Effect of vitamin E on oxidative stress status in small intestine of diabetic rat

AIM:To investigate the effect of vitamin E on oxidative stress status in the small intestine of diabetic rats. METHODS:Twenty-four male Wistar rats were randomly divided into three groups:Control (C),non-treated diabetic (NTD) and vitamin E-treated diabetic (VETD) groups. The increases in lipid peroxidation,protein oxidation and superoxide dismutase (SOD) in these three groups was compared after 6 wk. RESULTS:There was no significant difference in catalase activity between NTD and control rats. Compared to NTD rats,the treatment with vitamin E significantly decreased lipid peroxidation and protein oxidation,and also increased catalase activity and SOD. CONCLUSION:The results revealed the occurrence of oxidative stress in the small intestine of diabetic rats. Vitamin E,as an antioxidant,attenuates lipid peroxidation and protein oxidation,and increases antioxidant defense mechanism.     

QT prolongation in HIV-positive patients: Review article

IntroductionAntiretrovirals have immensely increased the average life expectancy of HIV-positive patients. However, the incidence of QT interval prolongation and other arrhythmias has also increased.MethodsPubmed and Google Scholar were searched for relevant literature published between 1990 and 2019.Results and discussionHIV-positive patients with high viral load, low CD4 count, chronic inflammation, and autonomic neuropathy can develop QT interval prolongation. Another factor prolonging QT interval includes exposure to the HIV transactivator protein, which inhibits hERG K (+) channels controlling IKr K (+) currents in cardiomyocytes. Protease inhibitors inhibiting the CYP3A4 enzyme can also lead to QT interval prolongation. QT interval prolongation can potentially be exacerbated by opioids, antipsychotics, antibiotics, and antifungals, the adjunct medications often used in HIV-positive patients. Hepatic insufficiency in seropositive patients on antiretrovirals may also increase the risk of QT interval prolongation.ConclusionBaseline and follow-up EKG in the susceptible population is suggested.     

Potentiation of acute paraquat toxicity by vitamin E deficiency

The present study evaluated the development and course of acute paraquat toxicity in rats deficient in vitamin E, a major biologic antioxidant which interrupts free radical chain reactions and blocks lipid peroxidation. Normal and vitamin E deficient rats were given 50 mg/kg paraquat dichloride in a single intraperitoneal (IP) injection. Both percent survival and duration of survival following paraquat were significantly reduced in vitamin E deficient rats. Only 1 (2.5%) of 40 vitamin E deficient rats survived 14 days compared to 12 (30%) of 40 (p < 0.001) normal rats, and deaths occurred much earlier (p < 0.001) in vitamin E deficient rats. In addition, histologic lung damage 24 to 48 h after paraquat administration was far more extensive in vitamin E deficient rats than normal rats. Vitamin E deficient rats treated (i. e., repleted) for 7 days prior to paraquat with vitamin E 1 mg/kg/day IP had a survival rate and duration of survival nearly identical to normal rats receiving paraquat. In contrast, vitamin E deficient rats treated for 3 days prior to and 3 days after paraquat administration with superoxide dismutase (SOD) 10 mg/kg bid IP had survival rates and lung histologic changes indistinguishable from vitamin E deficient rats not receiving SOD. These results (1) demonstrate that deficiency of vitamin E potentiates acute paraquat toxicity in rats, (2) indicate that this potentiation is readily reversed by administration of vitamin E but not SOD, and (3) provide in vivo evidence that paraquat toxicity may be mediated through lipid peroxidation.     

Autonomic neuropathy,QT interval lengthening,and unexpected deaths in male diabetic patients

Summary QT intervals were measured over RR intervals ranging from 500 ms to 1000 ms in 13 normal male subjects, 13 male diabetic subjects without and 13 with autonomic neuropathy. There was a close linear relationship between QT and RR in all subjects. The slope of the regression line was significantly greater in the autonomic neuropathy group than the normal group. Thirty-two male diabetic subjects with varying degrees of autonomic dysfunction had repeat QT measurements 3 (range 2–6) years later. QT and QTC lengthened significantly at the second visit, unrelated to age or time between recordings, but which corresponded with changes in autonomic function. Of 71 male diabetic subjects under 60 years followed for 3 years, 13 had died, 8 unexpectedly. Of those with autonomic neuropathy, QT and QTC were significantly longer in those who subsequently died, despite similar ages and duration of diabetes. We conclude that QT/RR interval relationships are altered in diabetic autonomic neuropathy, and that changes in QT length with time parallel changese in autonomic function. There may be an association between QT interval prolongation and the risk of dying unexpectedly in diabetic autonomic neuropathy.     

