Neuroinflammation and oxidative stress play critical role in the pathophysiology of
neurodegenerative diseases including
Parkinson's disease (PD). Recent reports indicate the beneficial effect of anti-inflammatory drugs in attenuating the progression of PD. Therefore, the present study is aimed to evaluate the possible role of
licofelone, a dual COX/LOX-inhibitor against
MPTP-induced neurotoxicity in mice. Administration of
MPTP (40 mg/kg in divided doses of four
injections of 10 mg/kg, i.p. each at 1 h interval) significantly impaired locomotor activity and induced
catatonia, oxidative damage (elevated levels of lipid peroxidation,
superoxide anion and
nitrite, and decreased levels of non-
protein thiols) as compared with vehicle-treated animals. Biochemical studies revealed significant alterations in mitochondrial
enzyme complex activities (decreased complex-I activity and mitochondrial viability) and increased levels of
caspase-3 and NF-κB/p65 as compared to vehicle treated group.
Licofelone (2.5, 5 or 10 mg/kg/day, p.o.) treatment for 7 days significantly improved locomotor activity, attenuated the severity of
catatonia, oxidative damage and restored mitochondrial
enzyme complex activity as compared to
MPTP-treated group.
Licofelone treatment also attenuated the expression of apoptotic factor (caspase-3) and
transcription factor (NF-κB/p65) as compared to
MPTP-treated group. The findings of the present study suggest that
licofelone (dual inhibitor of COX and LOX) represents a new class of
anti-inflammatory agent which may provide a novel therapeutic alternative for the treatment and management of PD.