8 research outputs found
Modulation of cytochrome P450 gene expression and arachidonic acid metabolism during isoproterenol-induced cardiac hypertrophy in rats,”DrugMetabolism and Disposition
ABSTRACT: Several cytochrome P450 (P450) enzymes have been identified in the heart, and their levels have been reported to be altered during cardiac hypertrophy. Moreover, there is a strong correlation between P450-mediated arachidonic acid metabolites and the pathogenesis of cardiac hypertrophy. Therefore, we investigated the effect of isoproterenol-induced cardiac hypertrophy on the expression of several P450 genes and their associated P450-derived metabolites of arachidonic acid. Cardiac hypertrophy was induced by seven daily i.p. injections of 5 mg/kg isoproterenol. Thereafter, the heart, lung, liver, and kidney were harvested, and the expression of different genes was determined by real-time polymerase chain reaction. Heart microsomal protein from control or isoproterenol treated rats was incubated with 50 M arachidonic acid, and arachidonic acid metabolites were determined by liquid chromatography-electron spray ionization-mass spectrometry. Our results show that isoproterenol treatment significantly increased the heart/body weight ratio and the hypertrophic markers. In addition, there was a significant induction of CYP1A1, CYP1B1, CYP4A3, and soluble epoxide hydrolase and a significant inhibition of CYP2C11 and CYP2E1 in the hypertrophied hearts as compared with the control. CYP1A1, CYP2E1, and CYP4A3 gene expression was induced in the kidney, and CYP4A3 was induced in the liver of isoproterenol-treated rats. Isoproterenol treatment significantly reduced 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid formation and significantly increased their corresponding 8,9-, and 14,15-dihydroxyeicosatrienoic acid and the 20-hydroxyeicosatetraenoic acid metabolite. In conclusion, isoproterenol-induced cardiac hypertrophy alters arachidonic acid metabolism and its associated P450 enzymes, suggesting their role in the development and/or progression of cardiac hypertrophy
Modulation of Cytochrome P450 Gene Expression and Arachidonic Acid Metabolism during Isoproterenol-Induced Cardiac Hypertrophy in Rats
MS/MS-based molecular networking for mapping the chemical diversity of the pulp and peel extracts from Citrus japonica Thunb.; in vivo evaluation of their anti-inflammatory and anti-ulcer potential
Although inflammation is a beneficial response to harmful triggers, the associated diseases develop the potential for death-threatening conditions. Citrus species are valuable sources of chemical compounds with diverse structural properties that could alleviate damaging inflammation and reduce serious side effects of synthetic drugs. Kumquats are the smallest trees among the citrus family widely distributed in Asia, Europe, and North America, with little cultivation in Africa. The current study aims to conduct comprehensive chemical, anti-inflammatory and anti-ulcer studies of Citrus japonica, thus focusing attention on extensive cultivation of these species in Africa to enhance their beneficial uses. A comparative chemical profiling of peel and pulp extracts was performed via HPLC-MS/MS analysis, 164 metabolites were annotated aided by the spectral similarity networks. Around 148 of which were visualized as a species-first documentation. Phenolics were the predominant classes including methoxylated flavonoids, O/C-glycosylated flavones, and flavanones with the less common O- or C-O-triglycosyl methoxylated flavones among the genus Citrus. Moreover, the anti-inflammatory study demonstrated the significant activity of the pulp and peel extracts (200 and 400 mg/kg, p.o.) via reducing paw swelling induced by carrageenan at all-time points and decreasing the formation of TNF-α and IL-1β. Moreover, in ethanol-induced gastric ulcer rat model, the high doses of both extracts significantly improved ulcer indexes and suppressed gastric inflammation by inhibiting myeloperoxidase activity and possessed an antioxidant effect via increasing reduced glutathione, decreasing malondialdehyde, and nitric oxide. Additionally, histopathological investigations confirmed the anti-inflammatory and anti-ulcer effects. Considering the two fruit tissues, peels markedly improved inflammatory and gastroprotective properties associated with the high diversity of their flavonoid structures
Modulation of cytochrome P450 gene expression and arachidonic acid metabolism during isoproterenol-induced cardiac hypertrophy in rats,”DrugMetabolism and Disposition
Abstract Several CYP enzymes have been identified in the heart and their levels have been reported to be altered during cardiac hypertrophy. Moreover, there is a strong correlation between CYPmediated arachidonic acid metabolites and the pathogenesis of cardiac hypertrophy. Therefore, we investigated the effect of isoproterenol-induced cardiac hypertrophy on the expression of several CYP genes and their associated CYP-dervided metabolites of arachidonic acid. Cardiac hypertrophy was induced by seven daily intraperitoneal injections of 5 mg/kg isoproterenol. Thereafter, the heart, lung, liver, and kidney were harvested and the expression of different genes was determined by real time-PCR. Heart microsomal protein from control or isoproterenol treated rats was incubated with 50 µM arachidonic acid, and arachidonic acid metabolites were determined by liquid chromatography-electron spray ionization-mass spectrometry. Our results show that isoproterenol treatment significantly increased the heart to body weight ratio as well as the hypertrophic markers. In addition, there was a significant induction of CYP1A1, CYP1B1, CYP4A3, and soluble epoxide hydrolase and a significant inhibition of CYP2C11 and CYP2E1 in the hypertrophied hearts as compared to the control. CYP1A1, CYP2E1, and CYP4A3 gene expression was induced in the kidney and CYP4A3 was induced in the liver of isoproterenoltreated rats. Isoproterenol treatment significantly reduced 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid formation and significantly increased their corresponding 8,9-, and 14,15-dihydroxyeicosatrienoic acid as well as the 20-hydroxyeicosatetraenoic acid metabolite. In conclusion, isoproterenol-induced cardiac hypertrophy alters arachidonic acid metabolism and its associated CYP enzymes, suggesting their role in the development and/or progression of cardiac hypertrophy