Nimodipine attenuates lipid peroxidation during the acute phase of head trauma in rats

Oxygen free radical-mediated lipid peroxidation is one of the major mechanisms of secondary damage in traumatic brain injury. We assessed the effects of nimodipine on lipid peroxidation 1 h after head trauma in rats. Nimodipine (1.5 μg/kg IV bolus injection) was given immediately after head trauma by either the carotid artery or the jugular vein. Placebo treated rats received saline by the same routes. Control rats received head trauma only. Sham-operated rats were the group without head trauma. Malondialdehyde (MDA), which is the end product of lipid peroxidation, was measured as an indicator of oxygen free radical formation in the brain tissue. The mean values for MDA in sham operated rats were 92.4±4.9 nanomoles/gram wet weight (nmol/gww) of brain tissue. In the control group, MDA content of the brain tissue was 120.8±9.4 nmol/gww. In placebo treated rats, the results were similar. In the groups receiving nimodipine via carotid artery or jugular vein, the mean values were 101.1±6.9 and 106.5±6.0 nmol/gww, respectively. These results indicate that nimodipine caused a significant decrease in lipid peroxidation when given in the acute phase of head trauma in rats. This occurred regardless of the route of injection. Received: 16 August 1999 / Accepted: 27 December 1999     

Moderate hypothermia prevents brain stem oxidative stress injury after hemorrhagic shock

BACKGROUND: The purpose of this study was to investigate the effects of temperature on oxidative stress in brain stem tissue induced by hemorrhagic shock. We researched the hemorrhagic oxidative stress at various core temperatures using reduced glutathione (GSH) levels and thiobarbituric acid-reactive substances (TBARS) as markers of lipid peroxidation in brain stem homogenate. METHODS: Forty rats were divided into four groups, of which one constituted the nonbleeding normothermia control group. In all of the three study groups, 40% of estimated blood volume was removed while they were being held at normothermia, mild hypothermia (32 degrees C), or moderate hypothermia (28 degrees C). Parameters including mean arterial pressure, rectal temperature, and heart and breathing rates were monitored and recorded during the procedures. After an hour at shock state, tissue samples were removed by craniectomy. RESULTS: The tissue levels of TBARS increased significantly in normothermic and mild hypothermic hemorrhagic shock groups (10.74 nmol/g and 8.26 nmol/g) as compared with the control group (3.50 nmol/g) (p < 0.001). However, the tissue TBARS level in the moderate hypothermia group was only minimally increased (4.53 nmol/g). GSH showed a slight decrease in normothermic and mild hypothermic bleeding rats, and were unchanged in the moderate hypothermic rats. CONCLUSION: Moderate systemic hypothermia (28 degrees C) appears to protect brain stem tissue from oxidative stress during severe hemorrhagic shock in rats, as indicated by insignificant change in tissue TBARS and GSH concentrations. These results suggest antioxidant protective effects of moderate systemic hypothermia in metabolically active brain stem tissue during hemorrhagic shock. Similar effects in humans remain to be studied.     

Experimental treatment of smoke inhalation injury with anti-lipid peroxidation agents

The role of oxygen free radicals in the mechanism of lung damage after smoke inhalation injury was investigated. 42 dogs were used and equally divided into control and treated group. In treated group, a comprehensive anti-lipid peroxidation treatment including Ginseng-ophiopgon, hydrocortisone sodium succinate, Vit. C and E were used at 5 min, 6 hr, and 12 hr postinjury. SOD activity in blood, hypoxanthine, xanthine, uric acid, MDA and SCL in plasma, C2H6 and C2H4 in exhaled breath of dogs after smoke inhalation injury were measured. In addition, blood gas analysis and EVLW were determined to evaluate the lung damage. The results demonstrated that the injured dogs suffered from lung edema and acute lung dysfunction. MDA, SCL in plasma and C2H6, C2H4 in exhaled breath increased markedly, reaching their first peaks at 30 min. and second peaks at 24-72 hours postinjury. The values revealing in first peak in treated group were lower than that in control group. The increase of SOD activity, however, was higher in treated group than in control group. Changes of oxygen free radicals and lipid peroxidation were closely related to lung damage and respiratory dysfunction. These data showed that in early postinjury period increase of oxygen free radicals and excessive lipid peroxidation existed in lungs of dogs. And in treated group, anti-lipid peroxidation activity was increased and lipid peroxidation was inhibited. Lung damage was improved obviously. It was believed that the first peak of changes in oxygen free radicals and lipid peroxidation was related to the onset of early pulmonary damage and the stress response, and the second peak to the development of pulmonary infection and lung repaired.     

