Silymarin, a natural antioxidant, protects cerebral cortex against manganese-induced neurotoxicity in adult rats

Chtourou, Yassine; Fetoui, Hamadi; Sefi, Mediha; Trabelsi, Khaled; Barkallah, Maher; Boudawara, Tahia; Kallel, Héla; Zeghal, Najiba

doi:10.1007/s10534-010-9345-x

Cited by 60 publications

(39 citation statements)

References 85 publications

(78 reference statements)

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“…including neuronal damage (10). Mn toxicity is seen in the CNS as degeneration of basal ganglia, particularly the medial segment of the globus pallidus, a finding that is consistent with the T1 hyperintensity of the globus pallidus found in the three cases of the present study (9).…”

Section: Discussionsupporting

confidence: 87%

Basal ganglia hyperintensity on T1‐weighted MRI in rendu–osler–weber disease

Oikonomou

Chatzistefanou

Zezos

et al. 2011

Magnetic Resonance Imaging

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The purpose of this study was to evaluate possible central nervous system (CNS) involvement in Rendu-OslerWeber (ROW) disease in magnetic resonance imaging (MRI). Three patients with symptomatic ROW disease underwent brain MRI. Brain MRI depicted in all three of them increased signal intensity on T1-weighted images involving the globus pallidus and cerebral crura bilaterally. Laboratory studies of the two men showed iron deficiency anemia, while all three of them had normal liver function tests and increased manganese blood concentration. Gastroscopy and colonoscopy revealed a gastric and a cecal arteriovenous malformation (AVM) in the first one, while pulmonary and hepatic computed tomography (CT) angiography did not detect any intrahepatic shunts. Liver ultrasound in the second one revealed dilatation of intrahepatic artery branches consistent with intrahepatic shunts, while it was normal in the third patient. Chest radiographs were normal in all three patients. Pallidal T1 hyperintensity on T1-weighted imaging may be a biomarker of manganese overload in ROW disease. RENDU-OSLER-WEBER DISEASE (ROW) is a dominantly inherited disorder characterized by the presence of angiodysplastic lesions, which can affect practically all organs with an extremely variable expressivity presenting with epistaxis and mucocutaneous telangiectases and visceral arteriovenous malformations, particularly in the brain, lungs, liver, and gastrointestinal tract (1).It has been reported in only two other case reports in the literature that in patients with ROW and documented intrahepatic portosystemic shunts manganese, a paramagnetic metal, escapes to the systemic circulation and accumulates at high doses in the brain, becoming neurotoxic (2,3). The purpose of this study was to describe the magnetic resonance imaging (MRI) findings of brain changes in ROW disease with or without obvious hepatic involvement. CASE SERIES PRESENTATIONA 53-year-old man (first patient) with history of ROW disease was admitted to the hospital with melenae. He also reported recurrent episodes of epistaxis. Physical examination revealed multiple telangiectases of the lips, tongue, and fingertips. Laboratory studies showed iron deficiency anemia with normal liver function and increased serum manganese concentration (5.2 mg/dL, normal values 0.8-2.5 mg/dL). Gastroscopy showed a small arteriovenous malformation (AVM) in the body of the stomach. Colonoscopy revealed a cecal AVM, with active bleeding. Pulmonary and hepatic computed tomography (CT) angiography did not detect any obvious AVMs.A 67-year-old man (second patient) with a family history of ROW disease presented with uncontrolled nasal bleeding. Physical examination revealed multiple telangiectases of the lips, tongue, and fingertips and nasal AVMs. Laboratory studies showed iron deficiency anemia with normal liver function and increased serum manganese concentration (4.9 mg/ dL, normal values 0.8-2.5 mg/dL). Ultrasound of the liver detected dilatation of the branches of the hepatic artery parallel to branche...

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Section: Discussionsupporting

confidence: 87%

Basal ganglia hyperintensity on T1‐weighted MRI in rendu–osler–weber disease

Oikonomou

Chatzistefanou

Zezos

et al. 2011

Magnetic Resonance Imaging

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“…Tissue samples for this study were obtained from rats treated in the same manner as in the animal model described and previously by us [7]. Briefly rats were randomly divided into four groups of seven animals each: The first group of rats served as the control, received ad libitum distilled water and 0.5 ml vehicle solution of silymarin given daily by intraperitoneal (i.p) injection.…”

