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PubMed1997

Therapy of post-renal transplantation hyperlipidaemia: comparative study with simvastatin and fish oil.

BACKGROUND: Recipients of renal transplantation (RT) exhibit disturbances of serum lipids and apoproteins that may contribute to their cardiovascular morbidity and mortality. In our renal transplant department the hypercholesterolaemia prevalence at the first and fifth year of RT is 70.0% and 81.2%, respectively. Lipid-lowering therapy has been utilized in many Transplant Units. The aim of our study was to evaluate post-RT hyperlipidaemia control with simvastatin or fish oil. METHODS: Forty-three RT patients (26 men and 17 women) with persistent hypercholesterolaemia and stable graft function which were resistant to a lipid-lowering diet (American Heart Association Step Two) were randomized into two groups and treated for 3 months with simvastatin (S) (10mg/day; n = 25) and fish oil (F) (6 g/day; n = 18). Total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), lipoprotein a (Lp(a)), apolipoprotein A1 (Apo A1), and apolipoprotein B (Apo B) were monitored and at the study baseline they were similar between the two groups. RESULTS: No side effects were detected after 3 months of therapy. In group S, the concentrations of TC (271 +/- 46 mg% vs 228 +/- 49 mg%; P < 0.001), TG (180 +/- 78 vs 134 +/- 45; P < 0.01), LDL-C (177 +/- 40 vs 144 +/- 43; P < 0.01) and Apo B (96 +/- 18 vs 82 +/- 16; P < 0.001) were significantly reduced, and Apo A1 concentration had increased (135 +/- 24 vs 149 +/- 30; P < 0.01). In group F, the concentrations of TC (266 +/- 25 vs 240 +/- 31; P < 0.001), TG (203 +/- 105 vs 156 +/- 72; P = 0.02) and HDL-C (63 +/- 15 vs 53 +/- 12; P < 0.01) were significantly reduced. CONCLUSIONS: We concluded that low-dose simvastatin and fish oil are both effective and safe in correcting post-RT hyperlipidaemia. Further prospective studies with larger follow-up are needed to clarify whether this therapy has an impact on cardiovascular morbidity and mortality in RT patients.

Adult↗
PubMed2005

Simvastatin inhibits T-cell activation by selectively impairing the function of Ras superfamily GTPases.

Statins are widely used hypocholesterolemic drugs that inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, a rate-limiting enzyme of the mevalonate pathway whose biosynthetic end product is cholesterol. In addition to lowering circulating cholesterol, statins perturb the composition of cell membranes, resulting in disruption of lipid rafts, which function as signaling platforms in immunoreceptor signaling. Furthermore, by inhibiting protein prenylation, a process also dependent on mevalonate, statins block membrane targeting and hence activity of small GTPases, which control multiple pathways triggered by these receptors. T-cell activation is crucially dependent on Ras, Rho and Rab GTPases. Furthermore TCR signaling is orchestrated at lipid rafts, identifying T-cells as potential cellular targets of statins. Here we report that simvastatin suppresses T-cell activation and proliferation as the result of its capacity to inhibit HMG-CoA reductase. T-cell treatment with simvastatin does not affect intracellular cholesterol levels or raft integrity nor, accordingly, the initial tyrosine phosphorylation-dependent cascade. Conversely, inhibition of protein prenylation by simvastatin results in a dramatic impairment in the pathways regulated by small GTPases, including the Ras/MAP kinase pathway, the Rac/stress kinase pathway, and the Rab-dependent pathway of receptor endocytosis. The results identify Ras superfamily GTPases as strategic molecular targets in T-cell immunosuppression by statins.

Endocytosis↗
PubMedDate not supplied

Colchicine-induced acute myopathy in a patient with concomitant use of simvastatin.

Colchicine and 3-hydroxy-3-methy-glutaryl coenzyme A (HMG-CoA) reductase inhibitors are well known to cause myopathy. Myotoxicity is dose-dependent in both drugs; therefore, the onset of symptoms usually takes months or years. We report the case of a patient with chronic renal failure who had been taking simvastatin for 2 years and developed acute weakness 2 weeks after the start of treatment with colchicines for recurrent gout. The electromyography and elevated muscle enzymes indicated that his symptoms were caused by myopathy. When this patient stopped taking both drugs, his weakness resolved rapidly. Acute myopathy induced by combination therapy with colchicines and simvastatin is rare. In patients with chronic renal failure, co-administration of colchicine with simvastatin may accelerate the onset of myopathy because CYP3A4 (part of cytochrome P450) is crucial in the breakdown of both drugs. When adding colchicine to a medication regimen that includes a HMG-CoA reductase inhibitor for patients with renal insufficiency, drugs that are metabolized outside the CYP3A4 system (e.g., fluvastatin and pravastatin) should be selected instead.