Postganglionic sympathetic nerve activity in halothane–anaesthetized rats during controlled and spontaneous ventilation

The aim of the study was to compare the effect of halothane anaesthesia on sympathetic nerve discharge in mechanically normoventilated and spontaneously breathing rats. Renal sympathetic nerve activity (rSNA), mean arterial pressure (MAP) and heart rate (HR) were measured in the conscious state and at the inspiratory halothane concentrations of 0.6%, 1.2% and 2.4% in one mechanically normoventilated and one spontaneously breathing group, while a third group was subjected to controlled hypoventilation at 1.2% halothane concentration. Halothane in blood was determined in two separate groups at 1.2%. In an additional group of spontaneously breathing rats, PaCO2 was analysed during consciousness and the halothane concentrations of 1.2% and 2.4%. There was a pronounced decrease in rSNA, MAP and HR at all levels of anaesthesia in the mechanically ventilated rats. However, rSNA, HR and MAP were significantly higher in the spontaneously breathing rats at increasing levels of halothane anaesthesia. Controlled hypoventilation at 1.2% halothane increased the variables significantly. In spontaneously breathing animals, PaCO2 increased significantly during the halothane exposure. The concentration of halothane in blood was significantly higher in the spontaneously breathing rats. Thus, the halothane-induced respiratory depression in the spontaneously breathing rats preserved rSNA during halothane anaesthesia, possibly via CO2-mediated chemoreceptor stimulation.     

Changes of free iron contents and its correlation with lipid peroxidation after experimental spinal cord injury

Objective: To observe the dynamic changes of free iron contents and its relationship to the changes of lipid peroxidation after experimental spinal cord injury (SCI). Methods: Sprague Dawley rats were randomly divided into three groups: Group A (n=6) received no operation; Group B (n=48) received only laminectomy (sham) ; and Group C (n=48) received both laminectomy and traumatic injury ( SCI model). The SCI animal models were made by using an modified Alien‘s weight-drop device (50 g. cm) on T12. Rats were sacrificed at 0.5, 1, 3, 6, 12, 24 hours after injury. The levels of free iron involved in spinal cord segments at different time points were measured by blcomycin assay. The malondialdehyde (MDA) was also measured by the thiobarbituric acid (TBA). Results: After SCI in Group C, the level of free iron showed a significant increase at 0.5 hour compared to Groups B and A, restored to the control level at 6 h; the level of MDA was increased at 0.5 hour, peaked at 3 hours, returned to the control level at 12 hours; the concentrations of free iron and lipid peroxidation in injured rats were significantly and positively correlated at 0.5-3 hours. Conclusions: After SCI the levels of free iron are increased quickly and might be a major contributor to lipid peroxidation in injured spinal cord.     

