Effects of Methotrexate on Acute Phrase of Spinal Cord Contusion-Induced Lipid Peroxidation in Rats

Abstract

Abstract: Objective：This study examined the effect of methotrexate on acute phrase of spinal cord contusion-induced lipid peroxidation in rats and the neuroprotective mechanism of its anti-oxidant action. Methods: Rat spinal cord contusion model was prepared by Pinpoint Precision Cortical Impactor™ apparatus and then methotrexate (0.5mg•kg^-1•BW)
was subcutaneously administrated at posttraumatic 30 min. ELISA method was used to determine the content of malondialdehyde（MDA）and 8-iso-PGF_2αin plasma and 4-hydroxynonenal-His adduct (HNE) in injury tissue. Results: Posttraumatic 1, 3, 6, 12, 24, 48, 72 h, the contents of MDA, 8-iso-PGF_2αand HNE in the methotrexate group were all lower than those in the model group, which achieved statistical significance at posttraumatic 6, 12 h (P<0.05). At posttraumatic 12 h, the content of 8-iso-PGF2α in plasma was also significantly lower than that in the model group (P<0.05). Conclusion: The appropriate doses, methotrexate could prevent secondary injury of spinal cord, which may be related to inhibiting or reducing the lipid peroxidation.

Key words: methotrexate, traumatic spinal cord injury, acute phase, lipid peroxidation, enzyme linked immunosorbent assay

ZHANG Si, GU Bing, WANG Shuo-yu, LI Hua-nan, ZHANG Guo-fu, ZHANG Shui-yin. Effects of Methotrexate on Acute Phrase of Spinal Cord Contusion-Induced Lipid Peroxidation in Rats[J]. Acta Neuropharmacologica, 2014, 4(1): 11-16.

References

[1] Cao He-Qi, Dong Er-Dong. An update on spinal cord injury research[J]. Neurosci Bull, 2013, 29(1): 94-102.

[2] Jia Z, Zhu H, Li J, et al. Oxidative stress in spinal cord injury and antioxidant-based intervention[J]. Spinal Cord, 2012, 50(4): 264-274.

[3] Mona Bains, Edward D Hall. Antioxidant therapies in traumatic brain and spinal cord injury[J]. Biochim Biophys Acta, 2012, 1822(5): 675-684.

[4] Radhika A Vaishnav, Indrapal N Singh, D M Miller, et al. Lipid peroxidation-derived reactive aldehydes directly and differentially impair spinal cord and brain mitochondrial function[J]. J Neurotrauma, 2010, 27(7): 1311-1320.

[5] Bao Feng, Chen Yu-hua, Gregory A Dekaban, et al. Early anti-inflammatory treatment reduces lipid peroxidation and protein nitration after spinal cord injury in rats[J]. J Neurochem, 2004, 88(6): 1335-1344.

[6] Hormoz Ayromlou, Babak Hajipour, Mohammad M Hossenian, et al. Oxidative effect of methotrexate administration in spinal cord of rabbits[J]. J Pak Med Assoc, 2011, 61(11): 1096-1099.

[7] Bulent Bakar, Emine Arzu Köse, Sebnem Kupana Ayva, et al. Effects of low-dose methotrexate in spinal cord injury in rats[J]. Ulus Travma Acil Cerrahi Derg, 2013, 19(4): 285-293.

[8] Ahmet M Sanli, Gokhan Serbes, Mustafa F Sargon, et al. Methothrexate attenuates early neutrophil infiltration and the associated lipid peroxidation in the injured spinal cord but does not induce neurotoxicity in the uninjured spinal cord in rats [J]. Acta Neurochir (Wien), 2012, 154(6): 1045-1054.

[9] Hayri Kertmen, Bora Gürer, Erdal Resit Y?lmaz, et al. The protective effect of low-dose methotrexate on ischemia-reperfusion injury of the rabbit spinal cord[J]. Eur J Pharmacol, 2013, 714(1-3): 148-156.

[10] 顾兵，金建波，李华南，等．大鼠创伤性脊髓损伤模型的建立[J]．中国临床药理学与治疗学，2011, 16(7): 721-728．

[11] 张思, 顾兵, 王烁宇, 等. TreadScan步态分析系统在评价大鼠脊髓挫伤模型中的应用[J]. 神经药理学报，2012, 2(5): 8-18.

[12] Somesree GhoshMitra, David R Diercks, Nathaniel C Mills, et al. Role of engineered nanocarriers for axon regeneration and guidance: current status and future trends[J]. Adv Drug Deliv Rev, 2012, 64(1): 110-125.

[13] 张思，王烁宇，李华南，等. 急性脊髓损伤后的氧化应激及其抗氧化治疗[J]. 神经药理学报，2012, 2(3): 52-64.

[14] Berker Cemil, Kivanc Topuz, Mehmet N Demircan, et al. Curcumin improves early functional results after experimental spinal cord injury[J]. Acta Neurochir (Wien), 2010, 152(9): 1583-1590.

[15] Song Yong-xing, Liu Juan, Zhang Feng, et al. Antioxidant effect of quercetin against acute spinal cord injury in rats and its correlation with the p38MAPK/iNOS signaling pathway[J]. Life Sci, 2013, 92(24-26): 1215-1221.

