document: oxidative stress can be described as an imbalance between the production of free radicals and antioxidant defence . over the last decades , 
   it has become amply evident that oxidative stress , usually in the form of reactive oxygen species ( ros ) , is a critical pathogenic factor in the development of several systemic diseases [ 1 , 2 ] . 
   therefore , inhibition of ros formation , scavenging of ros , or interfering with ros pathogenic signaling pathways might be the potential ways to protect against oxidative stress - induced ailments . 
   propofol ( 2,6-diisopropylphenol ) ( figure 1 ) , a highly lipid - soluble anaesthetic , is widely used for induction and maintenance of general anaesthesia . 
   propofol ameliorates oxidative injury in several organs , including the heart , lungs , brain , liver , and testis . 
   propofol is chemically similar to the endogenous antioxidant -tocopherol ( vitamin e ) and , theoretically , it should have similar properties . 
   it is not surprising therefore that many studies have demonstrated antioxidant effects of propofol in vitro [ 1012 ] and in vivo . 
   propofol has also been shown to elicit antiapoptotic effect in human umbilical vein endothelial cells by acting as an antioxidant . to the best of our knowledge , 
   the effects of propofol at high doses on the lipid profile , cardiovascular marker enzymes , and enzymatic and nonenzymatic antioxidant indices in rodents have not been determined . 
   propofol also called disoprivan by astrazeneca ( switzerland ) used for this study was obtained from one of the coauthors who is an anaesthetist ( dr . olugbenga akinwonmi of the department of anaesthesia , university college hospital , ibadan , nigeria ) . 
   glutathione , hydrogen peroxide , 5 ,  5-dithios - bis-2-nitrobenzoic acid ( dntb ) , and epinephrine were purchased from sigma chemical co. , saint louis , mo , usa . other chemicals were of analytical grade and purest quality available . 
   inbred male wistar rats weighing between 200 and 220  g were purchased from the central animal house located in the department of physiology , university of ibadan , nigeria . 
   the animals were kept in well - ventilated cages at room temperature ( 2830c ) , and maintained on laboratory chow ( ladokun feeds , ibadan , nigeria ) and water ad libitum . 
   rats handling and treatments protocol conforms to the guidelines of the faculty of basic medical sciences , university of ibadan animals ' ethical committee as well as the national institute of health ( nih publication 85 - 23 , 1985 ) for laboratory animals ' care and use . 
   twenty - one male albino rats ( wistar strain ) were randomly distributed into three groups of seven animals each . 
   the first group served as the control and was given corn oil ( vehicle for the drug ) . 
   the second group received propofol at a dose of 2  mg / kg body weight ( equivalent of human therapeutic dose ) , and the third group received propofol at a dose of 4  mg / kg body weight ( twice therapeutic dose ) . 
   propofol was prepared with corn oil and was administered intraperitoneally three times in a week for four consecutive weeks . 
   twenty - four hours after the last dose of the drug , the animals in each group were sacrificed by cervical dislocation , and blood was collected from the inferior vena cava of the heart into plain centrifuge tube . 
   blood was allowed to stand for 1  h and was then centrifuged at 3000  g for 15  min in a bench centrifuge to obtain serum . 
   the serum samples were used for the analysis of biochemical indices and lipid profile of the animals .   liver and kidney from the animals were quickly removed and washed in ice - cold 1.15% kcl solution , dried , and weighed . 
   the tissues were homogenized in 4 volumes of 50  mm phosphate buffer , ph 7.4 , and centrifuged at 10,000  g for 15  min to obtain postmitochondrial fraction ( pmf ) of the liver and kidney , which were used for assay of the antioxidant parameters . 
   protein levels in the samples were assayed by the method of lowry et al .   using bovine serum albumin as standard . 
   the activities of serum alanine and aspartate aminotransferases ( alt and ast ) were assayed by the combined methods of mohun and cook   and , reitman and frankel . 
   pmf lipid peroxidation levels were assayed by the reaction between 2-thiobarbituric acid and malondialdehyde , an end product of lipid peroxides , as described by walls et al . . 
   pmf - reduced glutathione ( gsh ) level was assayed by measuring the rate of formation of chromophoric product in a reaction between 5,5-dinitrobis-2-nitrobenzoic acid and free sulphydryl groups at 412  nm as described by moron et al . . 
