Targeting Oxidative Stress and Apoptosis with Levothyroxine in Experimental Parkinson's Disease in Rats.

Parkinson’s disease is a long-term, progressive condition that affects both movement and other parts of life that aren’t motor-related. Cognitive decline is one of the most impactful non-motor symptoms, as it can seriously affect overall quality of life. Although existing dopamine replacement therapies, including levodopa, mainly focus on alleviating motor symptoms, they do not adequately address issues such as dyskinesia, non-motor deficits, and the need for neuroprotective treatments. This research aimed to explore the neuroprotective properties of levothyroxine (L-T4) in a PD animal model. Female Wistar rats received 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle (MFB) and were treated with L-T4 (10–100 µg/kg) for 3 weeks. The Morris water maze (MWM), rotarod test, rotational behavior, and analyses of oxidative stress and apoptosis indices were conducted at the end of week 3 after surgery. In this study, L-T4 significantly enhanced learning and memory, improved motor balance and reduced the total number of rotations compared to the 6-OHDA-lesioned group. Biochemical analyses revealed that L-T4 enhanced the activity of superoxide dismutase (SOD) and catalase (CAT). It also lowered levels of lipid peroxidation and reduced the number of neurons dying through apoptosis in the striatum. These effects were seen when compared to the group that received 6-OHDA treatment. It was found that L-T4 treatment mitigated 6-OHDA induced motor and cognitive impairment, likely due to its antioxidant and anti-apoptotic effects. These findings propose that L-T4 may offer neuroprotective benefits for individuals with PD experiencing motor and memory deficits.