Combined effect of selenium and ascorbic acid on alcohol induced hyperlipidemia in male guinea pigs

Alcoholics usually suffer from malnutrition and are especially deficient in micronutrients like vitamin C, selenium and Zn. In the present study, combined effects of selenium and ascorbic acid on alcohol-induced hyperlipidemia were studied in guinea pigs. Four groups of male guinea pigs were maintained for 45 days as follows: control (1 mg ascorbate (AA)/100 g body mass/day), ethanol (900 mg ethanol/100 g body mass + 1 mg AA/100 g body mass/day), selenium+ascorbic acid [(25 mg AA + 0.05 mg Se)/100 g body mass/day], ethanol+selenium+ascorbic acid [(25 mg AA + 0.05 mg Se + 900 mg ethanol)/100 g body mass/day]. Co-administration of selenium and ascorbic acid along with alcohol reduced the concentration of all lipids, as also evidenced from the decreased activities of hydroxymethylglutaryl-CoA reductase and enhanced activities of plasma lecithin cholesterol acyl transferase and lipoprotein lipase. Concentrations of bile acids were increased. We conclude that the supplementation of Se and ascorbic acid reduced alcohol induced hyperlipidemia, by decreased synthesis and increased catabolism.     

Amelioration of age-dependent increase in protein carbonyls of cerebral hemispheres of mice by melatonin and ascorbic acid

Melatonin secreted by the pineal gland acts as a free radical scavenger besides its role as a hormonal signaling agent. It detoxifies a variety of free radicals and reactive oxygen intermediates including hydroxyl radical, peroxynitrite anion and singlet oxygen. Ascorbic acid (Vitamin C), a water soluble vitamin, is a naturally occurring antioxidant and cofactor in various enzymes. Protein carbonyls are formed as a consequence of the oxidative modification of proteins by reactive oxygen species. Oxidative modification alters the function of protein and is thought to play an important role in the decline of cellular functions during aging. In the present study, the effect of melatonin and ascorbic acid on age-related carbonyl content of cerebral hemispheres in mice was investigated. Protein carbonyls of cerebral hemispheres have been found to be significantly higher in 18-month-old mice as compared to 1-month old mice. Administration of a single dose of melatonin (10 mg/kg body weight) and ascorbic acid (10 mg/kg body weight) intraperitoneally for three consecutive days decreases the carbonyl content in 1- and 18-month-old mice significantly. The present study thus suggests that the formation of protein carbonyls in the cerebral hemispheres of the aging mice can be prevented by the antioxidative effects of melatonin and ascorbic acid that could in turn be beneficial in having health benefits from age-related neurodegenerative diseases.     

瑞舒伐他汀对载脂蛋白E基因敲除小鼠动脉粥样硬化中调节性T细胞的影响

目的：探讨瑞舒伐他汀对载脂蛋白E基因敲除（ApoEKO）小鼠动脉粥样硬化中调节性T细胞的影响。方法：首先将30只ApoEKO小鼠建立动脉粥样硬化模型,随机分为高胆固醇饮食组（对照组）、瑞舒伐他汀低剂量组和瑞舒伐他汀高剂量组,各组分别给予蒸馏水或瑞舒伐他汀进行干预8周;将主动脉根部行冰冻切片油红染色,评估粥样硬化斑块面积大小;免疫组织化学法检测主动脉根部粥样硬化斑块处调节性T细胞（Treg）的表达。结果：各组小鼠均有动脉粥样硬化斑块形成,采用瑞舒伐他汀治疗的小鼠动脉粥样硬化斑块的面积明显小于未经治疗的小鼠（P〈0.01）,同时瑞舒伐他汀能明显增加粥样硬化病变处调节性T细胞的表达,且呈现剂效关系。结论：本实验观察到瑞舒伐他汀不仅能减小ApoEKO小鼠的主动脉粥样硬化斑块,且能使调节性T细胞的表达增多,推测瑞舒伐他汀可以通过促进调节性T细胞的生成而起到抑制动脉粥样硬化的作用。     

