Preventive effect of S-allylcysteine on lipid peroxides and antioxidants in normal and isoproterenol-induced cardiotoxicity in rats: a histopathological study

The consumption of diets rich in plant foods are associated with a reduced risk of cardiovascular diseases. This study was aimed to evaluate the role of S-allylcysteine (SAC) in isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Subcutaneous injection of ISO (150 mg/kg) to Wistar rats showed a significant decrease in the activities of marker enzymes such as creatine kinase, lactate dehydrogenase, aspartate and alanine transaminases in heart and a significant increase in the levels of thiobarbituric acid reactive substances and lipid hydroperoxides in plasma and heart. ISO-induced rats also showed a significant decrease in the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase in heart and the levels of glutathione and ascorbic acid in plasma and heart. Oral administration of SAC (100 and 150 mg/kg) to ISO-treated rats daily for a period of 45 days caused a significant increase in the activities of marker enzymes and improved the antioxidant status by decreasing lipid peroxidative products and increasing the activities of antioxidant enzymes and the levels of nonenzyomic antioxidants. Administration of SAC to normal rats did not show any significant effect. Histopathological findings of the myocardial tissue showed a protective role of SAC in ISO-treated rats. The effect at a dose of 150 mg/kg of SAC was more pronounced than that of the dose 100mg/kg and brought back all the parameters to near normal. The effect exerted by 100 mg/kg of SAC was similar to that of alpha-tocopherol (60 mg/kg). The results of our study show that SAC possesses antioxidant activity in ISO-induced experimental MI.     

Preventive effect of naringin on isoproterenol-induced cardiotoxicity in Wistar rats: an in vivo and in vitro study

This study was aimed to evaluate the preventive role of naringin on heart weight, blood glucose, total proteins, albumin/globulin (A/G) ratio, serum uric acid, serum iron, plasma iron binding capacity and membrane bound enzymes such as sodium potassium-dependent adenosine triphosphatase (Na(+)/K(+) ATPase), calcium-dependent adenosine triphosphatase (Ca(2+) ATPase) and magnesium-dependent adenosine triphosphatase (Mg(2+) ATPase) and glycoproteins such as hexose, hexosamine, fucose and sialic acid in isoproterenol (ISO)-induced myocardial infarction (MI) in rats and in vitro free radical scavenging assay. Male albino Wistar rats were pretreated with naringin (10, 20 and 40 mg/kg, respectively) for a period of 56 days. After the treatment period, ISO (85 mg/kg) was subcutaneously injected to rats at an interval of 24 h for 2 days. ISO-induced rats showed a significant (P<0.05) increase in the heart weight, blood glucose, serum uric acid, serum iron and a significant (P<0.05) decrease in the levels of total proteins, A/G ratio and iron binding capacity. A significant (P<0.05) decrease in the activity of Na(+)/K(+) ATPase and increase in the activities of Ca(2+) and Mg(2+) ATPase in the heart and a significant (P<0.05) increase in the levels of glycoproteins in serum and the heart were also observed in ISO-induced rats. Pretreatment with naringin for a period of 56 days exhibited a significant (P<0.05) effect and altered these biochemical parameters positively in ISO-induced rats. Naringin also scavenges 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis-(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) and nitric oxide (NO) radicals in vitro. Thus, our study shows that naringin has cardioprotective role in ISO-induced MI in rats.     

