Demonstration of ameliorative effect of lacosamide: in a rat model of sepsis-induced critical illness polyneuropathy.
OBJECTIVE
Critical illness neuropathy (CIN) is a condition that may occur in diseases with severe systemic response, particularly in sepsis. The aim of this study is to investigate the potential anti-inflammatory and lipid-peroxidation inhibiting activities of lacosamide by measuring tumour necrotizing factor-alpha (TNF-alpha), C-reactive protein (CRP), malondialdehyde (MDA) and white blood cells (WBC) using electroneuromyography (ENMG) in rats with sepsis-induced critical illness neuropathy (SICIN).


METHODS
Cecal ligation and puncture (CLP) procedure was performed on 39 rats to induce a sepsis model. The study groups were designed as follows: Group 1: normal (nonoperative); Group 2: (sham-operated); Group 3: CLP (untreated group); Group 4: CLP and lacosamide 20 mg/kg; Group 5: CLP and lacosamide 40 mg/kg. TNF-alpha, C reactive protein, MDA and WBC levels was measured and compound muscle action potential (CMAP) distal latans, amplitudes were measured by using ENMG in rats with SICIN.


RESULTS
When untreated sepsis group was compared with both control and sham groups, CMAP amplitudes and latans were significantly lower (P < 000.1). When CLP, CLP+lacosamide 20 mg/kg and CLP+lacosamide 40 mg/kg groups were compared, plasma levels of TNF-alpha and MDA were significantly higher in the untreated CLP group (F = 12.74, P < 0.0001), (F = 19.43, P < 0.05). In the CLP+lacosamide 40 mg/kg group, CRP levels were significantly lower only compared to the CLP group (P < 0.001).


CONCLUSIONS
We have showed that lacosamide may have beneficial effects on early SICIN by its potential anti-inflammatory and lipid peroxidation inhibiting activities; however, further comprehensive studies are required to clarify these effects.
Volkan
V
Solmaz
Dürdane
D
Aksoy
Mustafa
M
Yılmaz
Enes
E
Eser
Oytun
O
Erbas
D000081:Acetamides / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000032:analysis; D004195:Disease Models, Animal; D000078334:Lacosamide; D007962:Leukocytes; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D018482:Muscle, Skeletal / Q000187:drug effects / Q000503:physiopathology; D011115:Polyneuropathies / Q000097:blood* / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000150:complications*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000081:Acetamides; D000893:Anti-Inflammatory Agents; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D000078334:Lacosamide; D002097:C-Reactive Protein
Critical illness polyneuropathy,; Electroneuromyography,; Lacosamide,; TNF-alpha