Effect of antioxidants on adriamycin-induced microsomal lipid peroxidation

Adriamycin (25 μM) stimulated NADPH-dependent microsomal lipid peroxidation about fourfold over control values. The tested antioxidants, zinc, superoxide dismutase, vitamin E, and desferrioxamine (Desferal) inhibited Adriamycin-enhanced lipid peroxidation to varying degrees. Others antioxidants, e.g., glutathione, catalase, and selenium, were found to have no effects. Our in vitro studies suggest that adriamycin effect is mediated by a complex oxyradical cascade involving superoxide, hydroxyl radical, and small amounts of iron.     

Effect of citrus flavonoids on lipid metabolism and glucose-regulating enzyme mRNA levels in type-2 diabetic mice

Flavonoids have been identified as the antidiabetic components in a number of traditional ethnic remedies. However, the mechanisms whereby these compounds exert their hypoglycemic and hypolipidemic action in type-2 diabetes have rarely been investigated. Therefore, this study investigated the effect of the flavonoids hesperidin and naringin on glucose and lipid regulation in C57BL/KsJ-db/db mice. Hesperidin and naringin both significantly increased the glucokinase mRNA level, while naringin also lowered the mRNA expression of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase in the liver. In addition, the hepatic glucose transporter 2 protein expression was significantly reduced, while the expression of adipocyte glucose transporter 4 and hepatic and adipocyte peroxisome proliferator-activated receptor gamma were elevated in the hesperidin and naringin groups when compared with the control group. Furthermore, hesperidin and naringin effectively lowered the plasma free fatty acid and plasma and hepatic triglyceride levels, and simultaneously reduced the hepatic fatty acid oxidation and carnitine palmitoyl transferase activity. These changes were seemingly attributable to a suppression of the hepatic fatty acid synthase, glucose-6-phosphate dehydrogenase, and phosphatidate phosphohydrolase activities and an increase in the fecal triglycerides. The two flavonoids also led to a decrease in the plasma and hepatic cholesterol levels that may have been partly due to the decreased hepatic 3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA) reductase and acyl CoA: cholesterol acyltransferase (ACAT) activities and increased fecal cholesterol. Consequently, the current results suggest that hesperidin and naringin are beneficial for improving hyperlipidemia and hyperglycemia in type-2 diabetic animals by partly regulating the fatty acid and cholesterol metabolism and affecting the gene expression of glucose-regulating enzymes.     

Effect of lecithin on liver microsomal lipid peroxidation]

The effect of exogeneous (egg) lecithin on peroxidation of microsomal lipids was studied with the view of elucidating the role of various components of lipid substrate in the overall oxidation rate of the lipids. The following processes were studied a) NADPH-dependent microsomal lipid peroxidation in the presence of lecithin; b) ascorbate-dependent microsomal lipid peroxidation in the presence of lecithin; c) oxidation of lipid mixture, isolated from the microsomes, and that of lecithin in the presence of the Fe2+ + ascorbate system; 4) oxidation of lecithin induced by the Fe2+ + ascorbate system. It was found that in the presence of exogeneous lecithin the oxidation of microsomal lipids in inhibited, which is probably due to the peculiarities of lecithin oxidation. It was shown that the specific rate of lecithin oxidation is decreased with an increase in lecithin concentration. Possible mechanisms of lecithin effect on microsomal lipid peroxidation are discussed.     

Interrelationship of antioxidative status, lipid peroxidation, and lipid profile in insulin-dependent and non-insulin-dependent diabetic patients

This study aimed to investigate the interrelationship of plasma lipid profile, lipid peroxidation, and erythrocyte antioxidative defense in patients with insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus. Plasma levels of total cholesterol, triglycerides, and lipid peroxides and the activities of copper, zinc superoxide dismutase (CuZnSOD), catalase, glutathione peroxidase (GSH-Px), as well as the amount of glutathione in erythrocytes, were determined in IDDM, NIDDM, and nondiabetic control subjects. Additionally, morphology of erythrocytes in all subjects was examined. Plasma levels of total cholesterol and triglycerides were significantly increased in NIDDM compared with controls. Also, the lipid peroxide level was higher in NIDDM than in either control or IDDM subjects. CuZnSOD activity in erythrocytes was elevated in NIDDM patients compared with the control. In NIDDM patients, more extensive erythrocyte spherocytosis and echinocytosis compared with both control and IDDM subjects were observed. In contrast with the IDDM group, the observed abnormality in lipid metabolism in NIDDM patients is closely associated with increased lipid peroxidation, changes in antioxidative defense, and erythrocyte morphology.     