Preventive effect of rutin, a bioflavonoid, on lipid peroxides and antioxidants in isoproterenol-induced myocardial infarction in rats

The consumption of diets rich in plant foods is associated with a reduced risk of cardiovascular diseases. This study aimed to evaluate the preventive role of rutin on lipid peroxides and antioxidants in normal and isoproterenol-induced myocardial infarction in rats. Subcutaneous injection of isoproterenol (150 mg kg(-1)) to male Wistar rats at an interval of 24 h for two days showed a significant increase in the activity of serum cardiac marker enzymes (creatine kinase, lactate dehydrogenase, aspartate transaminase and alanine transaminase) and a significant decrease in the activity of these enzymes in the heart. Lipid peroxidative products (thiobarbituricacid reactive substances and lipid hydroperoxides) were significantly increased and enzymic (superoxide dismutase, catalase and glutathione peroxidase) and non-enzymic (reduced glutathione and vitamin C) antioxidants showed a significant decrease in isoproterenol-treated rats. Pretreatment with rutin (40 or 80 mg kg(-1)) to isoproterenol-treated rats orally for a period of 42 days daily caused a significant effect. Administration of rutin to normal rats did not have any significant effect on any of the parameters studied. The results of our study show that rutin possesses antioxidant activity in isoproterenol-induced experimental myocardial infarction.     

Preventive effect of naringin on cardiac markers, electrocardiographic patterns and lysosomal hydrolases in normal and isoproterenol-induced myocardial infarction in Wistar rats

Diets rich in natural antioxidants are associated with reduced risk of heart diseases. This study was aimed to evaluate the preventive role of naringin on cardiac troponin T (cTnT), lactate dehydrogenase (LDH)-isoenzyme, cardiac marker enzymes, electrocardiographic (ECG)-patterns and lysosomal enzymes in isoproterenol (ISO)-induced myocardial infarction (MI) in male Wistar rats. Rats subcutaneously injected with ISO (85 mg/kg) at an interval of 24 h for 2 days showed a significant increase in the levels of cTnT, intensity of the bands of LDH-isoenzyme (LDH1 and LDH2) and the activities of cardiac marker enzymes such as creatine kinase-MB (CK-MB), creatine kinase (CK), LDH, aspartate transaminase (AST) and alanine transaminase (ALT) in serum with subsequent decrease in the activities of CK, LDH, AST and ALT in the heart and alterations in ECG-patterns. The activities of lysosomal enzymes (β-glucuronidase, β-N-acetyl glucosaminidase, β-galactosidase, cathepsin-B and cathepsin-D) were increased significantly in serum and the heart of ISO-induced rats, but the activities of β-glucuronidase and cathepsin-D were decreased significantly in the lysosomal fraction of the heart. Pretreatment with naringin (10, 20 or 40 mg/kg) daily for a period of 56 days positively altered the levels of cTnT, intensity of the bands of the LDH1 and LDH2-isoenzyme and the activities of cardiac marker enzymes, ECG-patterns and lysosomal hydrolases in ISO-induced rats. Thus, naringin possess cardioprotective effect in ISO-induced MI in rats.     

Expression of Concern: Preventive effect of nerolidol on isoproterenol induced myocardial damage in Wistar rats: Evidences from biochemical and histopathological studies

The present study aimed at investigating the protective effects of nerolidol (NRD) against myocardial infarction (MI) induced by isoproterenol (ISO) in Wistar rats. The rats were randomly divided into five groups, each group consisting of six rats. Group I were treated as control rats, group II received NRD (200 mg/kg b.w.) by intragastric intubation for 21 days, group III received ISO (60 mg/kg b.w) subcutaneously (s.c) for two consecutive days on 22nd and 23rd day, group IV and V received NRD (100 and 200 mg/kg b.w) as in group II and additionally ISO was given for two consecutive days (22nd and 23rd). On 24th day all the rats were sacrificed by cervical dislocation and the blood and heart samples were collected. In the present study, ISO-induced myocardial damage was indicated by the changes in body weight, heart weight and the cardiac and hepatic marker enzymes such as creatine kinase (CK), creatine kinase-MB (CK-MB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and troponin T and I (cTnT, cTnI) in the serum. In addition, the levels of lipid peroxidation products such as thiobarbituric acid reactive substances (TBARS), conjugated dines (CD), and lipid hydroperoxides (LHPs) increased significantly in the plasma and heart tissue. Activities of enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) in erythrocytes and heart tissue and the levels of nonenzymatic antioxidants like vitamin C, vitamin E, and reduced glutathione (GSH) in plasma and heart tissue were decreased in ISO-induced rats. Histopathological observations were also supported with the biochemical parameters. Pretreatment with NRD at different doses (100 and 200 mg/kg b.w) for 21 days prevented the above changes induced by ISO. The 200 mg/kg b.w of NRD was more pronounced than the other dose and brought back all the above parameters near to normalcy.     

