document: peripheral arterial disease ( pad ) commonly results from progressive narrowing of arteries in the lower extremities due to atherosclerosis . 
   it has become evident that pad is an important predictor of substantial coronary and cerebral vascular risk [ 2 , 3 ] . 
   the most common symptomatic manifestation of mild to moderate atherosclerotic pad is intermittent claudication , observed in ~5% of individuals older than 60 years [ 5 , 6 ] . 
   several studies , using the ankle - brachial index , have revealed that the presence of pad , even when being asymptomatic and in patients with no history of other cardiovascular diseases , is a marker of greatly increased cardiovascular morbidity and mortality [ 7 , 8 ] . 
   oxidative stress , through the extra generation of reactive oxygen species ( ros ) , is also involved in the development and progression of pad . 
   moreover , risk factors associated with pad , similar to those for coronary heart disease , include high blood concentrations of total cholesterol and ldl - cholesterol . 
   inhibitors of 3-hydroxy-3-methylglutaryl coenzyme a ( hmg - coa ) reductase , called statins , are well - known lipid - lowering drugs . 
   statins not only reduce lipid levels , but they also have important pleiotropic effects , improving endothelial function , reducing oxidative stress , affecting the lipid metabolism enzyme activities , and so forth [ 1214 ] . 
   three main reasons have been suggested for initiating statin therapy for patients with pad of the lower limbs : ( 1 ) prevention of coronary heart disease ; ( 2 ) treatment of lower extremity peripheral arterial disease ; and ( 3 ) perioperative treatment of patients with peripheral arterial disease . 
   although several trials have shown that treatment with statins is associated with a reduction in coronary heart disease events , such as stroke [ 18 , 19 ] and mortality [ 2023 ] , most of these trials did not specifically address the treatment of patients with pad . 
   the aim of the present study , therefore , was to evaluate lipid peroxidation parameters and total antioxidant capacity in the serum of patients with pad before surgery as well as 35 days and 710 days after surgery . 
   we also compared these parameters with those in a group of patients receiving simvastatin therapy . 
   the study group consisted of pad patients , treated either surgically ( group i , n = 35 males , aged 61  8 years ) or pharmacologically ( group ii , n = 18 males , aged 62    7 years ) in the department of general and vascular surgery at the poznan university of medical sciences . patients included in group i were admitted for surgical treatment ( implantation of an aortobifemoral bypass graft ) . 
   they were diagnosed by measurement of the ankle brachial index ( abi ) and arteriography of the lower limbs , and were clinically stable without any accompanying diseases . 
   the patients treated surgically had shown critical ischemia ( abi less than 0.90 , rest pain , ulcer or necrosis of the lower limbs , and ankle pressure  50  mmhg ) . 
   blood samples were collected without anticoagulant , in the fasting state , before surgery as well as 35 days and 710 days after surgical treatment . 
   group ii had been receiving statin therapy , with 20  mg of simvastatin daily , for at least 3 months . 
   the study protocol was approved by the ethics committee of poznan university of medical sciences , and the subjects were fully informed and gave their written consent . 
   all the reagents were of analytical grade of purity ( sigma - aldrich , st . 
   spectrophotometric measurements were carried out on sp-8001 uv / visible spectrophotometer ( metertech inc . , taiwan ) . 
   the subjects ' lipid profile ( total cholesterol , hdl cholesterol , ldl cholesterol , and triglycerides ) , glucose , uric acid , apolipoproteins ( apo a - i , apo b ) and fibrinogen concentrations in serum were measured by standard laboratory procedures , using the roche cobas 6000 analyzer system , dade behring bn ii system , and the sysmex ca-500 series system . the total antioxidant potential ( capacity ) of serum 
   was determined by ferric reducing antioxidant power ( frap ) assay according to the benzie and strain method , based on the reduction of ferric ion fe(iii ) to ferrous ion fe(ii ) at a low ph . 
   this method measures the change in absorbance at 593  nm owing to the formation of a blue - colored fe(ii)-tripyridyltriazine complex from the colorless oxidized fe(iii ) form , by the action of electron - donating antioxidants . 
   lipid peroxidation was measured by estimation of both lipid hydroperoxides ( loohs ) and malondialdehyde ( mda ) concentrations by the sodergren method   and ohkawa et al . 
   the concentration of thiol ( -sh ) groups was determined according to the hu method . 