Cardiac repolarization interval in end-stage diabetic and nondiabetic renal disease

Background and hypothesis: QT interval length is influenced by autonomic nervous activity. In patients with diabetic autonomic neuropathy, both prolongation and shortening of ventricular repolarization has been reported. We studied diabetic and nondiabetic uremic patients to assess the effects of autonomic neuropathy on QT interval length. Methods: 24-hour electrocardiogram recordings were performed in 12 diabetic and 11 nondiabetic renal transplantation patients, and in 12 control patients. Mean and corrected QT interval (QTc) during the 24-h period and intervals at predetermined heart rates at day and night periods were determined. The degree of autonomic neuropathy was assessed with cardiovascular autonomic function tests and measurement of heart rate variability. Results: In the diabetic group, severe autonomic neuropathy was present; in nondiabetic uremic patients, abnormalities were less severe. Mean QTc interval during 24 h was 444 ± 24,447 ± 21, and 442 ± 19 ms in the diabetic and nondiabetic uremic patients, and in the control groups, respectively, without any between-group difference. QT and QTc interval length did not differ among the groups when measured at heart rates of 70, 80, 90, or 100 beats/min. Conclusions: In patients with autonomic failure caused by diabetes and/or uremia, QT interval length cannot be used as a diagnostic indicator of cardiac autonomic neuropathy.     

Modification by vitamin E and exercise of oxidative stress in regions of aging rat brain: studies on superoxide dismutase isoenzymes and protein oxidation status

This study was aimed at determining the effect of exercise and vitamin E on age-associated changes in the superoxide dismutase (SOD), lipid (LPO) and protein oxidations (PO) in the cerebral cortex (CC), cerebellum (CB) and hippocampus (HC) of rat brain. For this, male Wistar albino rats of 4- (adult), 12- (middle-age) and 18-month (old) of age were orally supplemented with vitamin E and swim trained at 3% intensity for 30 min/day, 5 days/week, and for a period of 30 days. Reduced total SOD was evident with age in the CC while it was highest in the HC of old rats. Vitamin E elevated SOD in the old trainees. Mn-SOD increased in the middle-age and old trainees and Cu Zn-SOD increased in the supplemented and trained adults. Age-related and region-specific increase in protein carbonyl (PrC) content with decreased sulphydryl (P-SH) was seen. Vitamin E reduced PrC and advanced oxidation of protein products (AOPP) in all ages, and appreciably in the HC and CB. Our study emphasizes a correlation between mitochondrial H(2)O(2) generation, Mn-SOD activity and MDA level, and reveals in part an age-related increase in lipid peroxidation and protein oxidation, and that may occur under conditions such as vitamin E deficiency.     

Protective effects of vitamin C against propanil-induced hepatotoxicity in wistar rats

ObjectiveTo investigate the hepatoprotective effects of Vitamin C in propanil intoxiciated Wistar rats.MethodsTwenty-four adult male rats were divided into four equal groups of six each: control; 100mg propanil/kg; 100mg vitamin C/kg; propanil (100mg/kg) plus vitamin C (100mg/kg). Treatment was via oral route and was administered once daily for 7 days. Animals were orally treated once daily for 7 days. The effect of propanil on liver lipid peroxidation, antioxidant enzymes and biochemical parameters as well as the possible attenuation of its toxicity by vitamin C was studied.ResultsCompared to the control group, propanil treatment significantly increased serum total cholesterol, alkaline phosphatase (ALP), alanine aminotransferase(ALT), aspartate aminotransferase levels (AST), and significantly lowered triglyceride (TG), high density lipoprotein cholesterol (HDLC) and total protein (TP) levels. Results obtained furthermore showed that propanil significantly (P < 0.05) induced malondialdehyde (MDA) levels while the activities of glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) were decreased in the liver tissues. However, co-administration of propanil with vitamin C ameliorated the harmful effects of propanil in most of the tested parameters. Liver histological studies revealed changes in liver tissues and the protective role of vitamin C.ConclusionThe present study suggests that Vitamin C could be an important dietary component based on its ability to attenuate propanil induced hepatotoxicity.     