Iron and oxidative stress in renal insufficiency

BACKGROUND/AIMS: Iron (Fe) can cause tissue injury and oxidative stress by catalyzing hydroxyl radical production and lipid peroxidation. Intravenous (i.v.) Fe preparations are routinely administered to treat anemia in patients with chronic renal failure (CRF), a condition marked by oxidative stress and inflammation. In an earlier study, we showed that iron overload augments oxidative stress in the cardiovascular tissues of CRF rats. This study was designed to expand these observations to other major organs. METHODS: Rats were randomized into CRF (5/6 nephrectomized) and sham-operated control (CTL) groups. Each group was subdivided into Fe-loaded (single i.v. injection of iron dextran complex, 0.5 g/kg) and placebo-treated subgroups. After 13 weeks, systolic blood pressure, blood hemoglobin (Hb), plasma Fe concentration, lipid peroxidation products, superoxide generating enzyme, NAD(P)H oxidase, and antioxidant enzymes were determined. RESULTS: Systolic blood pressure was equally elevated and creatinine clearance was equally reduced in both CRF groups. Fe administration raised Hb, serum Fe and transferrin saturation in both CRF and CTL groups. The plasma concentration of lipid peroxidation product, malondialdehyde, was increased by Fe injection in CRF rats but not the control group. Renal tissue abundance of gp91(phox) subunit of NAD(P)H oxidase was elevated in the untreated CRF group and was partially reduced in the iron dextran-treated CRF group. Tissue abundance of the antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) were decreased in both untreated and iron dextran-treated CRF groups. CONCLUSION: CRF resulted in marked SOD, CAT and GPX deficiencies. A single i.v. administration of iron dextran in rats with CRF induced oxidative stress as measured by increased lipid peroxidation products and decreases in antioxidant enzymes.     

The novel 21-aminosteroid U74006F attenuates cerebral edema and improves survival after brain injury in the rat.

The present study evaluated the effect of the nonglucocorticoid 21-aminosteroid U74006F, an inhibitor of iron-dependent lipid peroxidation, on the development of regional cerebral edema after lateral fluid-percussion (FP) brain injury. Male Sprague-Dawley rats (n = 40) were anesthetized and subjected to FP brain injury of moderate severity centered over the left parietal cortex (2.5-2.6 atms). Fifteen minutes after brain injury, animals randomly received an i.v. bolus of either U74006F (3 mg/kg, n = 21) followed by a second bolus (3 mg/kg) at 3 hr or buffered sodium citrate vehicle (equal volume, n = 15). An additional group of 12 surgically prepared but uninjured animals served as preinjury controls. At 48 hr after injury, animals were sacrificed and brain tissue assayed for water content and regional cation concentrations. With the use of specific gravimetric techniques, no significant differences were observed in posttraumatic cerebral edema between drug- and control-treated animals. However, using wet weight/dry weight methodology, we found that administration of U74006F significantly reduced water content in the right hippocampus (contralateral to the site of injury) compared to saline-treated animals (p less than 0.05). U74006F also significantly prevented the postinjury increase in sodium concentrations in the ipsilateral hippocampus (p less than 0.05) and thalamus (p less than 0.03). Regional concentrations of potassium were unaltered after drug treatment. Administration of U74006F significantly reduced postinjury mortality, from 28% in control animals to zero in treated animals (p = 0.01). These results suggest that lipid peroxidation may be involved in the pathophysiological sequelae of brain injury and that 21-aminosteroids may be beneficial in the treatment of brain injury.     

吸入伤犬部分液体通气后血生化指标变化与动脉血氧分压的关系

目的　探讨部分液体通气对吸入性损伤的治疗作用。　方法　制作犬吸入性损伤模型 ,将氟碳缓慢注入肺内实施部分液体通气 ,分别于致伤前、致伤后 2h及部分液体通气治疗 6 0、90min时 ,抽血检测超氧化物歧化酶 (SOD)、丙二醛 (MDA)、一氧化氮 (NO)及动脉血氧分压 (PaO2 )的变化。　结果　与致伤前相比 ,致伤后 2h犬MDA、NO值明显升高 ,SOD、PaO2 值明显下降 (P <0 0 5 ) ;实施部分液体通气后 ,SOD、MDA、NO及PaO2 值基本恢复到伤前水平。　结论　部分液体通气可以提高氧分压 ,抗脂质过氧化 ,减少体内NO的生成 ,对吸入性损伤有一定的治疗作用     

