title: Neuroprotective Effect of Calpeptin on Acrylamide-Induced Neuropathy in Rats.
abstract: Acrylamide (ACR) is a vinyl monomer with established human neurotoxic effects, which is characterized by the accumulation of neurofilaments (NFs) in the distal swellings of large axons in peripheral and central nervous systems. However, the mechanisms of neurotoxicity remain unclear. The objective is to investigate the neuroprotective effect of calpeptin (CP) on ACR-induced neuropathy and its mechanism. Female adult Wistar rats were randomly divided into four groups (control, CP, ACR, and ACR + CP group). Control group received 0.9 % saline, ACR and ACR + CP groups received 30 mg/kg ACR by intraperitoneal injection. In addition, CP and ACR + CP groups also received 200 µg/kg CP. Gait analysis and hind limb splay were measured weekly to analyze neurobehavioral changes. The calpain activity and the changes of NFs protein levels in spinal cord are determined. Compared with control group, body weight of rats in ACR group decreased by 11.3 % (P < 0.01), while in ACR + CP group body weight increased significantly by 8.3 % (P < 0.01) compared with ACR group by the end of the 4th week; gait score of rats in both ACR and ACR + CP groups increased significantly by 167 % and 100 % (P < 0.01) compared with control group, while it decreased significantly by 25.1 % (P < 0.01) in ACR + CP group compared with ACR group; the distance of hind limb splay in both ACR and ACR + CP groups increased by 76.7 % and 49.5 % (P < 0.01) compared with control group, while it decreased by 15.4 % (P < 0.01) in ACR + CP group compared with ACR group; calpain activity of spinal cord at ACR and ACR + CP groups increased significantly by 14.9 % and 10.0 % (P < 0.01) compared with control group, while it decreased 4.2 % (P < 0.01) in ACR + CP group compared with ACR group; compared with control group, the levels of light NF (NF-L), medium NF (NF-M) and heavy NF (NF-H) subunits increased by 81.2 %, 263.6 % and 22.6 % (P < 0.01) in the supernatant of ACR group in spinal cord tissue and increased by 28.4 %, 96.6 % and 10.6 % (P < 0.01) in ACR + CP group, while the levels of NF-L, NF-M and NF-H subunits decreased by 29.1 %, 45.9 % and 9.8 % (P < 0.01) in ACR + CP group compared with ACR group. The present results suggested that CP can relieve ACR neuropathy by decrease calpain activity and NFs degradation. The changes of calpain activity and NFs may be one of the mechanisms of ACR-induced neuropathy.
authors.affiliation: School of Public Health, Shandong University, 44 Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Wei
authors.affiliation: School of Public Health, Shandong University, 44 Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.
authors.forename: Fengfeng
authors.initials: F
authors.lastname: Yan
authors.affiliation: School of Public Health, Shandong University, 44 Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.|Yangzhou Center for Disease Control and Prevention, 36 Yanfu Dong Road, Yangzhou, 225001, Jiangsu, People's Republic of China.
authors.forename: Meng
authors.initials: M
authors.lastname: E
authors.affiliation: School of Public Health, Shandong University, 44 Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.
authors.forename: Cuili
authors.initials: C
authors.lastname: Zhang
authors.affiliation: School of Public Health, Shandong University, 44 Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.|Beijing Municipal Institute of Labour Protection, No. 55, Taoranting Road, Xicheng District, Beijing, People's Republic of China.
authors.forename: Guozhen
authors.initials: G
authors.lastname: Li
authors.affiliation: School of Public Health, Shandong University, 44 Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.
authors.forename: Xiwei
authors.initials: X
authors.lastname: Yang
authors.affiliation: School of Public Health, Shandong University, 44 Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.
authors.forename: Fengmei
authors.initials: F
authors.lastname: Zhang
authors.affiliation: School of Public Health, Shandong University, 44 Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.
authors.forename: Shue
authors.initials: S
authors.lastname: Wang
authors.affiliation: School of Public Health, Shandong University, 44 Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China. sufangyu@sdu.edu.cn.
authors.forename: Sufang
authors.initials: S
authors.lastname: Yu
mesh_terms: D020106:Acrylamide / Q000633:toxicity*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002154:Calpain / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology*; D005260:Female; D020233:Gait Disorders, Neurologic / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D007274:Injections, Intraperitoneal; D016900:Neurofilament Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D016900:Neurofilament Proteins; D018696:Neuroprotective Agents; C071482:calpeptin; D020106:Acrylamide; D002154:Calpain
keywords: Acrylamide; Calpain; Calpeptin; Neurofilament; Neuropathy