title: The effects of alpha-lipoic acid on MMP-2 and MMP-9 activities in a rat renal ischemia and re-perfusion model.
abstract: Matrix metalloproteinases (MMPs) are enzymes that are responsible for degradation of extracellular matrix (ECM); they are involved in the pathogenesis of ischemia-re-perfusion (I-R) injury. We investigated the possible preventive effect of alpha-lipoic acid (LA) in a renal I-R injury model in rats by assessing its reducing effect on the expression and activation of MMP-2 and MMP-9 induced by I-R. Rats were assigned to four groups: control, sham-operated, I-R (saline, i.p.) and I-R+ LA (100 mg/kg, i.p.). After a right nephrectomy, I-R was induced by clamping the left renal pedicle for 1 h, followed by 6 h re-perfusion. In the sham group, a right nephrectomy was performed and left renal pedicles were dissected without clamping and the entire left kidney was excised after 6 h. LA pretreatment was started 30 min prior to induction of ischemia. Injury to tubules was evaluated using light and electron microscopy. The expressions of MMP-2 and MMP-9 were determined by immunohistochemistry and their activities were analyzed by gelatin zymography. Serum creatinine was measured using a quantitative kit based on the Jaffe colorimetric technique. Malondialdehyde (MDA) and glutathione (GSH) were analyzed using high performance liquid chromatography. Tissue inhibitor of metalloproteinase (TIMP)-2 and TIMP-1 were assessed using enzyme-linked immunosorbent assay (ELISA). I-R caused tubular dilatation and brush border loss. LA decreased both renal dysfunction and abnormal levels of MDA and GSH during I-R. Moreover, LA decreased significantly both MMP-2 and MMP-9 expressions and activations during I-R. TIMP-1 and TIMP-2 levels were increased significantly by LA administration. LA modulated increased MMP-2 and MMP-9 activities and decreased TIMP-1 and TIMP-2 levels during renal I-R.
authors.affiliation: Department of Molecular Medicine, Health Sciences Institute.
authors.forename: Z
authors.initials: Z
authors.lastname: Cavdar
authors.forename: S
authors.initials: S
authors.lastname: Ozbal
authors.forename: A
authors.initials: A
authors.lastname: Celik
authors.forename: B U
authors.initials: BU
authors.lastname: Ergur
authors.forename: E
authors.initials: E
authors.lastname: Guneli
authors.forename: C
authors.initials: C
authors.lastname: Ural
authors.forename: T
authors.initials: T
authors.lastname: Camsari
authors.forename: G A
authors.initials: GA
authors.lastname: Guner
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D004789:Enzyme Activation / Q000187:drug effects; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control*; D008063:Thioctic Acid / Q000008:administration & dosage*; D014018:Tissue Distribution / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants; D008063:Thioctic Acid; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat