Cannabidiol and low-dose γ-radiation regulate alterations consequences of hepatic-encephalopathy induced by thioacetamide: neuroprotective and anti-inflammatory role.

Abstract

Objectives: Cannabidiol (CBD), the primary component of Cannabis sativa, has a neuroprotective and anti-inflammatory properties. Due to its modulation of multiple molecular targets within the central nervous system, CBD holds therapeutic promise for various neurological and psychiatric disorders.

Methods: This study aimed to evaluate the potential protective effects of CBD and/or low-dose ionizing radiation (LDR) in a rat model of hepatic encephalopathy (HE) induced by thioacetamide (TAA). Male Wistar rats received two (i.p.) injections of thioacetamide (TAA) at a dose of 200 mg/kg b.w. with a one-day interval between doses. Cannabidiol was administered i.p. at a dose of 20 mg/kg b.w. for seven consecutive days. Two LDR doses were applied (0.2 Gy each) with a one-day interval between exposures. The experimental design included assessment of oxidative stress and inflammatory markers, as well as neurobehavioral and histopathological evaluations.

Results: Treatment with CBD and/or LDR significantly reduced oxidative stress and inflammation, as evidenced by modulation of nuclear factor kappa B (NF-κB), apoptosis signal-regulating kinase 1 (ASK1), and c-Jun N-terminal kinase (JNK). Additionally, notable improvements were observed in levels of nicotinamide adenine dinucleotide (NAD), serotonin (5-hydroxytryptamine, 5-HT), and liver function enzymes. Behavioral performance, assessed using the Morris water maze, revealed cognitive enhancement, which was further confirmed by histological examination of brain and liver tissues.

Conclusion: Both CBD and LDR exhibited promising protective effects against TAA-induced hepatic encephalopathy, mitigating brain and liver damage through anti-inflammatory and antioxidant mechanisms. Thus, this supporting their potential as adjunct therapies in managing HE and related neuroinflammation.