Induction of Renal Cytochrome P450 Arachidonic Acid Epoxygenase Activity by Dietary γ-Linolenic Acid

Zhang, Yu; Ng, Valerie Y.; Su, Ping; Engler, Marguerite M.; Engler, Mary B.; Huang, Yong; Lin, Emil T.; Kroetz, Deanna L.

doi:10.1124/jpet.105.098558

Cited by 12 publications

(10 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…P450 epoxygenases are induced by dietary fatty acids and during hypertension, but there is no evidence for selective induction of these enzymes by small molecules, including cisplatin (Yu et al, 2000a(Yu et al, , 2006. Induction of P450 epoxygenases as a viable approach for increasing EETs is therefore of limited use.…”

Section: Discussionmentioning

confidence: 99%

Attenuation of Cisplatin-Induced Renal Injury by Inhibition of Soluble Epoxide Hydrolase Involves Nuclear Factor κB Signaling

Liu

Webb²,

Fukushima³

et al. 2012

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

Acute kidney injury is associated with a significant inflammatory response that has been the target of renoprotection strategies. Epoxyeicosatrienoic acids (EETs) are anti-inflammatory cytochrome P450-derived eicosanoids that are abundantly produced in the kidney and metabolized by soluble epoxide hydrolase (sEH; Ephx2) to less active dihydroxyeicosatrienoic acids. Genetic disruption of Ephx2 and chemical inhibition of sEH were used to test whether the anti-inflammatory effects of EETs, and other lipid epoxide substrates of sEH, afford protection against cisplatin-induced nephrotoxicity. EET hydrolysis was significantly reduced in Ephx2(Ϫ/Ϫ) mice and was associated with an attenuation of cisplatin-induced increases in serum urea nitrogen and creatinine levels. Histological evidence of renal tubular damage and neutrophil infiltration was also reduced in the Ephx2(Ϫ/Ϫ) mice. Likewise, cisplatin had no effect on renal function, neutrophil infiltration, or tubular structure and integrity in mice treated with the potent sEH inhibitor 1-adamantan-1-yl-3-(1-methylsulfonyl-piperidin-4-yl-urea) (AR9273). Consistent with the ability of EETs to interfere with nuclear factor-B (NF-B) signaling, the observed renoprotection was associated with attenuation of renal NF-B activity and corresponding decreases in the expression of tumor necrosis factor (TNF) ␣, TNF receptor (TNFR) 1, TNFR2, and intercellular adhesive molecule-1 before the detection of tubular injury. These data suggest that EETs or other fatty acid epoxides can attenuate cisplatin-induced kidney injury and sEH inhibition is a novel renoprotective strategy.

show abstract

Section: Discussionmentioning

confidence: 99%

Attenuation of Cisplatin-Induced Renal Injury by Inhibition of Soluble Epoxide Hydrolase Involves Nuclear Factor κB Signaling

Liu

Webb²,

Fukushima³

et al. 2012

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

show abstract

“…Therefore, EETs or 20-HETE generated in liver or in extrahepatic organs such as the gastrointestinal tract or kidney, where TCDD-inducible CYP1A2 and PB-inducible CYP2 enzymes are present (Ding and Kaminsky, 2003;Yu et al, 2006), could have systemic as well as local effects.…”

Section: Discussionmentioning

confidence: 99%

Induction of Cyp1a and Cyp2-Mediated Arachidonic Acid Epoxygenation and Suppression of 20-Hydroxyeicosatetraenoic Acid by Imidazole Derivatives Including the Aromatase Inhibitor Vorozole