瑞舒伐他汀对载脂蛋白E 基因敲除小鼠动脉粥样硬化中 调节性T 细胞的影响

目的:探讨瑞舒伐他汀对载脂蛋白E基因敲除(ApoEKO)小鼠动脉粥样硬化中调节性T细胞的影响。方法:首先将30只ApoEKO小鼠建立动脉粥样硬化模型,随机分为高胆固醇饮食组(对照组)、瑞舒伐他汀低剂量组和瑞舒伐他汀高剂量组,各组分别给予蒸馏水或瑞舒伐他汀进行干预8周;将主动脉根部行冰冻切片油红染色,评估粥样硬化斑块面积大小;免疫组织化学法检测主动脉根部粥样硬化斑块处调节性T细胞(Treg)的表达。结果:各组小鼠均有动脉粥样硬化斑块形成,采用瑞舒伐他汀治疗的小鼠动脉粥样硬化斑块的面积明显小于未经治疗的小鼠(P<0.01),同时瑞舒伐他汀能明显增加粥样硬化病变处调节性T细胞的表达,且呈现剂效关系。结论:本实验观察到瑞舒伐他汀不仅能减小ApoEKO小鼠的主动脉粥样硬化斑块,且能使调节性T细胞的表达增多,推测瑞舒伐他汀可以通过促进调节性T细胞的生成而起到抑制动脉粥样硬化的作用。     

Relationship of vascular 15-lipoxygenase induction to atherosclerotic plaque formation in rabbits

Aortas from atherosclerotic rabbits have increased levels of 15-lipoxygenase, but the relationship between induction of this enzyme and the atherosclerotic process has not been defined. We found that dietary administration of cortisone acetate significantly suppressed atherosclerotic plaque formation in both Watanabe Heritable Hyperlipidemic (WHHL) and cholesterol-fed WHHL/NZW heterozygous rabbits. There was, however, no corresponding decrease in the elevated 15-lipoxygenase activity. In addition, the elevated 15-lipoxygenase activity in atherosclerotic rabbit aortas was uniformly distributed throughout the aorta, and was not preferentially localized in the lesions. These results indicate that induction of the 15-lipoxygenase is not necessarily causally related to plaque development, and that plaques are not the major source of the increased enzyme activity. However, the results confirm that hypercholesterolemia is a necessary condition for both atherosclerosis and 15-lipoxygenase induction, suggesting that perhaps the 15-lipoxygenase may represent a protective response to the hyperlipidemic stress. This possibility is supported by the finding that the induced 15-lipoxygenase converts linoleic acid, which is the predominant essential fatty acid in aorta, to 13-hydroxyoctadecadienoic acid (13-HODE). This compound is a chemorepellant factor for platelets, inhibits platelet thromboxane synthesis, and stimulates prostacyclin synthesis by endothelial cells.     

Rapid induction of atherosclerosis in rabbits.

Japanese white rabbits fed a restricted amount (100 g/head/day) of an atherogenic diet (AD) containing 0.2% cholesterol and 6% peanut oil showed mild and persistent hypercholesterolemia (338 +/- 79 mg/dl). They developed atherosclerotic lesions 4 weeks after deendothelialization of aorta carried out at the 4th week of AD-feeding. This rabbit model of atherosclerosis has such advantages as being able to be produced in a short period and having similar biochemical and pathological characteristics with those in human atherosclerosis.     

