The Impact of Background γ- Radiation on Erythrocyte Nuclear Pathology, The Serotonergic System, and Cytochrome P-450 in Hens (Gallus Gallus Domesticus) from Azerbaijan

High levels of background γ-radiation exist in the suburbs of Baku, Azerbaijan. We examined the impact of radiation on erythrocyte nuclear pathologies, levels of cytochrome P-450, and serotonin-modulating anticonsolidation protein (SMAP) in the tissues of the hens from three settlements with different levels of background radiation. Higher levels of radiation resulted in increased nuclear pathologies, upregulation of tissue SMAP levels, and downregulation of cytochrome P-450.We also carried out controlled dosage studies on Wistar male rats which showed significant upregulation of heat shock proteins with molecular mass 70 kDa (HSP70) in the bone marrow 3 and 5 h later of SMAP intraperitoneal administration. Administration of SMAP to rats 3 h prior to γ-radiation exposure (8 Gy) provided significant protection to somatic cell nuclei. We conclude that SMAP can provide protection from the genotoxic effects of γ-radiation through upregulation of HSP70 or the transformation of chromatin into a condensed, more protective conformational state.

A Genome-Wide Identification Study Reveals That HmoCYP76AD1, HmoDODAα1 and HmocDOPA5GT Involved in Betalain Biosynthesis in Hylocereus

Betalains are water-soluble nitrogen-containing pigments with multiple bioactivities. Pitayas are the only at large-scale commercially grown fruit containing abundant betalains for consumers. Currently, the key genes involved in betalain biosynthesis remain to be fully elucidated. Moreover, genome-wide analyses of these genes in betalain biosynthesis are not available in betalain-producing plant species. In this study, totally 53 genes related to betalain biosynthesis were identified from the genome data of Hylocereus undatus. Four candidate genes i.e., one cytochrome P-450 R gene (HmoCYP76AD1), two L-DOPA 4,5-dioxygenase genes (HmoDODAα1 and HmoDODAα2), and one cyclo-DOPA 5-O glucosyltransferase gene (HmocDOPA5GT) were initially screened according to bioinformatics and qRT-PCR analyses. Silencing HmoCYP76AD1, HmoDODAα1, HmoDODAα2 or HmocDOPA5GT resulted in loss of red pigment. HmoDODAα1 displayed a high level of L-DOPA 4,5-dioxygenase activity to produce betalamic acid and formed yellow betaxanthin. Co-expression of HmoCYP76AD1, HmoDODAα1 and HmocDOPA5GT in Nicotiana benthamiana and yeast resulted in high abundance of betalain pigments with a red color. These results suggested that HmoCYP76AD1, HmoDODAα1, and HmocDOPA5GT play key roles in betalain biosynthesis in Hylocereus. The results of the present study provide novel genes for molecular breeding programs of pitaya.

A Systematic Review on Anti-tubercular Therapy Induced Hepatotoxicity

Tuberculosis is the leading cause of major morbidities and mortalities around the globe. One in every three persons suffers from tubercular infection in their lifetime. Antitubercular therapy-induced hepatitis occurs due to toxicity from the primary compound, metabolite, or an immunologically mediated response. Risk factors associated with hepatotoxicity are age, sex, low BMI, hypoalbuminemia, alcohol consumption, HIV, hepatitis B, and C. There are 6 major pathways by which anti-TB drugs are involved in hepatotoxicity including hampering of intracellular calcium homeostasis, derangement of actin fibril assembly that occurs next to the canaliculus, the drug binds to the heme-containing cytochrome p-450 and forms enzyme-drug adduct and produces an immune response, The enzyme- drug addict when gets incorporated to vesicle acts as antigen for the production antibodies, some drugs also inhibit the ? oxidation and respiration and hence reduction in ATP production hence damaging cell and mitochondrial DNA, and some directly leads to apoptosis. Isoniazid is being metabolized to acetyl-isoniazid followed by hydrolysis to acetyl hydrazine via cytochrome P450 enzyme which produces toxic metabolites responsible for hepatotoxicity. Rifampicin activates the cytochrome enzyme and hence stimulates the production of harmful toxic materials leading to ATT-induced hepatotoxicity. It is the duty of the he pharmacist / medical staff has to provide the patient with adequate education about diseases and to inform them about their therapy regarding possible side effects and side effects. Pharmacists / medical staff must also train patients to comply with medication.

