Effects of diabetes on rabbit kidney and lung CYP2E1 and CYP2B4 expression and drug metabolism and potentiation of carcinogenic activity of N-nitrosodimethylamine in kidney and lung

Arınç, Emel; Arslan, Şevki; Bozcaarmutlu, Azra; Adalı, Orhan

doi:10.1016/j.fct.2006.07.026

Cited by 50 publications

(22 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, increased activity of CYP2E1 can be considered as increased risk for the development of cancer. It is well known that many substrates of CYP2E1, like ethanol, benzene and pyridine [10,11,12,13], as well as some pathophysiological conditions like diabetes, obesity and starvation [10,14,15,16,17], are also inducers of the enzyme. CYP2E1 possesses genetic polymorphisms that show variability between races and ethnicities [28], and the genotype distribution of CYP2E1 *5B, * 6 and * 7B polymorphisms in the Turkish population are found to be similar to other Caucasian populations [29, 30].…”

Section: Discussionmentioning

confidence: 99%

“…In this respect, the isoform CYP2E1 is of great interest due to its role in the metabolism and bioactivation of many low molecular weight compounds, including ethanol, acetone, drugs like acetaminophen, isoniazid, chlorzoxazone and fluorinated anesthetics [6,7,8], and many procarcinogens like benzene, N-nitrosodimethylamine and styrene [9]. Besides, the CYP2E1 isoform is induced by ethanol, benzene, pyridine and isoniazid [10,11,12,13], as well as by some pathophysiological conditions like diabetes, obesity and starvation [10,14,15,16,17]. CYP2E1 is especially important for the risk of development of leukemia as it has a major role in the bioactivation of benzene.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Significance of Genetic Polymorphisms at Multiple Loci of <i>CYP2E1</i> in the Risk of Development of Childhood Acute Lymphoblastic Leukemia

et al. 2007

Self Cite

View full text Add to dashboard Cite

Background/Aims: The molecular etiology of childhood acute lymphoblastic leukemia (ALL) is likely to involve interactions between environmental factors and genetic make up. Understanding these interactions between various predisposing genes for the risk of developing childhood leukemia is of considerable importance. CYP2E1 is a susceptible gene in this respect, especially for its capacity to bioactivate many procarcinogens including benzene and N-nitrosodimethylamine. The CYP2E1 gene possesses several polymorphisms in humans, and among them, CYP2E1*5B and *6 have been shown to be associated with increased risks of several chemical-induced diseases. There are limited and contradictory data on the association between the CYP2E1*5B variant allele and childhood ALL, and none on such associations of CYP2E1*6 and*7B variant alleles. The aim of this study was to investigate the possible association of CYP2E1*5B, *6 and *7B alleles, alone or in combination, with the risk of incidence of childhood ALL in a Turkish population. Methods: The genotypes for both polymorphisms were determined by polymerase chain reaction/restriction fragment length polymorphism techniques on 207 healthy controls and 168 patients. Results: Neither locus was associated with the occurrence of childhood ALL. On the other hand, when both CYP2E1*5B and *6 alleles were considered together, the risk of childhood ALL increased significantly (2.9-fold; OR = 2.9, 95% CI 1.0–8.5; p < 0.05). Moreover, the presence of at least 2 variant alleles of any combination increased the risk significantly 3.9 times, suggesting a combined effect (OR = 3.9, 95% CI 1.4–11.0). Conclusion: Individuals carrying combinations of CYP2E1*5B, *6 and *7B variants together are likely associated with the risk of developing childhood ALL.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Significance of Genetic Polymorphisms at Multiple Loci of <i>CYP2E1</i> in the Risk of Development of Childhood Acute Lymphoblastic Leukemia

et al. 2007

Self Cite

View full text Add to dashboard Cite

show abstract

“…Further, chronic alcohol consumption induces liver injury in Cu, Zn-superoxide dismutase-de fi cient mice (Sod1−/−), with extensive centrilobular necrosis, in fl ammation and mitochondrial dysfunction (Kessova and Cederbaum 2007 ) . Garro et al ( 1981 ) , Arinç et al ( 2007 ) , Ma et al ( 1991 ) , Dey et al ( 2002Dey et al ( , 2005 , Kapoor et al ( 2006 ) , Khan et al ( 2011) , Anandatheerthavarada et al ( 1993 , Bhagwat et al ( 1995 ) , Huan and Koop ( 1999 ) , Roberts et al ( 1995 ) , and Zaluzny et al ( 1990 ) N-methyl formamide Lerche et al ( 1996) Diethylnitrosamine Lerche et al ( 1996) Nicotine Howard et al ( 2001 Regulation of Hepatic CYP2E1 Mediated by Pathophysiological Conditions Such as Obesity, Diabetes and Chemical Inducers Treatment of rats with the chemical inducer-4-methylpyrazole and streptozotocin which is commonly used to induce diabetes, increases CYP2E1 protein and catalytic activity and the values are additive for each inducer alone suggesting that diabetes may increase the susceptibility to toxins which are activated by CYP2E1, more so if pre-exposure to chemical inducers similar to 4-methylpyrazole, e.g., ethanol, isoniazid occurs (Wu and Cederbaum 1993a ) . Pyrazole and 4-methylpyrazole, inducers for hepatic CYP2E1 induce renal CYP2E1, through a post-transcriptional mechanism-possibly involving increased protein stabilization .…”