Lipid peroxidation early after brain injury

The role of lipid peroxidation after brain injury is still not completely understood, and results of different studies have been equivocal. In this study, three proposed peroxidation markers were determined in patients early after isolated head injury and results compared to healthy controls. Malondialdehyde (MDA) and thiobarbituric acid-reactive substances (TBARS) were measured in plasma, and n-pentane was determined in patients' exhaled air. For MDA and TBARS no significant differences could be shown (0.267 vs. 0.358 ng/mL, and 0.896 vs. 0.814 ng/mL in patients vs. healthy volunteers, respectively). n-Pentane, however, was significantly increased in the expired air of patients (0.471 vs. 0.118 nmol/L in healthy volunteers). Similar results for n-pentane were obtained when only male patients and volunteers were considered (0.510 vs. 0.113 nmol/L). Stratification according to clinical outcome showed significantly higher values for n-pentane in male patients with poor outcome (0.656 nmol/L) in comparison with healthy male volunteers (0.113 nmol/L). No difference was found when patients were stratified according to the presence or absence of subarachnoid hemorrhage. It is concluded that, only in a sub-population of patients with brain injury, lipid-peroxidation is a crucial mechanism. n-Pentane seems to be a valuable marker to detect lipid peroxidation early after brain trauma. Malondialdehyde may be of value only later in the course of the disease. TBARS are not a specific marker and should therefore not be used.     

Effect of melatonin on burn-induced gastric mucosal injury in rats

We studied the effect of melatonin treatment on gastric mucosal damage induced by experimental burns and its possible relation to changes in gastric lipid peroxidation status. Melatonin was intraperitoneally applied immediately after third-degree burns over 30% of total body skin surface area of rats. Malondialdehyde (MDA), uric acid (UA) and sulphydril (SH) levels were determined in gastric mucosa and blood plasma and used as biomarkers of the oxidative stress. The results showed that the skin burn caused oxidative stress evidenced by accumulation of MDA and UA as well as the depletion of SHs in gastric mucosa. Plasma MDA concentrations were elevated, while plasma SH concentrations were decreased after burns. Melatonin (10 mg per kg body weight) protected gastric mucosa from oxidative damage by suppressing lipid peroxidation and activating the antioxidant defence. It may be hypothesised that melatonin restores the redox balance in the gastric mucosa and protects it from burn-induced oxidative injury. Melatonin has no significant influence on the concentrations of plasma MDA and antioxidants after burn; therefore, it should largely be considered as a limiting factor for tissue-damage.     

栀子提取液对重症胰腺炎大鼠过氧化损伤的影响

目的:探讨大鼠急性胰腺炎时的过氧化损伤以及栀子提取液对其影响.方法:SD大鼠造模后给予不同药物治疗,24h后采血测定淀粉酶、丙二醛、谷胱甘肽含量分组对比.结果:急性胰腺炎时血淀粉酶、丙二醛水平显著升高,谷胱甘肽水平显著降低.结论:急性胰腺炎时,栀子提取液能够降低丙二醛水平,升高谷胱甘肽水平,提示栀子对急性胰腺炎可发挥有益的影响.     

Alterations in phosphatidylcholine and phospholipase A2 of the renal tissue in gentamicin nephrotoxicity: comparative study with buthionine sulfoximine administered model]

We investigated to confirm the biochemical mechanisms of the hypothesis that lipid peroxidation participates in the pathogenesis of aminoglycoside-induced nephrotoxicity. Male Sprague-Dawley rats were injected with gentamicin (GM), 300mg/kg per day. Twenty-four hours after the injection the rats were killed and the renal cortex was processed for glutathione (GSH), malondialdehyde (MDA), phospholipase A2 (PLA2), phosphatidylcholine (PC), sphingomyelin (SPH) and phospholipids (PL). And we also studied the GSH reduced rats by buthionine sulfoximine (BSO) administration, to compare the biochemical differences with these parameters in two groups. GM induced a significant decrease of PLA2, SHP/PC ratio and GSH. Marked elevation of MDA (lipid peroxidation) and PC were observed after a single injection of GM. In contrast, BSO injected rats were not showed increment of tissue MDA, in spite of marked reduction of renal GSH. These data support the conclusion that accelerated lipid peroxidation occurs early in the course of GM administration and inhibition of lysosomal PLA2 activity involved in the degradation of lysosomal membrane which consisted of phospholipids.     

