Epigallocatechin-3-gallate ameliorates alcohol-induced cognitive dysfunctions and apoptotic neurodegeneration in the developing rat brain.
Clinical and experimental evidence has demonstrated that ethanol is a teratogen, and its consumption during pregnancy induces harmful effects on the developing fetus that leads to mental retardation and long-term cognitive and behavioural deficits in offspring. The brain growth spurt period is highly sensitive to the neurotoxic effects of ethanol and it corresponds to the last trimester in humans and the first two postnatal weeks in rodents. This study was designed to evaluate the effect of epigallocatechin-3-gallate (EGCG) on alcohol-induced behavioural, biochemical and molecular changes in rat pups. Pups were administered alcohol (5 g/kg, 12% v/v) by intragastric intubation on postnatal days (PD) 7, 8, and 9. Ethanol-exposed pups showed impaired spatial navigation in the Morris water maze test and poor retention in the elevated plus maze task conducted from PD 24 to 28 which was coupled with enhanced acetylcholinesterase activity, increased oxidative-nitrosative stress, cytokines (TNF-alpha and IL-1beta), NF-kappaB and caspase-3 levels in both the cortex and hippocampus of pups sacrificed at PD 28. Apart from this, the mean weight of the whole brain, cortex and hippocampus of ethanol-treated pups was decreased by 34.48%, 39.09% and 34.30%, respectively. EGCG (50 and 100 mg/kg) significantly attenuated all the behavioural, biochemical and molecular changes in the different brain regions of ethanol-treated pups. The current finding demonstrates the activation of oxidative-nitrosative stress-mediated apoptotic signalling in cognitive deficits associated with fetal alcohol spectrum disorders (FASDs) and suggests that EGCG may have potential in prevention of the cognitive impairment in children with FASDs.
Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC Center of Advanced Study, Panjab University, Chandigarh, India.
Vinod
V
Tiwari
Anurag
A
Kuhad
Kanwaljit
K
Chopra
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D003072:Cognition Disorders / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D000431:Ethanol / Q000633:toxicity*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D000431:Ethanol; D002392:Catechin; C045651:epigallocatechin gallate