BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, cilt.797, 2026 (SCI-Expanded, Scopus)
Neurotoxicity is an important side-effect of many chemotherapeutic agents, including doxorubicin (DXR). L-Theanine (LT) is a non-protein amino acid with a variety of beneficial health effects, involving anti-inflammatory, antimicrobial, anti-aging, antioxidant, antitumor, antihypertensive, and antistress properties. The aim of this study was to investigate the modulatory roles of LT on the electrophysiological, histopathological and biochemical effects of DXR on the rat hippocampus, cerebral cortex and cerebellum. Sixty-four male Wistar rats were randomly divided into four groups: Sham, DXR, DXR + LT200 and DXR + LT400. LT was administered via oral gavage at doses of 200 and 400 mg/kg/day for 21 days, while DXR was given cumulatively at 18 mg/kg (intraperitoneally on days 4, 11, and 18). Half the rats were used for brain electrophysiological assessments, and the remaining half for histological and biochemical analyses. DXR reduced total power in the electrocorticogram (ECoG) between 0.1 and 50 Hz, across all frequency ranges. The application of 400 mg/kg/day, but not 200 mg/kg/day, reduced the total power even further (p < 0.05). Conversely, both doses of LT treatment significantly reduced DXR-induced cell degeneration in all regions (p < 0.001). LT treatments also tended to reduce the levels of DXR-induced oxidative stress parameters, although these effects were not significant for every region of the brain. Considering the capacity of DXR to cause pathological conditions and the multifaceted effects of LT treatments on different regions of the brain, we conclude that the simultaneous administration of LT supplement with DXR treatment should be performed with caution.