Protective effects of silymarin, a milk thistle (Silybium marianum) derivative on ethanol-induced oxidative stress in liver

The production of reactive oxygen species (ROS) is considered to be a major factor in oxidative cell injury. The antioxidant activity or the inhibition of the generation of free radicals is important in providing protection against such hepatic damage. Silymarin, derived from the milk thistle plant, Silybium marianum, has been used in traditional medicine as a remedy for diseases of the liver and biliary tract. In the present study, the effect of hepatoprotective drug silymarin on body weight and biochemical parameters, particularly, antioxidant status of ethanol-exposed rats was studied and its efficacy was compared with the potent antioxidant, ascorbic acid as well as capacity of hepatic regeneration during abstention. Ethanol, at a dose of 1.6 g/kg body wt/day for 4 wks affected body weight in 16-18 week-old male albino rats (Wistar strain weighing 200-220 g). Thiobarbituric acid reactive substance (TBARS) level, superoxide dismutase (SOD), and glutathione-s-transferase (GST) activities were significantly increased, whereas GSH content, and catalase, glutathione reductase (GR) and GPx (glutathione peroxidase) activities significantly reduced, on ethanol exposure. These changes were reversed by silybin and ascorbic acid treatment. It was also observed that abstinence from ethanol might help in hepatic regeneration. Silybin showed a significant hepatoprotective activity, but activity was less than that of ascorbic acid. Furthermore, preventive measures were more effective than curative treatment.     

Studies on the mutagenic activity of ascorbic acid in vitro and in vivo

In vitro data are presented to show that ascorbic acid does not have intrinsic mutagenicity towards strain TA100 of S. typhimurium if deionized water is used to prepare the incubation medium. The addition of Cu2+ ions to the bacterial medium that contains ascorbic acid, or the use of tap water and ascorbic acid alone, causes a mutagenic and cytotoxic response that is blocked by EDTA. Additional in vitro data demonstrate that hydrogen peroxide is mutagenic to S. typhimurium strain TA100 and it is suggested that ascorbic acid may be mutagenic and cytotoxic through the generation of hydrogen peroxide. In vivo studies using a sensitive intrahepatic host-mediated mutagenicity assay indicate that ascorbic acid is not genotoxic in guinea pigs even when the dietary intake of vitamin C is above the level required for tissue saturation (5000 mg/kg body weight/day).     

Effects of seed priming with ascorbic acid to mitigate salinity stress on three wheat (Triticum aestivum L.) cultivars.

In this study, the effect of seed priming using ascorbic acid (ASA) on three commercial wheat cultivars i.e., Punjab-2011, Faisalabad-2008, and Ujala-2016 under salinity stress in both homogenous and heterogeneous environments has been investigated. It revealed that different levels of salinity have significantly reduced the growth attributes like percent germination, germination index, radical & plumule length, seed vigor index (In-vitro), seedling length, fresh & dry weight, and total chlorophyll content (In-vivo) with subsequent treatments. Salinity stress was induced by using NaCl in three different concentrations (100, 150, and 200 mM). Seeds of the three cultivars primed with 50, 100, and 150 mg/L ascorbic-acids have not only improved percent germination but also considerably reduced germination time and increased germination index (GI) indicating the potential for tolerating saline conditions. Seedling growth (seedling length, Fresh weight, and dry weight) of seeds primed with 50, 100, and 150 mg/L (ASA) was significantly higher than other non-primed seeds under the prevailing saline conditions. Hormonal priming with different concentrations of ascorbic acid was effective, nevertheless, the best results were obtained with 100 and 150 mg/L (ASA) concentrations. We concluded that the delay in germination and seedling growth was mainly due to excessive Na⁺ accumulation in the seeds of wheat cultivars. On the other hand, seed priming with various concentrations of ascorbic acid has proved to be effective in inducing salt tolerance in terms of germination parameters, seedling characteristics, and chlorophyll retention in the three local commercial wheat cultivars.     

