Pharmacological regulation of cytochrome P450 metabolites of arachidonic acid attenuates cardiac injury in diabetic rats

Metabonomic Characteristics of Myocardial Diastolic Dysfunction in Type 2 Diabetic Cardiomyopathy Patients

“…Metabolism of xenobiotics by cytochrome P450 pathways rich factor enrichment is significant and reliable, including two unique compounds, organoheterocyclic compounds, and organooxygen compounds. The study provides evidence that diabetes initiates cardiomyopathy by increasing sEH, reducing cytochrome P450 2J, and decreasing cardioprotective EETs, finally attenuating cardiotoxicity mediated by the reduction of high glucose in cardiac cells ( Alaeddine et al, 2021 ). In addition, cytochrome P450 has a close relationship with inflammation in T2DM thought to decrease P450 isoenzymes and rise in plasma levels of these enzymes, finally resulting in high expression of interleukin-6 (IL-6) and the tumor necrosis factor-alpha (TNF-α) ( Darakjian et al, 2021 ).…”

Plasma epoxyeicosatrienoic acids and diabetes-related cardiovascular disease: The cardiovascular health study

“… 35 In experimental models of diabetes in rodents, mice with cardiac hypertrophy show a decrease in 14,15-EET 33 ; overexpression of CYP2J2 in mice attenuates diabetes-induced myocardial hypertrophy 36 ; and treatment of diabetic rats with a sEH inhibitor attenuates the reduction in cardiac outputs, left ventricular hypertrophy and fibrosis induced by hyperglycemia. 37 These experimental models provide strong evidence that EETs protect the diabetic heart, although how this might translate to a reduced risk of MI in humans is not known. Findings from our prospective study complement the animal models and provide preliminary evidence in support of the hypothesis that EETs protect from MI in humans.…”

Activation of 20-HETE Synthase Triggers Oxidative Injury and Peripheral Nerve Damage in Type 2 Diabetic Mice

“…11,36 The specific inhibition of certain sources ameliorates diabetic renal, retinal, neural, and cardiac complications. 1,12,13,15,51 In DPN, oxidative stress mediates injury to the vasa nervorum and/or vascular endothelia and neurons 28 48 but limited studies investigate the effect on Schwann cell (SC) physiology and myelination. Our group shows the attenuation of diabetes-induced activation of NADPHoxidases and ROS production to confer anti-apoptotic effects, and neuroprotection to SCs and peripheral nerves.…”

“…51,58 20-HETE synthase has been shown to have high physiological relevance in maintaining homeostasis, vascular tone, and blood flow. 1,51 However, recent studies report 20-HETE alterations to mediate obesity, hyperglycemia, deficient insulin responses, 19,32 oxidative stress 58 and the onset of diabetic renal, retinal, and cardiac complications. 1,13,51 Yet, the role of 20-HETE in the nervous system (NS) is understudied.…”

“…1,51 However, recent studies report 20-HETE alterations to mediate obesity, hyperglycemia, deficient insulin responses, 19,32 oxidative stress 58 and the onset of diabetic renal, retinal, and cardiac complications. 1,13,51 Yet, the role of 20-HETE in the nervous system (NS) is understudied. In the central NS, CYP4A is highly expressed in cells lining the neurovascular unit, with 20-HETE playing developmental and regulatory roles, inflammation, and oxidative injury in neurodegenerative diseases.…”