Alterations in lipid peroxidation and antioxidant status in pregnancy with preeclampsia

Soy consumption is associated with a lower risk of atherosclerotic disease in the oriental population. Genistein is a soy isoflavone bearing estrogenic properties. Previous experiments in our laboratory demonstrated the potentiation of endothelium-independent relaxation of coronary artery by both estrogen and genistein. The potentiating effects of both estrogen and genistein were mediated through the cAMP-signaling pathway. We hypothesize that genistein could enhance protein kinase A (PKA) activity in porcine coronary artery smooth muscle, thereby offering a mechanism for the potentiation of vascular relaxation by genistein. In our study, a high concentration of genistein (10^−4.5 M) significantly increased PKA activity in porcine coronary artery rings. While genistein at 10^−5.5 M and forskolin at 10⁻⁷ M had no effect on PKA activity, the combination of the two compounds at the prescribed concentrations caused a significant increase in PKA activity. The increase in PKA activity by genistein was abolished by SQ 22536 (adenylate cyclase blocker), but not by NF 449 (Gs protein blocker) or ICI 182780 (estrogen receptor antagonist). Our results suggest that the action of genistein is mediated via adenylate cyclase, but does not appear to involve Gs protein or ICI 182780-sensitive estrogen receptor.     

Radioprotective effect of 2-mercaptopropionylglycine on radiation-induced microsomal lipid peroxidation

Radiation-induced microsomal lipid peroxidation was measured following gamma-irradiation (66-399 Gy) in the presence or absence of 2-mercaptopropionylglycine (MPG) at low and high concentrations (0.03 and 0.1 mg/ml). At high concentrations of MPG, enhancement of lipid peroxidation was observed instead of reduction. Following gamma-irradiation at 266.4 Gy, lipid peroxidation increased with increasing concentrations of MPG. The spontaneous lipid peroxidation also increased with increasing concentrations of MPG. When MPG and EDTA were added together, radioprotection was observed even at high concentrations of MPG after different doses of radiation. An increase in radioprotection with increasing concentrations of MPG in the presence of EDTA at 266.4 Gy was also observed. The exogenous supply of Fe2+ during irradiation was found to eliminate the 'threshold dose' which has to be delivered before MPG shows an 'enhancement effect'. A possible mechanism for the enhancement of radiation-induced lipid peroxidation is proposed.     

Effect of cadmium and aluminum intake on the antioxidant status and lipid peroxidation in rat tissues.

This work aimed to study the relationship between the accumulation of cadmium (Cd) or aluminum (Al) in certain tissues and the levels of lipid peroxides as well as tissue antioxidants. To carry out such investigations, CdCl2 was given to rats in two dose levels; 0.5 or 2.0 mg/kg i.p for 1 day or daily repeated doses for 2 weeks. Al was given as AlCl3 either in a single dose of 100 mg/kg or daily repeated doses of 20 mg/kg for 2 and 4 weeks. The measured parameters were tissue malondialdehyde (MDA, index of lipid peroxidation) and reduced glutathione (GSH) levels as well as the activities of glutathione peroxidase (GSH-PX), glutathione reductase (GSSG-R), and glucose-6-phosphate dehydrogenase (G-6-PDH) enzymes. Liver and kidney functions were assessed by measuring serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities as well as serum urea and creatinine concentrations. Cd and Al concentrations in the studied tissues were also measured. Results indicated that tissue Cd was significantly increased after administration of either Cd doses. After a single dose of 0.5 or 2.0 mg/kg CdCl2, the increase in tissue Cd levels were accompanied by an increase in MDA and a decrease in GSH levels. On the other hand, after repeated administration of Cd, tissue Cd accumulation was accompanied by increased hepatic and renal GSH levels with decrease in MDA content and a decrease in GSH-PX activity in liver. Liver function was affected at all dose regimens, whereas kidney function was affected only after 2 weeks administration of the higher dose. In Al treated rats, Al concentration was shown to be increased in liver much more than in brain. This was accompanied by a slight decrease in hepatic GSH level after 2 weeks and a decrease in GSH-PX activity after 4 weeks. Liver function was affected only after repeated injection of Al for 2 or 4 weeks. In general, Al administration exhibited safer pattern than Cd.     

