Volume 18, Issue 41, January - June, 2024

Effect of L-dopa or bromocryptine alone or in combination with cannabis on oxidative stress, inflammation and neurodegeneration in experimental Parkinson’s disease

Omar ME Abdel-Salam¹, Eman R Youness², Enayat A Omara³, Amany A Sleem⁴

¹Department of Toxicology and Narcotics, Medical Research and Clinical Studies Institute, National Research Centre, Tahrir Street, Cairo, Egypt
²Department of Medical Biochemistry, Medical Research and Clinical Studies Institute, National Research Centre, Tahrir Street, Cairo, Egypt
³Department of Pathology, Medical Research and Clinical Studies Institute, National Research Centre, Tahrir Street, Cairo, Egypt
⁴Department of Pharmacology, Medical Research and Clinical Studies Institute, National Research Centre, Tahrir Street, Cairo, Egypt

ABSTRACT

This study aimed to investigate whether cannabis would modulate the effects of the antiparkinsonian drugs L-dopa or bromocryptine on striatal oxidative stress, neuroinflammation, and neuronal integrity in an experimental Parkinson’s disease evoked by injection of the inflammogen lipopolysaccharide (LPS) into the rat striatum. Rats received intrastriatal injections of LPS or vehicle. They were treated with L-dopa (25 mg/kg), bromocryptine (0.6 mg/kg) or cannabis (20 mg/kg) combined with either L-dopa or bromocryptine once a day for 15 days. In striatal homogenates, the following parameters were measured: total antioxidant capacity (TAC), paraoxonase-1 activity (PON-1), reduced glutathione (GSH), glutathione peroxidase (GPx), nitric oxide, malondialdehyde (lipid peroxidation), and tumour necrosis factor-α (TNF-α). Brain histology and caspase-3 immunohistochemistry were done to assess neuronal damage. Results indicated that injection of LPS causes a significant increase in malondialdehyde, and nitric oxide along with decreased GSH, TAC and PON-1 activity in the striatum. There was also a substantial decrease in striatal GPx and increased TNF-α. LPS resulted in marked neuronal apoptosis. We found that treatment with either L-dopa or bromocryptine was associated with a significant reduction in malondialdehyde together with increased GSH levels. Nitric oxide showed a significant reduction by either drug and there was a modest though a significant reduction in striatal TNF- α. Additionally, PON-1 activity increased by Ldopa or bromocryptine. Neither bromocryptine nor L-dopa demonstrated a discernible protection against histologic neuronal injury. Combining L-dopa or bromocryptine with cannabis has an extra impact on oxidative stress and neurodegeneration. Nonetheless, apoptotic neuronal cells, pyknotic nuclei, and neuropil vacuolation remained. These results do not point to a cannabis-related benefit for Parkinson's disease patients

Keywords: Cannabis; L-dopa; bromocryptine; lipopolysaccharide; neuroinflammation; oxidative stress; neurodegeneration

Drug Discovery, 2024, 18(41), e7dd1970

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DOI: https://doi.org/10.54905/disssi.v18i41.e7dd1970

Published: 07 February 2024