Effect of Emilia sonchifolia (Linn.)DC on alcohol-induced oxidative stress in pancreas of male albino rats

ObjectiveTo explore the efficacy of n-hexane extract of Emilia sonchifolia (E. sonchifobia) against ethanol induced pancreatic dysfunction in the young Wistar albino rats.MethodsThe rats were divided into four groups. Control rats in group received distilled water orally, group received oral administration of 20% (w/v) ethanol dissolved in drinking water, group received oral administration of 20% (w/v) ethanol in distilled water+n-hexane extract of E. sonchifolia (250 mg/kg body weight), and group received oral administration of n-hexane extract of E. sonchifolia (250 mg/kg body weight) alone. Liver marker enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), pancreatic enzymatic antioxidants superoxide dismutase, lipid peroxidation, catalase, glutathione peroxidase, non-enzymatic antioxidants glutathione and vitamin C were measured and compared.ResultsAdministration of 20% ethanol for 16 weeks significantly increased the liver marker enzymes AST, ALT(P<0.05), reduced the pancreatic enzymatic antioxidants superoxide dismutase, lipid peroxidation, catalase, glutathione peroxidase, glutathione and vitamin C(P<0.05). Histopathological examination showed that the ethanol provoked the oxidative stress which was demonstrated as pancreatic necrosis and oedema. Simultaneous administration of n-hexane extract of E. sonchifolia (250 mg/kg body weight) protected the pancreas against the damage induced by ethanol which was confirmed by the histopathological studies and the normalization of biochemical parameters.ConclusionsThus n-hexane extract of E. sonchifolia shows a promise in therapeutic use in alcohol induced oxidative stress.     

Signal-averaged Electrocardiogram in Patients with Insulin-dependent (Type 1) Diabetes Mellitus With and Without Diabetic Neuropathy

The purpose of this study was to investigate the presence of ventricular late potentials derived from signal-averaged ECG in patients with IDDM with and without diabetic neuropathy. Eighty patients with IDDM but without evidence of cardiac disease and 80 age-matched healthy control subjects were investigated. The corrected QT interval was measured from the standard surface electrocardiogram. Ventricular late potentials were derived from signal-averaged electrocardiogram. Out of the 80 diabetic patients, 20 had an autonomic neuropathy, 20 had an isolated peripheral neuropathy, and 40 had no symptoms of neuropathy. The corrected QT interval was significantly prolonged in patients with an autonomic neuropathy as compared with the control group (436 ± 23 ms^.5 vs 384 ± 23 ms^.5, p < 0.001). In the other patient groups there was no significant prolongation of the corrected QT interval. Ventricular late potentials were present in 3 diabetic patients with an isolated peripheral neuropathy and in 1 control subject (NS). No diabetic patient with an autonomic neuropathy had ventricular late potentials. Our data did not indicate an increased incidence of ventricular late potentials derived from signal-averaged electrocardiogram in diabetic patients independent of a coexisting diabetic neuropathy or a prolonged corrected QT interval. © 1997 by John Wiley & Sons, Ltd.     

Lipid peroxidation in lung of rat stressed by immobilization: Effects of vitamin E supplementation

This study was carried out to examine the possibility of initiation of lipid peroxidation in the lung of Wistar albino male rats stressed by immobilization. The effects of vitamin E supplementation were also investigated. We found that immobilization of rats with normal pulmonary content of vitamin E caused lipid peroxidation in the lung. Decrease of the lung content of unsaturated fatty acids and vitamin E was also established. The immobilization-induced changes of all of these parameters were significantly inhibited by vitamin E injection (100 mg/kg body weight) for 7 days. A possible sequence of events leading to the initiation of lipid peroxidation and lung cell membrane damage in rats stressed by immobilization is discussed. Offprint requests to: Stefan Ribarov, PhD     

Prolonged QT period in diabetic autonomic neuropathy: a possible role in sudden cardiac death?