Preventive effect of phytic acid on lysosomal hydrolases in normal and isoproterenol-induced myocardial infarction in Wistar rats

Abstract

This study was aimed to evaluate the preventive role of phytic acid on lysosomal enzymes in isoproterenol (ISO)-induced myocardial infarction (MI) in male Wistar rats. Rats subcutaneously injected with ISO (85?mg/kg) at an interval of 24?h for two days showed a significant increase in the activities of lysosomal enzymes (glucuronidase, N-acetyl glucosaminidase, galactosidase, cathepsin-B and cathepsin-D) were increased significantly in serum and the heart of ISO-induced rats, but the activities of glucuronidase and cathepsin-D were decreased significantly in the lysosomal fraction of the heart. Pretreatment with phytic acid (25 and 50?mg/kg) daily for a period of 56?d positively altered activities of lysosomal hydrolases in ISO-induced rats. Thus, phytic acid possesses a cardioprotective effect in ISO-induced MI in rats.     

Cardioprotective effect of Saraca indica against cyclophosphamide induced cardiotoxicity in rats: A biochemical,electrocardiographic and histopathological study

Objectives:

Cardioprotective activity of alcoholic extract of Saraca indica (SI) bark was investigated against cyclophosphamide induced cardiotoxicity.

Materials and Methods:

Cardiotoxicity was induced in Wistar rats by administering cyclophosphamide (200 mg/kg, i.p.) single injection on first day of experimental period. Saraca indica (200 and 400 mg/kg, p.o.) was administered immediately after administration of cyclophosphamide on first day and daily for 10 days. The general observations and mortality were measured.

Results:

Cyclophosphamide administration significantly (p < 0.05) increased lipid peroxidation (LPO) and decreased the levels of antioxidant markers such as reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). Cyclophosphamide elevated the levels of biomarker enzymes like creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB), lactate dehydrogenase (LDH), aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP). Further, the cyclophosphamide treated rats showed changes in electrocardiogram (ECG) along with increased levels of cholesterol and triglycerides. Treatment with Saraca indica significantly (p < 0.05) reversed the status of cardiac biomarkers, ECG, oxidative enzymes and lipid profile in cyclophosphamide induced cardiotoxicity. Potential cardioprotective effect of Saraca indica was supported by histopathological examination that reduced severity of cellular damage of the myocardium.

Conclusion:

The biochemical, ECG and histopathology reports support the cardioprotective effect of Saraca indica which could be attributed to antioxidant activity.KEY WORDS: Cardioprotective, cyclophosphamide, ECG, free radicals, Saraca indica Linn     

Ameliorative effect of an ethanol extract of Embelia ribes fruits on isoproterenol-induced cardiotoxicity in diabetic rats

