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Study On The Oxidative Damage In Renal Mitochondria Of Experimental Diabetic Nephropathy And Protective Effects Of Alpha-lipoic Acid

Posted on:2008-02-01Degree:MasterType:Thesis
Country:ChinaCandidate:Q LiuFull Text:PDF
GTID:2144360215989096Subject:Endocrine and metabolic diseases
Abstract/Summary:PDF Full Text Request
Diabetic nephropathy is the main cause of end stage renal damage. Oxidativestress is involved in the etiology of diabetic nephropathy. The intake ofantioxidants, such as alpha-lipoic acid(LA), may reduce the level of oxidativestress associated with diabetes and hence help to restore the antioxidant defensesystem. We investigated the levels of malondialdehyde(MDA) and antioxidantenzymes in mitochondria from renal cortex of streptozotocin (STZ)-induceddiabetic rats and the effect of LA on the them.Male Wistar rats were randomly divided into three groups: control group(CN), streptozotocin (STZ)-induced diabetic rats group (DM) and STZ-induceddiabetic rats group treated with LA (DL). The following parameters weremeasured at 2,4,8 and 12 weeks just from the onset of diabetes in similar ratschosen randomly from each group: body and kidney weight, 24-hour urinaryalbumin excretion (UAE),urinary creatinine, biochemical indexes includingblood glucose (GLU), blood urea nitrogen (BUN), serum creatinine (SCr) andcounted endogenous creatinine clearance rate (Ccr). And we tested the level ofmitochondrial malondialdehyde(MDA) and the content/activity ofmitochondrial antioxidant enzymes including superoxide dismutase (SOD),catalase (CAT),glutathione peroxidase (GSH-Px) and reduced glutathione(GSH); we also observed the renal pathological changes by opticsmicroscope.The blood sugar,UAE,UTP Of rats in STZ-induced model group were higherthan those of rats in control group at 2w, 4w, 6w, 8w, 12w,.SCr, BUNof rats in model group were higher distinctly from 8 weeks than those of controlgroup, while Ccr of rats from model group was higher from 2 weeks and lowerfrom 8 weeks than that of control group, (respectively, P<0.05 or<0.01).MDA inmitochondria from renal cortex was significantly increased in the DMgroup,while Mn-SOD,GSH were significantly decreased from 2 weeks comparedwith those in the CN group. GSH-Px and CAT had differrent changesalso(respectively, P<0.05 or<0.01).However, in the DL group, changes ofmitochondrial antioxidant enzymes, UAE and pathological changes were lesspronounced than those in the DM group(respectively, P<0.05 or<0.01). Pearson'scorrelation analysis showed that MDA was increased while SOD, and CAT weredecreased with elevation of UAE(respectively, P<0.05 or<0.01).In our study, LA could reduce the level of mitochondrial Oxidative stress inSTZ-induced diabetic rats with diabetic nephropathy, which ccould reducedamage of renal tissue. Thus we concluded that LA may have potential protectiveeffect on diabetic nephropathy in STZ-induced rat models.
Keywords/Search Tags:Diabetes mellitus, Diabetic nephropathy, Oxidative stress, Mitochondria, Alpha-lipoic acid
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