Effects of nonsteroidal anti-inflammatory drugs on the expression of arachidonic acid-metabolizing Cyp450 genes in mouse hearts, kidneys and livers

Jarrar, Yazun; Jarrar, Qais; Abed, Abdulqader Fadhil; Abu-Shalhoob, Mohammad

doi:10.1016/j.prostaglandins.2019.02.003

Cited by 25 publications

(32 citation statements)

References 40 publications

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“…CYP4B metabolizes short-chain fatty acids (approximately 7 to 10 carbon fatty acids) [20], while CYP4A and CYP4V metabolize intermediate-chain fatty acids (C10 to 16) [19] and CYP4F catalyzes long-chain fatty acids (C16 to 26), such as prostanoids [43]. Decreasing the expression levels of the CYP4 family was associated with accumulation of fats in tissues such as the liver [44]. Therefore, decreased levels of CYP4 family proteins reduce the capacity for fat removal from tissues.…”

Section: Role Of the Cyp4 Family In The Metabolism Of Endogenous Cmentioning

confidence: 99%

“…Therefore, decreased levels of CYP4 family proteins reduce the capacity for fat removal from tissues. Jarrar et al [44] found that non-steroidal anti-inflammatory drugs caused fatty livers in treated mice, which were associated with significant downregulation of mouse cyp4a12 gene expression in liver tissues. CYP4F2, 4F3B, 4A11, and 4V2 were found to oxidize arachidonic acid through ω-hydroxylation to 20-hydroxyeicosatetraenoic acid (20-HETE) [6,9,45,46], which is a vasoconstrictor and activator of platelet aggregation [47].…”

Section: Role Of the Cyp4 Family In The Metabolism Of Endogenous Cmentioning

confidence: 99%

“…CYP4A was upregulated in studies of doxorubicin-induced cardiotoxicity, where it was associated with myocardial infarction and increased 20-HETE synthesis [51]. Furthermore, Jarrar et al found that heart cyp4a12 was highly upregulated in mice after cardiac toxicity induced by non-steroidal anti-inflammatory drugs [44]. Thus, targeting of 20-HETE synthesis or modulation of eicosanoid levels through manipulation of CYP4 enzymes can decrease the cardiotoxicity of such drugs.…”

Section: The Cyp4 Family and Cardiovascular Diseasesmentioning

confidence: 99%

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Molecular Functionality of Cytochrome P450 4 (CYP4) Genetic Polymorphisms and Their Clinical Implications

Jarrar

Lee

2019

IJMS

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Enzymes in the cytochrome P450 4 (CYP4) family are involved in the metabolism of fatty acids, xenobiotics, therapeutic drugs, and signaling molecules, including eicosanoids, leukotrienes, and prostanoids. As CYP4 enzymes play a role in the maintenance of fatty acids and fatty-acid-derived bioactive molecules within a normal range, they have been implicated in various biological functions, including inflammation, skin barrier, eye function, cardiovascular health, and cancer. Numerous studies have indicated that genetic variants of CYP4 genes cause inter-individual variations in metabolism and disease susceptibility. Genetic variants of CYP4A11, 4F2 genes are associated with cardiovascular diseases. Mutations of CYP4B1, CYP4Z1, and other CYP4 genes that generate 20-HETE are a potential risk for cancer. CYP4V2 gene variants are associated with ocular disease, while those of CYP4F22 are linked to skin disease and CYP4F3B is associated with the inflammatory response. The present study comprehensively collected research to provide an updated view of the molecular functionality of CYP4 genes and their associations with human diseases. Functional analysis of CYP4 genes with clinical implications is necessary to understand inter-individual variations in disease susceptibility and for the development of alternative treatment strategies.

