Effects of carnosine and lipoic acid in the late stage of Parkinson’s disease in rats

Abstract

The late stage of Parkinson’s disease is characterized by massive neuronal loss in the substantia nigra (SN) and degeneration of the dopaminergic innervation in the striatum. There is a need to assess the neuroprotective effect of antioxidants (AO) at this stage of the disease. The aim of our study was to assess the efficacy of two AO, carnosine and lipoic acid (LA), in the rat model of late-stage parkinsonism. The pathology was induced by a unilateral injection of 6-hydroxydopamine (6-OHDA) into the SN of the right brain hemisphere. AO were administered 4 times, starting on day 14 following the injection of the toxin. We investigated the effect of the injected drugs on the behavior of rats, the loss of neurons in the SN and the metabolism of biogenic neurotransmitter amines. Both AO dampened the development of 6-OHDA-induced neurological and behavioral symptoms. 6-OHDA induced a 90% drop (p = 0.01) in the levels of dopamine (DA) and its metabolites in the right striatum and caused death of over 95% of neurons (p = 0.01) in the SN of the right hemisphere (p = 0.01). AO did not have a significant effect on the number of neurons in the SN but caused an increase in the levels of DA metabolites, as compared to their levels in the animals exposed to 6-OHDA. Elevated DA (a 5.8-fold increase, p = 0.007) was observed only in the animals treated with carnosine. LA stimulated a 23% decline in serotonin levels (p = 0.06) and a 36% increase (p = 0.009) in its metabolite, 5-hydroxyindolacetic acid (5-HIAA). We conclude that although carnosine and LA did not have a direct neuroprotective effect, they could relieve the symptoms. This suggests that these AO could be used as an adjunctive component to antiparkinsonian therapy.