Effect and mechanism of Dichloroacetate in the treatment of stroke and the resolution strategy for side effect

Wang, Xu; Rong, Chunshu; Leng, Wei; Niu, Ping; He, Ziqiao; Wang, Gaihua; Qi, Xin; Zhao, Dexi; Li, Jinhua

doi:10.1186/s40001-025-02399-5

European Journal of Medical Research

Table 1 Details of included studies and results of DCA

From: Effect and mechanism of Dichloroacetate in the treatment of stroke and the resolution strategy for side effect

Model	Species	Dose and Time	Evidence	References
Ischemic stroke	Rat	25 mg/kg, 2 h	Brain temperature↑, Lactate level↓	[32]
Ischemic stroke	Gerbil	225 mg/kg, 72 h	Pyruvate dehydrogenase enzyme↑, Lactate level↓, Neuronal damage↓	[33]
Ischemic stroke	Sprague − Dawley rats	40 mg/kg, 24 h	Ischemic lesion volume↓, Neurological defects, Long-term Functional Recovery↑, Survival Proportions↑, Weight↑, BBB integrity↑, Brain edema volume ↓, ZO-1↑, Occludin↑, MMP9↓, TNF-α↓, IL6↓, iNOS↓, CD206↑, IL10↑, Arg1↑, ROCK↓, MYPT1↓, p38 MAPK↓, JNK↓, p-phd↓,	[48]
Ischemic stroke	Sprague − Dawley rats	80 mg/kg, 72 h	Survival time↑, Neurons↑, Apoptotic cells↓, TNF-α↓, IL-1β↓, Blood lactate ↓, Blood glucose levels↓, ATP↑, PDH activity↑, Pyruvate levels↓,	[26]
Ischemic stroke	Wistar rats	100 mg/kg, 105 min	DCA is ineffective in the treatment of ischemic stroke	[99]
Ischemic stroke	Wistar rats	25 mg/kg, 30 min	Brain lactate levels ↓, Brain glycogen↑	[34]
Ischemic stroke	Sprague − Dawley rats	100 mg/kg, 30 min	Brain lactate levels↓, Phosphocreatine↑, PH↑, ATP↑	[37]
Ischemic stroke	Wistar rats	300 mg/kg,30 min	Brain lactate levels↓	[100]
Ischemic stroke	UC-11MG cells	100 mm, 24 h	PDHC activity↑, Brain lactate levels↓	[28]
Ischemic stroke	Macaque monkeys	35 mg / kg, 24 h	Size of Infarct↓	[101]
Ischemic stroke	Wistar rats	25 mg / kg, 45 min	Glycogen levels↑, Brain lactate levels↓	[35]
Ischemic stroke	Mongolian gerbils	2.3 mmol/kg, 4.5 h	PCr↑, ATP↑, PDH activity↑	[27]
Hemorrhagic stroke	Sprague − Dawley rats	100 mg/kg, 2 d	PDK4↑, p-PDH↓, PDH↑, Pyruvate↓, p-ASK1↑, p-P38↑, Cleaved-caspase3↑	[102]
Ischemic stroke	C57BL/6 mice	200 mg/kg, 3 d	PDK4↓, PDH activity↑,p-PDH↓	[103]
Ischemic stroke	C57BL/6 mice	200 mg/kg, 24 h	Occludin↑, ZO-1↑, Neurological deficit score↓, Infarct volume↓, BBB↑, PDK2↓, PDH↑, SOD↑, MDA↓, NRF2↑, HO-1↑, Apoptosis↓	[49]
Ischemic stroke	Sprague − Dawley rats	100 mg/kg, 7 d	PDHC activity↑, Brain lactate levels↓, PCr↑, ATP↑,	[29]
Perinatal Asphyxia induced Hypoxic Ischemic Brain Injury	C57BL/6 mice	200 mg/kg, 3 d	Infarction volume↓, Myelin structure↑, MAP2↑, PDH activity↑, Acetyl-coenzyme A↑, Pgc-1α ↑, Nrf1↑, Tfam↑, COX-IV↑, Mfn1↑, Drp1↑, SQSTM↑, AIF↓, Caspase3↓	[8]
Ischemic stroke	Sprague − Dawley rats	50, 100 and 200 mg/kg, 21 d	Learning capacity↑, Neuronal death↓, Brain atrophy↓,VEGF↑, bFGF↑, Vitro tube forming ability↑, Endothelial progenitor function↑, NO↑, ROS↓, AKT↑, Nrf2↑, eNOS↑, GSK-3β↑	[89]

↑ = increased, ↓ = decreased. blood brain barrier(BBB), pyruvate dehydrogenase (PDH), pyruvate dehydrogenase complex (PDHC), phosphocreatine (PCr), SOD (superoxide dismutase), malondialdehyde (MDA). A total of 17 studies on ischemic stroke and one study on hemorrhagic stroke were included. The specific effects of DCA encompass improvements in energy metabolism, autophagy, oxidative stress, inflammation, the integrity of the blood–brain barrier, apoptosis, and angiogenesis in the context of ischemic stroke

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ISSN: 2047-783X

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