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

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. 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. 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. 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.