Effect of Hydroethanolic Extract of Citrus Aurantium Leaves and Magnesium Sulfate in Mice Model of Vincristine-Induced Neuropathy

Neuropathic pain due to vincristine administration is an important dose limiting adverse effect with no definiteefficient treatment. Citrus aurantium possesses multiple therapeutic potentials and is commonly used in traditionalmedicine. This study investigate the possible effects of the hydroethanolic extract of C. aurantium (CA) leaves andmagnesium sulfate (MgSO4) as a known analgesic in vincristine-induced peripheral neuropathy (VIN). Vincristinewas administered intraperitoneally (IP) to establish peripheral neuropathy in mice. Effects of CA (50,100 and 150mg/kg, IP) and MgSO4 (50, 75 and 100 mg mg/kg, IP) were assessed on pain threshold performed by hot plate test.Moreover, the serum levels of total antioxidant capacity (TAC) and malondialdehyde (MDA) were assayed.Administration of CA (100 and 150 mg/kg) showed significant (p<0.001) decrease in responses to pain. In addition,MgSO4 in high dose of 100 mg/kg could alleviate the neuropathic symptoms. The result of biochemical tests exertedhigh TAC level in all CA treated groups (p<0.01 in 50 mg/kg and p<0.001 for 100 and 150 mg/kg). MDA level wasdecreased significantly (p<0.001) by CA (100 and 150 mg/kg) and MgSO4 (100 mg/kg). However the combinationof low dose of CA and MgSO4 exerted no efficient antinociceptive effect. According to the results, it can beconcluded that MgSO4 and CA, in an effective dose range, can be effective in controlling the neuropathic painfollowed by vincristine, possibly through the modulation of antioxidant balance directed by CA or the NMDA andcalcium receptor blocking properties of MgSO4.