Melatonin, a pineal hormone with antioxidant property, protects against gentamicin-induced nephrotoxicity in rats

The present study investigated the effects of melatonin, an antioxidant, on gentamicin-induced nephrotoxicity in rats. Melatonin (5 mg/kg p.o.) was used 3 days before and 8 days simultaneously with gentamicin (80 mg/kg i.p.) Saline-treated animals served as controls. Determinations of urinary creatinine, N-acetyl-beta-D-glucosaminidase, glucose, protein, blood urea, serum creatinine, plasma and kidney tissue malondialdehyde (MDA), and antioxidant enzyme levels in kidney tissue were done after 8 days of gentamicin treatment. The kidneys were also examined for morphological changes using histological techniques. Gentamicin caused nephrotoxicity as evidenced by marked elevation in blood urea and serum creatinine. Mean blood urea and serum creatinine levels were 289+/-50, and 2.5+/-0.5 mg/dl, respectively, in rats treated with gentamicin. Melatonin significantly protected the rats from gentamicin-induced nephrotoxicity; blood urea and serum creatinine levels were 23+/-2.7 and 0.88+/-0.19 mg/dl, respectively. The creatinine clearance was decreased with gentamicin treatment (0.048+/- 0.007 ml/min) as compared with controls (0.41+/-0.08 ml/h/kg). In rats treated with melatonin plus gentamicin, the creatinine clearance was similar to controls (0.41+/-0.08 ml/h/kg). The product of lipid peroxidation (MDA) was markedly increased in plasma (2.10+/-0.15 nmol) and kidney tissue (8.87+/-3.2 nmol/mg protein) with gentamicin treatment. Melatonin prevented the gentamicin-induced rise in plasma MDA (1.03+/-0.27 nmol) and kidney tissue MDA (2.57+/-0.87 nmol/mg protein). An increased excretion of urinary N-acetyl-beta-D-glucosaminidase, glucose, and protein by gentamicin was also prevented by melatonin. Kidneys from gentamicin-treated rats showed tubular epithelial loss with intense granular degeneration involving more than 50% of renal cortex, while there were findings comparable to controls in melatonin plus gentamicin treated rats. The present study indicates that melatonin significantly protects against gentamicin-induced renal toxicity in Wistar rats.     

Changes in Serum and Renal Vitamin E Levels in Deoxycorticosterone Acetate-Salt Hypertensive Rats

Background

Hypertension is an important risk factor for the progression of chronic renal disease, which may result in the development of end-stage renal disease. Since reactive oxygen species are implicated in the induction of hypertension, antioxidants have been used to reduce blood pressure and renal impairment in animal models and in human hypertension. However, the available data are not conclusive.

Methods

To investigate oxidative stress in hypertension, we evaluated renal and serum vitamin E levels as the most effective antioxidant to reduce lipid peroxidation by high-performance liquid chromatography among rats subjected to deoxycorticosterone acetate (DOCA)-salt treatment for 4 weeks. Renal levels of malondialdehyde (MDA) as a marker of cell lipid peroxidation were also assayed in treated rats. Systolic blood pressure (SBP) was measured in conscious rats by the tail-cuff method using a PowerLab/4sp data acquisition system.

Results

SBP increased significantly in DOCA-salt-treated rats compared to the sham group after 4 weeks of treatment. Serum vitamin E levels were significantly lower and renal MDA concentrations significantly higher in treated compared to sham rats. However, renal vitamin E levels were also significantly higher among treated compared to sham rats.

Discussion

Decreased plasma vitamin E levels and increased renal MDA levels show systemic and local oxidative stress in DOCA-salt-treated rats. However, the higher renal vitamin E level suggested a local compensatory mechanism. Vitamin E administration might be appropriate, as significant decreases in vitamin E levels were observed in the serum of DOCA-salt-treated rats.     