Molecular Markers For Selection of Resistance to Facial Eczema

<p>The disease facial eczema is caused by the fungal metabolite sporidesmin which produces photosensitisation of animals whose liver and biliary tract have been damaged by the toxin. Sporidesmin is produced by the pasture fungus Pithomyces chartarum and affects ruminant animals that graze on contaminated pasture. Previous studies have shown that sporidesmin is metabolised in the liver and have suggested that the toxin is metabolically inactivated by enzymes in the glutathione S-transferase and cytochrome P-450 families. The activities of these enzymes were therefore measured in liver extracts from Romneys that had been selected for resistance or susceptibility to sporidesmin - induced liver damage. Although there were no differences in cytochrome P-450 CO binding spectra or cytochrome c reductase between the selection lines, resistant Romneys had greater nitroanisole O-demethylase activity and this difference was apparently enhanced two days after dosing with sporidesmin. Dose-dependent differences occurred in the absence of major hepatocellular injury suggesting that they reflected changes in enzyme activity rather than changes in tissue mass. Aminopyrine N-demethylase did not vary significantly between the selection lines. Some differences in GSH-dependent metabolism were also observed. Undosed resistant Romneys showed greater GSH-dependent metabolism of sporidesmin in a spectrophotometric assay. It is possible that glutathione S-transferase Mu or Theta isoforms had greater activity in the resistant lines as differences were observed using p-nitrobenzyl chloride and 1,2 epoxy-3-p-nitrophenoxypropanol but not with 1-chloro-2,4-dinitrobenzene or 1,2-dichloro-4-nitrobenzene that are good substrates for these isoforms. 2-D PAGE was applied to the separation of whole homogenate and soluble proteins. Variations in expression of some proteins including GST Mu isoforms were found between the selection lines. Roles of cytochrome P-450 and glutathione S-transferase in the hepatic detoxication of sporidesmin have previously been demonstrated. Results obtained in this study suggest that resistant Romneys may have greater cytochrome P-450 O-demethylase and glutathione S-transferase activities that could be responsible for increased metabolic inactivation of sporidesmin. These differences may in the future be of use in design of DNA probes to enhance detection and selection of facial eczema resistant livestock.</p>

Molecular Markers For Selection of Resistance to Facial Eczema

<p>The disease facial eczema is caused by the fungal metabolite sporidesmin which produces photosensitisation of animals whose liver and biliary tract have been damaged by the toxin. Sporidesmin is produced by the pasture fungus Pithomyces chartarum and affects ruminant animals that graze on contaminated pasture. Previous studies have shown that sporidesmin is metabolised in the liver and have suggested that the toxin is metabolically inactivated by enzymes in the glutathione S-transferase and cytochrome P-450 families. The activities of these enzymes were therefore measured in liver extracts from Romneys that had been selected for resistance or susceptibility to sporidesmin - induced liver damage. Although there were no differences in cytochrome P-450 CO binding spectra or cytochrome c reductase between the selection lines, resistant Romneys had greater nitroanisole O-demethylase activity and this difference was apparently enhanced two days after dosing with sporidesmin. Dose-dependent differences occurred in the absence of major hepatocellular injury suggesting that they reflected changes in enzyme activity rather than changes in tissue mass. Aminopyrine N-demethylase did not vary significantly between the selection lines. Some differences in GSH-dependent metabolism were also observed. Undosed resistant Romneys showed greater GSH-dependent metabolism of sporidesmin in a spectrophotometric assay. It is possible that glutathione S-transferase Mu or Theta isoforms had greater activity in the resistant lines as differences were observed using p-nitrobenzyl chloride and 1,2 epoxy-3-p-nitrophenoxypropanol but not with 1-chloro-2,4-dinitrobenzene or 1,2-dichloro-4-nitrobenzene that are good substrates for these isoforms. 2-D PAGE was applied to the separation of whole homogenate and soluble proteins. Variations in expression of some proteins including GST Mu isoforms were found between the selection lines. Roles of cytochrome P-450 and glutathione S-transferase in the hepatic detoxication of sporidesmin have previously been demonstrated. Results obtained in this study suggest that resistant Romneys may have greater cytochrome P-450 O-demethylase and glutathione S-transferase activities that could be responsible for increased metabolic inactivation of sporidesmin. These differences may in the future be of use in design of DNA probes to enhance detection and selection of facial eczema resistant livestock.</p>

Repercussion of piperine on pharmacokinetics parameters of eletriptan in albino rats: Involvement of CYP3A and P-GP inhibition

