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https://www.readbyqxmd.com/read/28236470/effect-of-alcohol-and-its-metabolites-in-lung-cancer-capua-study
#1
Sara M Álvarez-Avellón, Ana Fernández-Somoano, Eva M Navarrete-Muñoz, Jesús Vioque, Adonina Tardón
BACKGROUND AND OBJECTIVE: Alcohol and its metabolites play an important role in carcinogenesis. This effect could be modulated by polymorphisms in genes encoding enzymes involved in the metabolism of alcohol and folate. Therefore, we analyzed the effect of alcohol consumption and ADH1B Arg48His, ADH1B Arg370Cys, ADH1C Ile349Val, ALDH2 Glu540Lys, CYP2E1 RsaI, CYP2E1 DraI, CYP2E1 TaqI and MTHFR C677T polymorphisms on the risk of developing lung cancer. PATIENTS AND METHODS: We included 876 lung cancer cases and 840 controls of the CAPUA hospital-based case-control study...
February 21, 2017: Medicina Clínica
https://www.readbyqxmd.com/read/28229921/protective-effect-of-a-polysaccharide-from-anoectochilus-roxburghii-against-carbon-tetrachloride-induced-acute-liver-injury-in-mice
#2
Biyu Zeng, Minghua Su, Qingxi Chen, Qiang Chang, Wei Wang, Huihua Li
ETHNOPHARMACOLOGICAL RELEVANCE: Anoectochilus roxburghii (Wall.) Lindl. is traditionally used for the treatment of various types of chronic and acute hepatitis in China. Considering that Anoectochilus roxburghii polysaccharide (ARPT) is the main constituent of Anoectochilus roxburghii, the present study was designed to investigate the hepatoprotective effect of ARPT and its possible mechanism in carbon tetrachloride (CCl4)-induced mice. MATERIAL AND METHODS: The hepatoprotective activity of ARPT (150, 300 and 500 mg/kg) were investigated on CCl4-induced acute liver damage in mice...
February 13, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28219698/protective-effects-of-diallyl-disulfide-against-acetaminophen-induced-nephrotoxicity-a-possible-role-of-cyp2e1-and-nf-%C3%AE%C2%BAb
#3
Je-Won Ko, Jin-Young Shin, Jeong-Won Kim, Sung-Hyeuk Park, Na-Rae Shin, In-Chul Lee, In-Sik Shin, Changjong Moon, Sung-Ho Kim, Sung-Hwan Kim, Jong-Choon Kim
Diallyl disulfide (DADS) is a degradation product of allicin which is contained in garlic. This study investigated the protective effects of DADS against acetaminophen (AAP)-induced nephrotoxicity and the molecular mechanisms of nephroprotective effects in rats. AAP caused severe nephrotoxicity as evidenced by significant increases in renal tubular cell apoptosis, mitochondria-mediated apoptosis, and up-regulation of nuclear transcription factor kappa-B (NF-κB), cyclooxygenase-2 (Cox-2), and tumor necrosis factor-α (TNF-α) in the kidney with histopathological alterations...
February 17, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28210203/wnt-%C3%AE-catenin-signaling-drives-thioacetamide-mediated-heteroprotection-against-acetaminophen-induced-lethal-liver-injury
#4
Vivekkumar P Dadhania, Bharat Bhushan, Udayan Apte, Harihara M Mehendale
Preplacement of compensatory tissue repair (CTR) by exposure to a nonlethal dose of a toxicant protects animals against a lethal dose of another toxicant. Although CTR is known to heteroprotect, the underlying molecular mechanisms are not completely known. Here, we investigated the mechanisms of heteroprotection using thioacetamide (TA): acetaminophen (APAP) heteroprotection model. Male Swiss Webster mice received a low dose of TA or distilled water (DW) vehicle 24 hours prior to a lethal dose of APAP. Liver injury, tissue repair, and promitogenic signaling were studied over a time course of 24 hours after APAP overdose to the TA- and DW-primed mice (TA + APAP and DW + APAP, respectively)...