Blood antioxidant status and erythrocyte lipid peroxidation following distance running

The relationship between prolonged exercise, oxidative stress, and the protective capacity of the antioxidant defense system has been determined. Venous blood samples were removed from seven trained athletes before and up to 120 h after completion of a half-marathon for measurements of blood antioxidants, antioxidant enzymes, and indices of lipid peroxidation. Plasma creatine kinase (CK) activity, an index of muscle damage, increased (P less than 0.05) to a maximum 24 h after the race but this was not accompanied by changes in conjugated dienes and thiobarbituric acid reactive substances (TBARS), which are indices of lipid peroxidation. An increase (P less than 0.05) in plasma cholesterol concentration (4%) immediately after the race was similar to the change in plasma volume (6%). However, transient increases (P less than 0.05) immediately postrace in the plasma concentrations of uric acid (24%), vitamin A (18%), and vitamin C (34%) were only partly accounted for by the fluid shifts. The immediate postrace increases in alpha- and gamma-tocopherol did not attain statistical significance. Erythrocyte antioxidant enzyme activities were unaffected by the exercise but the alpha- and gamma-tocopherol concentrations progressively increased (P less than 0.001 and P less than 0.05, respectively) up to 48 h postrace. Paradoxically, 24 h after the race erythrocyte susceptibility to in vitro peroxidation was markedly elevated (P less than 0.01). This enhanced susceptibility to peroxidation was maintained even at 120 h postrace and did not correspond to changes in the age of the red cell population. A decrease (P less than 0.001) in total erythrocyte glutathione immediately after the half-marathon was mainly due to a reduction in the reduced form (GSH). The results show that when trained athletes run a comparatively short distance sufficient to result in some degree of muscle damage but which is insufficient to cause elevations in plasma indices of lipid peroxidation, significant alterations in erythrocyte antioxidant status do occur.     

Effect of seminal plasma antioxidant on lipid peroxidation in spermatozoa, mitochondria and microsomes

Seminal plasma antioxidant inhibited ascorbate/iron-induced lipid peroxidation in spermatozoa, brain and liver mitochondria. The concentration required to produce inhibition in brain and liver mitochondria was high. Denaturation of spermatozoa resulted in complete loss of antioxidant action. Maintenance of native structure was essential for action of seminal plasma antioxidant in spermatozoal lipid peroxidation. The antioxidant inhibited NADPH, Fe3+-ADP induced lipid peroxidation in microsomes and consequences of lipid peroxidation such as glucose-6-phosphatase inactivation were prevented by presence of antioxidant. It did not inhibit microsomal lipid peroxidation induced by ascorbate and iron and xanthine-xanthine oxidase.     

Effect of zinc on the lipid peroxidation and the antioxidant defense systems of the alloxan-induced diabetic rabbits

The effects of oral zinc supplementation on lipid peroxidation and the antioxidant defense system of alloxan (80-90 mg/kg)-induced diabetic rabbits were examined. Forty-five New Zealand male rabbits, 1 year old, weighing approximately 2.5 kg, were allocated randomly and equally as control, diabetic, and zinc-supplemented diabetic groups. After diabetes was induced, zinc-supplemented diabetic rabbits had 150 mg/L of zinc as zinc sulfate (ZnSO(4)) in their drinking tap water for 3 months. The feed and water consumption was higher in diabetic groups than (P<0.01) healthy rabbits. The body weight was lower in diabetic rabbits compared to control. The blood glucose levels were higher in diabetic groups than controls. The elevated plasma malondialdehyde (MDA) levels were determined in the diabetic group (P<0.01). The glutathione peroxidase (GSH-Px), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), and ceruloplasmin levels in the diabetic group were decreased by the effect of diabetes but there was no difference between zinc-supplemented diabetic and control rabbits. Serum zinc concentrations were lower in diabetic rabbits but iron (Fe) and copper (Cu) levels in sera were not different among the groups. As a result, it was concluded that daily zinc supplementation could reduce the harmful effects of oxidative stress in diabetics.     