Acute Disease↗
PubMed1998

Simvastatin-induced lupus erythematosus.

We report the case of a 79-year-old man who had onset of fatigue, myalgia, and pleuritic chest pain 3 months after initiation of therapy with simvastatin. He had signs of pleuropericarditis due to simvastatin-induced lupus erythematosus. This should alert clinicians to this possible adverse effect of simvastatin and other statins.

Aged↗
PubMed2001

The influence of short-term treatment with simvastatin on the inflammatory profile of patients with hypercholesterolaemia.

BACKGROUND: Treatment with 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors can reduce cardiovascular mortality of patients with atherosclerosis. This effect is probably due not only to a decrease in concentration of cholesterol, but also to non-lipid-involving mechanisms elicited by the action of statin drugs. OBJECTIVE: To investigate the influence of short-term therapy with simvastatin on markers of inflammation and oxidation processes in patients with hypercholesterolaemia. DESIGN: We administered 20mg simvastatin daily for 12 weeks to 19 patients with hypercholesterolaemia (250-400 mg/dl). Peripheral blood samples for evaluation of plasma concentrations of thiobarbituric acid reactive substances (malonaldehyde), stable metabolites of nitric oxide (NOx) and interleukin 6 (11-6) were taken before and after the therapy. RESULTS: Plasma levels of malonaldehyde decreased significantly (from 4.533+/-0.428 versus 3.690+/-0.310 micromol/l, P = 0.04) during the study period. Similarly, there was a significant decrease in the plasma concentrations of NOx (from 33.477+/-4.352 micromol/l versus 25.919+/-2.561 micromol/l, P = 0.02). There were significant positive correlations between concentrations of total cholesterol and NOx in plasma (r = 0.4397, P = 0.008) and of low-density lipoprotein and NOx (r = 0.3987, P = 0.02). The plasma level of interleukin 6 remained unchanged by the intervention (1.837+/-0.200 versus 1.820+/-0.169 pg/ml, P = 0.54). CONCLUSIONS: Short-term therapy with simvastatin decreases the plasma concentrations of markers of peroxidation of lipids and of stable metabolites of nitric oxide in hypercholesterolaemic patients, but leaves levels of interleukin 6 unaffected.

Female↗
PubMed2005

Time as a variable with niacin extended-release/lovastatin vs. atorvastatin and simvastatin.

Time may be an important variable when evaluating the efficacy of lipid-altering drugs. In this analysis of the Advicor Versus Other Cholesterol-Modulating Agents Trial Evaluation, niacin extended-release/lovastatin 1000/40 mg was as effective as atorvastatin 10 mg and more effective than simvastatin (both 10 mg and 20 mg) in achieving low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol treatment goals. The titration schedule for this study included the initiation of niacin-extended release/lovastatin 500/20 mg once a day for 4 weeks, titrated to the starting dose of 1000/40 mg after 4 weeks, and then titrated to the final dose of 2000/40 mg. The titration schedule for both atorvastatin and simvastatin was 10 mg per day for 8 weeks and then titrated to 40 mg per day. Using this schedule, 50% of niacin extended-release/lovastatin and atorvastatin patients reached low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol treatment goals within approximately 7 weeks, compared with simvastatin, in which 50% reached both treatment goals in 13-14 weeks. These time differences may have potential clinical relevance in reducing coronary heart disease risk.

Atorvastatin↗
PubMed1991

Simvastatin in severe hypercholesterolaemia: a placebo controlled trial.