[16] Kimberly M Carrico, Radhika Vaishnav, Edward D Hall. Temporal and spatial dynamics of peroxynitrite-induced oxidative damage after spinal cord contusion injury[J]. J Neurotrauma, 2009, 26(8): 1369-1378.

[17] Fredrik Clausen, Niklas Marklund, Anders Lewén, et al. Interstitial F(2)-isoprostane 8-iso-PGF(2α) as a biomarker of oxidative stress after severe human traumatic brain injury[J]. J Neurotrauma, 2012, 29(5): 766-775.

[18] Huang Yi, Xie Ke-liang, Li Ji-peng, et al. Beneficial effects of hydrogen gas against spinal cord ischemia-reperfusion injury in rabbits[J]. Brain Res, 2011, 1378: 125-136.

[19] Zhou Le-shun, Wang Xiao-wu, Xue Wei-ning, et al. Beneficial effects of hydrogen-rich saline against spinal cord ischemia-reperfusion injury in rabbits[J]. Brain Res, 2013, 1517: 150-160.

[20] Souichi Ohta, Yasushi Iwashita, Ryosuke Kakinoki, et al. Effects of continuous intravenous infusion of MCI-186 on functional recovery after spinal cord injury in rats[J]. J Neurotrauma, 2011, 28(2): 289-298.

[21] M P Keith, J D Edison, W R Gilliland. Progress toward personalized treatment of rheumatoid arthritis[J]. Clin Pharmacol Ther, 2012, 92(4): 440-442.

[22] J A Wessels, T W Huizinga, H J Guchelaar. Recent insights in the pharmacological actions of methotrexate in the treatment of rheumatoid arthritis[J]. Rheumatology (Oxford), 2008, 47(3): 249-255.

[23] Edwin S L Chan, Bruce N Cronstein. Methotrexate--how does it really work?[J]. Nat Rev Rheumatol, 2010, 6(3): 175-178.

[24] Irene Paterniti, Alessia Melani, Sara Cipriani, et al. Selective adenosine A2A receptor agonists and antagonists protect against spinal cord injury through peripheral and central effects[J]. J Neuroinflammation, 2011, 8: 31.

[25] M Carmen Montesinos, Avani Desai, Dave Delano, et al. Adenosine A2A or A3 receptors are required for inhibition of inflammation by methotrexate and its analog MX-68[J]. Arthritis Rheum, 2003, 48(1): 240-247.

[26] Chen Zhe, Tu Sheng-hao, Hu Yong-hong, et al. Prediction of response of collagen-induced arthritis rats to methotrexate: an (1)H-NMR-based urine metabolomic analysis[J]. J Huazhong Univ Sci Technolog Med Sci, 2012, 32(3): 438-443.

[27] Wang Zhi-gang, Chen Zhe, Yang S, et al. (1)H NMR-based metabolomic analysis for identifying serum biomarkers to evaluate methotrexate treatment in patients with early rheumatoid arthritis[J]. Exp Ther Med, 2012, 4(1): 165-171.

[28] Tomoya Nishino, Takeaki Shinzato, Yuuki Ohta, et al. A case of acute kidney injury with marked hyperuricemia during mizoribine administration[J]. Intern Med, 2012, 51(10): 1239-1243.

[29] Gene L Bowman, Jackilen Shannon, Balz Frei, et al. Uric acid as a CNS antioxidant[J]. J Alzheimers Dis, 2010, 19(4): 1331-1336.

[30] Beth Stinefelt, Stephen S Leonard, Kenneth P Blemings, et al. Free radical scavenging, DNA protection, and inhibition of lipid peroxidation mediated by uric acid[J]. Ann Clin Lab Sci, 2005, 35(1): 37-45.

[31] K Aoyama, N Matsumura, M Watabe, et al. Caffeine and uric acid mediate glutathione synthesis for neuroprotection[J]. Neuroscience, 2011, 181: 206-215.

[32] Stefano Zoccolella, Carla Tortorella, Pietro Iaffaldano, et al. Low serum urate levels are associated to female gender in multiple sclerosis patients[J]. PLoS One, 2012, 7(7): e40608.

[33] Tua Annanmaki, Antti Muuronen, Kari Murros. Low plasma uric acid level in Parkinson's disease[J]. Mov Disord, 2007, 22(8): 1133-1137.

[34] Tae-Suk Kim, Chi-Un Pae, Su-Jung Yoon, et al. Decreased plasma antioxidants in patients with Alzheimer's disease[J]. Int J Geriatr Psychiatry, 2006, 21(4): 344-348.

[35] C M Knapp, C S Constantinescu, J H Tan, et al. Serum uric acid levels in optic neuritis[J]. Mult Scler, 2004, 10(3): 278-280.

[36] F Peng, Y Yang, J Liu, et al. Low antioxidant status of serum uric acid, bilirubin and albumin in patients with neuromyelitis optica[J]. Eur J Neurol, 2012, 19(2): 277-283.

[37] Gwen S Scott, Salvatore Cuzzocrea, Tiziana Genovese, et al. Uric acid protects against secondary damage after spinal cord injury[J]. Proc Natl Acad Sci USA, 2005, 102(9): 3483-3488.