Reduction of oxidative stress and apoptosis in hyperlipidemic rabbits by ellagic acid

Oxidative stress is one of the major risk factors for coronary artery disease. Ellagic acid is a phenolic compound present in fruits and nuts, and has been found to have antioxidative property. Twenty-four New Zealand white (NZW) rabbits were assigned randomly into four dietary groups. The normal group was fed regular rabbit chow, and the cholesterol group was fed a high fat and cholesterol diet. The ellagic acid (E) group and probucol group were fed the same diet as the cholesterol group plus the addition of 1% (w/w diet) ellagic acid and probucol, respectively. Oxidative stress [as measured by plasma lipids, oxygen free radicals and thiobarbituric acid reactive substances (TBARS)] increased in the cholesterol group compared with the normal group; however, it decreased in the probucol and E groups compared with the cholesterol group. Forty-five percent of the intimal surface of the thoracic aorta was covered with atherosclerotic lesions in the cholesterol group, but only 2-3% was covered in the E and probucol groups. The aortic level of 8-(OH)dG and the expression of caspase-8, caspase-9 and Fas ligand were also suppressed after ellagic acid supplement. These results indicated that ellagic acid could prevent atherosclerosis via suppression of oxidative stress and apoptosis in hyperlipidemic rabbits.     

Oxidative renal injury and lipoprotein oxidation in hypercholesterolemic atherogenesis: Role of eicosapentaenoate-lipoate (EPA-LA) derivative

Hypercholesterolemia, an independent risk factor for increased oxidative renal injury, is associated with the formation of oxidized low-density lipoprotein. Production of reactive oxygen species and nitrogen species have been implicated in diet-induced hypercholesterolemia, principally as means of oxidising low-density lipoproteins. This in turn initiates the accumulation of cholesterol in macrophages, which sets key event in the initiation of atherosclerosis. The aim of the present work is to evaluate the effects of eicosapentaenoic acid (EPA), DL alpha-lipoic acid (LA) and eicosapentaenoate-lipoate derivative (EPA-LA) in controlling the atherogenic disturbances. Four groups of male Wistar rats were fed with a high cholesterol diet (rat chow supplemented with 4% cholesterol and 1% cholic acid; HCD) for 30 days. Among them, 3 groups of rats were treated with either EPA (35 mg/kg body weight/day, oral gavage), LA (20 mg/kg body weight/day, oral gavage) or EPA-LA derivative (50 mg/kg body weight/day, oral gavage) from 16th day to 30th day of the experimental period. Abnormal increase in the levels of reactive oxygen species, 3-nitrotyrosine, malondialdehyde and protein carbonyl as well as an elevation in the activities of xanthine oxidase, lactate dehydrogenase, alkaline phosphatase and acid phosphatase was observed in renal tissue of HCD fed rats. HCD fed rats also showed an increased susceptibility of the apo B-containing lipoproteins to in vitro oxidation. These changes were restored partially in the EPA and LA administered groups. However, the combined derivative EPA-LA almost ameliorated the hypercholesterolemic-oxidative changes in the HCD fed rats.     

The influence of maternal nicotine exposure on neonatal lung metabolism. Protective effect of ascorbic acid.

The aim of the present study was to establish whether ascorbic acid supplementation (1 mg/kg/body mass/day) during pregnancy and lactation will prevent the effect of maternal nicotine exposure (1 mg/kg body weight/day) on neonatal lung carbohydrate, DNA and protein metabolism. The data show that the adult lung ascorbic acid content was reduced by 76% after exposure to nicotine. In contrast, maternal nicotine exposure during pregnancy and lactation has no effect on neonatal lung ascorbic acid content. However, ascorbic acid supplementation during pregnancy and lactation prevented the adverse effects of maternal nicotine exposure on neonatal lung carbohydrate, DNA and protein metabolism.     