The effect of simvastatin in 27 patients with severe primary hypercholesterolaemia was assessed by a double-blind placebo controlled parallel group trial. Total serum cholesterol, LDL-cholesterol and apoprotein B (ApoB) were significantly reduced by simvastatin 40 mg daily. Reductions in triglyceride and VLDL-cholesterol and an increase in HDL-cholesterol levels were only significant when calculated as a percentage of baseline, because of wide inter-individual variability. No changes in apoprotein A1, lipoprotein (a), fibrinogen, viscosity or blood pressure were observed. Leucocyte HMG-CoA reductase activity was unchanged after 4 weeks of active treatment but increased by 87% after 3 months (n = 21, P less than 0.05). No severe adverse effects or changes in CK or AST levels were noted. We conclude that simvastatin is effective in the treatment of severe and resistant hypercholesterolaemia, and well tolerated in the short term.

Adult↗
PubMed2006

Effects of simvastatin withdrawal on serum matrix metalloproteinases in hypercholesterolaemic patients.

BACKGROUND: Serum matrix metalloproteinase (MMP) levels have been related to clinical outcomes in patients with coronary artery disease. Though statin treatment might reduce serum MMPs the change of levels after statin withdrawal remains obscure. MATERIALS AND METHOD: Sixty-one consecutive hypercholesterolaemic patients whose lipid profiles had been well controlled by regular simvastatin (20 mg day(-1)) treatment for more than 6 months were enrolled. Statin was discontinued after their lipid profiles reached the treatment goal of the ATP-III guideline. The lipid profiles, serum MMP-2, MMP-3 and MMP-9, tissue inhibitor of MMP and highly sensitive C-reactive protein (hsCRP) levels were measured on the day of simvastatin withdrawal and 120 days later. A further 50 hyperlipidaemia patients who had never received statin treatment (positive control group) and 28 healthy patients with normal lipid profiles (negative control group) were also studied as control groups. RESULTS: While the lipid profiles had been normalized, the levels of serum inflammatory markers were still higher in hypercholesterolaemic patients than in the healthy subjects. Up to 120 days after statin withdrawal there was no coronary event, but the lipid profiles and serum hsCRP levels had significantly rebounded in study patients. However, serum MMP-2 and MMP-9 levels remained unchanged and the MMP-3 level was even further reduced after statin withdrawal (115.04 +/- 84.54 vs. 92.71 +/- 66.71 ng mL(-1), P = 0.022). Moreover, the amplitudes of variation (%) of each parameter including MMPs, TIMP, hsCRP and lipid profiles after statin withdrawal were inversely correlated to their respective baseline levels before withdrawal (r = -0.702 to -0.284; P < 0.005). CONCLUSIONS: The effects of short-term discontinuation of statin were different on serum hsCRP and MMPs levels in hypercholesterolaemic patients. While lipid profiles and serum hsCRP level had rebounded the serum MMPs levels were still unchanged, or even reduced, suggesting the prolonged effect of statin treatment, especially on serum MMP-3 level up to 120 days after simvastatin withdrawal. Further work is required to clarify the situation both in terms of these serum markers and clinical effects.

Aged↗
PubMed1997

Rapid reversal of endothelial dysfunction in hypercholesterolaemic rabbits treated with simvastatin and pravastatin.

1. The main objective of the present study was to verify the speed with which two 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, simvastatin and pravastatin, could revert endothelial cell dysfunction in hypercholesterolaemic rabbits. An attempt was also made to correlate the plasma cholesterol level and the tissue cholesterol and malondialdehyde (MDA) contents of the aortae with the endothelium-dependent relaxation on the assumption that any endothelial dysfunction could be rapidly and partially reversed, even in the presence of relatively high serum cholesterol levels. 2. Ninety-one male New Zealand white rabbits were randomly assigned to hypercholesterolaemic (control), simvastatin or pravastatin groups. All rabbits were fed a diet supplemented with cholesterol (0.5%) and coconut oil (2%) for 8 weeks. Simvastatin (10 and 20 mg/day) and pravastatin (15 and 30 mg/day) were administered 6, 4 and 2 days before the end of the experiment. At the end of the 8th week, animals were killed and the aortae were removed for histological examination as well as for the measurement of cholesterol and MDA contents and for endothelium-dependent relaxation studies. 3. The results showed that significant improvement in endothelium-dependent relaxation was obtained only with pravastatin and only with 4 or 6 days of administration. In these cases, the cholesterol and MDA contents of the vessel wall were reduced, although no significant changes were observed in plasma total cholesterol. Higher doses of the drugs did not alter these results. 4. We conclude that pravastatin enhances endothelium-dependent relaxation when administered to cholesterol-fed rabbits, probably via an anti-oxidant action. This effect, which was observed to start on the 4th day of drug administration, may represent a new therapeutic approach for the treatment of acute coronary syndromes in hypercholesterolaemic patients.