Twenty four men with insulin dependent diabetes and different degrees of autonomic neuropathy were studied to establish the response of the QT interval to various heart rates. Nine men with autonomic neuropathy had a longer QT interval than 13 healthy individuals and 15 patients who had diabetes without, or with only mild, autonomic neuropathy. Those with autonomic neuropathy also had a proportionally greater lengthening of the QT interval for a given increase in RR interval. The results of this study suggest a basis for the finding that sudden death is more common in patients with diabetic autonomic neuropathy.     

Prolonged QT period in diabetic autonomic neuropathy: a possible role in sudden cardiac death?

Twenty four men with insulin dependent diabetes and different degrees of autonomic neuropathy were studied to establish the response of the QT interval to various heart rates. Nine men with autonomic neuropathy had a longer QT interval than 13 healthy individuals and 15 patients who had diabetes without, or with only mild, autonomic neuropathy. Those with autonomic neuropathy also had a proportionally greater lengthening of the QT interval for a given increase in RR interval. The results of this study suggest a basis for the finding that sudden death is more common in patients with diabetic autonomic neuropathy.     

The effect of carnosine treatment on prooxidant–antioxidant balance in liver,heart and brain tissues of male aged rats

Carnosine (β-alanyl-l-histidine) is a dipeptide with antioxidant properties. Oxidative damage by free radicals is one of the mechanisms underlying the aging process. This study was done to investigate the effects of carnosine treatment on lipid peroxidation and antioxidant status of liver, heart, brain in male young and aged rats. At the initiation of study, young and aged rats were 5 and 22 months old, respectively. Carnosine (250 mg/kg, daily, i.p.) was administered for 1 month to rats. At the end of this period, malondialdehyde (MDA) and diene conjugate (DC) and protein carbonyl (PC) levels, glutathione (GSH), vitamin E and vitamin C levels and Cu,Zn-superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities were determined in tissues of carnosine-treated young and old rats. Liver and heart, but not brain MDA and DC levels increased significantly in aged rats as compared to young rats. Liver PC levels were also significantly elevated. Significant decreases in GSH and vitamin C levels and SOD activities were detected in liver of aged rats, but vitamin E levels and GSH-Px and GST activities remained unchanged. Non-enzymatic and enzymatic antioxidants did not change in heart and brain of aged rats. Carnosine treatment decreased high MDA, DC and PC levels and caused significant increases in vitamin E level and SOD activity in the liver of aged rats. There were no changes in non-enzymatic and enzymatic antioxidants in the heart and brain of carnosine-treated aged rats. In conclusion, carnosine treatment was found to be useful in the decrease of age-related oxidative stress in the liver.     

Vitamin E attenuates alcohol-induced aortic wall damage in rats

BackgroundIn this study the effect of chronic ethanol consumption on vascular wall abnormality via oxidative stress was examined. It was also intended to find out whether vitamin E inhibits the abnormality induced by ethanol in rat vascular wall.MethodsTwenty-four male wistar rats were divided into three groups, namely, control, ethanol (4.5 g/kgBW intragastrically), and vitamin E treated ethanolic groups(VETE) (300 mg interagastrically).ResultsAfter 6 weeks treatment of rats, the results revealed that along with a significant increase VSMC proliferation and aorta wall thickness with the increase in the level of Ox-LDL, protein carbonyl, as well as decrease total antioxidant capacity in animal that received ethanol compared to the control group. Significant amelioration of aorta wall changes, along restoration of the elevated level of Ox-LDL, protein carbonyl, lipid profile, and decreased level of total antioxidant capacity to that of controls were found in vitamin E-treated animals.ConclusionsThese findings strongly support the idea that heavy and chronic ethanol consumption initiate atherosclerosis by oxidative stress, and that these effects can be alleviated by vitamin E as an antioxidant.     