January 2017: Dose-response: a Publication of International Hormesis Society
https://www.readbyqxmd.com/read/28205631/immature-mice-are-more-susceptible-than-adult-mice-to-acetaminophen-induced-acute-liver-injury
#5
Yan Lu, Cheng Zhang, Yuan-Hua Chen, Hua Wang, Zhi-Hui Zhang, Xi Chen, De-Xiang Xu
Acetaminophen (APAP) overdose induces acute liver injury. The aim of the present study was to analyze the difference of susceptibility between immature and adult mice to APAP-induced acute liver injury. Weanling immature and adult mice were injected with APAP (300 mg/kg). As expected, immature mice were more susceptible than adult mice to APAP-induced acute liver injury. APAP-evoked hepatic c-Jun N-terminal kinase phosphorylation was stronger in immature mice than in adult mice. Hepatic receptor-interacting protein (RIP)1 was obviously activated at APAP-exposed immature and adult mice...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28199000/overexpression-of-pregnane-x-and-glucocorticoid-receptors-and-the-regulation-of-cytochrome-p450-in-human-epileptic-brain-endothelial-cells
#6
Chaitali Ghosh, Mohammed Hossain, Jesal Solanki, Imad M Najm, Nicola Marchi, Damir Janigro
OBJECTIVE: Recent evidence suggests a metabolic contribution of cytochrome P450 enzymes (CYPs) to the drug-resistant phenotype in human epilepsy. However, the upstream molecular regulators of CYP in the epileptic brain remain understudied. We therefore investigated the expression and function of pregnane xenobiotic (PXR) and glucocorticoid (GR) nuclear receptors in endothelial cells established from post-epilepsy surgery brain samples. METHODS: PXR/GR localization was evaluated by immunohistochemistry in specimens from subjects who underwent temporal lobe resections to relieve drug-resistant seizures...
February 15, 2017: Epilepsia
https://www.readbyqxmd.com/read/28184028/long-term-administration-of-tacrolimus-and-everolimus-prevents-high-cholesterol-high-fructose-induced-steatosis-in-c57bl-6j-mice-by-inhibiting-de-novo-lipogenesis
#7
Sharma Love, Malik A Mudasir, Subhash C Bhardwaj, Gurdarshan Singh, Sheikh A Tasduq
AIM: To investigate the effects of tacrolimus (TC) and everolimus (EV) on non-alcoholic steatohepatitis (NASH) induced by high fat, high cholesterol and fructose (fast food) diet in C57BL/6J mice. MATERIALS AND METHODS: C57BL/6J mice were divided into four groups (n=8). 1) Standard Chow (SC); 2) Fast food (FF) diet; 3) FF + Tacrolimus (TC, 1mg/kg) and; 4) FF + Everolimus (EV, 1mg/kg) and treated for 16 weeks. Serum and tissue samples were analyzed for evidence of inflammation, fibrosis, lipogenesis, and apoptosis...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28163821/the-role-of-cyp2e1-in-the-drug-metabolism-or-bioactivation-in-the-brain
#8
REVIEW
W A García-Suástegui, L A Ramos-Chávez, M Rubio-Osornio, M Calvillo-Velasco, J A Atzin-Méndez, J Guevara, D Silva-Adaya
Organisms have metabolic pathways that are responsible for removing toxic agents. We always associate the liver as the major organ responsible for detoxification of the body; however this process occurs in many tissues. In the same way, as in the liver, the brain expresses metabolic pathways associated with the elimination of xenobiotics. Besides the detoxifying role of CYP2E1 for compounds such as electrophilic agents, reactive oxygen species, free radical products, and the bioactivation of xenobiotics, CYP2E1 is also related in several diseases and pathophysiological conditions...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28149008/transforming-growth-factor-%C3%AE-1-smad3-signaling-and-redox-status-in-experimentally-induced-nephrotoxicity-impact-of-carnosine
#9
Walaa Arafa Keshk, Mohamed Alaa Katary
: Exposure to various organic compounds including drugs and environmental toxins causes cellular damage through generation of free radicals. Carnosine a dipeptide was used in this study to evaluate its effect against CCl4-induced nephrotoxicity. Sixty male albino rats were involved in this study and were equally divided into four groups. CCl4 (3 ml/kg body weight; biweekly for 4 weeks) was given to group II and III. Carnosine (10 mg/kg body weight; once daily for 4 weeks) was given to group III and VI...
March 2017: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/28126494/metallothionein-protects-against-isoniazid-induced-liver-injury-through-the-inhibition-of-cyp2e1-dependent-oxidative-and-nitrosative-impairment-in-mice
#10
Yong Lian, Jing Zhao, Yi-Mei Wang, Jun Zhao, Shuang-Qing Peng
Oxidative stress mediated by hepatic CYP2E1 during isoniazid (INH) metabolism is considered responsible for INH hepatotoxicity. This study attempts to determine whether metallothionein (MT), a cysteine-rich antioxidant can protect against INH-induced liver injury by using a MT-I/II deficient mouse model (MT-/- mice). MT-/- mice and the corresponding wild-type mice received intragastric administrations of 0, 75, 150 and 300 mg/kg of INH for 15 days. The results showed that 150 and 300 mg/kg of INH induced liver injury in both types of mice, as evidenced by increased liver index and histopathological change of liver vacuolar degeneration...
January 23, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28115069/diallyl-trisulfide-attenuated-n-hexane-induced-neurotoxicity-in-rats-by-modulating-p450-enzymes
#11
Shuo Wang, Ming Li, Xujing Wang, Xianjie Li, Hongyin Yin, Lulu Jiang, Wenting Han, Gleniece Irving, Tao Zeng, Keqin Xie
Chronic exposure to n-hexane can induce serious nerve system impairments without effective preventive medicines. Diallyl trisulfide (DATS) is a garlic-derived organosulfur compound, which has been demonstrated to have many beneficial effects. The current study was designed to evaluate whether DATS could restrain n-hexane induced neurotoxicity in rats and to explore the underlying mechanisms. Rats were treated with n-hexane (3 g/kg, p.o.) and different doses of DATS (10, 20 and 30 mg/kg, p.o.) for 8 weeks...
January 20, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28111763/cytochrome-p450-reaction-phenotyping-and-inhibition-and-induction-studies-of-pinostrobin-in-human-liver-microsomes-and-hepatocytes
#12
Shengnan Tan, Zhimin Dong, Jiashuo Zhang, Thomas Efferth, Yujie Fu, Xin Hua
Pinostrobin (PI, 5-hydroxy-7-methoxyflavanone) is a natural flavonoid known for its rich pharmacological activities. The objective of this study was to identify the human liver cytochrome P450 (CYP450) isoenzymes involved in the metabolism of PI. A single hydoxylated metabolite was obtained from PI after an incubation with pooled human liver microsomes (HLMs). The relative contributions of different CYP450s were evaluated using CYP450-selective inhibitors in HLMs and recombinant human CYP450 enzymes, and the results revealed the major involvement of CYP1A2, CYP2C9 and CYP2E1 in PI metabolism...
November 7, 2016: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28107387/neuronal-cell-death-and-degeneration-through-increased-nitroxidative-stress-and-tau-phosphorylation-in-hiv-1-transgenic-rats
#13
Young-Eun Cho, Myoung-Hwa Lee, Byoung-Joon Song
The underlying mechanisms for increased neurodegeneration and neurocognitive deficits in HIV-infected people are unclear. Therefore, this study was aimed to investigate the mechanisms of increased neurodegeneration in 5-month old male HIV-1 Transgenic (Tg) rats compared to the age- and gender-matched wild-type (WT) by evaluating histological changes and biochemical parameters of the key proteins involved in the cell death signaling and apoptosis. Histological and immunohistochemical analyses revealed decreased neuronal cells with elevated astrogliosis in HIV-1 Tg rats compared to WT...
2017: PloS One
https://www.readbyqxmd.com/read/28103636/limited-excessive-voluntary-alcohol-drinking-leads-to-liver-dysfunction-in-mice
#14
Scott A Wegner, Katherine A Pollard, Viktor Kharazia, David Darevsky, Luz Perez, Sanjoy Roychowdhury, Allison Xu, Dorit Ron, Laura E Nagy, Frederic Woodward Hopf
BACKGROUND: Liver damage is a serious and sometimes fatal consequence of long-term alcohol intake, which progresses from early-stage fatty liver (steatosis) to later-stage steatohepatitis with inflammation and fibrosis/necrosis. However, very little is known about earlier stages of liver disruption that may occur in problem drinkers, those who drink excessively but are not dependent on alcohol. METHODS: We examined how repeated binge-like alcohol drinking in C57BL/6 mice altered liver function, as compared with a single binge-intake session and with repeated moderate alcohol consumption...
February 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28101459/venlafaxine-induced-cytotoxicity-towards-isolated-rat-hepatocytes-involves-oxidative-stress-and-mitochondrial-lysosomal-dysfunction
#15
Elham Ahmadian, Hossein Babaei, Alireza Mohajjel Nayebi, Aziz Eftekhari, Mohammad Ali Eghbal
Purpose: Depression is a public disorder worldwide. Despite the widespread use of venlafaxine in the treatment of depression, it has been associated with the incidence of toxicities. Hence, the goal of the current investigation was to evaluate the mechanisms of venlafaxine-induced cell death in the model of the freshly isolated rat hepatocytes. Methods: Collagenase-perfused rat hepatocytes were treated with venlafaxine and other agents. Cell damage, reactive oxygen species (ROS) formation, lipid peroxidation, mitochondrial membrane potential decline, lysosomal damage, glutathione (GSH) level were analyzed...