Biomarkers of antioxidant status and lipid peroxidation in elderly patients with hypertension

Objective: The objective of the present study was to examine selected parameters of the blood redox system in elderly patients with hypertension.examine selected parameters of the blood redox system in elderly patients with hypertension. Methods: We analyzed differences in redox-associated molecules and enzymes among elderly hypertensive subjects (age above 65?years, n?=?49) and two groups of normotensive subjects (<65 years old – Control group I; n?=?27, and >65 – Control group II; n?=?30). Results: Decreased activity of antioxidant enzymes, increased lipid peroxidation and reduced production of nitric oxide were observed in hypertensive subjects, compared to healthy younger controls, or those of the same age. In healthy controls, an age-related decrease in the production of nitric oxide and the activities of SOD-1 and GPx-1 was also evident. The pathology of hypertension was characterised by further, significant decreases in the values of these parameters. When the subgroups of females and males were compared to their respective controls, a compromised redox balance was observed that was more evident in female hypertensives. Discussion: Hypertension in elderly patients is accompanied by changes in biomarkers of antioxidant status and lipid peroxidation status, which significantly differ from those observed in healthy ageing subjects. Our study also suggests that the relationship of gender and changes in redox balance with regard to hypertension should be further explored.     

Hesperidin, a flavanone glycoside, on lipid peroxidation and antioxidant status in experimental myocardial ischemic rats

Myocardial infarction continues to be a leading cause of mortality world-wide. Novel therapies are needed to treat the myocardial ischemia. This study was undertaken to evaluate the cardioprotective role of hesperidin on isoproterenol-induced myocardial ischemia in rats. Myocardial ischemia was induced by subcutaneous injection of isoproterenol hydrochloride (85 mg/kg body weight), for two consecutive days. Isoproterenol-administered rats showed elevated levels of cardiac markers (aspartate transaminase, alanine transaminase, lactate dehydrogenase, creatine kinase, creatine kinase-MB, cardiac troponins T and I) when compared with control and hesperidin treatment groups (100, 200 and 400 mg/kg body weight). The serum levels of cardiac markers were significantly reduced at the doses of 200 mg and 400 mg. All further experiments were carried out at the 200 mg dose. Lipid peroxidation markers (thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes) were elevated significantly in the plasma and heart whereas non-enzymic antioxidants (vitamin C, vitamin E and reduced glutathione) were decreased significantly. Activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and glutathione reductase declined significantly in the heart of ischemic rats. However, after hesperidin treatment, all the above parameters reverted to normal levels. This study demonstrated that the cardioprotective effect of hesperidin on ischemic rats could be due to its anti-lipid peroxidative and antioxidant properties.     

Regional differences in microsomal lipid peroxidation and antioxidant levels in the guinea pig adrenal cortex

Lipid peroxidation (LP) and antioxidant levels were studied in the chromatically distinct inner (zona reticularis) and outer (zona fasciculata + zona glomerulosa) zones of the guinea pig adrenal cortex. Ferrous ion (Fe2+) produced a concentration-dependent (10(-5) to 10(-3) M) stimulation of microsomal LP in both zones, but LP, as estimated by malonaldehyde production, was far greater in the inner zone. Although cytosolic ascorbic acid content was similar in the two zones, microsomal tocopherol levels were approx 4 times greater in the outer than inner zone. Subphysiological concentrations of ascorbic acid, like Fe2+, initiated LP to a greater extent in inner than outer zone microsomes; optimal stimulation of LP by ascorbic acid occurred at concentrations of 100-200 microM in both zones. Physiological concentrations of ascorbic acid (1-5 mM), by contrast, did not initiate LP and, in fact, markedly inhibited Fe2+-induced LP in both inner and outer zone microsomal preparations. Outer zone microsomes were more sensitive to the antioxidant effects of ascorbic acid than were inner zone preparations. Addition of alpha-tocopherol to inner zone microsomal suspensions inhibited Fe2+-induced LP. The results indicate that there are regional differences in adrenocortical LP which may be caused by differences in tocopherol content. alpha-Tocopherol may serve important antioxidant functions within the adrenal cortex, thereby contributing to the functional zonation of the gland.     