The present study explored the protective effect of Embelia ribes Burm. (Myrsinaceae) fruit ethanol extract on isoproterenol (ISO)-induced cardiomyopathy in streptozotocin (STZ)-induced diabetic rats. STZ (40?mg/kg, intravenously, single-injection)-induced diabetic rats had significantly (p?<?0.01) increased heart rate (HR), systolic blood pressure (SBP), blood glucose, HbA_1C, serum LDH, serum CK, and myocardial TBARS levels, and decreased blood glutathione and myocardial endogenous antioxidants, viz. SOD, CAT, and GSH levels in comparison to group I rats. ISO (5.25 and 8.?5?mg/kg, s.c., for two consecutive days) administration produced myocardial necrosis as evidenced by a significant (p?<?0.01) increase in HR, SBP, serum LDH, serum CK, and myocardial TBARS levels and a significant (p?<?0.01) decrease in blood glutathione, and myocardial endogenous antioxidant levels in comparison to group I rats. Further, ISO administration to diabetic rats showed a significant (p?<?0.01) increase in SBP, blood glucose, and HbA_1C levels along with a significant (p?<?0.01) decrease in HR, blood glutathione, serum LDH, serum CK, myocardial TBARS, SOD, CAT, and GSH levels as compared to ISO-only treated (i.e. group IV) rats. Forty days treatment of Embelia ribes ethanol extract (200?mg/kg) to pathogenic (STZ + ISO treated) rats resulted in a significant (p?<?0.01) increase in HR, blood glutathione, serum LDH, and myocardial endogenous antioxidant levels with a significant (p?<?0.01) decrease in SBP, blood glucose, HbA_1C, serum CK, and myocardial TBARS levels as compared to pathogenic (STZ + ISO treated) rats. The study demonstrates the ability of Embelia ribes extract to attenuate ISO-induced oxidative stress in diabetic rats, enhancing cellular antioxidant defense.     

Protective effects of the standardized extract of Zingiber officinale on myocardium against isoproterenol-induced biochemical and histopathological alterations in rats

Abstract

Context: Ginger [Zingiber officinale Roscoe. (Zingiberaceae)] has been universally used as a spice as well as for its health benefits.

Objective: The present study evaluates the protective effect of the standardized extract of ginger against isoproterenol (ISO)-induced myocardial infarction (MI) in rats.

Materials and methods: Wistar rats were pretreated orally with three doses of standardized ginger extract (100, 200, and 400?mg/kg of body weight) or propranolol (5?mg/mL) for 28?d prior to ISO (85?mg/kg) induced MI in two doses on days 29 and 30. The rats were sacrificed 48?h after the first induction; serum and hearts were collected for biochemical and histopathological analysis.

Results: Gingerols and shogaols were identified and quantitatively analyzed in the extracts using validated reversed phase HPLC methods. Pretreatment with ginger extract at 400?mg/kg showed a significant decrease (p?<?0.05) in all the cardiac enzyme activities, i.e., cardiac troponin I (cTnI) (0.57?ng/mL), creatine kinase MB isoenzyme (CK-MB) (10.34?pg/mL), lactate dehydrogenase (LDH) (115.22?U/L), alanine transaminase (ALT) (15.79?U/L), and aspartate transaminase (AST) (46.72?U/L) when compared with ISO-control rats. There were significant rises (p?<?0.05) in the activity of glutathione peroxide (GPx) (53.16?U/L), catalase (CAT) (210.41?U/L), and superoxide dismutase (SOD) (280.89?U/mL) of the pretreated rats when compared with the ISO-control. Histopathological examination showed an improvement in membrane cell integrity in pretreated rats compared with untreated rats.

Conclusion: The ethanol extract of ginger exhibited cardioprotective potential in treating myocardial injury following ISO administration.     

Hepatoprotective role of naringin on nickel-induced toxicity in male Wistar rats

Aim of the present study was planned to determine the protective role of naringin in attenuating the toxicity induced by nickel sulfate in rat liver. In this investigation nickel sulfate (20 mg/kg body weight) was administered intraperitoneally for 20 days to induce toxicity. Naringin was administered orally (20, 40 and 80 mg/kg body weight) for 20 days with intraperitoneal administration of nickel sulfate. Liver injury was measured by the increased activities of serum hepatic enzymes namely aspartate transaminase, alanine transaminase, alkaline phosphatase, gamma glutamyl transferase, lactate dehydrogenase and total bilirubin along with increased elevation of lipid peroxidation markers, thiobarbituric reactive acid substances, lipid hydroperoxides, protein carbonyl content and conjugated dienes. The toxic effect of nickel was also indicated by significantly decreased activities of enzymatic antioxidants like superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase and glucose-6-phosphate dehydrogenase and non-enzymatic antioxidants like reduced glutathione, total sulfhydryl groups, vitamin C and vitamin E levels were significantly decreased. Naringin administered at a dose of 80 mg/kg body weight significantly reversed the activities of hepatic marker enzymes, decreasing lipid peroxidative markers, increasing the antioxidant cascade and decreasing the nickel concentration in the liver. The effect at a dose of 80 mg/kg body weight was more pronounced than that of other two doses (20 and 40 mg/kg body weight). All these changes were supported by histopathological observations. These results clearly demonstrate that naringin has the potential in alleviating the toxic effects of nickel in rat liver.     

