Analgesic and neuroprotective effect of a lipid transfer protein isolated from Morinda citrifolia L. (noni) seeds on oxaliplatin-induced peripheral sensory neuropathy in mice.

Abstract

Oxaliplatin, a 3rd-generation platinum compound, has a dose-limiting effect: neurotoxicity manifests as peripheral sensory neuropathy (PNS). Many studies have assessed the different pharmacological properties of a lipid transfer protein isolated from Morinda citrifolia L. (McLTP₁) seeds. This study aimed to evaluate the analgesic and neuroprotective effects of McLTP₁ on oxaliplatin-induced peripheral sensory neuropathy in mice and the mechanisms involved. Male Swiss mice received oxaliplatin twice a week for 28 days. McLTP₁ (1 to 4 mg/kg, p.o.) was administered 60 min before oxaliplatin injection. Mechanical and cold allodynia were assessed once a week via electronic von Frey and acetone tests. TRPA1 and TRPM8 receptor agonists were applied intraplantarly to the hind paw to evaluate their involvement in the antiallodynic mechanism of McLTP₁. ATF3 and c-Fos expression was assessed in the dorsal root ganglia (DRG) or spinal cord (SC) to investigate nociceptive pathway activation and neurotoxic injury. MDA and GSH assays were performed in the sciatic nerve and spinal cord, and histological analysis was performed in the sciatic nerve. Total and differential leukocyte counts were analyzed in the peripheral blood. McLTP₁ prevented the mechanical and cold allodynia and increase in c-Fos and ATF3 expression induced by oxaliplatin in the DRG and SC, possibly involving TRPM8 receptors. McLTP₁ prevented the oxidative stress caused by oxaliplatin in the sciatic nerve and spinal cord and the histological changes associated with oxaliplatin in the sciatic nerve. McLTP₁ inhibited leukopenia, mainly lymphopenia caused by oxaliplatin. McLTP₁ prevents oxaliplatin-induced peripheral sensory neuropathy through its antiallodynic, antioxidant and neuroprotective properties.