Investigation of the Protective Effects of Cannabidiol on Rat Maternal and Fetal Brain Tissues in Lipopolysaccharide-induced Pregnancy Inflammation Model

Aim: Preterm labor (PE) is one of the most common causes of neonatal death world-wide and inflammation during pregnancy is thought to be one of the underlying causes of PE. In this study, inflammation and oxidative stress-mediated protective effects of Cannabidiol (CBD) isolated from Cannabis sativa L. were investigated in a lipopolysaccharide (LPS)-induced systemic inflammation model in pregnancy. Materials and Methods: Adult Wistar albino pregnant rats (n=30) were randomly divided into 5 groups; 1) Control, 2) LPS, 3) LPS + CBD 5 mg/kg, 4) LPS + CBD 10 mg/kg and 5) LPS + CBD 30 mg/kg. On days 15, 16 and 17 of gestation, intraperitoneal (i.p.) CBD injections at doses of 5 mg/kg, 10 mg/kg and 30 mg/kg were performed in the three treatment groups. Following the last CBD injection, 1 mg/kg LPS (i.p.) injection was performed. Fetal and maternal brain tissues were collected 6 hours after LPS injection. To understand the effect of CBD on inflammation and oxidative stress-mediated mechanisms in collected tissues, hematoxylin-eosin staining, immunohistochemical analysis, ELISA and biochemical methods were used to evaluate the levels of inflammatory markers interleukin 1β (IL-1β), hypoxia-induced factor-1α (HIF-1α), immün cell activation marker CD45 and oxidative stress parameters; total antioxidant level (TAS), total oxidant level (TOS) and oxidative stress index (OSI). Results: CBD administration decreased increased IL-1β levels and CD45 expression levels in maternal brain tissue due to LPS-mediated inflammation. Furthermore, CBD treatment increased TAS levels and decreased TOS and OSI values in maternal and fetal brain tissues. In parallel with oxidative stress parameters, CBD treatment decreased HIF-1α expression levels in maternal and brain tissues. Conclusion: CBD may have a protective effect on oxidative stress in the maternal and fetal brain due to inflammation in the LPS-induced pregnancy inflammation model. These results suggest that CBD may be a potential agent in the prevention and treatment of PE and related complications.