Protective effects of crude garlic by reducing iron-mediated oxidative stress, proliferation and autophagy in rats.
The impact of garlic, known for its antioxidant activities, on iron metabolism has been poorly investigated. The aim of this work was to study the effect of crude garlic pre-treatment on iron-mediated lipid peroxidation, proliferation and autophagy for 5 weeks. Rats were fed distilled water or garlic solution (1 g/kg body weight) by gavage for the first 3 weeks as pre-treatment and received a basal diet supplemented or not with ferrous sulfate (650 mg Fe/kg diet) for the last 2 weeks of treatment. Immunohistochemistry labeling and ultrastuctural observations were used to evaluate the iron deleterious effects in the liver. Iron supplementation induced cell proliferation predominantly in non parenchymal cells comparing to hepatocytes, but not apoptosis. In addition, iron was accumulated within the hepatic lysosomes where it triggers autophagy as evidenced by the formation of autophagic vesicles detected by LC3-II staining. It also induced morphologic alterations of the mitochondrial membranes due to increased lipid peroxidation as shown by elevated iron and malondialdehyde concentrations in serum and tissues. Garlic pre-treatment reduced iron-catalyzed lipid peroxidation by decreasing the malondialdehyde level in the liver and colon and by enhancing the status of antioxidants. In addition, garlic reduced the iron-mediated cell proliferation and autophagy by lowering iron storage in the liver and protected mitochondrial membrane. Based on these results, garlic treatment significantly prevented iron-induced oxidative stress, proliferation and autophagy at both biochemical and histological levels due to its potent free radical scavenging and antioxidant properties.
Nahdi
Afef
A
Laboratory of Histology, Embryology and Cell Biology, Faculty of Medicine, Research Unit No 01/UR/08-07, 15 rue Djebel Lakhdar, Tunis 1007, Tunisia.
Hammami
Imen
I
Kouidhi
Wided
W
Chargui
Abderrahman
A
Ben Ammar
Awatef
A
Hamdaoui
Mohamed Hédi
MH
El May
Ahmed
A
El May
Michèle
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D045424:Complex Mixtures / Q000494:pharmacology*; D019587:Dietary Supplements; D005247:Feeding Behavior / Q000187:drug effects; D005737:Garlic / Q000737:chemistry*; D007501:Iron / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009928:Organ Specificity / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
D045424:Complex Mixtures; D010936:Plant Extracts; D020011:Protective Agents; D008315:Malondialdehyde; D007501:Iron; D013482:Superoxide Dismutase