Preventive effect of glycosaminoglycans from Amussium pleuronectus (Linne) on biomolecules, lactate dehydrogenase-isoenzyme and electrocardiographic patterns in isoproterenol-induced myocardial infarction in Wistar rats

Objectives:

This study was aimed to assess the cardioprotective role of low molecular weight glycosaminoglycans (LMW-GAG) in isoproterenol (ISO)-induced myocardial infarction (MI) in male Wistar rats. Effect of LMW-GAG on biomolecules, lactate dehydrogenase (LDH)-isoenzyme, and electrocardiographic (ECG)-patterns was studied as evidence of cardioprotection.

Materials and Methods:

Male Wistar rats (140 ± 10 g) were divided into four groups; untreated control (group I), LMW-GAG treated (300 μg/day s. c. for 2 weeks—group II), ISO (85 mg s.c. injected on 13^th and 14^th days—group III), and LMW-GAG plus ISO (300 μg/day s. c. for 12 days followed by 85 mg/kg ISO on the end of 13^th and 14^th days—group IV). At the end of the experimental period, all animals were terminated.

Results:

Rats treated with LMW-GAG (300 μg/kg) for 12 days showed significant increasing levels of triglyceride (TG) (both serum and heart tissue), low density lipoprotein (LDL), very low density lipoprotein (VLDL), total cholesterol, uric acid, creatinine, and glucose. However, it significantly decreased the levels of high density lipoprotein (HDL) (serum), plasma total protein, and albumin/globulin (A/G) ratio. ISO also adversely affected the LDH-isoenzymes and caused marked elevation in ST segment. Pretreatment with LMW-GAG (300 μg/kg) daily for a period of 2 weeks prevented the ISO-treated changes.

Conclusions:

The results indicate that LMW-GAG exhibits a cardioprotective effect in ISO-induced MI in rats, by maintaining the biomolecules and LDH-isoenzymes.KEY WORDS: A. pleuronectus, ECG, LDH-isoenzyme, LMW-GAG, myocardial infarction     

Cardioprotective effect of lemon grass as evidenced by biochemical and histopathological changes in experimentally induced cardiotoxicity

Isoproterenol is a synthetic catecholamine found to cause toxicity leading to severe stress in the myocardium of experimental animals. The aim of the present study is to evaluate the cardioprotective effect of Cymbopogon citratus, which is used as a culinary item and commonly known as lemon grass (LG), in isoproterenol-induced cardiotoxicity. Male Wistar albino rats were segregated into five different groups as follows. Groups I and II rats were treated with vehicle. Groups III and IV rats were treated with 100 and 200 mg/kg b.wt. of LG. Group V with 100 mg/kg b.wt. of vitamin E. Myocardial necrosis was induced in Groups II, III, IV and V on 58(th) and 59(th) day using isoproterenol at a dose of 85 mg/kg twice at 24-hour interval. Animals were sacrificed on the 60( th) day. LG pretreatment exhibited cardioprotective activity as evidenced by decreased activity of cardiac markers in serum and increased the same in heart homogenate (p < 0.05). LG administration decreased the toxic events of lipid peroxidation (TBARS) in both serum and heart tissue, by increasing the level of enzymatic antioxidants and non-enzymatic antioxidants significantly in both heart homogenate and serum sample (p < 0.05). The histopathological observations also revealed that the cardioprotective effect of LG extract was observed at a dose of 200 mg/kg b.wt. The results of the present study reveal that LG is cardioprotective and antilipid peroxidative by increasing various antioxidants at a dose of 200 mg/kg b.wt., which is comparable with that of vitamin E.     

