Abstract
Haloperidol is an antipsychotic drug that exerts its' antipsychotic effects by inhibiting dopaminergic neurons. Although the exact pathophysiology of haloperidol extrapyramidal symptoms are not known, the role of reactive oxygen species in inducing oxidative stress has been proposed as one of the mechanisms of prolonged haloperidol-induced neurotoxicity. In the present study, we evaluate the protective effect of alpha lipoic acid against haloperidol-induced oxidative stress in the rat brain. Sprague Dawley rats were divided into control, alpha lipoic acid alone (100 mg/kg p.o for 21 days), haloperidol alone (2 mg/kg i.p for 21 days), and haloperidol with alpha lipoic acid groups (for 21 days). Haloperidol treatment significantly decreased levels of the brain antioxidant enzymes super oxide dismutase and glutathione peroxidase and concurrent treatment with alpha lipoic acid significantly reversed the oxidative effects of haloperidol. Histopathological changes revealed significant haloperidol-induced damage in the cerebral cortex, internal capsule, and substantia nigra. Alpha lipoic acid significantly reduced this damage and there were very little neuronal atrophy. Areas of angiogenesis were also seen in the alpha lipoic acid-treated group. In conclusion, the study proves that alpha lipoic acid treatment significantly reduces haloperidol-induced neuronal damage.
Highlights
Haloperidol (HP) is a first generation antipsychotic frequently used in the treatment of schizophrenia
Huge interest has been garnered in recent times on the antioxidant properties of Alpha lipoic acid (ALA) and its reduced form dihydrolipoic acid (DHLA)
Comparing group 3 and group 4, it was noticed that the rats that were co-administered HP and ALA showed a significantly higher (p < 0.01) increase in Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity in serum and brain compared to the rats that were given HP alone
Summary
Haloperidol (HP) is a first generation antipsychotic frequently used in the treatment of schizophrenia. Previous research has shown that coadministration of haloperidol and antioxidants such as vitamin E resulted in beneficial effect in patients with tardive dyskinesia [8]. Huge interest has been garnered in recent times on the antioxidant properties of ALA and its reduced form dihydrolipoic acid (DHLA). Both ALA and DHLA are able to cross the blood-brain barrier and act as a redox couple with very low reduction potentials [13]. Due to these properties ALA is capable of regenerating other important antioxidants such as glutathione, vitamin C, and vitamin E [16,17]. Due to its action in both the membranous and aqueous phase, ALA is frequently referred to as a universal antioxidant
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