   ceruloplasmin , in the presence of o - dianisidine hydrochloride in an acidic solution ( ph 5.0 ) , forms a stable yellow - brownish product . 
   absorbance was measured at 540  nm and ceruloplasmin activity was expressed in u / l ( mol of oxidized substrate in 1  ml of serum in 1  min ) . 
   the paired student 's t - test ( to compare the values before and after surgery ) , the two - tailed unpaired t - test ( to compare group i and group ii ) , and the f - test were used for statistical analysis of the data .   the mean changes (  ) in lipid peroxidation parameters and antioxidant capacity , that is , 35 days ( 1 ) and 710 days ( 2 ) after surgery , in relation to the values obtained before surgery , were calculated . 
   pearson 's correlation coefficients r1 and r2 were computed for the results found before surgery and the changes observed during treatment ( 1 , 2 ) . 
   as shown in table 1 , generally , the clinical parameters of the two groups of patients included in this study did not differ significantly . 
   however , the concentrations of total cholesterol and ldl cholesterol were found to be significantly higher in group i before surgery than those in group ii on simvastatin therapy . 
   group i patients before surgery had enhanced oxidative stress , as demonstrated by elevated serum levels of mda , in comparison to those treated pharmacologically . 
   we did not observe any significant decrease in looh and mda concentrations in group i patients after surgery ( figures 1 and 2 ) .   the total antioxidant capacity ( expressed as frap ) and -sh group concentrations in the serum of patients on statin therapy and in those before surgery were similar ( figures 3 and 4 ) . 
   however , a decrease was observed in frap level 35 days after surgery , and 710 days after surgery , it was significantly lower in comparison to the values before surgery and on simvastatin therapy . 
   moreover , thiol group concentrations 35 days postoperatively were lower than those before surgery and 710 days after surgery and were lower than those in patients treated with simvastatin ( figure 4 ) . a significant difference in the oxidase activity of ceruloplasmin between group ii and group i before surgery was observed . 
   its oxidase activity in serum was higher in group ii and 710 days after surgery in group i , in comparison to the values before and 35 days after surgery ( figure 5 ) . 
   in addition , all the studied parameters ( looh , mda , frap , -sh groups , and ceruloplasmin ) in group i patients before surgery were significantly correlated with mean changes at 35 days ( 1 ) and/or 710 days ( 2 ) after surgery ( table 2 ) . 
   oxidized ldl is a biochemical marker of oxidative damage and has atherogenic effects , including the stimulation of foam cell formation and activation of the inflammatory process in the vascular wall . 
   the findings of the present study are broadly consistent with the hypothesis that lipid peroxidation may be one mechanism through which several risk factors may promote pad . 
   , we observed an increased mda level in the patients before surgery , which suggests that they were in a state of high oxidative stress . at neutral ph , mda exists as a low reactive enolate anion , but it is still toxic and may damage many biologically important molecules . 
   determination of the lipid peroxidation product mda in pad is important because , as was shown earlier , mda damages collagen by forming transverse intramolecular bonds that cause rigidity of blood vessels . 
   in addition , modification of native ldl by mda causes the accumulation of cholesteryl esters within the cell in which the atherosclerotic reaction takes place . 
   several trials have shown that statin therapy relieves symptoms and improves function in patients with lower extremity pad [ 32 , 33 ] . 
   mda concentrations in the serum of the patients treated with simvastatin were lower than those in group i patients before surgery . since pad patients are usually undertreated with regard to the use of lipid - lowering agents , compared to patients with coronary heart disease , our results provide strong support for the efficacy of statin therapy in pad . 
   human cells and tissues contain many antioxidant enzyme systems and nonenzymatic antioxidants , which protect against the action of toxic free radicals . 
   the frap assay used here is a useful indicator of the body 's antioxidant status , which determines the level of non - enzymatic antioxidants , such as uric acid , ascorbic acid , -tocopherol , and some protein - containing -sh groups . 
   an increase in frap level in the patients before surgical treatment is consistent with similar results obtained by gawron et al .   in a group of patients with coronary heart disease and by lantos et al .   in patients with hypertension . 
   an increased antioxidant capacity of serum seems to be response to an increase in the concentration of lipid peroxidation products . 