Effect of cyclosporine A on accumulation of tetraethylammonium and p-aminohippurate, and on lipid peroxidation in rat renal microsomes and cortical slices

The effect of cyclosporine A (CsA) on lipid peroxidation (LPO) was assessed in renal cortical slices and renal microsomes. Cortical slices were incubated with 1500 micrograms/ml CsA and microsomes with 0.5-20 micrograms/ml under identical conditions (pH 7.4, 37 degrees C) for 3 hours, and LPO monitored by the formation of malondialdehyde (MDA). CsA at concentrations of 3 micrograms/ml and higher caused a significant increase MDA in microsomes and renal cortical slices showed a time dependent release of MDA into the incubation medium. The influence of CsA on tetraethammonium (TEA) and p-aminohippurate (PAH) accumulation in renal cortical slices was investigated for up to 3 hours with concentration of CsA from 10 to 1000 micrograms/ml. CsA caused a time- and concentration-dependent decrease of TEA accumulation and higher concentrations of CsA decreased PAH accumulation in renal cortical slices. The results add further evidence to the suggestion that lipid peroxidation participate in CsA-induced impairment of kidney function.     

一氧化氮胰腺保护作用与巯基物质和氧自由基的关系

目的　探讨内源性一氧化氮 (NO)对大鼠急性坏死性胰腺炎的作用及其与巯基物质和脂质过氧化之间的关系。　方法　以 5 %牛磺胆酸钠溶液胰胆管注射 (1ml/kg)制成大鼠急性坏死性胰腺炎模型 ,以工具药L 硝基精氨酸 (L NNA)为内源性NO的阻断剂 ,观察内源性NO对胰腺损伤程度、血清淀粉酶浓度、胰腺组织内巯基物质含量和脂质过氧化终产物丙二醛 (MDA)含量的影响。　结果　牛磺胆酸钠胰胆管注射可造成胰腺组织明显的水肿和坏死 ,部分 (2 / 7)发生胰腺实质内出血 ;血清淀粉酶浓度显著升高 ,胰腺组织巯基物质含量降低 ,MDA含量增加 [(1 2 5± 0 2 8)nmol/mg蛋白质vs.(0 5± 0 0 3)nmol/mg蛋白质 ,P <0 0 5 ]。以L NNA(12 5mg/kg)阻断内源性NO ,可明显加重胰腺组织坏死 ,胰腺实质内出血率增加 (10 / 12 ,83 3 % ) ,并血清淀粉酶浓度进一步升高 ,胰腺组织MDA含量进一步增加 [(3 0± 0 40 )nmol/mg蛋白质vs.(1 2 5± 0 2 8)nmol/mg蛋白质 ,P <0 0 5 ]。但对胰腺组织内巯基物质的含量没有影响。　结论　内源性NO具有胰腺保护作用 ,其保护机制可能与抗氧自由基有关。巯基物质可能不参与NO的胰腺保护机制。     

Effect of Cyclosporine a on Accumulation of Tetraethylammonium and p-Aminohippurate,and on Lipid Peroxidation in Rat Renal Microsomes and Cortical Slices

The effect of cyclosporine A (CsA) on lipid peroxidation (LPO) was assessed in renal cortical slices and renal microsomes. Cortical slices were incubated with 1500 μg/ml CsA and microsomes with 0.5–20 μg/ml under identical conditions (pH 7.4,37d`C) for 3 hours, and LPO monitored by the formation of malondialdehyde (MDA). CsA at concentrations of 3 μg/ml and higher caused a significant increase MDA in microsomes and renal cortical slices showed a time dependent release of MDA into the incubation medium. The influence of CsA on tetraethammonium (TEA) and p-ami-nohippurate (PAH) accumulation in renal cortical slices was investigated for up to 3 hours with concentration of CsA from 10 to 1000 μg/ml. CsA caused a time-and concentration-dependent decrease of TEA accumulation and higher concentrations of CsA decreased PAH accumulation in renal cortical slices. The results add further evidence to the suggestion that lipid peroxidation participate in CsA-induced impairment of kidney function.     