Section: Antioxidant Depletion Promotes Cyp2e1 Mediated Liver Injury:mentioning

confidence: 97%

Cytochrome P450 2E1: Its Clinical Aspects and a Brief Perspective on the Current Research Scenario

Dey

2013

Subcellular Biochemistry

View full text Add to dashboard Cite

Research on Cytochrome P450 2E1 (CYP2E1), a key enzyme in alcohol metabolism has been very well documented in literature. Besides the involvement of CYP2E1 in alcohol metabolism as illustrated through the studies discussed in the chapter, recent studies have thrown light on several other aspects of CYP2E1 i.e. its extrahepatic expression, its involvement in several diseases and pathophysiological conditions; and CYP2E1 mediated carcinogenesis and modulation of drug efficacy. Studies involving these interesting facets of CYP2E1 have been discussed in the chapter focusing on the recent observations or ongoing studies illustrating the crucial role of CYP2E1 in disease development and drug metabolism.

show abstract

“…Because caderofloxacin is a newly developed active quinolone derivatized from ciprofloxacin, more attention should be paid to the liver injury induced by caderofloxacin in its future clinical use. In addition, CYP2E1 is involved in the diverse oxidative metabolism of a wide spectrum of endogenous compounds as well as xenobiotics, including procarcinogens, such as benzene [36] and the commonly recognized hepatocarcinogen, caderofloxacin. This may lead to the accumulation of carcinogenic metabolites in vivo, and it is possibly harmful to the human body when it is used in long term.…”

Section: Wwwnaturecom/aps Liu L Et Almentioning

confidence: 99%

Chronic administration of caderofloxacin, a new fluoroquinolone, increases hepatic CYP2E1 expression and activity in rats

et al. 2016

View full text Add to dashboard Cite

Aim: Caderofloxacin is a new fluoroquinolone that is under phase III clinical trials in China. Here we examined the effects of caderofloxacin on rat hepatic cytochrome P450 (CYP450) isoforms as well as the potential of caderofloxacin interacting with co-administered drugs. Methods: Male rats were treated with caderofloxacin (9 mg/kg, ig) once or twice daily for 14 consecutive days. The effects of caderofloxacin on CYP3A, 2D6, 2C19, 1A2, 2E1 and 2C9 were evaluated using a "cocktail" of 6 probes (midazolam, dextromethorphan, omeprazole, theophylline, chlorzoxazone and diclofenac) injected on d 0 (prior to caderofloxacin exposure) and d 15 (after caderofloxacin exposure). Hepatic microsomes from the caderofloxacin-treated rats were used to assess CYP2E1 activity and chlorzoxazone metabolism. The expression of CYP2E1 mRNA and protein in hepatic microsomes was analyzed with RT-PCR and Western blotting, respectively. Results: Fourteen-day administration of caderofloxacin significantly increased the activity of hepatic CYP2E1, leading to enhanced metabolism of chlorzoxazone. In vitro microsomal study confirmed that CYP2E1 was a major metabolic enzyme involved in chlorzoxazone metabolism, and the 14-d administration of caderofloxacin significantly increased the activity of CYP2E1 in hepatic microsomes, resulting in increased formation of 6-hydroxychlorzoxazone. Furthermore, the 14-d administration of caderofloxacin significantly increased the expression of CYP2E1 mRNA and protein in liver microsomes, which was consistent with the pharmacokinetic results. Conclusion: Fourteen-day administration of caderofloxacin can induce the expression and activity of hepatic CYP2E1 in rats. When caderofloxacin is administered, a potential drug-drug interaction mediated by CYP2E1 induction should be considered.

show abstract

Effects of diabetes on rabbit kidney and lung CYP2E1 and CYP2B4 expression and drug metabolism and potentiation of carcinogenic activity of N-nitrosodimethylamine in kidney and lung

Cited by 50 publications

References 36 publications

Significance of Genetic Polymorphisms at Multiple Loci of <i>CYP2E1</i> in the Risk of Development of Childhood Acute Lymphoblastic Leukemia

Significance of Genetic Polymorphisms at Multiple Loci of <i>CYP2E1</i> in the Risk of Development of Childhood Acute Lymphoblastic Leukemia

Cytochrome P450 2E1: Its Clinical Aspects and a Brief Perspective on the Current Research Scenario

Chronic administration of caderofloxacin, a new fluoroquinolone, increases hepatic CYP2E1 expression and activity in rats

Contact Info

Product

Resources

About