Sodium para-aminosalicylate protected cultured basal ganglia astrocytes from manganese-induced DNA damages and alteration of amino acid neurotransmitter levels.
Sodium para-aminosalicylate (PAS-Na) was first applied successfully in clinical treatment of two manganism patients with good prognosis. However, the mechanism of how PAS-Na protects against Mn-induced neurotoxicity is still elusive. The current study was conducted to explore the effects of PAS-Na on Mn-induced basal ganglia astrocyte injury, and the involvement of amino acid neurotransmitter in vitro. Basal ganglia astrocytes were exposed to 500 μM manganese chloride (MnCl2) for 24 hr, following by 50, 150, or 450 μM PAS-Na treatment for another 24 hr. MnCl2 significantly decreased viability of astrocytes and induced DNA damages via increasing the percentage of tail DNA and Olive tail moment of DNA. Moreover, Mn interrupted amino acid neurotransmitters by decreasing Gln levels and increasing Glu, Gly levels. In contrast, PAS-Na treatment reversed the aforementioned Mn-induced toxic effects on basal ganglia astrocytes. Taken together, our results demonstrated that excessive Mn exposure may induce toxic effects on basal ganglia astrocytes, while PAS-Na could protect basal ganglia astrocytes from Mn-induced neurotoxicity.
Department of Toxicology, School of Public Health, Guangxi Medical University, China.
Shao-Jun
SJ
Li
Yi-Ni
YN
Luo
Yong
Y
Li
Jing-Wen
JW
Chen
Yu-Huan
YH
Mo
Zong-Xiang
ZX
Yuan
Shi-Yan
SY
Ou
Chao-Yan
CY
Ou
Yue-Ming
YM
Jiang
Xiang-Fa
XF
Deng
D010131:Aminosalicylic Acid / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001479:Basal Ganglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D002712:Chlorides / Q000633:toxicity*; D019610:Cytoprotection; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D005998:Glycine / Q000378:metabolism*; D017895:Manganese Compounds; D020149:Manganese Poisoning / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D020011:Protective Agents / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley
D002712:Chlorides; D017895:Manganese Compounds; D020011:Protective Agents; D005973:Glutamine; D018698:Glutamic Acid; D010131:Aminosalicylic Acid; C025340:manganese chloride; D005998:Glycine