Aortic ascorbic acid, trace elements, and superoxide dismutase activity in human aneurysmal and occlusive disease

Altered trace elements and ascorbic acid metabolism have been implicated in the pathogenesis of atherosclerotic cardiovascular disease. However, their role in the disease process, or the effect of atherosclerosis on their tissue levels within plaque, is poorly understood. The present study analyzes the concentrations of Fe, Cu, Zn, and Mn, and ascorbic acid and superoxide dismutase (SOD) activity in tissue samples from 29 patients with abdominal aortic aneurysms (AAA) and 14 patients with atherosclerotic occlusive disease (AOD). It was observed that the Fe and Mn concentrations in AAA and AOD tissue were higher than the levels in nondiseased control aorta, whereas Cu and Zn levels in AAA and AOD tissue were similar to the levels in controls. The Zn:Cu ratio was significantly lower in the AAA tissue in comparison to both AOD and control tissue. In addition, AAA and AOD tissue had low ascorbic acid levels and low Cu,Zn-SOD activity with Cu,Zn-SOD:Mn-SOD ratios of 0.27 and 0.19, respectively, compared to a ratio of 3.20 in control aorta. These data indicate that aorta affected by aneurysms and occlusive disease have altered trace element and ascorbic acid concentrations, as well as low Cu,Zn-SOD activity. Although these observations do not directly support the hypothesis that AAA is associated with aortic Cu deficiency they do suggest a role for oxygen radicals or increased lipid peroxidation in occlusive and aneurysmal disease of the aorta.     

Alpha-lipoic acid attenuates atherosclerotic lesions and inhibits proliferation of vascular smooth muscle cells through targeting of the Ras/MEK/ERK signaling pathway

An infectious burden has been suggested to be associated with atherosclerosis in humans, based on the shared and underlying inflammatory responses during infection and atherosclerosis. However, the efficacy of anti-atherogenic drugs is yet to be tested against atherosclerosis in a scenario involving an infectious burden. We have examined alpha-lipoic acid (ALA) for anti-atherogenic effects in a hypercholesterolemic diet-induced atherosclerotic mouse model with inflammatory stimulation. C57BL/6 mice were fed with a hypercholesterolemic diet for 12 weeks to induce atherosclerosis. Lipopolysaccharide was intraperitoneally injected for the 1st week of study to simulate underlying infectious burden during development of atherosclerosis. ALA treatment alleviated atherosclerotic pathologies and reduced serum cholesterol and inflammatory cytokines. Consistently, atherosclerotic markers were improved by ALA treatment. In addition, ALA attenuated the proliferation and migration of vascular smooth muscle cells upon platelet-derived growth factor stimulation through the targeting of the Ras-MEK1/2-ERK1/2 pathway. This study demonstrates the efficacy of ALA on atherosclerosis with immunological complication, by showing that ALA modulates multiple pathogenic aspects of atherosclerosis induced by a hypercholesterolemic diet with inflammatory stimulation consisting of hypercholesterolemia, inflammation and VSMC activation.     

Free radical scavenging and radioprotective activity of dehydrozingerone against whole body gamma irradiation in Swiss albino mice

