EFFICACY OF TAUROURSODEOXYCHOLIC ACID ON BIOCHEMICAL AND HISTOPATHOLOGICAL CHANGES IN 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE INDUCED PARKINSON’S DISEASE MICE MODEL
DOI:
https://doi.org/10.22159/ajpcr.2025v18i12.57160Keywords:
Parkinson’s disease, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Tauroursodeoxycholic acid, Syndopa, Oxidative biomarkers, Histomorphometry, C57BL/6 miceAbstract
Objectives: One of the main pathological features of Parkinson’s disease (PD) is the loss of dopaminergic neurons in the nigrostriatal pathway. Pre-clinical research has shown that tauroursodeoxycholic acid (TUDCA) monotherapy can alleviate the neuropathological complications of PD. The present study aimed to compare the therapeutic benefits of combination TUDCA and syndopa therapy with those of TUDCA and syndopa monotherapy in a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
Methods: Male C57BL/6 mice received MPTP (30 mg/kg body weight/day, intraperitoneal, 5 days) to induce PD, followed by TUDCA (150 mg/kg body weight/day, intraperitoneal), syndopa (12 mg/kg body weight/day, oral), or both for 21 days. The midbrain reactive oxygen species (ROS), malondialdehyde (MDA), peroxynitrite, nitric oxide (NO), and urea contents, as well as the total antioxidant capacity (TAC), were measured. Midbrain and liver histopathology and histomorphometry assessed neuronal and hepatic damage.
Results: MPTP increased the ROS (2.41-fold, p<0.01), MDA (2.07-fold, p<0.01), peroxynitrite (1.62-fold, p<0.01), NO (2.23-fold, p<0.01), and urea (1.88-fold, p<0.01) contents and reduced the TAC (1.92-fold, p<0.01) compared with the control. Combination therapy reduced the ROS content by 2.33 fold, the MDA content by 2.12 fold, the urea levels by 1.83 fold, peroxynitrite levels by 1.59 fold, NO by 2.65 fold, and neuronal loss by 3.68 fold (all p<0.05 vs. the MPTP group), outperforming both TUDCA (1.66 fold reduction in the ROS content, p>0.05, NS) and syndopa (1.38 fold reduction in the ROS content, p>0.05, NS) monotherapy. The same trend followed for other parameters, such as urea, TAC, MDA, NO and peroxynitrite. Moreover, the histopathology and histomorphometric results confirmed that TUDCA monotherapy and combination therapy markedly attenuated MPTP-induced neuronal and liver damage, with the combination therapy showing superior efficacy.
Conclusions: TUDCA + syndopa offers synergistic neuroprotection and represents a novel therapeutic strategy for PD.
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