Neuroprotective effects of agmatine in experimental peripheral nerve injury in rats: a prospective randomized and placebo-controlled trial

Abstract

AIm:The purpose of this study was to demonstrate the activity of agmatine, an inducible nitric oxide synthase (iNOS) inhibitor and selective N-methyl-D-aspartate receptor (NMDAR) antagonist, on reducing tissue damage in distal part of traumatic nerve in an experimental rat peripheral nerve injury model. mATeRIAL and meTHods: Sciatic nerves of 30 Sprague Dawley male rats were used. Rats were divided into 5 groups; group 1 (n=6), control group; group 2 (n=6), axonotmesis + placebo group; group 3 (n=6), axonotmesis + 50 mg/kg agmatine treatment group; group 4 (n=6), neurotmesis + placebo group; group 5 (n=6), neurotmesis + 50 mg/kg agmatine treatment group. Axonolysis, axon degeneration, edema, hemorrhage, and inflammation were evaluated in histopathologic examinations of all the groups.ResuLTs: When group 2 was compared with group 3 in histopathologic sections, axonolysis was less in group 3 (p=0.007), as was axon degeneration (p=0.022) and edema (p=0.018). When group 4 was compared with group 5, axonolysis was less in group 5 (p=0.009), as was axon degeneration (p=0.006) and edema (p=0.021). CoNCLusIoN:This study demonstrated agmatine to have antioxidant and antineurotoxic effects in an experimental rat peripheral nerve injury model. KeywoRds: Agmatine, Axonotmesis, Neurotmesis, Peripheral nerve injury, Rat ÖZ AmAÇ: Bu çalışmanın amacı, indüklenebilir nitrik oksit sentetaz inhibitörü (iNOS) ve selektif N-metil-D-aspartat reseptörü (NMDAR) antagonisti olan agmatinin sıçanlarda yapılan deneysel periferik sinir yaralanma modelinde hasarlı sinirin distal bölumündeki doku hasarını azaltmadaki etkisini göstermekti. yÖNTem ve GeReÇLeR: Otuz tane Sprague Dawley sıçanının siyatik sinirleri kullanıldı. Sıçanlar beş gruba bölündü: birinci grup (n=6), kontrol grubu; ikinci grup (n=6), aksonotmezis + plasebo grubu; üçüncü grup (n=6), aksonotmezis + 50 mg/kg agmatin tedavi grubu; dördüncü Grup (n=6), neurotmesis + plasebo grubu; beşinci grup (n=6), neurotmesis + 50 mg/kg agmatin tedavi grubu. Aksonolizis, akson dejenerasyonu, ödem, hemoraji ve inflammasyon bütün gruplarda histopatolojik olarak değerlendirildi.BuLGuLAR: İkinci grup ile üçüncü grup histopatolojik kesitlerde kıyasladığında, aksonolizis üçüncü grupta daha azdı (p=0,007), aynı şekilde akson dejenerasyonu (p=0,022) ve ödem (p=0,018) üçüncü grupta daha azdı. Dördüncü grup ile beşinci grup histopatolojik kesitlerde kıyasladığında, aksonolizis beşinci grupta daha azdı (p=0,009), aynı şekilde akson dejenerasyonu (p=0,006) ve ödem (p=0,021) beşinci grupta daha azdı. soNuÇ: Bu çalışma, agmatinin sıçanlarda yapılan deneysel periferik sinir yaralanmalarında antioksidan ve antinörotoksik etkileri olduğunu göstermiştir.

Antinociceptive and Anti-Inflammatory Effects of Nypa fruticans Wurmb by Suppressing TRPV1 in the Sciatic Neuropathies

“…Additionally, inflammation of the central and peripheral nervous system helps to cause and sustain chronic neuropathic pain [1]. Issues related to crushing injuries include increased endoneurial edema, free oxygen radicals, inflammatory reactions, de-and remyelination, axonolysis, regeneration, and degeneration [2][3][4]. Inflammatory mediators such as prostaglandins, histamines, cytokines, chemokines, and growth factors are involved in nerve regeneration and degeneration that is associated with neuropathic pain [5][6][7].…”

Effect of gabapentin on primary surgical treatment of experimental sciatic nerve injury in rats

“…[8] Peripheral nerve injury, which is currently a major health problem, causes a high rate of disablement and an enormous economic burden. [17] It constitutes an important group of diseases, especially in industrialized countries. [18] More than 350,000 people per year in the United States are exposed to upper extremity injury.…”

Effects of alpha lipoic acid on motor function and antioxidant enzyme activity of nerve tissue after sciatic nerve crush injury in rats

“…There are a lot of studies evaluating the protective or therapeutic effects of various antioxidants related to the peripheral nerve injury model such as vitamin E, ubiquinone, L-carnitine and agmatine (1,22,33,38) or other substances such as cytidinediphosphocholine, rapamycin, tetanus toxin, platelet-rich plasma, insulin-like growth factor I, dexamethasone and acetyl salicylic acid (5,8,9,12,17,23,29,39), or some energy types such as low level laser irradiation and low-frequency magnetic fields (30,44).…”

“…Therefore, we decided to evaluate the functional status of the subjects by SFI in addition to nerve tissue levels of antioxidants. A rat model was chosen because the rat sciatic nerve can be easily dissected and it is a well-studied model in literature (2,5,9,12,17,29,31,(37)(38)(39)44).…”