Protective effect of Artemisia afra Jacq. on isoproterenol-induced myocardial injury in Wistar rats

Artemisiaafra Jacq. ex Willd. is a widely used medicinal plant in South Africa for the treatment of various diseases. In this study, the effect of the herb on isoproterenol (ISO)-induced myocardial injury in rats was investigated. Pretreatment with the aqueous leaf extract of the plant at 100 and 200 mg/kg body weight for 30 days prevented the elevation of serum marker enzymes namely lactate dehydrogenase (LDH), aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) in myocardial injured rats. ISO-induced animals exhibited decreased levels of glutathione reductase (GR), glutathione peroxides (GPx), superoxide dismutase (SOD) and glutathione (GSH) in the heart, which were restored to near normal levels following treatment with the herb. The extract also attenuated lipid peroxidation (LPO) in the heart and improved the imbalance in lipid profile caused by ISO. The effect was more prominent at 200 mg/kg body weight. These findings revealed the cardioprotective effect of A. afra against isoproterenol-induced myocardial injury.     

Efficacy of sesamol on plasma and tissue lipids in isoproterenol-induced cardiotoxicity in wistar rats

Myocardial infarction is the leading cause of death all over the world. Sesamol is a potent phenolic antioxidant contained only in processed sesame oil and possesses potent chemopreventive, antimutagenic, antihepatotoxic and antioxidation properties. This study was undertaken to investigate the effect of sesamol on plasma and tissue lipid profiles in isoproterenol (ISO) - induced rats. Myocardial infarction was induced in adult male albino rats of the Wistar strain, weighing 180-200 g, by administration of isoproterenol (85 mg/kg of body weight), subcutaneously for 2 consecutive days. Sesamol dissolved in saline (0.9% NaCl) was administered intraperitoneally once in a day in the morning for 7 days. Increased levels of total cholesterol, phospholipids, triglycerides and free fatty acids in the plasma and the decreased levels of phospholipids in tissues were observed in ISO-induced rats. Very low density lipoprotein cholesterol (VLDL-C) and low density lipoprotein cholesterol (LDL-C) increased while high density lipoprotein cholesterol (HDL-C) decreased in the plasma of ISO-induced rats. Administration of sesamol (50, 100 and 200 mg/kg of body weight) improved the above changes and brought towards normal level. The protective role of sesamol against isoproterenol-induced myocardial infarction was further confirmed by histopathological examination. These results suggest that sesamol has antihyperlipidaemic effect against cardiotoxicity.     

Seabuckthorn attenuates cardiac dysfunction and oxidative stress in isoproterenol-induced cardiotoxicity in rats

We investigated the effects of seabuckthorn (SBT) oil in isoproterenol (ISO)-induced cardiotoxicity with reference to hemodynamic, antioxidant, histopathological, and ultrastructural parameters. Rats were administered SBT oil (5, 10, and 20 mL/kg per d) or vehicle orally for 30 days along with ISO (85 mg/kg, subcutaneously, at 24-hour interval) on 29th and 30th day. On 31st day, ISO control rats showed cardiac dysfunction, increased lipid peroxidation, depletion of cardiac injury marker enzymes, and antioxidant activities. Myocardial necrosis, edema, and inflammation were evident from the light microscopic and ultrastructural changes. Seabuckthorn oil at the dose of 20 mL/kg per d significantly modulates hemodynamic and antioxidant derangements. The preventive role of SBT oil on ISO-induced cardiotoxicity was reconfirmed by histopathological and ultrastructural examinations. Thus, the present study reveals that SBT oil mitigates myocardial damage in ISO-induced cardiac injury in rats by maintaining hemodynamic, biochemical, histopathological, and ultrastructural perturbations owing to its free radical scavenging and antioxidant activities.     

