Acute doxorubicin cardiotoxicity alters cardiac cytochrome P450 expression and arachidonic acid metabolism in rats

Zordoky, Beshay N.; Anwar-Mohamed, Anwar; Aboutabl, Mona E.; El‐Kadi, Ayman O.S.

doi:10.1016/j.taap.2009.09.012

Cited by 102 publications

(72 citation statements)

References 45 publications

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“…14 The increased CYP4A11expression in the cardiovascular toxicity was accompanied with increased 20-HETE levels. 12 In this study, it is found that smokers had higher platelet CYP4A11protein expression which may play a role in the cardiovascular complications induced by smoking.…”

Section: Discussionmentioning

confidence: 62%

“…9 In addition, CYP4A11 expression was reported to be increased in endothelial dysfunction, in hypertensive animal models and in doxorubicin induced cardiotoxity. 12,13 Furthermore, genetic polymorphism on CYP4A11 gene was associated with cardiovascular diseases such as hypertension. 14 The increased CYP4A11expression in the cardiovascular toxicity was accompanied with increased 20-HETE levels.…”

Section: Discussionmentioning

confidence: 99%

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Effect of Cigarette Smoking on the Production of 20-Hydroxyeicosatetraenoic Acid in Human Platelet

Jarrar¹

2017

Int. J. Res. Ayurveda Pharm.

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Smoking showed to effect on platelet aggregation and the response to anti-platelet drugs. The arachidonic acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) increases platelet aggregation and blood pressure. In this study, we investigated the influence of cigarette smoking on plasma 20-HETE levels and protein expression of 20-HETE producing enzyme CYP4A11 in isolated platelets from smoker (N=6) and non-smoker (N=6) volunteers. The protein expression and 20-HETE levels were analyzed using immunublot and high-performance liquid chromatography with Mass spectrometry assays, respectively. The results showed that plasma 20-HETE level was significantly higher among smokers than non-smokers (t test, pvalue<0.05). The protein expression of CYP4A11 was significantly higher (t test, p-value<0.05) in platelets isolated from smokers, which was correlated with in vitro higher 20-HETE production, than non-smoker platelets. We concluded from this study that cigarette smoking increased the level of platelet activator 20-HETE through increasing the protein expression of CYP4A11. These findings may increase our understanding of the molecular mechanism of smoking in platelet aggregation and in the variation of anti-platelet drug response induced by smoking.

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Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Effect of Cigarette Smoking on the Production of 20-Hydroxyeicosatetraenoic Acid in Human Platelet

Jarrar¹

2017

Int. J. Res. Ayurveda Pharm.

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“…The CYP450 enzyme is of the most important xenobioticbiotransformation enzymes that has high catalytic potential. It detoxifies xenobiotic or activates it to reactive inter- mediates (14). The highest level of CYP enzymes are found in the liver endoplasmic reticulum (microsome).…”

Section: Discussionmentioning

confidence: 99%

“…For above reasons, in this study a toxicological evaluation was carried out to investigate its potential toxicity after single and 45-day repeated dosing of osthole in mice and Wistar rats, respectively. In the current study, osthole was isolated from and toxins (14). CYP enzymes are found approximately in all living organisms but the highest level of them is found in the liver endoplasmic reticulum (microsome).…”

Section: Introductionmentioning

confidence: 92%

“…Quantitative specific RNA expression was performed in one-step Express one-step SYBR R Green ER™ kit (Invitrogen, cat #11780-200). The primers used in this study were selected from an already published study (Table 1) (14). The performances of all primer pairs were tested by primer concentration to determine the optimal reaction conditions.…”

Section: Real Time Rt-pcr Analysismentioning

confidence: 99%

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Safety Assessment of Osthole Isolated from Prangos ferulacea: Acute and Subchronic Toxicities and Modulation of Cytochrome P450