Animals↗
PubMedDate not supplied

The effect of simvastatin and bezafibrate on bile composition and gall-bladder emptying in female non-insulin-dependent diabetics.

Female non-insulin-dependent diabetics have a high prevalence of gallstones. Treatment of hyperlipidaemia in these patients may modify the risk. Seventeen female non-insulin-dependent diabetics (age 35-65) were treated with simvastatin (n = 10) or bezafibrate (n = 7) and had the cholesterol saturation index (CSI) of bile and gall-bladder emptying measured before and after 3 months therapy. In both groups, there was a significant reduction in serum cholesterol following treatment. The mean pretreatment cholesterol saturation indices of bile did not differ between the two groups but, after 3 months therapy, there was a highly significant difference in CSI between the bezafibrate group (2.0 +/- 0.33) and the simvastatin group (1.1 +/- 0.14) P < 0.002. Whereas the increase in the CSI (42%) observed with bezafibrate therapy was significant, the decrease in the simvastatin group (14%) was only significant in those whose pretreatment cholesterol saturation indices were elevated. Despite the differences in CSI observed between the two treatment groups, no changes in gall-bladder emptying were detected.

Adult↗
PubMedDate not supplied

Improvement in the regulation of cellular cholesterologenesis in diabetes: the effect of reduction in serum cholesterol by simvastatin.

Cellular cholesterol homeostasis was examined in 11 hypercholesterolaemic Type 2 diabetic patients prior to and following reduction of serum cholesterol using simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase. Following 12 weeks of treatment with simvastatin (10-40 mg day-1), serum cholesterol decreased by 30 +/- 3% from 7.8 +/- 0.2 mmol l-1 to 5.5 +/- 0.2 mmol l-1 (p less than 0.001) and LDL-cholesterol by 35 +/- 4% from 5.7 +/- 0.2 to 3.6 +/- 0.1 mmol l-1 (p less than 0.001). The esterified/free cholesterol ratio in LDL also decreased from 2.75 +/- 0.18 to 1.94 +/- 0.10 (p less than 0.01) after treatment. Cellular cholesterol synthesis, measured by [14C] acetate incorporation into mononuclear leucocytes, decreased by 39 +/- 11% from 231 +/- 13 to 140 +/- 25 mumol g-protein-1 (p less than 0.01). The degree of suppression of [14C]acetate incorporation into cholesterol in normal mononuclear cells by diabetic patients' LDL increased from 32.1 +/- 4.0% to 48.8 +/- 2.5% (p less than 0.001) following simvastatin. The activity of acyl coenzyme A:cholesterol-0-acyltransferase (ACAT) increased significantly by 55 +/- 18% (p less than 0.05) after treatment. Cholesterol synthesis in patients' mononuclear cells correlated positively (r = 0.66, p less than 0.05) with the esterified/free cholesterol ratio of their LDL, while suppression of cholesterol synthesis by patients' LDL correlated negatively (r = -0.64, p less than 0.05) with the esterified/free cholesterol ratio of the LDL following treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗
PubMed2004

Differential effects of simvastatin on mesangial cells.

BACKGROUND: Statins are increasingly recognized as mediators of direct cellular effects independent of their lipid lowering capacity. Therefore, the time and concentration dependence of various statin-mediated cellular alterations was compared in renal mesangial cells. METHODS: The effects of statins on cell proliferation, gene expression, cytoskeletal alterations, apoptosis, and cytotoxicity were analyzed in cultured mesangial cells using standard techniques. RESULTS: Simvastatin and lovastatin decreased proliferation and cell number of rat mesangial cells concentration-dependently. Concurrently, the expression of the fibrogenic protein connective tissue growth factor (CTGF) was impaired and actin stress fibers, which are typical of mesangial cells in culture, became disassembled by simvastatin. A decrease of the posttranslational modification of RhoA by geranylgeranyl moieties was detected, supporting a role for RhoA as mediator of statin effects. Induction of apoptosis, determined by activation of caspase-3 and DNA fragmentation, and necrosis only occurred at later time points, when the morphology of the cells was strongly altered and the cells detached from the surface due to changes in the actin cytoskeleton. Basically, the same results were obtained with a human mesangial cell line. Furthermore, statin effects were mimicked by inhibition of the geranylgeranyltransferase. CONCLUSION: Most of the cellular effects of the lipophilic statins occurred within the same time and concentration range, suggesting a common molecular mechanism. Only apoptosis and necrosis were observed at later time points or with higher concentrations of simvastatin and thus seem to be secondary to the changes in gene expression and alterations of the actin cytoskeleton.

