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

Haddad, Mary; Eid, Stéphanie; Harb, Frédéric; Massry, Mohamed El; Azar, Sami T.; Sauleau, Erik-André; Eid, Assaad A.

doi:10.1016/j.jpain.2022.02.011

Cited by 8 publications

(9 citation statements)

References 60 publications

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“…CYP enzyme is the main source of reactive oxygen species (ROS), and 20‐HETE mediates inflammation and oxidation. The expression lever of CYP4A, 20‐HETE, and ROS was increased in sciatic nerve tissues of MKR nonobese T2DM mice, both HET0016 (a specific 20‐HETE synthase and/or CYP4A inhibitor) and metformin reduced ROS and corrected neural sensory and motor abnormalities of T2DM mice 27 . In addition, metformin reduced the level of 20‐HETE, and HET0016 restored the expression of P‐AMPK, which suggested that CYP4A/20‐HETE/AMPK mediate nerve damage through oxidative stress and an interaction existed between them.…”

Section: Effects and Mechanisms Of Metformin On Pdpnmentioning

confidence: 95%

“…Beclin‐1 and LC3B, the key proteins of the autophagic response, significantly increased in the sciatic nerve of mice with diabetes and were also affected by CYP4A/20‐HETE/AMPK. 27 A cell‐level study showed that high glucose increased autophagosome and LC3B in PC12 cells. 43 Metformin can alleviate autophagy (decreased beclin‐1 and LC3B expression in sciatic nerve) by activating CYP4A/20‐HETE/AMPK pathological axis, saving peripheral nerve injury in diabetic mice.…”

Section: Effects and Mechanisms Of Metformin On Pdpnmentioning

confidence: 99%

“… 43 Metformin can alleviate autophagy (decreased beclin‐1 and LC3B expression in sciatic nerve) by activating CYP4A/20‐HETE/AMPK pathological axis, saving peripheral nerve injury in diabetic mice. 27 However, there are conflicting conclusions regarding autophagy in DN. The level of beclin‐1 in sciatic nerve decreased in STZ‐induced diabetic rats, and P‐AMPK enhanced autophagy response by promoting autophagosome formation.…”

Section: Effects and Mechanisms Of Metformin On Pdpnmentioning

confidence: 99%

Section: Effects and Mechanisms Of Metformin On Pdpnmentioning

confidence: 99%

“…A cell‐level study showed that high glucose increased autophagosome and LC3B in PC12 cells 43 . Metformin can alleviate autophagy (decreased beclin‐1 and LC3B expression in sciatic nerve) by activating CYP4A/20‐HETE/AMPK pathological axis, saving peripheral nerve injury in diabetic mice 27 . However, there are conflicting conclusions regarding autophagy in DN.…”

Section: Effects and Mechanisms Of Metformin On Pdpnmentioning

confidence: 99%

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Is metformin a possible treatment for diabetic neuropathy?

Wei

Wei²,

Huang

et al. 2022

Journal of Diabetes

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Metformin is a hypoglycemic drug widely used in the treatment of type 2 diabetes. It has been proven to have analgesic and neuroprotective effects. Metformin can reverse pain in rodents, such as diabetic neuropathic pain, neuropathic pain caused by chemotherapy drugs, inflammatory pain and pain caused by surgical incision. In clinical use, however, metformin is associated with reduced plasma vitamin B12 levels, which can further neuropathy. In rodent diabetes models, metformin plays a neuroprotective and analgesic role by activating adenosine monophosphate‐activated protein kinase, clearing methylgloxal, reducing insulin resistance, and neuroinflammation. This paper also summarized the neurological adverse reactions of metformin in diabetic patients. In addition, whether metformin has sexual dimorphism needs further study.

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Section: Effects and Mechanisms Of Metformin On Pdpnmentioning

confidence: 95%

Section: Effects and Mechanisms Of Metformin On Pdpnmentioning

confidence: 99%

Section: Effects and Mechanisms Of Metformin On Pdpnmentioning

confidence: 99%

Section: Effects and Mechanisms Of Metformin On Pdpnmentioning

confidence: 99%

Section: Effects and Mechanisms Of Metformin On Pdpnmentioning

confidence: 99%

See 3 more Smart Citations

Is metformin a possible treatment for diabetic neuropathy?

Wei

Wei²,

Huang

et al. 2022

Journal of Diabetes

View full text Add to dashboard Cite

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Three Potential Elements of Developing Nerve Guidance Conduit for Peripheral Nerve Regeneration

Zhang,

Gong,

Zhang

et al. 2023

Adv Funct Materials

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Autograft replaced by a nerve guidance conduit (NGC) is challenging in peripheral nerve injury because current NGC is still limited by precise conductivity and excellent biocompatibility in vivo, which influences the peripheral nerve repair even for a long lesion gap repair. Several particular elements have the potential function for nerve conductivity acceleration based on the traditional three factors of neural tissue engineering. The review aims to address three questions: 1) What is the superior factor for nerve conduction in the application? 2) How can a more conductive regenerative scaffold be constructed in vivo? 3) What is the next step in nerve regeneration for NGC? The bibliometrics analysis of NGC‐related references is adopted to acquire that the conductive material, manufacturing technology of neural scaffold, and electrical stimulation (ES) play essential roles in the acceleration of nerve conduction. This review visually analyses the research status and summarizes the main types of conductive materials, the manufacturing technologies of neural scaffolds, and the characteristics of ES. The viewpoints and outlook of developing NGC are also discussed in this review. The proposed three elements are expected to improve the nerve conduction of NGC in vivo and even address the dilemma of long‐distance peripheral nerve injury.

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