   pmf superoxide dismutase ( sod ) activity was measured by the nitro blue tetrazolium reduction method of mccord and fridovich . 
   pmf catalase ( cat ) activity was assayed spectrophotometrically by measuring the rate of decomposition of hydrogen peroxide at 240  nm as described by aebi   while glutathione - s - transferase ( gst ) activity was determined by the method of habig et al . . 
   the activities of serum creatinine phosphokinase ( ck - mb ) were estimated using immune - inhibition kinetic assay according to the method of okinaka et al . . 
   lactate dehydrogenase ( ldh ) activities in the serum were determined according to the method of zimmerman and weinstein . 
   the total bilirubin levels were assayed by the method of rutkowski and debaare   while serum creatinine and urea were estimated by the methods of  jaffe   and talke and schubert , respectively . 
   serumtriglyceride ( tg ) and total cholesterol ( tc ) levels were assayed using commercial diagnostic kits ( randox ) . for the determination of hdl level , vldl and 
   after centrifugation , the supernatant containing the hdl fraction was assayed for cholesterol using randox diagnostic kit . 
   ldl - cholesterol ( ldl - c ) was calculated using the formula of friedewald et al . . 
   data were analyzed using one - way anova followed by the post - hoc duncan 's multiple - range test for analysis of biochemical data using spss version 10.0 ( spss inc . 
   reactive oxygen species ( ros ) attack cellular components containing polyunsaturated fatty acid residues of phospholipids , which are sensitive to oxidation . 
   the peroxyl radicals formed by the attack can be rearranged via a cyclization reaction to endoperoxides which are precursors of mda , which subsequently lead to lipid peroxidation . 
   lipid peroxidation ( lpo ) has been implicated in the pathogenesis of several injuries by many toxicants and may be responsible for cell membrane alterations which can result into enzymes leakage in animals . in this study , 
   administration of propofol did not significantly ( p > 0.05 ) affect the levels of serum and renal and hepatic mda in the rats ( table 3 ) , indicating that the metabolism of propofol may not be linked to the generation of free radicals within the animal tissues . this observation is not strange since propofol has a very active phenolic ring within its structure which resembles -tocopherol and may release electron to terminate free radical reactions during its metabolism in the rats . 
   however , table 2 shows that the levels of serum total cholesterol , triglycerides , and ldl - cholesterol were significantly ( p < 0.05 ) increased following administration of propofol . 
   precisely , propofol at 2 and 4  mg / kg increased the levels of serum total cholesterol by 74% and 55% , triglycerides by 97% and 115% , and ldl - cholesterol by 45% and 73% , respectively . 
   in addition , propofol at both doses significantly ( p < 0.05 ) decreased the levels of serum hdl - cholesterol in the rats by 41% and 54% . 
   lipids are a heterogeneous group containing active metabolic substances that play an important role in the pathogenesis of drugs - induced liver disease . 
   the most common lipid abnormalities during drug toxicity are hypercholesterolemia and hypertriglyceridemia , which was confirmed in this study . 
   also , in propofol - treated rats , ldl - c was remarkably increased in the serum , while hdl - c was found to be reduced . 
   the increased cholesterol level during propofol administration may be linked to increase in alpha - hydroxyl methyl glutaryl coa reductase activity , which is the rate limiting step in cholesterol biosynthesis . 
   likewise , the increased triglycerides levels may be due to the increased availability of free fatty acid , glycerophosphates , decreased triglycerides lipase activity , or decreased fatty oxidation . in the present study 
   propofol at 2 and 4  mg / kg increased the levels of hepatic gsh by 42% and 37% , respectively , when compared to the control ( table 3 ) . 
   in addition , propofol at 2 and 4  mg / kg dose dependently and significantly ( p < 0.05 ) increased the activities of hepatic glutathione peroxidase by 1.9 and 2.1 folds and glutathione - s - transferase by 2.3 and 2.4 folds , respectively ( figure 3 ) . 
   however , there were no significant ( p > 0.05 ) differences in the activities of renal and hepatic sod and cat of propofol - treated rats relative to controls ( figure 2 ) . 