   the reduction in frap level observed in our group i patients 35 and 710 days after surgery can be partly explained by a decrease in their serum antioxidant status and an increase in serum oxidant levels following surgery , as indicated by the negative correlations found ( table 2 ) . in their study , girona et al . 
   they showed that simvastatin therapy increases the resistance of both ldl and hdl to oxidation . 
   in addition , simvastatin inhibits the ability of activated macrophages to oxidize ldl in vitro in a dose - dependent manner . 
   a similar effect has been shown for other statins , such as atorvastatin , which reduces ldl levels and hdl oxidation and protects paraoxonase  an enzyme bound to hdl .   with regard to frap in our study , simvastatin therapy ( 20  mg daily ) did not influence the total antioxidant potential 
   . however , shin et al .   found a significant increase in antioxidant ability in their group of hypercholesterolemic patients treated with 40  mg simvastatin daily . 
   they suggested the possibility of a dose - dependent effect of simvastatin on plasma antioxidant status . 
   this could be the reason why we did not detect any effect of simvastatin on frap in our study . 
   glutathione and other proteins , such as albumin , are an important part of serum antioxidant activity against free radicals . 
   the thiol groups react with peroxide radicals in the first stage of the oxidation reaction and also act in the lag phase , which is an accepted marker of serum oxidizability . in our group of patients with pad , 
   the decrease in thiol group concentrations , observed 35 days after surgery , followed by an increase 710 days after surgery , may be explained by oxidative stress intensification in reperfusion and by the actions of -sh groups , leading to their reduction . 
   furthermore , a decrease in both lag phase and albumin level has also been reported in the serum of patients with aneurysmal or arterial occlusive disease . 
   some studies have confirmed that ceruloplasmin is an independent risk factor for cardiovascular disease [ 43 , 44 ] . 
   authors of that study suggest that increased ceruloplasmin activity is related to the acute phase response to inflammation and necrosis in atherosclerosis obliterans and results from increased ros production , mostly of superoxide radicals . 
   therefore , the preferential oxidative destruction of thiol groups can explain the greater susceptibility of ceruloplasmin to oxidative stress . 
   recent data show that statins may reduce oxidative stress   by decreasing the generation of ros , thereby synergizing with the biological effects of antioxidants . 
   the results of our study show that ceruloplasmin activity was influenced by both simvastatin therapy and surgical treatment , but only 710 days postoperatively . in our opinion , simvastatin may be implicated in antioxidant properties of ceruloplasmin , as reflected by the increase in its activity in men on simvastatin therapy . 
   several in vitro studies have indicated that ceruloplasmin is a potent catalyst of ldl oxidation and that has been attributed to the presence of a reduced copper atom on its surface . 
   ros dissociate copper from ceruloplasmin and therefore can markedly alter its structure and function , which could explain the initial lack of differences in its activity 35 days after surgery . in view of the escalating prevalence of pad in our aging population , 
   further studies are needed to clarify precisely not only the mechanisms involved but the relative importance of the lipid - related and nonlipid - related effects of statins as well . 
   results of this study show diverse oxidative state responses to surgical treatment and confirm the beneficial effects of statin therapy in pad .
summary: the various risk factors for peripheral arterial disease ( pad ) are almost identical to those for atherosclerosis and include abnormal levels of lipids or lipoproteins . lipid peroxidation parameters and total antioxidant capacity in the serum of male patients with pad before surgery as well as 
   35 days and 710 days after surgery were measured . 
   we also compared these parameters with those in a group of patients receiving simvastatin therapy . 
   concentrations of lipid hydroperoxides ( loohs ) and malondialdehyde , the total antioxidant capacity ( assessed by ferric reducing antioxidant power assay ) , concentration of thiol ( -sh ) groups , and ceruloplasmin activity were determined spectrophotometrically in pad patients treated surgically ( group i ) or pharmacologically ( group ii ) . 
   the patients before surgical treatment had significantly higher concentrations of malondialdehyde but lower ceruloplasmin activity than those observed in group ii , treated with simvastatin . 
   no significant differences before surgery in ferric reducing antioxidant power or thiol concentrations were found between the two groups . 
   however , in group i , both ferric reducing antioxidant power and thiol group concentrations decreased 35 days postoperatively , and ceruloplasmin activity increased 710 days after surgical treatment . 
   the presented results demonstrate diverse oxidative stress responses to surgical treatment and confirm the beneficial effects of statin therapy in pad .