RESUMO
Sodium-glucose co-transporter 2 (SGLT 2) inhibitors are a relatively new antidiabetic drug with antioxidant and anti-inflammatory properties. Therefore, this study aimed to investigate whether SGLT 2 inhibitors have a neuroprotective effect in PD. Twenty-four Wistar rats were randomized into four groups. The first one (control group) received dimethyl sulfoxide (DMSO) as a vehicle (0.2 mL/48 hr, S.C). The second group (positive control) received rotenone (ROT) (2.5 mg/kg/48 hr, S.C) for 20 successive days, whereas the third and fourth groups received empagliflozin (EMP) (1 and 2 mg/kg/day, orally), respectively. The two groups received rotenone (2.5 mg/kg/48 hr S.C) concomitantly with EMP for another 20 days on the fifth day. By the end of the experimental period, behavioral examinations were done. Subsequently, rats were sacrificed, blood samples and brain tissues were collected for analysis. ROT significantly elevated oxidative stress and proinflammatory markers as well as α-synuclein. However, dopamine (DP), antioxidants, tyrosine hydroxylase (TH), and Parkin were significantly decreased. Groups of (EMP + ROT) significantly maintained oxidative stress and inflammatory markers elevation, maintained α-synuclein and Parkin levels, and elevated TH activity and dopamine level. In both low and high doses, EMP produced a neuroprotective effect against the PD rat model, with the high dose inducing a more significant effect.
RESUMO
Parkinson's disease (PD) drugs treat symptoms without inhibiting progression. In recent years, finding novel therapeutic medications that can halt disease progression has become crucial. Research on antidiabetic medicines is valuable in these investigations because of the parallels between the two disorders. Using Rotenone (ROT), a frequently used PD model, the possible neuroprotective benefits of Dulaglutide (DUL), an extended-acting glucagon-like peptide-1 agonist, were considered. Twenty-four rats were randomly assigned to 4 groups to complete this experiment (n = 6). 0.2 ml of the vehicle (1 ml of dimethyl sulfoxide (DMSO) diluted in sunflower oil) was administered to the standard control group subcutaneously with a 48-hour pause. The second group was administered ROT 2.5 mg/kg SC every 48 h for 20 days as a positive control group. The third and fourth groups were administered one dose of DUL each week (0.05 and 0.1 mg/kg SC, respectively) to their regimens. The mice received ROT (2.5 mg/kg SC) every 48 h for 20 days after receiving DUL for the initial dose (96 h later). The current study focused on the DUL's ability to preserve usual behavioral function, enhance antioxidant and anti-inflammatory pathways, inhibit alpha-synuclein (α-syn), and increase parkin levels. It is concluded that DUL acts as an antioxidant and an anti-inflammatory to protect against ROT-induced PD. However, more studies are required to support this finding.