Actins↗
PubMed1990

Lens changes in matched normals and hyperlipidemic patients treated with simvastatin for 2 years.

Simvastatin, a potent blood lipid reducer, has been suspected of inducing cataract in dogs. Twenty-nine type II hyperlipidemic patients on simvastatin were followed over 2 years at half-year intervals. A parallel group of sex- and age-matched normolipidemics were followed over a half year. Patients and controls had similar nuclear and cortical lens opacities, and water clefts. Vacuole number did not differ significantly between right and left eyes, nor between nasal and temporal parts of the lenses. General vacuole index (total vacuole number in a patient) for left eyes was analysed further. Controls showed significantly higher indices than patients, for no obvious reason. Indices for controls increased significantly over the half-year test period, and among patients over each half-year interval. The speed of this increase did not differ significantly from that of the controls. Furthermore, the increase was judged to be clinically insignificant. No deleterious effect of simvastatin on the lens could be established.

Adult↗
PubMed1994

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors lovastatin and simvastatin inhibit in vitro development of Plasmodium falciparum and Babesia divergens in human erythrocytes.

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors lovastatin and simvastatin inhibit the in vitro intraerythrocytic development of Plasmodium falciparum and Babesia divergens, with concentrations inhibiting parasite growth by 50% in the ranges of 10 to 20 and 5 to 10 micrograms.ml-1, respectively. For P. falciparum, the 50% inhibitory concentrations were in the same range whatever the chloroquine susceptibility of the strains tested (strain F32/Tanzania [chloroquine susceptible] or FcB.1/Columbia [resistant]). The stage-dependent susceptibility of P. falciparum to simvastatin was studied by subjecting synchronized cultures to 6-h pulses of drug throughout the 48-h erythrocytic life cycle. The most important inhibitory effects were observed between the 12th and 30th hours of the cycle, corresponding to the trophozoite stage. This period precedes the S phase and the nuclear divisions. Parasites in the newly formed ring stage (time zero to the 6th hour of the cycle) and the schizont stage (30th to 48th hour of the cycle) were weakly or not susceptible to simvastatin pulses.

Animals↗
PubMed2005

Effect of simvastatin, an established lipid-lowering drug, on pulmonary Chlamydia pneumoniae infection in mice.

The effects of simvastatin treatment on Chlamydia pneumoniae lung infection, inflammation, and serum lipids in mouse model were studied. Simvastatin decreased viable chlamydial counts and increased inflammatory cell infiltrates in the lung tissue, suggesting that simvastatin treatment had both antichlamydial and immunomodulatory effects during an acute C. pneumoniae infection.

Animals↗
PubMed2004

Effects of atorvastatin and simvastatin on low-density lipoprotein subfraction profile, low-density lipoprotein oxidizability, and antibodies to oxidized low-density lipoprotein in relation to carotid intima media thickness in familial hypercholesterolemia.

