We have located links that may give you full text access.
Artesunate restores spatial learning of rats with hepatic encephalopathy by inhibiting ammonia-induced oxidative damage in neurons and dysfunction of glutamate signaling in astroglial cells.
Biomedicine & Pharmacotherapy 2016 December
BACKGROUND: Artesunate (ART) is an antimalarial drug with potential anti-inflammatory effect. This study aimed to explore the potential protective role of ART in hepatic encephalopathy (HE), involving its function against ammonia toxicity.
METHODS: HE rats were induced by the administration of thioacetamide (TAA, 300mg/kg/day). Spatial learning ability was tested in both Morris water and eight-arm radial maze. Rat cerebellar granule neurons (CGNs) were prepared for ammonia treatment in vitro, in line with SH-SY5Y and C6 cells. ART was administrated at 50 or 100mg/kg/day in vivo or added at 50 or 100μM in vitro. Oxidative damages were evaluated by the changes of cell viability, reactive oxygen species (ROS) levels and glutathione (GSH) content, while glutamate uptake and release, and the activities of glutamine synthetase (GS) and Na+ K+ -ATPase were measured to indicate the dysfunction of glutamate signaling.
RESULTS: Decreased escape latency and increased numbers of working errors were observed in TAA-induced HE rats, which could be significantly restored by ART at a dosage-dependent manner. Decreased cell viability and GSH content and increased ROS accumulation were detected in ammonia-treated SH-SY5Y and CGNs, while ammonia-treated C6 cells showed reduced glutamate uptake, increased glutamate release, and decrease of GSH content, GS and Na+ K+ -ATPase activity. In contrast, ART, especially at 100μM, strongly reversed all changes induced by ammonia, showing a similar dosage-dependent manner in vitro.
CONCLUSION: This study revealed a new neuroprotective role of ART in the pathogenesis of HE, by protecting neurons and astroglial cells from ammonia-induced damages and dysfunctions.
METHODS: HE rats were induced by the administration of thioacetamide (TAA, 300mg/kg/day). Spatial learning ability was tested in both Morris water and eight-arm radial maze. Rat cerebellar granule neurons (CGNs) were prepared for ammonia treatment in vitro, in line with SH-SY5Y and C6 cells. ART was administrated at 50 or 100mg/kg/day in vivo or added at 50 or 100μM in vitro. Oxidative damages were evaluated by the changes of cell viability, reactive oxygen species (ROS) levels and glutathione (GSH) content, while glutamate uptake and release, and the activities of glutamine synthetase (GS) and Na+ K+ -ATPase were measured to indicate the dysfunction of glutamate signaling.
RESULTS: Decreased escape latency and increased numbers of working errors were observed in TAA-induced HE rats, which could be significantly restored by ART at a dosage-dependent manner. Decreased cell viability and GSH content and increased ROS accumulation were detected in ammonia-treated SH-SY5Y and CGNs, while ammonia-treated C6 cells showed reduced glutamate uptake, increased glutamate release, and decrease of GSH content, GS and Na+ K+ -ATPase activity. In contrast, ART, especially at 100μM, strongly reversed all changes induced by ammonia, showing a similar dosage-dependent manner in vitro.
CONCLUSION: This study revealed a new neuroprotective role of ART in the pathogenesis of HE, by protecting neurons and astroglial cells from ammonia-induced damages and dysfunctions.
Full text links
Related Resources
Trending Papers
Challenges in Septic Shock: From New Hemodynamics to Blood Purification Therapies.Journal of Personalized Medicine 2024 Februrary 4
Molecular Targets of Novel Therapeutics for Diabetic Kidney Disease: A New Era of Nephroprotection.International Journal of Molecular Sciences 2024 April 4
The 'Ten Commandments' for the 2023 European Society of Cardiology guidelines for the management of endocarditis.European Heart Journal 2024 April 18
A Guide to the Use of Vasopressors and Inotropes for Patients in Shock.Journal of Intensive Care Medicine 2024 April 14
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app