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<p>Stroke is a public health problem for which there is currently no effective therapy. In this work, we investigated the protective effect of grapeseed extract (GSE) and orlistat (ORL) against brain ischemia/reperfusion (IR) injury. Rats were treated daily with GSE (2.5 g/kg), ORL (4 mg/kg), or both drugs for 1 week, and a transient incomplete global ischemia was performed (30-min ischemia followed by 60-min reperfusion). Animals were then sacrificed and their brains dissected into cortex, hippocampus, and cerebellum for analysis of oxidative stress, lipid metabolism, and cholinergic neurotransmission. Especially within the cortex and hippocampus, IR induced oxidative damage to biomolecules such as protein thiols and nonprotein thiols, lipid peroxidation, and DNA fragmentation. Moreover, IR altered the lipid profile through disturbed triglyceride, cholesterol, and free fatty acids, as well as lipase activity. IR also altered cholinergic transmission by increasing acetylcholinesterase activity. Interestingly, pretreatment with GSE prevented all the detrimental effects generated by IR, and the best protection was obtained following addition of ORL. Association of GSE and ORL is a promising approach to protecting the brain from IR injury.</p>

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Grapeseed Extract and Orlistat Association Prevent Ischemia/Reperfusion-Induced Oxidative Stress, Lipid Disturbance, and Cholinergic Transmission Alteration in Rat Brain

  • 期刊论文

  • 发表日期：

    2025年12月1日

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  • Slim Ghrir,
  • Amani Ben Alaya,
  • Selim Jallouli,
  • Ferid Limam,
  • Ezzedine Aouani,
  • Kamel Charradi

摘要

Stroke is a public health problem for which there is currently no effective therapy. In this work, we investigated the protective effect of grapeseed extract (GSE) and orlistat (ORL) against brain ischemia/reperfusion (IR) injury. Rats were treated daily with GSE (2.5 g/kg), ORL (4 mg/kg), or both drugs for 1 week, and a transient incomplete global ischemia was performed (30-min ischemia followed by 60-min reperfusion). Animals were then sacrificed and their brains dissected into cortex, hippocampus, and cerebellum for analysis of oxidative stress, lipid metabolism, and cholinergic neurotransmission. Especially within the cortex and hippocampus, IR induced oxidative damage to biomolecules such as protein thiols and nonprotein thiols, lipid peroxidation, and DNA fragmentation. Moreover, IR altered the lipid profile through disturbed triglyceride, cholesterol, and free fatty acids, as well as lipase activity. IR also altered cholinergic transmission by increasing acetylcholinesterase activity. Interestingly, pretreatment with GSE prevented all the detrimental effects generated by IR, and the best protection was obtained following addition of ORL. Association of GSE and ORL is a promising approach to protecting the brain from IR injury.