Dehydrozingerone (DZ) was explored for in vitro-in vivo antioxidant potential and in vivo radioprotective activity against whole body gamma irradiation in Swiss albino mice. DZ scavenged the ABTS (2, 2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) and DPPH (1, 1-dipehnyl-2-picrylhydrazyl) free radicals at room temp. DZ reduced Fe (III) to Fe (II) at pH 7.4 and scavenged the NADH/phenazine methosulfate generated superoxide radical in cell free system. DZ also scavenged the nitric oxide radical generated by sodium nitroprusside. To evaluate the radioprotective activity, mice were exposed to whole body gamma irradiation 30 min after the drug treatment at a dose rate of 1.66 Gy/min. Pretreatment with DZ 75, 100 and 125 mg/kg, i.p. reduced the radiation induced mortality and increased the mean survival times (MSTs). An i.p. dose of DZ 100 mg/kg was found the most effective dose in preventing radiation sickness and increasing the MST. Pretreatment DZ100 mg/kg maintained the spleen index (spleen weight/body weight x 100) and stimulates the endogenous spleen colony forming units (CFU). Pretreatment with DZ100 mg/kg maintained the villus height close to normal, prevents mucosal erosion and basement membrane damage in irradiated mice jejunum. However, no significant reductions in dead, inflammatory and mitotic cells were observed in DZ pretreated mice, but there was an increased in crypt cells proliferation and regeneration. Pretreatment with DZ100 mg/kg significantly elevated the endogenous antioxidant enzymes (GSH, GST and SOD) in mice at 2, 4 and 8 h post sham irradiation. Radiation induced fall in endogenous antioxidant enzymes was significantly prevented by DZ pretreatment. Pretreatment with DZ 75 and 100 mg/kg reduced the radiation induced micronucleated polychromatic erythrocytes (MPCE) and normochromatic erythrocytes (MNCE) in mice bone marrow. DZ also maintained the polychromatic erythrocytes (PCE) and normochromatic erythrocytes (NCE) ratio (P/N ratio) in irradiated mice. Dose modifying factor (DMF) was calculated by using the graded radiation dose (8.0, 9.0, 9.5 and 10 Gy). DZ 100 mg/kg elevated radiation LD(50) from 9.1 to 10.0 Gy, indicating the DMF of 1.09.     

Amelioration of ionizing radiation induced lipid peroxidation in mouse liver by Moringa oleifera Lam. leaf extract

Protective effect of Moringa oleifera leaf extract (MoLE) against radiation-induced lipid peroxidation has been investigated. Swiss albino mice, selected from an inbred colony, were administered with MoLE (300 mg/kg body wt) for 15 days before exposing to a single dose of 5 Gy 60Co-gamma radiation. After treatments, animals were necropsied at different post irradiation intervals (days 1, 7 and 15) and hepatic lipid peroxidation and reduced glutathione (GSH) contents were estimated to observe the relative changes due to irradiation and its possible amelioration by MoLE. It was observed that, MoLE treatment restored GSH in liver and prevented radiation induced augmentation in hepatic lipid peroxidation. Phytochemical analysis showed that MoLE possess various phytochemicals such as ascorbic acid, phenolics (catechin, epicatechin, ferulic acid, ellagic acid, myricetin) etc., which may play the key role in prevention of hepatic lipid peroxidation by scavenging radiation induced free radicals.     

Trehalose administration attenuates atherosclerosis in rabbits fed a high-fat diet

Disruption of macrophage autophagy is a major contributor to macrophage dysfunction and subsequent inflammation leading to atherosclerosis. Trehalose is a natural disaccharide that is able to induce macrophage autophagy-lysosomal biogenesis and reduce inflammation. Here, we studied the efficacy of intravenous trehalose administration in reducing atherosclerotic plaque burden in high-cholesterol-fed rabbits. Adult male New Zealand white Rabbits were fed with a high-fat diet containing 1% cholesterol for 8 weeks followed by a cholesterol-free diet for the next 4 weeks. In the latter 4-week phase of the cholesterol-free diet, one group received intravenous trehalose solution at a dose of 350 mg/kg, three times per week. In the control group, an equivalent volume of PBS (3 mL) was administered with the same protocol. At the end of the 12th week of the study, all rabbits were anesthetized and aortic arch sections were collected followed by hematoxylin and eosin staining and assessment of plaque grading. Fasting serum lipids were also measured using routine enzymatic methods. At the end of the 12th week, there were no significant differences in the body weight and blood lipids between the control- and trehalose-treated groups. Intravenous trehalose administration significantly attenuated atherosclerotic plaque development as revealed by reduced plaque grading ( P = 0.048) and intima/media thickness ratio ( P = 0.017). Intimal thickening was also found to be reduced in the trehalose versus control group, though this reduction did not reach statistical significance. The present study provided evidence as to the efficacy of short-term intravenous trehalose administration in regressing atherosclerotic plaque in high-fat-fed rabbits.     

