Datura metel and Alcohol Cocktail Potentiates Hepatic Encephalopathy by Exacerbating Impairment via the Hepato-Prefrontal Cortical Axis

Objectives Substance abuse among adolescents is a major concern not only in developing countries but also worldwide. Datura metel (D. metel), commonly known as Datura or Devil’s Trumpet, is a plant containing several toxic compounds, including alkaloids (such as scopolamine, hyoscyamine, and atropine). However, consuming D. metel or its derivatives can significantly impact the brain, though its mechanism remains elusive. Therefore, this study evaluated the effects of D. metel and alcohol cocktail on the hepato-prefrontal-cortical axis. Methods Thirty-five male Sprague Dawley rats were divided randomly into five groups (A–E). Group A received distilled water, Group B received 300 mg/kg of D. metel, and Group C received 700 mg/kg of alcohol. Group D received 300 mg/kg of D. metel + 700 mg/kg of alcohol, while Group E received 150 mg/kg of D. metel + 350 mg/kg of alcohol. Tissues from the liver and prefrontal cortex (PFC) were collected for morphological, histological, and immunohistochemical studies. Results There was a significant increase in body weight in control group A compared to other experimental groups. Hematoxylin and eosin staining revealed a mild attenuation in the cytoarchitecture of the liver and PFC with increased necrosis, apoptosis, vacuolation, and neuronal death in experimental groups compared to control group A. Increased microglial activity was observed in groups B–E, whereas group A showed normal neuronal arrangement with the NeuN antibody compared to experimental groups. Serum liver function biomarkers (alkaline phosphatase, alanine transaminase, and aspartate aminotransferase) were statistically significantly higher in Groups C and D when compared to Group A. Conclusion Combined D. metel and alcohol negatively impact the liver and PFC of experimental rats.