A study of lipid peroxidation in neonates--(1) Daily change of serum lipid peroxides in full term neonates

Lipid peroxide has been highlighted as a possible marker of cell destruction by oxygen derived free radical reactions. We, therefore, examined serum lipid peroxides, malondialdehydes (MDA) in 106 healthy full term neonates (aged 0.5 to 317 hrs, averaged 79.3 +/- 69.9 hrs). Their lipid peroxides in capillary blood were determined by the luminescence method (Yagi method). Based on our data, we conclude as follows: 1) MDA concentrations were influenced by the serum bilirubin concentrations. We, therefore, adjusted our data according to the serum bilirubin concentrations. 2) We found significantly higher values of MDA (4.76 +/- 1.35 nmol.ml-1) than those in adult (3.12 +/- 0.35 nmol.ml-1). In fact, these values increased gradually on the second day, and the high values were maintained until the fifth day. 3) The values of MDA and total bilirubin concentrations in the vaginally delivered neonates were significantly higher than those delivered by Cesarean section (P less than 0.05). 4) There were no correlations between the values of MDA and values of other serum lipid and bilirubin.     

The time course and regional variations of lipid peroxidation after diffuse brain injury in rats

Summary Free radicals are generated after head injury. These radicals rapidly react with polyunsaturated fatty acids in the cell membrane and cause membrane destruction. This process is called lipid per-oxidation. Malondialdehyde (MDA) is one of the end products of lipid peroxidation, and it is a frequently used indicator of lipid per-oxidation in biological tissues. Using a diffuse head injury animal model, we studied the time course of lipid peroxidation in different regions of injured rat brains. In the present study, the MDA levels were 36.7%, 41.8%, and 35.1% greater than sham at one hour after injury at the frontal, parietal, and brain stem, respectively (p<0.0001). The MDA levels in these regions continued to increase and peaked a 4 hours after the injury. The levels slowly decreased, and by 24 hours, they were still significantly higher than the sham control's. The elevation of MDA levels was less in the striatum and the temporal regions at one hour. They were 16.9% and 13.3%, respectively (p<0.002). The MDA levels in these two regions continued to increase even after 4 hours of injury, but the degree of elevation never exceeded 35%. The results demonstrate that there is an immediate, posttraumatic burst of MDA production, suggesting the formation of free radicals after diffuse head injury. Even though all the regions sampled show the same effect, certain regions are less affected by this diffuse head injury animal model.     

Increased glomerular and urinary malondialdehyde in puromycin aminonucleoside-induced proteinuria in rats

Puromycin aminonucleoside (PAN)-induced proteinuria in rats may be mediated by reactive oxygen metabolites (ROM), which are injurious to several cell components including membrane lipids. Increased malondialdehyde (MDA) production is indicative of lipid peroxidation. We examined if MDA content of glomeruli and its urinary excretion were increased in rats administered PAN. Of three groups of 8 Sprague-Dawley rats each, group 1 served a control, group 2 animals received a single intravenous injection of PAN (5 mg/100 g body weight) and group 3 animals PAN with intraperitoneal injections of dimethylthiourea (DMTU), a free radical scavenger of oxidants such as hydroxyl radicals, for 4 days. The rats were sacrificed on day 8 after PAN injection. Increasing proteinuria, starting on day 4, developed in animals in group 2 but not in the others. The glomerular MDA (nmol/mg protein) in group 2 animals was 2.93±1.91, significantly higher than 0.87±0.63 and 1.26±0.76 in groups 1 and 3, respectively. urinary levels of MDA markedly increased in group 2 rats on day 3 and remained high thereafter, but no such increase occurred in the control animals and those administered PAN with DMTU; the latter was thus protective against PAN toxicity. Our observations support the view that ROM are involved in PAN-induced glomerular injury and that increased urinary MDA excretion can be a marker of ROM-mediated lipid peroxidation.