A comparative study on the effect of homobrassinolide and gibberellic acid on lipid peroxidation and antioxidant status in normal and diabetic rats

Dietary content of phytohormones may potentially influence metabolic processes in animal cells. This study therefore aimed to investigate the effect of two plant growth regulators homobrassinolide (HB) and gibberellic acid (GBA) on the antioxidant defense status and lipid peroxidation level in the tissues of normal and streptozotocin- induced diabetic rats. Normal and diabetic rats (Albino –wistar strain) were administered 50μg HB and GBA intradermally each day for seven days and their tissue and blood levels of malondialdehyde (MDA), 4-hydroxy-2-nonenol (4-HNE), reduced glutathione (GSH) content and catalase (CAT) activity were determined. Subchronic treatment of rats with HB reduced lipid perioxidation and elevated antioxidant defense whereas GBA caused enhancement of lipid peroxidation and reduction of antioxidant defense in treated animals compared to the control rats.     

Effects of lipid peroxidation on adrenal microsomal monooxygenases

Incubation of guinea pig adrenal microsomes with 10^?6 M ferrous (Fe²⁺) ion and adrenal cytosol initiated high levels of lipid peroxidation as measured by the production of malonaldehyde. Cytosol or Fe²⁺ alone had little effect on microsomal malonaldehyde formation. When microsomes were incubated in the presence of Fe²⁺ and cytosol, malonaldehyde levels continued to increase for at least 60 min. Accompanying the lipid peroxidation was a decline in adrenal microsomal monooxygenase activities. The rates of metabolism of xenobiotics (benzphetamine demethylase, benzo[α]pyrene hydroxylase) as well as steroids (21-hydroxylation) decreased as malonaldehyde levels increased. In addition, cytochrome P-450 levels, NADPH- and NADH-cytochrome c reductase activities, and substrate interactions with cytochrome(s) P-450 decreased as lipid peroxidation progressed. Inhibition of lipid peroxidation by increasing microsomal protein concentrations during the incubation period prevented the changes in microsomal metabolism. Malonaldehyde had no direct effects on adrenal microsomal enzyme activities. The results indicate that lipid peroxidation may have significant effects on adrenocortical function, diminishing the capacity for both xenobiotic and steroid metabolism.     

Antioxidant effect of caeruloplasmin on microsomal lipid peroxidation

Microsomal NADPH-dependent lipid peroxidation catalyzed by ADP-Fe³⁺ was inhibited by the addition of caeruloplasmin. The antioxidant effect of caeruloplasmin was independent of the superoxide anion (O^?₂ scavenging activity. Since caeruloplasmin enhanced the function of ADP-Fe³⁺ acting as electron acceptor for microsomal electron transport system, the antioxidant effect of caeruloplasmin is considered to depend on the ferroxidase activity.     

Combined effect of alcohol and cigarette smoke on lipid peroxidation and antioxidant status in rats

The effect of long-term administration of alcohol and cigarette smoke independently and both in combination on lipid peroxidation and antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) was studied in liver, kidney, heart and lungs of albino rats. The levels of peroxidation products viz., malondialdehyde, hydroperoxides and conjugated dienes were increased in all the tissues of alcohol administered and smoke-exposed rats. Activities of SOD and CAT were decreased in alcohol-treated and alcohol and smoke combination groups, but increased in smoke-exposed group. Activities of GPx and GST have shown an increase, while concentration of reduced glutathione was found decreased in all the three groups.     

