Safety evaluation, anti-oxidative and anti-inflammatory effects of subchronically dietary supplemented high dosing grape seed powder (GSP) to healthy rat

• Published in: Biomedicine & pharmacotherapy 2018-11, Vol.107, p.534-546
• Main Authors: Charradi, Kamel, Mahmoudi, Mohamed, Bedhiafi, Takwa, Jebari, Khawla, El May, Michèle Veronique, Limam, Ferid, Aouani, Ezzedine
• Format: Article
• Language: English
• Subjects: Animals; Anti-inflammatory; Anti-Inflammatory Agents - pharmacology; Antioxidant; Antioxidants - pharmacology; Dietary Supplements; Grape Seed Extract - pharmacology; GSP; High dosing range; Hippocampal neurogenesis; Hippocampus - drug effects; Hippocampus - pathology; Lipid Peroxidation - drug effects; Male; Neurogenesis - drug effects; Organ Size - drug effects; Organ Specificity; Powders; Rats, Wistar; Vital organs safety; Weight Gain - drug effects
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2018.08.031

[Display omitted] •High dosing GSP is highly safe with no obvious toxicity till the NOAEL of 5% or 4 g/kg.•High and repeated dosing GSP exert anti-oxidative and anti-inflammatory properties.•High dosing GSP is a multi-targeted and multi-faceted polyphenol mixture.•GSP prevents from metabolic syndrome related pathologies as neuro-degenerative diseases. Grape seed powder (GSP) contains high amount of bioactive polyphenols usually used as nutritional supplement or food preservatives due to their antioxidant and scavenging properties. The purpose of the present work was to evaluate the safety of increasing dosage GSP (w/w) of 0.5%, 5%, 10% and 20% corresponding to 0.4, 4, 8 and 16 g/kg bw respectively, when administered sub-chronically to Wistar rats in a 2 month-repeated dosing oral toxicity trial. Overally GSP had no effect on food intake, decreased body weight gain without affecting brain, liver, heart or kidney relative weight. GSP did not alter haematology except an increase in platelets, slightly decreased plasma transaminases, creatinine, urea and xanthine oxidase activity, without affecting uricemia, glycemia, triglyceridemia and cholesterolemia. GSP did not affect intracellular mediators as calcium, free iron or H2O2, but exerted real anti-oxidative properties in the four selected organs as assessed by lower lipoperoxidation and carbonylation, higher non protein thiols and antioxidant enzyme activities as CAT, GPx and SOD. Besides GSP exerted anti-inflammatory properties as supported by lower plasma IL17 A and CRP and higher IL10 and adiponectin. Histopathologically GSP provoked the dilation of heart and kidney arterioles and increased the size of the hippocampal dentate gyrus reflecting higher neurogenesis as assessed by Ki-67 labeling. Under the experimental conditions of the current study, GSP appeared as highly safe even when administered at very high dosage and could find potential applications in a variety of biotic or abiotic stresses-induced multi-organ dysfunction.