Effect of quercetin on galactose-induced hyperglycaemic oxidative stress in hepatic and neuronal tissues of Wistar rats

Abstract In recent times there has been great demand for natural products that have possible preventive action against diabetes and its secondary complications. Keeping this in mind, this study was undertaken to investigate the influence of the flavonoid, quercetin, on oxidative stress markers and the antioxidant defence system of hepatic and neuronal tissues from galactose-induced hyperglycaemic rats. Weanling male Wistar rats were treated with 30% galactose in AIN 93 diet (group B, n=8) to induce hyperglycaemia. Control rats received normal Stock AIN 93 diet (group A, n=8). The third set of rats received group B diet with quercetin at 400 mg/100 g diet (group C, n=8). Glucose levels and body weights were measured on a weekly basis for four weeks to monitor the hyperglycaemia induced by galactose feeding. Parameters involved in the pathogenesis of galactose-induced hyperglycaemia, which included organosomatic index, protein content, antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), tryptophan fluorescence, content of protein carbonyls, prooxidant malonaldehyde (MDA) and glutathione (GSH) in hepatic and neuronal tissues were determined at the end of the fourth week. The study suggest that quercetin counters the pro-oxidant effects of galactose-induced hyperglycaemic stress, as there was a significant reversal of changes with respect to body weights, organosomatic index of hepatic and neuronal tissues, lipid peroxidation, protein carbonyl content, reduced glutathione and activities of antioxidant enzymes. In addition, treatment with quercetin appears to reduce the osmotic stress induced by hyperglycaemia, as assessed by polyol pathway enzyme aldose reductase. These results imply that inclusion of quercetin in the diet controls, to some extent, galactose-induced hyperglycaemia and its attendant complications.     

The antioxidant status and lipid peroxidation product of newly diagnosed and 6 weeks follow–up patients with pulmonary tuberculosis in Owerri,Imo state,Nigeria

ObjectiveTo determine the levels of antioxidants vitamins C and E as well as lipid peroxidation product malondialdehyde (MDA) in Mycobacterium tuberculosis (M. tuberculosis) patients.MethodsSixty two M. tuberculosis positive patients and fifty five healthy controls within the age of twenty five to forty years without any systemic disease attending General Hospital Owerri were involved in this study. Forty one cases were longitudinally followed up with standard anti-tuberculosis chemotherapy (ATT) for six weeks.ResultsThe results obtained showed that the levels of vitamin C (0.91±0.42 mg/dL) and vitamin E (0.84±0.31 mg/dL) were significantly decreased in M. tuberculosis patients before treatment when compared to the healthy controls [(1.64±0.41 mg/dL) and (1.46±0.38 mg/dL)] respectively at P<0.05, while the level of MDA (8.7±1.81 nM/mL) in M. tuberculosis patients was significantly higher (P<0.05) before anti-tuberculosis treatment as compared with the healthy control (4.91±1.9 nM/mL). Also, there was a significant increase in vitamin C and E levels after 6 weeks of ATT, while MDA levels was decreased when compared with the control (P<0.05).ConclusionsThe depletion of vitamins C and E as well as elevation of MDA in tuberculosis patients is suggestive of lipid peroxidation and oxidative stress. The increase in vitamin C and E as well as decrease in MDA after 6 weeks of anti-tuberculosis treatment is suggestive of good response to treatment with standard ATT. Hence, vitamin C and E supplementation improves the quality of life of tuberculosis patients.     

QT Interval Length and Diabetic Autonomic Neuropathy

QT interval length was measured in ECG recordings from three groups of age-matched male subjects: 36 normal subjects, 41 diabetic patients without (DAN-ve), and 34 with (DAN+ve) autonomic neuropathy. ECG samples were selected from previously recorded 24-h ECGs on the basis of a clearly defined T wave and a steady RR interval over 2 min of around 750 ms (80 beats min^?1). There were no significant differences in RR interval between the groups. The two diabetic groups had slightly longer QT measurements (normal 365 ± 14 (±SD) ms, DAN-ve 373 ± 18 ms, DAN+ve 375 ± 23 ms, p = 0.05), and corrected QT (QTc) values (normal 423 ± 15 ms, DAN-ve 430 ± 20 ms, DAN+ve 435 ± 24 ms, p = 0.05). Ten diabetic patients fell above our defined upper limit of normal for QTc (>mean + 2SD). There was a significant correlation in the DAN-ve group between the QT indices and 24-h RR counts (QT r = ?0.38, p < 0.01; QTc r = ?0.40, p < 0.01). We conclude that there are some small alterations in QT interval length in the steady state in diabetic autonomic neuropathy. The changes appear to be due to autonomic impairment, rather than diabetes per se.     

