Use of corn oil nanoemulsion enriched with CBD and THC in the treatment of Parkinson's disease induced in wistar rats
neurogeneration; phytocannabinoids; dopamine; rotenone
Parkinson's disease (PD) affects 1% of the world's population and is a neurodegenerative disorder that compromises the functioning of dopaminergic neurons in the substantia nigra. The pathogenesis of PD is believed to involve several critical abnormalities, each of which may be the result of genetic or environmental factors, characterized by the formation of abnormal protein aggregates with mitochondrial dysfunction and increased oxidative stress. Cannabidiol (CBD) and Δ-9-tetrahydrocannabinol (Δ-9-THC) are lipophilic cannabinoids, which have pharmacological effects on the central nervous system, which can bring benefits to individuals with PD since there is no treatment that impacts the evolution of the disease. It is also possible to use derivatives of cannabis sp. in preparations that increase the effectiveness of substances, offering greater bioavailability and acting quickly in the therapeutic context, as is the case with nanoemulsions. Thus, this study aimed to systematically review the use of preclinical models of PD in animals treated with cannabis sp., as well as analyze the effect of corn oil nanoemulsion enriched with CBD and THC in the treatment of Parkinson's disease induced in Wistar rats. . According to the literature consulted, experimental models of PD were developed in mice, rats and marmosets using 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), Haloperidol, Levodopa (L-DOPA) + Benserazide, Lipopolysaccharide (LPS), L-nitro-N-arginine (L-NOARG), WIN55,212-2, Rotenone and Reserpine. The most used treatments were CBD, Δ-9-THC and Delta-9-tetrahydrocannabivarin (Δ-9 THCV), representing an improvement in locomotor activity and involuntary movement and a reduction in catalepsy. Inflammation, microglial/astrocyte activation and oxidative stress were reduced after treatment with phytocannabinoids, the same was observed in the results of allodynia and hyperalgesia tests. For the experiment, Wistar rats were induced to PD with rotenone (2.5mg/kg/sc), once a day for 21 days. And subsequently treated with corn oil nanoemulsion enriched with CBD:THC (0.5%, 1% and 2%), 1ml being administered twice a day for 60 days. During treatment, the animals were evaluated in the open field and bar tests. After euthanasia, tissues were collected for biochemical, histopathological and morphometric tests. Superoxide dismutase (SOD), catalase (CAT), glutathione (GST) were determined in serum. The brain was processed and stained in HE and the living and dead neurons of the midbrain and hippocampus were measured. All groups treated with CBD:THC showed a reduction in non-enzymatic antioxidant activity and a reestablishment in the percentage of living neurons in the hippocampus. However, treatment with the combination of CBD:THC 0.5% and 1% caused an increase only in GST activity while the group treated with CBD:THC 2% showed an increase in the enzymatic antioxidant response of SOD, CAT and GST.