December 2016: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28078076/sex-dependent-alteration-of-cardiac-cytochrome-p450-gene-expression-by-doxorubicin-in-c57bl-6-mice
#16
Marianne K O Grant, Davis M Seelig, Leslie C Sharkey, Beshay N Zordoky
BACKGROUND: There is inconclusive evidence about the role of sex as a risk factor for doxorubicin (DOX)-induced cardiotoxicity. Recent experimental studies have shown that adult female rats are protected against DOX-induced cardiotoxicity. However, the mechanisms of this sexual dimorphism are not fully elucidated. We have previously demonstrated that DOX alters the expression of several cytochrome P450 (CYP) enzymes in the hearts of male rats. Nevertheless, the sex-dependent effect of DOX on the expression of CYP enzymes is still not known...
2017: Biology of Sex Differences
https://www.readbyqxmd.com/read/28074333/rosiglitazone-metabolism-in-human-liver-microsomes-using-a-substrate-depletion-method
#17
Maryam Bazargan, David J R Foster, Andrew K Davey, Beverly S Muhlhausler
BACKGROUND: Elimination of rosiglitazone in humans is via hepatic metabolism. The existing studies suggest that CYP2C8 is the major enzyme responsible, with a minor contribution from CYP2C9; however, other studies suggest the involvement of additional cytochrome P450 enzymes and metabolic pathways. Thus a full picture of rosiglitazone metabolism is unclear. OBJECTIVE: This study aimed to improve the current understanding of potential drug-drug interactions and implications for therapy by evaluating the kinetics of rosiglitazone metabolism and examining the impact of specific inhibitors on its metabolism using the substrate depletion method...
January 10, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28074086/role-of-cyp2e1-polymorphisms-in-breast-cancer-a-systematic-review-and-meta-analysis
#18
Yu Lu, Xuan Zhu, Cuiping Zhang, Kongmei Jiang, Chunni Huang, Xue Qin
BACKGROUND: CYP2E1 polymorphisms have been reported to influence individual's breast cancer susceptibility as a phase I enzyme, but the results of these previous studies remain controversial. We performed a comprehensive meta-analysis to assess their association. METHODS: A comprehensive search of literature included in various databases (PubMed, Web of Science and Google scholar), published before August 2016, was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) calculated in fixed or random-effects models were used to estimate the strength of the associations between three polymorphisms of CYP2E1 and breast cancer susceptibility...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28073119/in-vitro-inhibition-of-human-cyp450s-1a2-2c9-3a4-5-2d6-and-2e1-by-grandisin
#19
Maísa Daniela Habenschus, Fernanda de Lima Moreira, Norberto Peporine Lopes, Anderson R M de Oliveira
Grandisin, a lignan isolated from many species of plants, such as Virola surinamensis, is a potential drug candidate due to its biological properties, highlighted by its antitumor and trypanocidal activities. In this study, the inhibitory effects of grandisin on the activities of human cytochrome P450 enzymes were investigated by using human liver microsomes. Results showed that grandisin is a competitive inhibitor of CYP2C9 and a competitive and mechanism-based inhibitor of CYP3A4/5. The apparent Ki value for CYP2C9 was 50...
January 10, 2017: Planta Medica
https://www.readbyqxmd.com/read/28073118/in-vitro-metabolism-of-artepillin-c-by-rat-and-human-liver-microsomes
#20
Daniel Blascke Carrão, Nayara Cristina Perez de Albuquerque, Lucas Maciel Mauriz Marques, Antônio Eduardo Miller Crotti, Alan Cesar Pilon, Vanderlan Da Silva Bolzani, Andresa Aparecida Berretta, Anderson Rodrigo Moraes de Oliveira
Artepillin C, a natural product present in the Brazilian green propolis, has several biological properties. Among these properties, the antitumor action of this product is noteworthy and makes it a promising drug candidate for the treatment of several types of cancer. This paper describes the in vitro metabolism of Artepillin C in rat and human liver microsomes. The rat model suggested a sigmoidal profile for the metabolism, adapted to the Hill's kinetic model. The enzymatic kinetic parameters were as follows: maximal velocity = 0...
January 10, 2017: Planta Medica
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