BACKGROUND: Little is known about the effects of statins on the quality of circulating low-density lipoprotein (LDL) in relation to atherosclerosis progression. METHODS: In a double-blind, randomized trial of 325 patients with familial hypercholesterolemia (FH), we assessed the effects of high-dose atorvastatin (80 mg) and conventional-dose simvastatin (40 mg) on LDL subfraction profile (n = 289), LDL oxidizability (n = 121), and circulating autoantibodies to oxidized LDL (n = 220). Progression of atherosclerosis was measured by carotid intima media thickness (IMT) (n = 325). RESULTS: At baseline, the patients showed an intermediate LDL subfraction profile composed of three LDL subfractions (LDL1, LDL2, LDL3), with LDL2 as the predominant subfraction. A strong negative correlation was found between plasma triglycerides and the LDL subfraction profile (r = -.64, p = .000). Both plasma levels of triglycerides and small dense LDL3 correlated weakly with baseline IMT (r = .11, p = .04 and r = .15, p = .01, respectively; n = 289). No association was found between baseline IMT and oxidation parameters or circulating antibodies to oxidized LDL. Atorvastatin reduced triglycerides, LDL cholesterol, and all LDL subfractions to a greater extent than did simvastatin and led to regression of carotid IMT. However, LDL subfraction pattern and plasma levels of autoantibodies to oxidized LDL remained unchanged in both treatment groups, and LDL oxidizability increased minimally to a similar extent in both groups. Significant treatment differences were found for the rate of in vitro oxidation of LDL and the amount of dienes formed during in vitro oxidation of LDL, which both decreased more following atorvastatin than after simvastatin. CONCLUSION: Change of IMT after statin treatment was associated with baseline IMT (r = .41), LDL cholesterol (r = -.20), and the amount of dienes formed during in vitro oxidation of LOL (r = .28) but not with plasma levels of antibodies to oxidized LDL, in vitro LDL oxidizability, and LDL subfraction profile.

Anticholesteremic Agents↗
PubMed2005

The effect of simvastatin treatment on the amyloid precursor protein and brain cholesterol metabolism in patients with Alzheimer's disease.

During the last years, several clinical studies have been published trying to elucidate the effect of statin treatment on amyloid precursor protein (APP) processing and metabolism of brain cholesterol in Alzheimer's disease (AD) in humans. We present an open biochemical study where 19 patients with AD have been treated with simvastatin (20 mg/day) for 12 months. The aim was to further investigate the effect of simvastatin treatment on cerebrospinal fluid (CSF) biomarkers of APP processing, AD biomarkers as total tau and tau phosphorylated at threonine 181, brain cholesterol metabolism as well as on cognitive decline in patients with AD. Despite biochemical data suggesting that treatment with 20 mg/day of simvastatin for 12 months does affect the brain cholesterol metabolism, we did not find any change in CSF or plasma levels of beta-amyloid (Abeta)(1-42). However, by analysis of APP isoforms, we found that statin treatment may favor the nonamyloidogenic pathway of APP processing. The relevance and mechanism between statin treatment and AD has to be further elucidated by using statins of different lipophility in different dosages over a longer period of time.

Aged↗
PubMed2005

Effects of simvastatin on oxidative stress in streptozotocin-induced diabetic rats: a role for glomeruli protection.

AIMS: To study the effects of simvastatin on oxidative stress in rats with early stage diabetic nephropathy. METHODS: 60 male Sprague-Dawley rats were divided into three groups: control group (CN), streptozotocin (STZ)-induced diabetic rats group (DM) and STZ-induced diabetic rats group treated with simvastatin (DM+S). The following parameters were measured at weeks 6 and 12 in similar rats chosen randomly from each group: body and kidney weight, 24-hour urinary albumin excretion (UAE), biochemical indexes including blood glucose (GLU), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), serum creatinine (SCr), antioxidant enzymes including superoxide dismutase (SOD), glutathione S-transferase (GST), catalase (CAT) in plasma, lipid peroxidation production as malondialdehyde in plasma (MDAp) and erythrocytes (MDAe), morphology parameters such as glomerular volume (GV) and mesangial area/total glomerular area (M/T). RESULTS: At weeks 6 and 12, GLU and kidney weight to body weight ratio were notably increased in both of the diabetic groups compared with those in the CN group without significant differences between the two diabetic groups. There were no significant differences of SCr, LDL, HDL and TG among all groups within all the experimental time. MDAp and MDAe were significantly increased in both of the diabetic groups, especially at week 12, while SOD, GST and CAT were significantly decreased compared with those in the CN group. At week 12, GV, M/T and UAE were also increased in the two diabetic groups. However, in the DM+S group, changes of lipid peroxidation production, antioxidant enzymes, UAE and GV were less pronounced than those in the DM group. Pearson's correlation analysis and regression analysis shown that MDAp was increased while SOD, GST and CAT in plasma were decreased with elevation of UAE, GV and M/T. CONCLUSION: Increased lipid peroxidation and decreased antioxidant enzymes in plasma may play a role in the progression of diabetic nephropathy. Simvastatin may ameliorate these changes to protect kidney from oxidative lesion in diabetes even in the absence of lipid abnormalities.

Albuminuria↗