Diani-Moore¹,

Papachristou²,

Labitzke³

et al. 2006

Drug Metab Dispos

View full text Add to dashboard Cite

ABSTRACT:Cytochrome P450 (P450) enzymes metabolize the membrane lipid arachidonic acid to stable biologically active epoxides [eicosatrienoic acids (EETs)] and 20-hydroxyeicosatetraenoic acid (20-HETE). These products have cardiovascular activity, primarily acting as vasodilators and vasoconstrictors, respectively. EET formation can be increased by the prototype CYP1A or CYP2 inducers, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or phenobarbital (PB), respectively. We report here that imidazole derivative drugs: the anthelminthics, albendazole and thiabendazole; the proton pump inhibitor, omeprazole; the thromboxane synthase inhibitor, benzylimidazole; and the aromatase (CYP19) inhibitor vorozole (R76713, racemate; and R83842, (؉) enantiomer) increased hepatic microsomal EET formation in a chick embryo model. Albendazole increased EETs by transcriptional induction of CYP1A5 and the others by combined induction of CYP1A5 and CYP2H, the avian orthologs of mammalian CYP1A2 and CYP2B, respectively. All inducers increased formation of the four EET regioisomers, but TCDD and albendazole had preference for 5,6-EET and PB and omeprazole for 14,15-EET. Vorozole, benzylimidazole, and TCDD also suppressed 20-HETE formation. Vorozole was a remarkably effective and potent inducer of multiple hepatic P450s at a dose range which overlapped its inhibition of ovarian aromatase. Increased CYP1A activity in mouse Hepa 1-6 and human HepG2 cells by vorozole and other imidazole derivatives demonstrated applicability of the findings to mammalian cells. The findings suggest that changes in P450-dependent arachidonic acid metabolism may be a new source of side effects for drugs that induce CYP1A or CYP2. They demonstrate further that in vivo induction of multiple hepatic P450s produces additive increases in arachidonic acid epoxygenase activity and can occur concurrently with inhibition of ovarian aromatase activity.

show abstract

“…Several studies have reported the modulation of renal and hepatic P450-mediated arachidonic acid metabolism in several pathophysiological and experimental conditions, most notably fasting, increased dietary ␥-linolenic acid, and inflammation (Qu et al, 1998;Yu et al, 2006;Anwar-Mohamed et al, 2010;Theken et al, 2011). However, there is little information about the effect of DOX toxicity on the expression of P450 enzymes in the kidney and liver.…”

Section: Introductionmentioning

confidence: 97%

Acute Doxorubicin Toxicity Differentially Alters Cytochrome P450 Expression and Arachidonic Acid Metabolism in Rat Kidney and Liver

Zordoky¹,

Anwar-Mohamed²,

Aboutabl³

et al. 2011

Drug Metab Dispos

View full text Add to dashboard Cite

ABSTRACT:The use of doxorubicin (DOX) is limited by significant cardiotoxicity, nephrotoxicity, and hepatotoxicity. We have previously shown that DOX cardiotoxicity induces several cardiac cytochrome P450 (P450) enzymes with subsequent alteration in P450-mediated arachidonic acid metabolism. Therefore, in the current study, we investigated the effect of acute DOX toxicity on P450 expression and arachidonic acid metabolism in the kidney and liver of male Sprague-Dawley rats. Acute DOX toxicity was induced by a single intraperitoneal injection (15 mg/kg) of the drug. After 6 and 24 h, the kidneys and livers were harvested, and several P450 gene and protein expressions were determined by real-time polymerase chain reaction and Western blot analyses, respectively. Kidney and liver microsomal protein from control or DOX-treated rats was incubated with arachidonic acid, and its metabolites were determined by liquid chromatography-electron spray ionization-mass spectrometry. Our results showed that acute DOX toxicity caused an induction of CYP1B1 and CYP4A enzymes and an inhibition of CYP2B1 and CYP2C11 in both the kidney and liver. CYP2E1 was induced and soluble epoxide hydrolase (sEH) was inhibited in the kidney only. In addition, DOX toxicity caused a significant increase in epoxyeicosatrienoic acids formation in the kidney and a significant increase in 20-hydroxyeicosatetraenoic acid formation in both the kidney and the liver. In conclusion, acute DOX toxicity alters the expression of several P450 and sEH enzymes in an organ-specific manner. These changes can be attributed to DOXinduced inflammation and resulted in altered P450-mediated arachidonic acid metabolism.

show abstract

Induction of Renal Cytochrome P450 Arachidonic Acid Epoxygenase Activity by Dietary γ-Linolenic Acid

Cited by 12 publications

References 37 publications

Attenuation of Cisplatin-Induced Renal Injury by Inhibition of Soluble Epoxide Hydrolase Involves Nuclear Factor κB Signaling

Attenuation of Cisplatin-Induced Renal Injury by Inhibition of Soluble Epoxide Hydrolase Involves Nuclear Factor κB Signaling

Induction of Cyp1a and Cyp2-Mediated Arachidonic Acid Epoxygenation and Suppression of 20-Hydroxyeicosatetraenoic Acid by Imidazole Derivatives Including the Aromatase Inhibitor Vorozole

Acute Doxorubicin Toxicity Differentially Alters Cytochrome P450 Expression and Arachidonic Acid Metabolism in Rat Kidney and Liver

Contact Info

Product

Resources

About