The effect of adenosine triphosphate on propofol-induced myopathy in rats: a biochemical and histopathological evaluation

Propofol infusion syndrome characterized by rhabdomyolysis, metabolic acidosis, kidney, and heart failure has been reported in long-term propofol use for sedation. It has been reported that intracellular adenosine triphosphate (ATP) is reduced in rhabdomyolysis. The study aims to investigate the protective effect of ATP against possible skeletal muscle damage of propofol in albino Wistar male rats biochemically and histopathologically. PA-50 (n = 6) and PA-100 (n = 6) groups of animals was injected intraperitoneally to 4 mg/kg ATP. An equal volume (0.5 ml) of distilled water was administered intraperitoneally to the P-50, P-100, and HG groups. One hour after the administration of ATP and distilled water, 50 mg/kg propofol was injected intraperitoneally to the P-50 and PA-50 groups. This procedure was repeated once a day for 30 days. The dose of 100 mg/kg propofol was injected intraperitoneally to the P-100 and PA-100 groups. This procedure was performed three times with an interval of 1 days. Our experimental results showed that propofol increased serum CK, CK-MB, creatinine, BUN, TP I, ALT, AST levels, and muscle tissue MDA levels at 100 mg/kg compared to 50 mg/kg and decreased tGSH levels. At a dose of 100 mg/kg, propofol caused more severe histopathological damage compared to 50 mg/kg. It was found that ATP prevented propofol-induced muscle damage and organ dysfunction at a dose of 50 mg/kg at a higher level compared to 100 mg/kg. ATP may be useful in the treatment of propofol-induced rhabdomyolysis and multiple organ damage.     

The relationship between nutritional antioxidants and serum lipid peroxides in cancer patients

A new parameter, the ratio of lipid peroxide and vitamins E and C [LPO/(VE + VC)], has been proposed and used to reflect the balance between lipid peroxidation and antioxidation capability of cancer patients and of healthy human controls. The effects of vitamins E, C, and selenium on the serum LPO level in mice bearing Ascites Hepatomas (H22) have also been examined. The results showed that the average of LPO/(VE + VC) ratios in cancer patients (135 cases) was significantly higher than that of the normal controls (222 cases). The authors suggest that this ratio might be used as one of the parameters for early diagnosis and prognosis of diseases (including cancers) caused by free radicals and lipid peroxides. The results also showed that antioxidants - Se(Na2SeO3, 1mg/kg) or vitamin E (5mg/kg) could markedly decrease the level of serum LPO in the tumor-bearing animals. A smaller dose of VE (1mg/kg) and doses of Vc up to 300mg/kg showed no effect on the serum LPO levels when given separately. However, synergistic effects were observed when any 2 out of 3 or three nutrients were given together. Those with three nutrients significantly lowered the serum LPO level. These antioxidants also inhibited the proliferation of tumour cells.     

Electrocardiographic and biochemical evidence for the cardioprotective effect of antioxidants in acute doxorubicin-induced cardiotoxicity in the beagle dogs

Doxorubicin (DOX) is a potent antitumor agent, but the cardiotoxicity mediated by the formation of reactive oxygen species limit its clinical use. The present study aims to explore electrocardiographic and biochemical evidence for the cardioprotective effect of two antioxidants, Lycium barbarum polysaccharides (LBP, the main antioxidant in Lycium barbarum) and edaravone (a potent free radical scavenger, EDA) against DOX-induced acute cardiotoxicity in beagle dogs. In this study, male beagle dogs received daily treatment of either LBP (20 mg/kg, per os (p.o.)) or EDA (2 mg/kg, intravenously (i.v.)) for 7 d and then followed by an intravenous injection of DOX (1.5 mg/kg). DOX (15 mg/kg) significantly induced acute cardiotoxicity in dogs characterized by conduction abnormalities (including decreased heart rate, ST segment elevation, QT intervals prolongation, inverted T wave, arrhythmia, and myocardial ischemia) and increased serum creatine kinase (CK) and aspartate aminotransferase (AST). Pretreatment with LBP or EDA effectively alleviated both DOX-associated conduction abnormalities and increased serum CK and AST. Moreover, physiological and serum biochemical evidences demonstrated that EDA is more effective than LBP in alleviating these abnormalities produced by DOX in heart. All these results confirm and extend previous observations in rats concerning the effectiveness of LBP or EDA against DOX-induced cardiomyopathy.     

