Neurobehavioral deficits, oxidative dysregulation, and inflammatory responses in male Swiss mice following sub-acute exposure to ethanol extract of Leiotrametes lactinea Berk

BACKGROUND: Leiotrametes lactinea (Berk.) Welti & Courtec. a mushroom reported to possess antimicrobial, antioxidant, antitumor and analgesic activities. However, there is limited information on its safety profile in the central nervous system. This study thus evaluates the neurotoxic effect of ethanol extract of Leiotrametes lactinea (EELL) in male Swiss mice following 30 days oral exposure. METHOD: day, and on day 30, the animals were euthanised. Brain tissues were collected for biochemical assays (Superoxide dismutase, Catalase activity, reduced glutathione, malondialdehyde and acetylcholinesterase activity). Tumour necrosis factor-alpha and interleukin-6 levels were also measured. RESULTS: There was a reduction in body weight gain of EELL administered groups (3.38 ± 0.68 - 4.28 ± 0.85 g) compared to the control group (7.21 ± 0.87 g), while relative organ weights were unaffected. Also, a significant reduction in locomotor activity and rearing behaviour was recorded with an increased anxiety-like behaviour in the extract treated groups. Cognitive performance evaluated with the Morris water maze demonstrated impaired retention, evidenced by reduced time spent in the target platform zone and increased proximity to the platform at higher doses. Biochemical evaluation of brain tissue showed pronounced oxidative stress, indicated by significant reductions in reduced glutathione (71.06 ± 4.74 - 124.36 ± 5.35 µg/mol vs 149.88 ± 7.07 µg/mol), catalase, and superoxide dismutase activities, alongside elevated malondialdehyde levels, especially at 100 and 200 mg/kg doses in comparison to the control. In addition, acetylcholinesterase activity was significantly increased in 100 and 200 mg/kg EELL treated groups compared to the control (0.121 ± 0.01 & 0.160 ± 0.01 µmol/min/g tissue vs. 0.049 ± 0.01 µmol/min/g tissue). Likewise, increased levels of pro-inflammatory cytokines (interleukin-6 and tumour necrosis factor-α) was recorded in the treated groups. CONCLUSION: These findings demonstrated that sub-acute exposure to EELL induces neurobehavioral deficits, oxidative stress, and neuroinflammatory responses, suggesting potential neurotoxic effects at higher doses.