Modification of clastogenicity of lead and aluminium in mouse bone marrow cells by dietary ingestion of Phyllanthus emblica fruit extract

Extract of Phyllanthus emblica fruit and ascorbic acid were evaluated separately for protection against clastogenicity induced by lead (Pb) and aluminium (Al) salts on mouse bone marrow chromosomes. Oral administration of Phyllanthus fruit extract (PFE) for 7 days before exposure to both metals by intraperitoneal injection increased the frequency of cell division and reduced the frequency of chromosome breaks significantly. Comparable doses of synthetic ascorbic acid (AA) were less effective and could protect against the effects of Al and only a low dose of Pb (10 mg/kg body weight). AA administered before treatment in mice given higher doses of Pb (40 mg/kg body weight) enhanced the frequency of chromosome breaks, giving a synergistic effect. The higher protection afforded by PFE may be due to the combined action of all ingredients, rather than to AA alone.     

Suppression of high lipid diet induced by atherosclerosis sarpogrelate

Sarpogrelate (SP), a serotonin (5‐HT2A) receptor antagonist, is used as an anti‐platelet agent for the treatment of some vascular diseases. SP has been reported to inhibit 5‐HT induced coronary artery spasm, increase in intracellular calcium and smooth muscle cells proliferation. This study was undertaken to test that SP suppresses the development of atherosclerosis due to high cholesterol diet (HCD) by decreasing blood viscosity and oxidative stress. For this purpose, 29 rabbits were divided into four groups: control group (normal diet); normal diet group with SP at the dose of 5 mg/kg/day; HCD group fed 1% cholesterol; and HCD group with SP at the dose of 5 mg/kg/day. After 90 days of the experiment, blood samples were collected and the animals were killed; the thoracic aorta was stained by the Oil Red O staining method. The results indicate that plasma levels of cholesterol, triglycerides and malondialdehyde were increased in rabbits fed HCD. Plasma viscosity and whole blood viscosity were also higher in the HCD group than that in normal diet group. Treatment with SP prevented these alterations induced by HCD whereas this agent had no significant effect in rabbits fed normal diet. Morphological examination of the aorta revealed that SP treatment prevented the formation of foam cells and atherosclerotic plaque. It is suggested that the beneficial effects of SP in atherosclerosis may be due to actions on blood viscosity, lipid levels and oxidative stress.     

Synergistic interactions of Ferulic acid with Ascorbic acid: Its cardioprotective role during isoproterenol induced myocardial infarction in rats

Studies on the lipid peroxidation and antioxidant changes and their significance during myocardial injury have provided a new insight into the pathogenesis of heart disease. The heart failure subsequent to myocardial infarction may be associated with an antioxidant deficit as well as increased myocardial oxidative stress. The present study was designed to evaluate the effect of the combination of ferulic acid and ascorbic acid on antioxidant defense system and lipid peroxidation against isoproterenol (ISO)-induced myocardial infarction in rats. Induction of rats with isoproterenol (150 mg/kg body weight daily, i.p.) for 2 days resulted in a marked elevation in lipid peroxidation, serum marker enzymes (LDH, CPK, GOT, and GPT), and a significant decrease in activities of endogenous antioxidants (SOD, GPx, GST, CAT, and GSH). Pre-co-treatment with the combination of ferulic acid (20 mg/kg body weight/day) and ascorbic acid (80 mg/kg body weight/day) orally for 6 days, significantly attenuated these changes when compared to the individual treatment groups. Histopathological observations were also in correlation with the biochemical parameters. Thus, ferulic acid and ascorbic acid significantly counteracted the pronounced oxidative stress effect of ISO by the inhibition of lipid peroxidation, restoration of antioxidant status, and myocardial marker enzymes levels. In conclusion, these findings indicate the synergistic protective effect of ferulic acid and ascorbic acid on lipid peroxidation and antioxidant defense system during ISO-induced myocardial infarction and associated oxidative stress in rats.