Substantial evidences suggest that reactive oxygen species participate in the normal aging process and in cancer and neurodegenerative age-related diseases. Parkinson's disease (PD), one of the most common oxidative stress-associated pathology in aging people, is treated with a standard pharmacological protocol consisting in a combined therapy L-dopa plus an inhibitor of dopa-decarboxylase, such as carbidopa. The therapy is well validated for the ability to restoring dopaminergic neurotransmission in PD patients, while L-dopa and carbidopa ability in modulating oxidative stress is currently under discussion. Our aim was to evaluate the impact of L-dopa and carbidopa on several biomarkers of exogenously-induced oxidative stress to validate the overall antioxidant effectiveness of the therapy. For this purpose we used peripheral blood lymphocytes from healthy donors treated in vitro with L-dopa and carbidopa and then challenged by different concentrations of H2O2. Glutathione (GSH, GSSG, GSH/GSSG), malondialdehyde (TBARs), protein carbonyls as well as DNA damage (8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and micronuclei (MN)), modulation was evaluated. Our results show that L-dopa, but not carbidopa, decreases the markers of lipid and protein oxidation and increases the total content of glutathione. Both L-dopa and carbidopa (alone or in combination) are able to counteract the formation of 8-oxodG and to reduce H2O2-induced micronuclei. © 2017 Elsevier Ltd
A multi-biomarker analysis of the antioxidant efficacy of Parkinson's disease therapy
Testa, A.
2018-01-01
Abstract
Substantial evidences suggest that reactive oxygen species participate in the normal aging process and in cancer and neurodegenerative age-related diseases. Parkinson's disease (PD), one of the most common oxidative stress-associated pathology in aging people, is treated with a standard pharmacological protocol consisting in a combined therapy L-dopa plus an inhibitor of dopa-decarboxylase, such as carbidopa. The therapy is well validated for the ability to restoring dopaminergic neurotransmission in PD patients, while L-dopa and carbidopa ability in modulating oxidative stress is currently under discussion. Our aim was to evaluate the impact of L-dopa and carbidopa on several biomarkers of exogenously-induced oxidative stress to validate the overall antioxidant effectiveness of the therapy. For this purpose we used peripheral blood lymphocytes from healthy donors treated in vitro with L-dopa and carbidopa and then challenged by different concentrations of H2O2. Glutathione (GSH, GSSG, GSH/GSSG), malondialdehyde (TBARs), protein carbonyls as well as DNA damage (8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and micronuclei (MN)), modulation was evaluated. Our results show that L-dopa, but not carbidopa, decreases the markers of lipid and protein oxidation and increases the total content of glutathione. Both L-dopa and carbidopa (alone or in combination) are able to counteract the formation of 8-oxodG and to reduce H2O2-induced micronuclei. © 2017 Elsevier LtdI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