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Section: Role Of the Cyp4 Family In The Metabolism Of Endogenous Cmentioning

confidence: 99%

Section: Role Of the Cyp4 Family In The Metabolism Of Endogenous Cmentioning

confidence: 99%

Section: The Cyp4 Family and Cardiovascular Diseasesmentioning

confidence: 99%

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Molecular Functionality of Cytochrome P450 4 (CYP4) Genetic Polymorphisms and Their Clinical Implications

Jarrar

Lee

2019

IJMS

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“…Drug-induced hepatic injury is a common complication of NSAIDs 8 . To reduce NSAID-induced gastropathic bleeding, it is administered in combination with proton pump inhibitors 9 .…”

Section: Introductionmentioning

confidence: 99%

Protective effects of Ajwa date extract against tissue damage induced by acute diclofenac toxicity

Aljuhani

Elkablawy

Elbadawy

et al. 2019

Journal of Taibah University Medical Sciences

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ObjectivesTo investigate the tissue-protective effects of Ajwa date fruits (a Prophetic medicinal remedy) against acute diclofenac toxicity.MethodsAlbino Sprague–Dawley rats were allocated to four experimental groups: a negative control group, an Ajwa-only group that received 2 g/kg of Ajwa date extract (ADE) orally, an acute diclofenac toxicity group that received 200 mg diclofenac once intraperitoneally, and a treatment group that received diclofenac and ADE after 4 h. Histological examinations of rat lung and liver tissues were performed.ResultsAcute diclofenac toxicity caused marked hepatic derangements, such as congested central veins, congested blood sinusoids, hyaline degeneration, and hepatocyte necrosis. Toxic diclofenac overdose resulted in markedly congested alveolar capillaries and alveolar haemorrhages, thick edematous alveolar walls, and edema fluid exudates in the alveoli. Upon treatment with ADE, significant reduction in diclofenac-induced hepatic and pulmonary derangements were observed.ConclusionADE is a safe, tissue-protective nutritional agent that alleviates cellular and tissue-damaging effects due to acute diclofenac toxicity. ADE relieved hepatic and pulmonary changes induced by acute diclofenac toxicity. The use of ADE is recommended for the treatment of acute diclofenac toxicity.

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“…These effects vary by drug, but include antioxidant activity, inhibition of Nuclear Factor-κ B, inhibition of 5-lipoxygenase, prostaglandin receptor antagonism, antibradykinin actions and inhibition of fatty acid amide hydrolase, cytokine release, cell adhesion, and metabolism of arachidonic acid. 27,46,48,56,79,89,93,115,157,188 Since virtually every cell in the body constitutively expresses COX1, and COX2 can be markedly induced by inflammatory mediators, inhibition of COX has been ascribed to anti-inflammatory action in a staggering number of human and animal models. In addition, a wide range of behavioral actions have been associated with NSAID inhibition of COX.…”

Section: Local Anestheticsmentioning

confidence: 99%

A Review of the Effects of Pain and Analgesia on Immune System Function and Inflammation: Relevance for Preclinical Studies

DeMarco

Nunamaker

2019

comp med

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One of the most significant challenges facing investigators, laboratory animal veterinarians, and IACUCs, is how to balance appropriate analgesic use, animal welfare, and analgesic impact on experimental results. This is particularly true for in vivo studies on immune system function and inflammatory disease. Often times the effects of analgesic drugs on a particular immune function or model are incomplete or don't exist. Further complicating the picture is evidence of the very tight integration and bidirectional functionality between the immune system and branches of the nervous system involved in nociception and pain. These relationships have advanced the concept of understanding pain as a protective neuroimmune function and recognizing pathologic pain as a neuroimmune disease. This review strives to summarize extant literature on the effects of pain and analgesia on immune system function and inflammation in the context of preclinical in vivo studies. The authors hope this work will help to guide selection of analgesics for preclinical studies of inflammatory disease and immune system function.

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Effects of nonsteroidal anti-inflammatory drugs on the expression of arachidonic acid-metabolizing Cyp450 genes in mouse hearts, kidneys and livers

Cited by 25 publications

References 40 publications

Molecular Functionality of Cytochrome P450 4 (CYP4) Genetic Polymorphisms and Their Clinical Implications

Molecular Functionality of Cytochrome P450 4 (CYP4) Genetic Polymorphisms and Their Clinical Implications

Protective effects of Ajwa date extract against tissue damage induced by acute diclofenac toxicity

A Review of the Effects of Pain and Analgesia on Immune System Function and Inflammation: Relevance for Preclinical Studies

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