Effect of ginsenoside Rh1 on myocardial injury and heart function in isoproterenol-induced cardiotoxicity in rats

The present study was designed to investigate the effect of ginsenoside Rh1 on myocardial injury and heart function in isoproterenol-induced cardiotoxicity in rats. Sprague–Dawley rats were subcutaneously injected with isoproterenol (20?mg/kg). Cardiac marker enzymes in serum, antioxidative parameters and inflammatory cytokines in left ventricles were measured. Hemodynamic parameters were monitored and recorded as well. Histopathological examination of left ventricles was performed. It was found that creatine kinase-MB (CK-MB) activity and troponin T level in isoproterenol-treated rats were significantly increased. Isoproterenol caused declines of left ventricular systolic pressure, positive and negative maximal values of the first derivative of left ventricular pressure, and an elevation of left ventricular end diastolic pressure. Isoproterenol enhanced the content of malondialdehyde (MDA), tumor necrosis-α (TNF-α), interleukin-1β (IL-1β) and decreased the activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) in left ventricles. Ginsenoside Rh1 significantly ameliorated myocardial injury and heart function impairment induced by isoproterenol. The cardioprotective effect of ginsenoside Rh1 was further confirmed by histopathological examination. Ginsenoside Rh1 also partially inhibited the increase of MDA, TNF-α, IL-1β contents and the decrease of SOD, catalase, and GSH-Px activities in left ventricles. The results indicated that ginsenoside Rh1 possessed the effect against isoproterenol-induced cardiotoxicity, and that the mechanism of pharmacological action was related to regulating the activities of SOD, catalase, and GSH-Px and decreasing the contents of TNF-α and IL-1β.     

Effect of ginsenoside Rh1 on myocardial injury and heart function in isoproterenol-induced cardiotoxicity in rats

The present study was designed to investigate the effect of ginsenoside Rh1 on myocardial injury and heart function in isoproterenol-induced cardiotoxicity in rats. Sprague-Dawley rats were subcutaneously injected with isoproterenol (20?mg/kg). Cardiac marker enzymes in serum, antioxidative parameters and inflammatory cytokines in left ventricles were measured. Hemodynamic parameters were monitored and recorded as well. Histopathological examination of left ventricles was performed. It was found that creatine kinase-MB (CK-MB) activity and troponin T level in isoproterenol-treated rats were significantly increased. Isoproterenol caused declines of left ventricular systolic pressure, positive and negative maximal values of the first derivative of left ventricular pressure, and an elevation of left ventricular end diastolic pressure. Isoproterenol enhanced the content of malondialdehyde (MDA), tumor necrosis-α (TNF-α), interleukin-1β (IL-1β) and decreased the activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) in left ventricles. Ginsenoside Rh1 significantly ameliorated myocardial injury and heart function impairment induced by isoproterenol. The cardioprotective effect of ginsenoside Rh1 was further confirmed by histopathological examination. Ginsenoside Rh1 also partially inhibited the increase of MDA, TNF-α, IL-1β contents and the decrease of SOD, catalase, and GSH-Px activities in left ventricles. The results indicated that ginsenoside Rh1 possessed the effect against isoproterenol-induced cardiotoxicity, and that the mechanism of pharmacological action was related to regulating the activities of SOD, catalase, and GSH-Px and decreasing the contents of TNF-α and IL-1β.