Shokoohinia

Bazargan

Miraghaee

et al. 2017

Jundishapur J Nat Pharm Prod

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Background: Osthole (7-methoxy-8-(3-methyl-2-butenyl)-2H-1-benzopyran-2-one), a natural coumarin derivative, has exhibited various pharmacological properties. In addition, the possibility of its development as a promising lead compound for drug discovery has been proposed. However, there is little toxicological information regarding safety of repeated exposure to this coumarin. Objective: The present study evaluated the potential toxicity of osthole after acute and subchronic administration in rodents. In addition, we investigated the effect of osthole on different hepatic CYP gene expressions in male rats receiving the highest dose of osthole. Methods: In the acute toxicity study, single doses of osthole (100, 500, and 1000 mg/kg) were administered intraperitoneally to mice and the mice were then monitored for 14 days. In the subchronic toxicity study, osthole was administered orally to rats at doses of 5, 25, and 50 mg/kg/day for 45 days. Results:The results of acute study indicated that LD50 of osthole is about 710 mg/kg. There was no significant difference in body weight, relative organ weight, and hematological parameters in the subchronic toxicity study. Biochemical analysis showed some significant changes including in creatinine, potassium, glucose, albumin, and urea levels. The results of histopathological studies showed that all the removed organs, specially kidney, were affected by subchronic exposure to osthole. The change in the kidney included peritubular capillary congestion, hemorrhage in renal parenchyma, mild tubular dilatation, and mild interstitial infiltration of inflammatory cells. Furthermore, osthole treatment caused an induction in CYP1A2, CYP2E1, and CYP2C11. Conclusions: Finally, concerning the common classification of relative toxicity of chemicals, acute toxicity results suggested that osthole is a moderately toxic substance when administered i.p. The obtained data from subchronic study supported the evidence of renal function impairment by osthole. The no-observed adverse-effect level (NOAEL) of the extract for both male and female rats is considered less than 5 mg/kg.

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Absolute protein assay for the simultaneous quantification of two epoxide hydrolases in rats by mass spectrometry–based targeted proteomics

Chen

et al. 2021

J of Separation Science

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Epoxide hydrolases catalyze the hydrolysis of both exogenous and endogenous epoxides to the corresponding vicinal diols by adding water. Microsomal and soluble epoxide hydrolase are two main mammalian enzymes that have been intensely characterized. The purpose of this investigation was to develop and validate a proteomics assay allowing the simultaneous quantification of microsomal and soluble epoxide hydrolase in rats. Protein quantification was realized through targeted proteomics using liquid chromatography with tandem mass spectrometry for the determination of trypsin-specific surrogate peptides after digestion. Stable isotope-labeled peptides were used as the internal standards. The chromatography of the surrogate peptides was performed on an Agilent SB C 18 column (100 mm × 4.6 mm, 1.8 µm) with gradient elution. Acetonitrile containing 0.1% formic acid and 0.1% formic acid aqueous solution were used as mobile phases. A multiple reaction monitoring method in a positive ionization mode was used for the simultaneous detection of the peptides. The method was validated concerning the specificity, linearity, within-day and between-day accuracy and precision, matrix effect, stability, and digestion efficiency. The developed assay was successfully used to quantify the protein levels of microsomal and soluble epoxide hydrolase in rat liver, kidney, and heart S9 samples.

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Acute doxorubicin cardiotoxicity alters cardiac cytochrome P450 expression and arachidonic acid metabolism in rats

Cited by 102 publications

References 45 publications

Effect of Cigarette Smoking on the Production of 20-Hydroxyeicosatetraenoic Acid in Human Platelet

Effect of Cigarette Smoking on the Production of 20-Hydroxyeicosatetraenoic Acid in Human Platelet

Safety Assessment of Osthole Isolated from Prangos ferulacea: Acute and Subchronic Toxicities and Modulation of Cytochrome P450

Absolute protein assay for the simultaneous quantification of two epoxide hydrolases in rats by mass spectrometry–based targeted proteomics

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