   reduced glutathione acts as a free radical scavenger and regenerator of alpha - tocopherol , and it plays a significant role in sustaining protein sulfhydryl groups in proteins and other key molecules . 
   in addition , gsh may act as an essential cofactor for antioxidant enzymes , especially gpx and gst . 
   the increase in the levels of hepatic gsh observed in this study may result in increased detoxifying and antioxidant capability of the liver . 
   the gst and gpx are groups of multifunctional proteins that play a central role in the detoxification of electrophilic chemicals and the hepatic removal of potentially harmful hydrophobic compounds from blood 
   . the increased activities of hepatic gst and gpx observed may partly be due to increase in their substrate or induction of de novo synthesis of the enzymes . 
   importantly , propofol increased the levels of gsh and activities of gst and gpx in the liver and thus enhancing the detoxifying potential of the animals . 
   the cardiotoxicity of xenobiotics can be evaluated using the serum activities of marker enzymes especially ldh and ck - mb , which are distributed throughout the body and have isoenzymes that are recognized as markers for muscle and heart lesion . 
   results from this study showed that propofol at 2 and 4  mg / kg significantly ( p < 0.05 ) increased the activities of serum ldh by 1.7 and 1.8 folds and ck - mb by 2.0 and 2.1 folds , respectively ( figure 4 ) . in their studies , hayden and tyagi   linked the increase in serum ck - mb and ldh of diabetic rats to cardiac muscular damage caused by the disease . 
   similarly , wiernsperger   stated that the activities of serum ck - mb and ldh are a measure of the state of necrosis in cardiac tissues . in view of the observed increase in ck - mb and ldh activities in propofol - treated rats 
   administration of propofol at 2 and 4  mg / kg significantly ( p < 0.05 ) increased the level of total bilirubin by 52% and 53% , respectively , while serum urea , alanine and aspartate aminotransferases ( alt and ast ) , and creatinine levels were insignificantly ( p > 0.05 ) affected ( table 1 ) . 
   it is established that ast can be found in the liver , cardiac muscle , skeletal muscle , kidney , brain , pancreas , lungs , leukocytes , and erythrocytes , whereas alt is predominantly present in the liver . 
   also , serum creatinine and urea levels are the sensitive and reliable biochemical indices for evaluation of renal function in animal models . 
   the insignificant effects of propofol on the levels of ast , alt , and creatinine indicate that the drug has no adverse effect on the hepatic and renal tissues of the rats . 
   our data showed that propofol promotes the antioxidant status of the rats by increasing the levels of reduced glutathione and gsh - dependent enzymes . 
   however , propofol elicited a detrimental effect on the lipid profile resulting in hypercholesterolemia which subsequently leads to abnormally high activities of serum creatinine phosphokinase and lactate dehydrogenase in the rats . 
   the study , therefore , suggests that the use of propofol in patients with cardiovascular or lipid disorders should be carefully reviewed .
summary: in recent years , the activity of anaesthetic propofol on biological processes has been attracting attention . 
   the effect of propofol on biochemical indices in animals is unknown . in this study 
   , we examined the effects of propofol on lipid profile , antioxidant indices , and cardiovascular marker ( cvm ) enzymes in rats . 
   the study consists of three groups of seven rats each . 
   group one received corn oil ( control ) while groups two and three received propofol ( doses of 2 and 4  mg / kg body weight , resp . ) . 
   results showed that administration of propofol caused a significant ( p < 0.05 ) and dose - dependent increase in the levels of total bilirubin . 
   propofol at 2 and 4  mg / kg increased the levels of serum total cholesterol by 74% and 55% , triglycerides by 97% and 115% , and ldl - c ( low - density lipoprotein - cholesterol ) by 45% and 73% , respectively , while hdl - c ( high - density lipoprotein - cholesterol ) decreased by 41% and 54% , respectively . 
   propofol significantly ( p < 0.05 ) increased the levels of the hepatic reduced glutathione ( gsh ) and activities of gsh - dependent enzymes . 
   propofol at 2 and 4  mg / kg increased the activities of cvm enzymes : lactate dehydrogenase by 1.7 and 1.8 folds and creatinine phosphokinase by 2.0 and 2.1 folds , respectively . 
   taken together , propofol increased the levels of gsh and gsh - dependent enzymes but adversely affected the lipid profile of the rats .