Neuroprotective Effect of Calpeptin on Acrylamide-Induced Neuropathy in Rats

Neurochem Res. 2015 Nov;40(11):2325-32. doi: 10.1007/s11064-015-1722-y. Epub 2015 Sep 30.

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.

Keywords: Acrylamide; Calpain; Calpeptin; Neurofilament; Neuropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylamide / toxicity*
  • Animals
  • Behavior, Animal / drug effects
  • Calpain / metabolism
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Dipeptides / pharmacology*
  • Female
  • Gait Disorders, Neurologic / chemically induced
  • Gait Disorders, Neurologic / physiopathology
  • Gait Disorders, Neurologic / prevention & control
  • Injections, Intraperitoneal
  • Neurofilament Proteins / metabolism
  • Neuroprotective Agents / pharmacology*
  • Neurotoxicity Syndromes / drug therapy*
  • Neurotoxicity Syndromes / pathology
  • Neurotoxicity Syndromes / psychology
  • Rats
  • Rats, Wistar
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism
  • Spinal Cord / pathology

Substances

  • Cysteine Proteinase Inhibitors
  • Dipeptides
  • Neurofilament Proteins
  • Neuroprotective Agents
  • calpeptin
  • Acrylamide
  • Calpain