Protective effect of Mollugo nudicaulis Lam. on acute liver injury induced by perchloroethylene in experimental rats

ObjectiveTo evaluate the protective effect of ethanol extract of Mollugo nudicaulis (M. nudicaulis) against perchloroethylene-induced hepatotoxicity.MethodsThe hepatoprotective activity of the ethanol extract of M. nudicaulis (200 mg/kg body wt) was studied in percholoroethylene (1 000 mg/kg body wt) induced hepatotoxicity in Wistar albino rats. The serum levels of AST, ALT, ALP, bilirubin and the liver content of SOD, CAT, GPx, GST, GSH, vitamin C were assessed to evaluate the hepatoprotective and antioxidant activities of the extract. The activity of the extract was compared with silymarin, a standard reference drug. In addition, serum urea, uric acid and creatinine levels were measured to evaluate the kidney function. The histopathological examination of the liver tissues was observed to support the biochemical parameters.ResultsThe results revealed that the extract significantly (P<0.05) restored the serum levels of AST, ALT, ALP, bilirubin and significantly (P<0.05) increased the antioxidant enzymes SOD, CAT, GPx, GST, GSH, vitamin C in perchloroethylene-induced rats to its normalcy. The biochemical observations were supported by the histopathological studies of the liver tissues.ConclusionsThe results led to the conclusion that M. nudicaulis possess hepatoprotective and antioxidant activites against perchloroethylene-induced hepatotoxicity in rats.     

Efficacy evaluation of the protein isolated from Peganum harmala seeds as an antioxidant in liver of rats

ObjectiveTo evaluate the curative effect of the 132 KD protein isolated from the seeds of Peganum harmala (P. harmala) L. against carbon tetrachloride (CCl₄) induced oxidative stress in rats.MethodsAnimals were post treated intraperitoneally with 132 KD isolated protein at doses of 4 and 8 mg/kg body weight and bovine serum albumin (BSA) (8 mg/kg body weight) as well as vitamin C (250 mg/kg body weight p.o.) for 7 d after they challenged with CCl₄ orally (1 mL/kg body weight) in olive oil (50%) for 2 d.ResultsThe purified protein from seeds of P. harmala plant showed in vitro antioxidant activity with DPPH assay. Administration of CCl₄ induced induction in serum aminotransferases (AST, ALT), alkaline phosphatase (ALP), lipid profile parameters and liver malondialdehyde (MDA) and decrease in serum total protein, liver superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) levels. 132 KD protein treatment of rats post CCl₄ intoxication successfully alleviated the toxic effects of CCl₄.ConclusionsThe isolated protein possessed strong antioxidant activity comparable to that of BSA (negative control) and vitamin C (positive control).     

Markers of oxidative damage and antioxidant enzyme activities as predictors of morbidity and mortality in patients with chronic heart failure

BackgroundAlthough the majority of previous findings unequivocally confirmed the existence of systemic oxidative stress in chronic heart failure (CHF) patients, data on prognostic potential of biomarkers of oxidative lipid and protein damage are limited. We aimed to address the relation of oxidative stress markers to severity and prognosis in CHF secondary to ischemic cardiomyopathy.Methods and ResultsPlasma malondialdehyde (MDA), protein thiol groups (P-SH), reactive carbonyl derivatives (RCD), together with glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were determined in 120 CHF patients and 69 healthy controls. Increased lipid peroxidation (MDA) and oxidation of plasma proteins (RCD; P-SH) s well as downregulated GSH-Px activity were found in CHF patients compared with controls. Significant correlation was obtained only for RCD content and remodeling indices (LVEDV: r = 0.469, P = .008; LVESV: r = 0.452; P = .011). Cox regression analysis demonstrated only MDA (HR = 3.33; CI: 1.55–7.12; P = .002) as independent predictor of death, whereas SOD was associated with unstable angina pectoris (HR = 2.09; CI: 1.16–3.78; P = .011).ConclusionsIn the course of CHF progression, carbonyl stress is implicated in the LV remodeling. Malondialdehyde level might be a useful parameter for monitoring and planning management of CHF patients.