Neuroprotective and blood-retinal barrier-preserving effects of cannabidiol in experimental diabetes.
نویسندگان
چکیده
Diabetic retinopathy is characterized by blood-retinal barrier (BRB) breakdown and neurotoxicity. These pathologies have been associated with oxidative stress and proinflammatory cytokines, which may operate by activating their downstream target p38 MAP kinase. In the present study, the protective effects of a nonpsychotropic cannabinoid, cannabidiol (CBD), were examined in streptozotocin-induced diabetic rats after 1, 2, or 4 weeks. Retinal cell death was determined by terminal dUTP nick-end labeling assay; BRB function by quantifying extravasation of bovine serum albumin-fluorescein; and oxidative stress by assays for lipid peroxidation, dichlorofluorescein fluorescence, and tyrosine nitration. Experimental diabetes induced significant increases in oxidative stress, retinal neuronal cell death, and vascular permeability. These effects were associated with increased levels of tumor necrosis factor-alpha, vascular endothelial growth factor, and intercellular adhesion molecule-1 and activation of p38 MAP kinase, as assessed by enzyme-linked immunosorbent assay, immunohistochemistry, and/or Western blot. CBD treatment significantly reduced oxidative stress; decreased the levels of tumor necrosis factor-alpha, vascular endothelial growth factor, and intercellular adhesion molecule-1; and prevented retinal cell death and vascular hyperpermeability in the diabetic retina. Consistent with these effects, CBD treatment also significantly inhibited p38 MAP kinase in the diabetic retina. These results demonstrate that CBD treatment reduces neurotoxicity, inflammation, and BRB breakdown in diabetic animals through activities that may involve inhibition of p38 MAP kinase.
منابع مشابه
اثر محافظتی دوزهای مختلف کانابیدیول بر میزان نفوذپذیری سد خونی– مغزی و آسیبهای حاصل از مدل ایسکمی مغزی در موش صحرایی
Background and Objective: Stroke is a neurological disease with a rapid increase in incidence across developing world. Cannabidiol is a non- psychoactive constituent of cannabis which has attracted the attention of investigators in basic and therapeutic research. The most significant property of cannabidiol is its strong neuroprotective effect manifested in animal model of epilepsy, Alzheimer, ...
متن کاملCannabidiol attenuates high glucose-induced endothelial cell inflammatory response and barrier disruption.
A nonpsychoactive cannabinoid cannabidiol (CBD) has been shown to exert potent anti-inflammatory and antioxidant effects and has recently been reported to lower the incidence of diabetes in nonobese diabetic mice and to preserve the blood-retinal barrier in experimental diabetes. In this study we have investigated the effects of CBD on high glucose (HG)-induced, mitochondrial superoxide generat...
متن کاملFull retraction: A.B. El-Remessy, Y. Khalifa, S. Ola, A.S. Ibrahim, G.I. Liou. Cannabidiol protects retinal neurons by preserving glutamine synthetase activity in diabetes. Mol Vis. 2010; 16:1487-1495.
متن کامل
Neuroprotective Effects of Allicin on Neurological Scores, Blood Brain Barrier Permeability and Brain Edema Following Severe Traumatic Brain Injury in Male Rats: A Behavioral, Biochemical and Histological Study
Background and purpose: Allicin has a wide range of pharmacological functions, all of which can be demonstrated in anti-inflammatory, antioxidant, antifungal and anti-tumor activities. In this research, we investigated the neuroprotective role of allicin in the process of diffuse traumatic brain injury and its effect on interleukin levels and histological changes in rats. Materials and method...
متن کاملCannabidiol prevents cerebral infarction via a serotonergic 5-hydroxytryptamine1A receptor-dependent mechanism.
BACKGROUND AND PURPOSE Cannabidiol has been reported to be a neuroprotectant, but the neuroprotective mechanism of cannabidiol remains unclear. We studied the neuroprotective mechanism of cannabidiol in 4-hour middle cerebral artery (MCA) occlusion mice. METHODS Male MCA occluded mice were treated with cannabidiol, abnormal cannabidiol, anandamide, methanandamide, cannabidiol plus capsazepine...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The American journal of pathology
دوره 168 1 شماره
صفحات -
تاریخ انتشار 2006