Platelet dopamine receptors and oxidative stress parameters as markers of manganese toxicity
1Developmental Toxicology Division, Industrial Toxicology Research Centre, MG Marg, Lucknow, India.
Abstract:
The present study has been undertaken to investigate whether neurotoxic effects of manganese (Mn) are reflected in platelets in rats to monitor the usefulness of platelet as peripheral model. Exposure of rats to Mn (10 or 15 mg/kg bw, i.p.) for 45 days caused a significant increase in membrane fluidity as evidenced by decrease in fluorescence polarisation in platelets (11% and 14%) and striatum (9% and 13%). These rats exhibited a significant increase in superoxide dismutase activity both in platelets (24% and 37%) and striatum (31% and 42%), respectively, in comparison to controls. Exposure of rats to Mn for 45 days (15 mg/kg bw, i.p.) caused a significant decrease in reduced glutathione content (platelets 20%, striatum 24%) and catalase activity (platelets 35%, striatum 44%) compared to control rats. Rats exposed to Mn (10 or 15 mg/ kg bw, i.p.) for 15 days exhibited a significant increase in dopamine receptors both in platelets (55% and 40%) and striatum (38% and 31%). The results suggest that exposure to Mn may alter the membrane functions and impair the anti-oxidant defense mechanism both in platelets and brain. The study also suggests that dopaminergic mechanisms are impaired following Mn exposure and such changes are reflected in platelets. Interestingly, parallel changes both in striatum and platelets, as observed in the present study, strengthen the usefulness of platelets as a peripheral neuronal model.
Insights
Manganese (Mn) exposure alters platelet membrane fluidity and antioxidant defenses in rats. These changes, along with altered dopamine receptors, suggest platelets can serve as a peripheral model for neurotoxic effects.
Area of Science:
- Neurotoxicology
- Biochemistry
- Peripheral Biomarkers
Background:
- Manganese (Mn) is a vital element, but excessive exposure can lead to neurotoxicity.
- Investigating peripheral markers for central nervous system (CNS) effects is crucial for monitoring Mn exposure.
- Platelets offer a potentially accessible model for studying neurotoxic mechanisms.
Purpose of the Study:
- To determine if neurotoxic effects of manganese are detectable in rat platelets.
- To evaluate the utility of platelets as a peripheral model for manganese-induced neurotoxicity.
- To assess the impact of manganese on platelet and striatal membrane fluidity, antioxidant status, and dopaminergic receptors.
Main Methods:
- Rats were exposed intraperitoneally to manganese (10 or 15 mg/kg bw) for 15 or 45 days.
- Measurements included platelet and striatal membrane fluidity (fluorescence polarization).
- Assessed superoxide dismutase activity, reduced glutathione content, catalase activity, and dopamine receptor levels.
Main Results:
- Manganese exposure significantly increased platelet and striatal membrane fluidity and superoxide dismutase activity.
- Reduced glutathione content and catalase activity decreased in both platelets and striatum following manganese exposure.
- Dopamine receptor levels increased in both platelets and striatum after manganese exposure.
Conclusions:
- Manganese exposure alters platelet membrane function and impairs antioxidant defense mechanisms, mirroring changes in the brain.
- Dopaminergic mechanisms are affected by manganese exposure, with parallel changes observed in platelets.
- Platelets serve as a valuable peripheral model for monitoring manganese-induced neurotoxic effects due to observed parallel changes with the striatum.
