Involvement of cannabidiol in the reduction of lipid peroxidation in Wistar rats induced intra uterus with valproic acid

*Correspondence: [e-mail].

Abstract

Background: The production of reactive oxygen species (ROS) is an integral part of human metabolism and is observed in different physiological conditions as a form of defense. However, when its production is exacerbated, it generates oxidative stress, resulting from the imbalance between the pro and antioxidant systems, as happens in the use of intrauterine valproic acid, as this is toxic to neurons. Furthermore, oxidative stress seems to be involved in the pathophysiology of autism and cannabidiol has demonstrated antioxidant effects, making it a possible therapeutic choice.

Objective: To demonstrate the involvement of cannabidiol in the reduction of lipid peroxidation in the brains of Wistar rats induced intra utero with valproic acid.

Methods: 105 male Wistar rats were used, which were exposed in utero with 600mg/kg of valproic acid or saline. After completing 27 days, they were treated for 15 days with cannabidiol (CBD) at a dosage of 60 mg/kg or sesame oil (vehicle) and after the treatment period, the animals were sacrificed, and the cerebral cortex was collected for analysis of substances reactive to thiobarbituric acid (TBARS).

Results: In autism, neuroinflammation may be mediated by oxidative stress, in which there is cellular damage by increasing lipid peroxidation of the cell membrane, elevating TBARS levels in brain tissue. TBARS measures malondialdehyde (MDA), a product of lipid peroxidation, caused primarily by the presence of free hydroxyl radicals. CBD appears to be involved in the antioxidant process by increasing the availability of anandamide in the brain, an endogenous agonist of cannabinoid receptors. There were increased levels of TBARS in the vehicle-treated autistic control when compared to the non-autistic vehicle-treated control group. CBD at a dose of 60 mg/kg reversed the increase in TBARS levels observed in the autistic group.

Conclusion: It is thus demonstrated that oxidative stress is involved in the pathophysiology of autism through the increase in lipid peroxidation in the cell membrane and that CBD at a dosage of 60 mg/kg in progressive treatment was able to decrease this marker, acting as an antioxidant.

 

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Publication History

Article published online:
12 May 2025