title: Long-term administration of Silymarin augments proinflammatory mediators in the hippocampus of rats: evidence for antioxidant and pro-oxidant effects.
abstract: Silymarin (SMN) is used as an antioxidant complex to attenuate the pro-oxidant effects of toxic agents. This study was designed to investigate the impact of a long-term administration of SMN on proinflammatory mediators, oxidative stress biomarkers and on the levels of interleukin-1β (IL-1β) transcript in the hippocampus. A total of 40 adult male Wistar rats were assigned into control and test groups. Animals in the test group were subdivided into four subgroups according to the following treatment profile: carbon tetrachloride (CCl(4), 0.5 ml/kg), SMN 25, SMN 50 and SMN 100 (mg/kg). The animals received the compounds by gastric gavage. Following the 8-week treatment period, animals in the CCl(4) group showed body weight loss, while the test groups except SMN 100 revealed a significant (p < 0.05) positive body weight gain. The levels of nitric oxide (NO) and malondialdehyde (MDA) as pro-oxidant and lipid peroxidation index, respectively, increased in CCl(4)- and SMN 100-treated groups, while SMN at lower dose levels did not alter the NO and MDA content. The concentration of total thiol molecules increased in the SMN 50 group and showed a remarkable decrease in CCl(4) and SMN 100 groups. Animals treated with CCl(4) or SMN 100 showed an upregulation of IL-1β, while animals in SMN 25 and SMN 50 groups showed a slight downregulation of expression of IL-1β at the messenger RNA level. These findings suggest that SMN at higher dosage level might exert pro-oxidant effect as an increase in the level of MDA and proinflammatory mediators such as NO, and upregulation of IL-1β in the hippocampus were shown.
authors.affiliation: Department of Pharmacology and Toxicology, Urmia University, Urmia, Iran. hassanmalekinejad@yahoo.com
authors.forename: H
authors.initials: H
authors.lastname: Malekinejad
authors.forename: F
authors.initials: F
authors.lastname: Rahmani
authors.forename: S
authors.initials: S
authors.lastname: Valivande-Azar
authors.forename: M
authors.initials: M
authors.lastname: Taheri-Broujerdi
authors.forename: B
authors.initials: B
authors.lastname: Bazargani-Gilani
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000008:administration & dosage*; D012838:Silymarin / Q000008:administration & dosage*
chemical_list: D000975:Antioxidants; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D012838:Silymarin; D009569:Nitric Oxide; D008315:Malondialdehyde; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase