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D-ribose-L-cysteine Attenuates manganese-induced Oxidative Stress, Neuromorphological Deficits, Bax/Bcl-2 Response
Happiness O Inyang1,2,3, Uchenna K Ezemagu3, Stephen O Okori2
1Laboratory for Experimental and Translational Neurobiology, University of Medical Sciences, Ondo, Nigeria.
Abstract:
Manganese (Mn), though an essential trace element, can become neurotoxic after excessive exposure. Established mechanisms of Mn neurotoxicity include oxidative stress, apoptotic signalling, and inflammatory responses. D-ribose-L-cysteine (RibCys), a cysteine derivative, is reported to mitigate oxidative damage. In this study, we investigated its effects on B-cell lymphoma 2-associated X protein (Bax)/B-cell lymphoma 2 (Bcl-2) apoptotic signaling, tumor necrosis factor-alpha (TNF-α) inflammatory response, and extracellular signal-regulated kinase (ERK) pathway across various brain regions. Adult male Wistar rats were treated with saline (control), Mn (25 mg/kg intraperitoneally for 2 weeks, 8 doses at 48-hour intervals), RibCys (200 mg/kg orally for 2 weeks), or both Mn and RibCys. Biochemical assays for oxidative stress and antioxidant activity, Golgi staining for dendritic morphology, and immunohistochemistry for key protein markers were performed. Results showed that RibCys reduced Mn-induced distortions in brain neurochemistry and dendritic morphology. Mn increased lipid peroxidation, myeloperoxidase, and nitric oxide levels while decreasing glutathione peroxidase and sulfhydryl content, and these effects were attenuated by RibCys. Mn also disrupted dendritic arborization, which improved with RibCys treatment. Furthermore, Mn exposure elevated Bax/Bcl-2, TNF-α, and ERK1/2 expression in selected brain regions. RibCys co-administration mitigated these molecular alterations. Our findings suggest that RibCys is a promising therapeutic agent against Mn-induced neurotoxicity with potential for broader application. A notable limitation of this study was the absence of direct measurements of reduced and oxidized glutathione, and cysteine. Future studies should include these key antioxidant markers, assess long-term outcomes of RibCys treatment, and incorporate female animal models to evaluate potential sex-specific responses to Mn toxicity and intervention.
Insights
D-ribose-L-cysteine (RibCys) effectively counteracts manganese (Mn) neurotoxicity by reducing oxidative stress and inflammation. This study shows RibCys protects brain cells from Mn-induced damage, suggesting its therapeutic potential.
Area of Science:
- Neuroscience
- Toxicology
- Biochemistry
Background:
- Manganese (Mn) is an essential trace element, but excessive exposure leads to neurotoxicity.
- Established mechanisms of Mn neurotoxicity involve oxidative stress, apoptosis, and inflammation.
- D-ribose-L-cysteine (RibCys), a cysteine derivative, shows potential in mitigating oxidative damage.
Purpose of the Study:
- To investigate the neuroprotective effects of RibCys against manganese-induced toxicity.
- To evaluate RibCys's impact on apoptotic signaling (Bax/Bcl-2), inflammation (TNF-α), and the ERK pathway in rat brain regions.
Main Methods:
- Adult male Wistar rats were administered Mn, RibCys, or both.
- Biochemical assays measured oxidative stress and antioxidant activity.
- Golgi staining assessed dendritic morphology, and immunohistochemistry analyzed protein markers.
Main Results:
- RibCys attenuated Mn-induced increases in lipid peroxidation, myeloperoxidase, and nitric oxide.
- RibCys improved Mn-induced disruptions in dendritic morphology and arborization.
- Co-administration of RibCys mitigated elevated Bax/Bcl-2, TNF-α, and ERK1/2 expression caused by Mn.
Conclusions:
- RibCys demonstrates significant neuroprotective effects against manganese toxicity.
- RibCys mitigates Mn-induced oxidative stress, inflammation, and apoptotic signaling.
- RibCys shows promise as a therapeutic agent for manganese neurotoxicity.
