Volume 59, Issue 329, May 2023

Effect of cannabis in the intrastriatal lipopolysaccharide model of Parkinson’s disease in the rat

Omar ME Abdel-Salam^1♦, 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

^♦Corresponding author
Department of Toxicology and Narcotics, Medical Research and Clinical Studies Institute, National Research Centre, Tahrir Street, Cairo, Egypt

ABSTRACT

Cannabis is used by Parkinson’s disease (PD) patients. Therefore, the present study investigated oxidative stress and neurodegeneration in brain subsequent to treatment with Cannabis sativa extract. The rat model of PD induced by intrastriatal injection of lipopolysaccharide (LPS) was used for this purpose. LPS or vehicle was injected into the striatum and rats were then treated daily for 15 days with cannabis extract at doses of 5, 20, 20 or 40 mg/kg (expressed as delta-9-tetrahydrocannabinol). Biochemical markers of oxidative stress and tumour necrosis factor-α (TNF-α) were determined besides brain histopathology and caspase-3 expression. Results showed that intrastriatal LPS increased oxidative/nitrosative stress indicated by increased malondialdehyde (MDA) and nitric oxide combined with decreased reduced glutathione (GSH) and paroxonase-1 (PON-1) activity in different brain regions. There were also decreased striatal levels of glutathione peroxidase (GPx) and increased TNF-α. LPS caused neuronal necrosis and apoptosis and intense caspase-3 immunostaining. Cannabis treatment decreased the elevated MDA and nitric oxide levels while increasing GSH and PON-1 activity in different brain regions. Cannabis also increased GPx activity and markedly reduced TNF-α in the striatum. Cannabis, however, did not protect against neuronal damage caused by LPS. These findings do not suggest a benefit from using cannabis in PD.

Keywords: Cannabis, lipopolysaccharide, oxidative stress, neuroinflammation, apoptosis, caspase-3

Discovery, 2023, 59, e58d1228

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Published: May 2023