Effect of isoproterenol on lipid peroxidation and antioxidant enzymes of myocardial tissue of mice and protection by quinidine

administration of isoproterenol to mice at a dose of 30 mg/100 g body weight for 3 consecutive days at an interval of 24 h induced lipid peroxidation in cardiac tissue and exhibited a significantly elevated serum glutamate oxaloacetate transaminase (SGOT) level. Increased superoxide dismutase (SOD) activity with a concomitant decrease in catalase activity has also been observed in cardiac tissue with isoproterenol treatment. Quinidine, a class I antiarrhythmic agent has been found to exhibit a protective role in isoproterenol induced myocardial ischaemia. Cardiac tissue of quinidine treated mice showed reduction of lipid peroxidation reaction. In addition, quinidine treatment is found to influence the cardiac antioxidant enzymes – catalase and SOD. The decrease of SOD activity and increase of catalase activity suggests that quinidine also exerts an indirect antioxidant effect in protecting the myocardial tissue from reactive oxygen species. Furthermore, our current in vitro studies with quinidine have clearly shown in this work that it possesses a very convincing hydroxyl radical scavenging potential with almost no ability to scavenge superoxide anion and hydrogen peroxide (H₂O₂) in vitro. Thus, our present investigation suggests that quinidine, when administered to mice, strengthens the antioxidant defense system to resist the free radical induced damage brought about by isoproterenol induced ischaemic condition.     

Modulations by dietary restriction on antioxidant enzymes and lipid peroxidation in developing mice.

The effects of dietary restriction (DR) on the activities of liver superoxide dismutase (SOD), catalase (Cat), and glutathione peroxidase (GPX) and the level of lipid peroxidation (LP) in developing mice were investigated in this study. Male and female Kunmin mice were fed a standard rodent diet ad libitum (AL), 80% of AL food intake (20% DR), or 65% of AL food intake (35% DR) for 12 or 24 wk. Both 12 and 24 wk of DR resulted in retarded body weight gain in male and female mice. The activities of SOD, Cat, and GPX and the content of LP in DR male and female mice were not different (P > 0.05) from those in controls after 12 wk of DR. However, the SOD activity was increased at 24 wk in 20% DR (P < 0.05) and 35% DR (P < 0.01) male, but not in DR female, mice. The Cat activity was elevated at 24 wk in both DR male (P < 0.05 for 20% DR, P < 0.01 for 35% DR) and female (P < 0.01) mice with a greater increase in DR female (P < 0.05) than in DR male animals. GPX activity was also increased at 24 wk in DR male (P < 0.01) and female (P < 0.01) mice with a greater elevation in DR females (P < 0.05) than in DR males. Furthermore, LP was decreased at 24 wk in both DR male (P < 0.01) and female (P < 0.01) animals with a greater reduction in DR females (P < 0.01) compared with DR males. These findings indicated that 24 wk, but not 12 wk, of DR led to differential effects on liver SOD, Cat, and GPX activities and LP content in male and female mice during development, suggesting sex-associated modulations of DR on antioxidant systems in developing animals.     

Protective influences of alpha-ketoglutarate on lipid peroxidation and antioxidant status in ammonium acetate treated rats

The effects of alpha-ketoglutarate on ammonium acetate induced hyperammonemia were studied biochemically in experimental rats. The levels of circulatory, non-protein nitrogen, serum transaminases and thiobarbituric acid reactive substances were significantly increased in ammonium acetate treated rats. These levels were significantly decreased in alpha-ketoglutarate and ammonium acetate treated rats. Similar patterns of alterations were observed in the levels of free fatty acids, triglycerides, phopholipids and cholesterol inbetween various groups. Further non-enzymatic (vitamins C and E) and enzymatic (superoxide dismutase and catalase) antioxidants were significantly decreased in ammonium acetate treated rats; and were significantly increased in alpha-ketoglutarate and ammonium acetate treated rats. The biochemical alterations during alpha-ketoglutarate treatment could be due to (i) the detoxification of excess ammonia, (ii) by participating in the non-enzymatic oxidative decarboxylation in the hydrogen peroxide decomposition process and (iii) by enhancing the proper metabolism of fats which could suppress oxygen radicals generation and thus prevent the lipid peroxidative damages in rats.