Section: Animal Treatments and Experimental Protocolmentioning

confidence: 99%

“…Recently, several studies demonstrate that under high-doses exposure, Mn accumulated in various brain regions [4]. The mechanism by which manganese may elicit damaging effects in disease states is unknown although oxidative stress, energy failure, and the disturbance of neurotransmitter metabolism may be the primary pathway of actions [5][6][7]. Several neurotransmitter systems, such as glutamatergic, GABAergic, dopaminergic, noradrenalinergic and cholinergic, seem to be involved in the cognitive function and other neurological functions [8].…”

Section: Introductionmentioning

confidence: 99%

Improvement of Cerebellum Redox States and Cholinergic Functions Contribute to the Beneficial Effects of Silymarin Against Manganese-Induced Neurotoxicity

et al. 2011

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Manganese (Mn) is a potent neurotoxin involved in the initiation and progression of various cognitive disorders. Oxidative stress is reported as one of accepted mechanisms of Mn toxicity. The present study was designed to explore the effects of silymarin, a natural antioxidant, in attenuating the toxicity induced by Mn in rat cerebellum. In this investigation, rats were treated orally with MnCl₂ (20 mg/ml) for 30 days, subsets of these animals were treated intraperitoneally daily with silymarin (100 mg/kg) along with respective controls. Mn exposure caused a marked oxidative stress in cerebellum as indicated by a significant decrease in the activities of enzymatic antioxidants like superoxide dismutase, catalase and glutathione peroxidase and in the levels of non-enzymatic antioxidants like reduced glutathione (GSH), total thiols and vitamin C. Conversely an increase was obtained in lipid and protein markers such as thiobarbituric reactive acid substances, lipid hydroperoxide and protein carbonyl products contents. A significant increase in acetylcholinesterase and a decrease in Na⁺/K⁺-ATPase activities were also shown, with a substantial rise in the expression of acetylcholinesterase and inducible nitric oxide synthase (iNOS), and nitric oxide levels. The potential effect of SIL to prevent Mn induced neurotoxicity was also reflected by histopathological observations. Rats exposed to Mn showed a reduced number and morphological alterations of cerebellar Purkinje cells. These phenomenons were completely reversed by SIL co-treatment. We concluded that silymarin may protect against Mn-induced oxidative stress in cerebellum by inhibiting both lipid and protein oxidation and by activating acetylcholinesterase and inducible nitric oxide synthase (iNOS) gene expression.

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“…Silymarin is composed primarily of three polyphenolic benzopyranone components, silybin, silydianin, and silychristin (Lee and Liu 2003). Silymarin has anti-inflammatory, anti-oxidative and anti-carcinogenic activities and so it has been tested in various in-vitro and in-vivo models of oxidative stress for protection of oxidative injuries in different tissues (Chtourou et al 2010).…”

Section: Resultsmentioning

confidence: 99%

Effect of silymarin on sodium fluoride-induced toxicity and oxidative stress in rat cardiac tissues

Nabavi

Moghaddam

et al. 2012

An. Acad. Bras. Ciênc.

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This study aim to evaluate the protective effect of silymarin on sodium fluoride-induced oxidative stress in rat cardiac tissues. Animals were pretreated with silymarin at 20 and 10 mg/kg prior to sodium fluoride consumption (600 ppm through drinking water). Vitamin C at 10 mg/kg was used as standard antioxidant. There was a significant increase in thiobarbituric acid reactive substances level (59.36 ± 2.19 nmol MDA eq/g tissue) along with a decrease in antioxidant enzymes activity (64.27 ± 1.98 U/g tissue for superoxide dismutase activity and 29.17 ± 1.01 µmol/min/mg protein for catalase activity) and reduced glutathione level (3.8 ± 0.15 µg/mg protein) in the tissues homogenates of the sodium fluoride-intoxicated rats. Silymarin administration to animals before sodium fluoride consumption modified the levels of biochemical parameters.

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Silymarin, a natural antioxidant, protects cerebral cortex against manganese-induced neurotoxicity in adult rats

Cited by 60 publications

References 85 publications

Basal ganglia hyperintensity on T1‐weighted MRI in rendu–osler–weber disease

Basal ganglia hyperintensity on T1‐weighted MRI in rendu–osler–weber disease

Improvement of Cerebellum Redox States and Cholinergic Functions Contribute to the Beneficial Effects of Silymarin Against Manganese-Induced Neurotoxicity

Effect of silymarin on sodium fluoride-induced toxicity and oxidative stress in rat cardiac tissues

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