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AIM: To analyze the distribution frequency of gene polymorphisms of β receptor blockers, angiotensin receptor antagonists, angiotensin converting enzyme inhibitors, calcium antagonists, and diuretics in hypertensive patients from southern Anhui province, and provide a theoretical basis for gene detection of hypertension drugs and personalized medication. METHODS: Drug gene testing information from 839 hospitalized patients with hypertension at Yijishan Hospital of Wannan Medical College from July 2021 to April 2023 were collected, and the distribution frequency of each gene locus were analyzed. RESULTS: The genotype frequencies of ACE (I/D) I/I, I/D, and D/D were 42.1%, 46.0%, and 11.9%, respectively. the genotype frequencies of ADRB1 (1165G>C) G/G, G/C, and C/C were 8.3%, 40.0%, and 51.6%, respectively. The genotype frequencies of AGTR1 (1166A>C) A/A, A/C, and C/C were 90.2%, 9.8%, and 0.0%. The genotype frequencies of CYP2C9*3 (1075A>C) *1/*1, *1/*3, and *3/*3 were 91.3%, 8.7%, and 0.0%, respectively; the genotype frequencies of CYP2D6* 10 (100C > T) *1/*1, *1/*10, and *10/*10 were 25.0%, 36.6%, and 38.4%, respectively. The genotype frequencies of CYP3A5*3 (6986A>G) *1/*1, *1/*3, and *3/*3 were 7.0%, 39.0%, and 54.0%, respectively. The frequencies of NPPA (2238T>C) T/T, T / C, and C / C genotypes were 97.9%, 2.1%, and 0.0%, respectively. In addition, there was a significant difference in the genotype distribution frequency of multiple drug related gene loci in southern Anhui compared to other regions in China (P< 0.05). CONCLUSION: The genotype distribution frequency of hypertensive drug related gene loci had certain bias in southern Anhui, and were significant different from other regions in China, indicating that conducting genetic polymorphism testing of hypertensive drugs had certain guiding significance for the individualized application of hypertensive drugs in southern Anhui.
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The radiation is regarded as the fourth biggest pollution following the water, air and noise pollution, which generates a broad impact on human physiology and healthy. The radiation mainly comes from medical rays, industrial rays, nuclear wastes and atmospheric ultraviolet rays. The universality makes people pay more and more attention to the damage effect and mechanism of radiation. The radiation is divided into ionizing and non-ionizing radiation. It is a good idea to study the effect of ionizing and non-ionizing radiation on drug's metabolism, which may give a guidance to clinical medication to avoid adverse reactions and to support personalized medicine. This article reviews the effect of ionizing radiation (γ-rays, X-rays, uranium and cesium) and non-ionizing radiation (ultraviolet rays) on drug metabolism, their impact on metabolic characteristics of some drugs and the impact on expression of enzymes and transporters in drug metabolism, which is conducted with a focus on clinical significance.
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Antitumor drugs have the characteristics of low therapeutic index, narrow safety window, and so on, which are prone to have toxic and side effects in the course of clinical therapy, thus limiting their use. In recent years, some studies have pointed out that the mechanism of adverse reactions of antitumor drugs is related to drug metabolism enzymes, receptors and transporters. Among them, drug metabolism enzymes and their gene polymorphisms play an important role in the toxic and side effects of antitumor drugs. In this paper, we analyze and summarize the side effects of antitumor drugs mediated by drug metabolism enzymes, mainly from the aspects of the roles of metabolic enzymes and their gene polymorphism in the metabolic activation and metabolic detoxification of antitumor drugs, in order to effectively avoid or reduce the toxic side effects of antitumor drugs, and to provide a reference for individualized treatment of cancer.
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Objective: To study the effect of arecoline hydrobromide (AH) on rat hepatic CYP2B expression/activity, as well as the underlying regulation mechanism in vivo. Methods: After oral administration of AH (4, 20, and 100 mg/kg/d) to rats for 7 consecutive days, the hepatic CYP2B activity was detected by LC-MS/MS method, the protein levels of hepatic CYP2B, total CAR, and endonuclear CAR were detected by Western blotting, and the hepatic CYP2B1 mRNA level was detected by real-time PCR. Results: AH treatment had no effect on rat hepatic CYP2B protein level, but the hepatic CYP2B1 mRNA level was dose-dependently increased. Additionally, although the hepatic CYP2B activity was induced by AH treatment, the induction was weakened with the dose increase of AH. Furthermore, the protein content of hepatic endonuclear CAR was increased while the total CAR protein remained unchanged following AH treatment. Conclusion: AH induces rat hepatic CYP2B by promoting nuclear translocation of CAR. The regulation of AH on rat hepatic CYP2B largely involve transcriptional activation of the gene, partially involve the post-translational modification of CYP2B protein. Our results also suggest that the risk of metabolic interaction could be existed when the substrate drugs of CYP2B are administered in betel-quid used human.
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OBJECTIVE: To make a review of nowadays related dissertations about epigenetic modifications (DNA methylation, histone modifications, chromatin remodeling and the non-coding microRNA interruption, etc.) mediating the abnormal expression of drug metabolic enzymes and inactive metabolism of substances in organisms. METHODS: Researches on epigenetic modifications regulating the genes expression or activity change of drug metabolism enzymes were reviewed. RESULTS AND CONCLUSION: The research in this field can provide reference for determining biomarkers in clinical diagnosis and therapies of tumors.
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Objective: To investigate the effects of Curcuma Rhizoma before and after being processed with vinegar on hepatic fibrosis in rats induced by CCl4 composited factors and to discuss their mechanism. Methods: Rat models of hepatic fibrosis were established by sc injection of 40% CCl4 olive solution and ig administration with alcohol and high fat food for seven weeks. The rats were randomly divided into control, model, colchicin (0.2 mg/kg, positive), raw Curcuma Rhizoma (RCR, 0.95 and 1.90 g/kg), and Curcuma Rhizoma after being processed with vinegar (CRV, 0.95 and 1.90 g/kg) groups. The rats in each group were administered with the corresponding drugs once daily for eight weeks. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBiL), hyaluronic acid (HA), and laminin (LN) in serum, liver index, the activity of superoxide dismutase (SOD), and the contents of malondialdehyde (MDA) and hydroxyproline (Hyp) in liver tissue were determined. Liver pathology and fibrosis were observed by HE staining and Masson staining. Results: Compared with the control group, there were classic liver cirrhosis pathological changes in model groups, and the levels of serum ALT, AST, TBiL, HA, and LN and the contents of Hyp and MDA were significantly increased. The activity of SOD was significantly decreased. In comparison with the model group, both RCR and CRV could improve the liver function parameters in different degrees. But the effect of CRV was superior to that of RCR, and the high-dose group of CRV had obvious advantages. Conclusion: CRV shows the better prevention and treatment on hepatic fibrosis induced by CCl4 composited factor in rats.