray ionization mass spectrometry (HPLC/ESI-MS). The pharmacokinetic parameters (t(max), c(max), AUC(0-->t) and AUC(0-->infinity)) were determined for sanguinarine and dihydrosanguinarine, the major components detected in plasma. The first step in sanguinarine metabolism in the rat was the reduction of the iminium bond resulting in formation of the less toxic dihydrosanguinarine. Both compounds were completely eliminated from the plasma and liver after 24 h and not detected in urine. After a single oral dose of (3)H-sanguinarine, more than 42% of the ingested radioactivity was present in gastrointestinal tract. Benz[c]acridine, up to date the only sanguinarine metabolite referred to in the literature, was not detected in the plasma, liver or urine.

• MeSH
• akridiny chemie   MeSH
• alkaloidy aplikace a dávkování   farmakokinetika   chemie   krev   MeSH
• antiinfekční látky aplikace a dávkování   farmakokinetika   chemie   krev   MeSH
• aplikace orální MeSH
• benzofenantridiny aplikace a dávkování   farmakokinetika   chemie   krev   MeSH
• časové faktory MeSH
• financování organizované MeSH
• hmotnostní spektrometrie MeSH
• isochinoliny aplikace a dávkování   farmakokinetika   chemie   krev   MeSH
• krysa rodu rattus MeSH
• potkani Wistar MeSH
• tkáňová distribuce MeSH
• tritium MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH

• MeSH
• biochemie MeSH
• chemické techniky analytické MeSH
• klinická chemie MeSH

• Konspekt
• Lékařské vědy. Lékařství
• Učební osnovy. Vyučovací předměty. Učebnice
• NLK Obory
• biochemie
• chemie, klinická chemie
• chemie, klinická chemie
• NLK Publikační typ
• učebnice vysokých škol