Eletriptan is at the type of triptan medication suggested for the management of episodes of severe headache with or without aura. Piperine (1-piperoylpiperidine) is a pure alkaloid as well as the basic tanginess material from the pipli and peppercorn. There are signs that piperine inhibits Cytochrome P-450 enzymes and P-glycoprotein, rather than arouses, drug metabolism generally, thus increasing the bioavailability and effect of several medications. The analysis was undertaken to assess the results of Piperine on the pharmacokinetics of Eletriptan. Samples of blood were taken at different time points for example 0 (predose), 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, 8.0, 12, 24 hours post-treatment. The plasma concentration of Eletriptan was estimated with the HPLC procedure. In our study Cmax, Tmax, AUC0-24 , AUC0-8, AUC%, AUMC0-24, AUMC0-8, t1/2, MRT0-24, MRT0-8 and Volume of distribution were increased by approximately 51.76%, 7.55%, 72.93%, 84.42%, 42.72%, 93.56%, 128.82%, 19.97%, 11.74%, 23.96% and 3% respectively, where as clearance decreased by 42.10% when eletriptan co-administered with piperine. In summary, the results obtained herein imply that Piperine is improving the bioavailability of Eletriptan by strengthening the exposure (AUC) of their Eletriptan when concomitantly administered by the oral route. The Piperine improved the oral bioavailability of eletriptan by inhibiting CYP3A and P-GP in rats. This observation indicates the possibility that the combo of piperine along with other CYP3A and P-GP double substrates can also enhance bioavailability.

Personalized approach to the administration of haloperidol in patients with acute alcoholic hallucinatie (literature review)

To date, it is known that haloperidol is used to treat productive psychopathological symptoms in acute alcoholic hallucinosis, but its use is associated with a high risk of developing undesirable drug reactions (NLR). A number of isoenzymes of the cytochrome P-450 family take part in the metabolism of haloperidol. The biotransformation of haloperidol occurs with the participation of the CYP2D6 isoenzyme encoded by the gene of the same name. The CYP2D6 gene is highly polymorphic, and this polymorphism can lead to a change in the activity of the encoded isoenzyme. Changes in the rate of biotransformation of haloperidol may affect the profile of its effectiveness and safety. This review is aimed at analyzing the information accumulated in the literature on the role of genetic factors in the formation of an individual response to haloperidol therapy in patients with acute alcoholic hallucinosis.

Effects of CYP2C19 Polymorphism on Metabolism and Effectiveness of Proton Pump Inhibitors: A Review of Clinical and Laboratory Studies

Introduction: Establishing the reasons for the decrease in the effectiveness of anti-Helicobacter pylori therapy and proton pump inhibitors in the treatment of acid-dependent diseases is an urgent task due to high prevalence of these disorders undermining population health. Our objective was to conduct a literature review to assess the influence of the genetic polymorphism of cytochrome P-450 CYP2C19 on the eradication rate of Helicobacter pylori and the metabolism of proton pump inhibitors, to evaluate the effectiveness of their use, and to determine possible ways of overcoming refractoriness to these drugs in the clinic. Materials and methods: We analyzed published studies found in domestic (eLibrary, CyberLeninka.ru) and international (PubMed, Cochrane Library) databases. Results: We revealed a genetic polymorphism CYP2C19 of cytochrome P-450, according to which different types of drug metabolism were identified: fast, intermediate, slow, and ultrafast. The relationship of this polymorphism with biotransformation of proton pump inhibitors was then analyzed. In Russia, the predominance of fast and intermediate metabolism in individuals of the Caucasian race decreases the efficacy of acid-suppressive therapy and the Helicobacter pylori eradication rate. Correction of the daily dose and frequency of drug administration are necessary to increase the antisecretory effect of proton pump inhibitors. Discussion: The dependence of proton pump inhibitor biotransformation on the CYP2C19 polymorphism determines the differences between patients with different types of metabolism in the effectiveness of these drugs, the success of anti-Helicobacter pylori treatment, and clinical outcomes. Pharmacogenetic testing is useful for predicting the response to proton pump inhibitors, the likelihood of developing adverse events, and the possibility of personalized prescriptions in patients with acid-related diseases. Conclusion: Genetic testing of cytochrome CYP2C19 helps optimize the use of proton pump inhibitors, overcome refractoriness, and improve the quality of treatment of acid-dependent diseases and the overall Helicobacter pylori eradication rate.