title: Neuroprotective effect of silibinin in diabetic mice.
abstract: Diabetes mellitus is associated with a higher oxidative stress and reduced activity of the antioxidant defense system in different brain regions. Results from numerous studies reported impaired cognitive and neurochemical function in diabetic patients and streptozotocin induced diabetic rodents. It is well established that polyphenols exert potent antioxidant and protective functions. Based on recent findings, one potential target for the antioxidant/antinflammatory properties of polyphenols is the heme oxygenase (HO)-1 pathway. Among various compounds tested silibinin, the main component of silymarin, has been shown to possess a strong antioxidant effect in various experimental models; however a study on the possible neuroprotective effect of this compound on the brain of diabetic animals is currently lacking. Therefore, we studied and measured in lean mice (db/m) and knock out mice for the leptin receptors mice (db/db) the effect of silibinin on HO-1 protein levels, non proteic thiol groups, isoprostanes and 8-OH deoxyguanosine (markers of lipid peroxidation and DNA damage, respectively) in different brain regions. Our results showed that HO-1 is differently expressed in various brain regions in db/db mice when compared to lean animals. Furthermore, silibinin provides DNA protection and reduces oxidative stress in a brain specific area, in part via the activation of the HO system. Silibinin may provide a valid tool to counteract oxidative stress in the diabetic status in the central nervous system under diabetic condition.
authors.affiliation: Department of Drug Sciences, Section of Biochemistry, University of Catania, Catania, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Marrazzo
authors.forename: Paolo
authors.initials: P
authors.lastname: Bosco
authors.forename: Francesco
authors.initials: F
authors.lastname: La Delia
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scapagnini
authors.forename: Claudia
authors.initials: C
authors.lastname: Di Giacomo
authors.forename: Michele
authors.initials: M
authors.lastname: Malaguarnera
authors.forename: Fabio
authors.initials: F
authors.lastname: Galvano
authors.forename: Anna
authors.initials: A
authors.lastname: Nicolosi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Li Volti
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001835:Body Weight; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008665:Metalloporphyrins / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D054411:Receptors, Leptin / Q000172:deficiency; D000077385:Silybin; D012838:Silymarin / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D008565:Membrane Proteins; D008665:Metalloporphyrins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D054411:Receptors, Leptin; D012838:Silymarin; C515447:leptin receptor, mouse; C055421:tin mesoporphyrin; D000077385:Silybin; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse