Hypoglycemic effect of Costus pictus D. Don on alloxan induced type 2 diabetes mellitus in albino rats

ObjectiveTo demonstrate the effect of aqueous extract of Costus pictus (C. pictus) leaves on blood glucose, lipid profile and liver antioxidant enzymes and lipid peroxidation in alloxan induced diabetic rats.MethodsAqueous extract of C. pictus (AECP) leaves was administered orally for 30 days and its effect on blood glucose, lipid profile, hepatic marker enzymes such as serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), serum urea, creatinine, protein and albumin content and liver antioxidant enzymes such as catalase, peroxidase, superoxide dismutase and lipid peroxidation in alloxan induced diabetic rats were examined.ResultsOral administration of aqueous extract of C. pictus leaves to diabetic rats for 30 days significantly reduced the levels of blood glucose, lipid profile, lipid peroxidation, liver marker enzymes, urea, creatinine and increased the levels of antioxidant enzymes.ConclusionsThe aqueous extract of C. pictus leaves controls the blood glucose level, improves lipid metabolism and prevents diabetic complications associated with lipid peroxidation and also maintains the antioxidant enzymes in experimental diabetic rats. Therefore, it can be recommeded for the prevention of diabetes mellitus.     

Hypoglycemic activity of Hemidesmus indicus R. Br. on streptozotocin-induced diabetic rats

OBJECTIVE:

To evaluate the antidiabetic activity of an aqueous extract of the roots of Hemidesmus indicus on blood glucose, serum electrolytes, serum marker enzymes, liver microsomal P-450 enzymes, and lipid peroxidation in the liver and kidney of streptozotocin-induced diabetic rats.

MATERIALS AND METHODS:

Effect of H. indicus extract on blood glucose was studied with fed, fasted and glucose-loaded diabetic and nondiabetic rat models. The effect of the extract on serum electrolytes, serum levels of key glucose metabolizing enzymes, hepatic microsomal protein and hepatic cytochrome P-450-dependent mono-oxygenase enzyme systems and lipid peroxidation in the liver and kidney of diabetic rats. One way analysis of variance and Duncan''s multiple range test was used for statistical analysis.

RESULTS:

Oral administration of H. indicus aqueous extract to fed, fasted and glucose-loaded diabetic rats decreased blood glucose level significantly at 5 h and restored serum electrolytes, glycolytic enzymes and hepatic cytochrome P-450-dependent enzyme systems by preventing the formation of liver and kidney lipid peroxides at the end of 12 weeks of the study period.

CONCLUSION:

From the studies, it can be concluded that the aqueous extract of the roots of H. indicus at a dosage of 500 mg/kg/day exhibits significant antidiabetic activity. It restores the concentrations of electrolytes, glucose metabolizing enzymes, hepatic microsomal protein and hepatic cytochrome P-450-dependent mono-oxygenase enzyme systems to near normal level and also corrects the related metabolic alterations in experimentally induced diabetic rats. H. indicus administration also decreased liver and kidney lipid peroxidation products. On the basis of our findings, H. indicus could be used as an antidiabetic and antioxidant agent for the prevention and treatment of diabetes mellitus.     

Calorie restriction up-regulates the plasma membrane redox system in brain cells and suppresses oxidative stress during aging

The plasma membrane (PM) contains redox enzymes that provide electrons for energy metabolism and recycling of antioxidants such as coenzyme Q and alpha-tocopherol. Brain aging and neurodegenerative disorders involve impaired energy metabolism and oxidative damage, but the involvement of the PM redox system (PMRS) in these processes is unknown. Caloric restriction (CR), a manipulation that protects the brain against aging and disease, increased activities of PMRS enzymes (NADH-ascorbate free radical reductase, NADH-quinone oxidoreductase 1, NADH-ferrocyanide reductase, NADH-coenzyme Q10 reductase, and NADH-cytochrome c reductase) and antioxidant levels (alpha-tocopherol and coenzyme Q10) in brain PM during aging. Age-related increases in PM lipid peroxidation, protein carbonyls, and nitrotyrosine were attenuated by CR, levels of PMRS enzyme activities were higher, and markers of oxidative stress were lower in cultured neuronal cells treated with CR serum compared with those treated with ad libitum serum. These findings suggest important roles for the PMRS in protecting brain cells against age-related increases in oxidative and metabolic stress.     

褪黑素对糖尿病大鼠肾脏抗氧化物酶的影响

与正常大鼠比较,STZ诱发的糖尿病大鼠肾与血清的丙二醛水平升高,以及抗氧化物酶活性降低,在褪黑素治疗后均见明显改善,同时伴随出现尿白蛋白排泄率、血尿酸、血脂谱以及肾重对体重的比值等的降低。     

Influence of mulberry (Morus indica L.) leaves on antioxidants and antioxidant enzymes in STZ-diabetic rats

To assess the influence of mulberry (Morus indica L.) leaves on antioxidants and antioxidant enzymes in STZ- diabetic rats as the leaves of mulberry (Morus indica L.) of Moraceae, are reported to be rich in a no. of bioactive principles i.e. antioxidant vitamins, flavonoids and moracins that can fight against oxidative stress in diabetes. STZ-diabetic rats were treated with dried mulberry leaves incorporated in the feed at 25 % level (as per dose response) for 8 weeks in standard experimental conditions in comparison with diabetic glibenclamide–treated and diabetic control rats. At the end of experimental period, fasting blood glucose, serum non-enzymatic antioxidants, hepatic lipid peroxidation and antioxidant enzymes were assayed in all the experimental groups. Hyperglycemia, a 274 % (P?<?0.01) rise in fasting blood glucose and increased oxidative stress as shown by a two fold increase in lipid peroxidation in hepatic tissue, decreased serum non enzymatic antioxidants viz. vit.C (51 %) and E (47 %), significantly decreased activities of hepatic antioxidant enzymes such as glucose-6-phosphate dehydrogenase (43 %), glutathione peroxidase (41 %) and superoxide dismutase (44 %) and significantly increased activity of catalase (39 %) in STZ-diabetic rats were ameliorated by mulberry leaves which is evidenced by significant fall in fasting glucose, and lipid peroxidation, rise in antioxidants as well as the activities of defense enzymes and decrease in the activity of catalase while the antidiabetic drug, glibenclamide showed lesser effects than mulberry leaves. Mulberry leaves protected STZ-diabetic rats against oxidative stress by improving antioxidants and the activities of defense enzymes and controlling hyperglycemia and lipid peroxidation in a better way than the drug.     

Coenzyme Q10 protects from aging-related oxidative stress and improves mitochondrial function in heart of rats fed a polyunsaturated fatty acid (PUFA)-rich diet

Coenzyme Q(10) supplementation on age-related changes in oxidative stress and function of heart mitochondria in rats fed a polyunsaturated fatty acid (PUFA)-rich diet was investigated. Two groups of rats were fed for 24 months on a PUFA-rich diet, differing in supplementation or not with coenzyme Q(10). Animals were killed at 6, 12, or 24 months. Fatty-acid profile, hydroperoxides, alpha-tocopherol, coenzyme Q, catalase and glutathione peroxidase activities, and cytochromes a+a(3), b, c+c(1) and cytochrome c oxidase activity were measured. Coenzyme Q(10)-supplemented animals showed lower hydroperoxide levels; higher content and/or activity of alpha-tocopherol, coenzyme Q, and catalase; and a slightly lower decrease in mitochondrial function. According to that, previously reported positive effects of coenzyme Q supplementation on the life span of rats fed a PUFA-rich diet might be a consequence, at least in part, of a lower oxidative stress level and perhaps, to a minor extent, of a smaller decrease in mitochondrial function.     

Melatonin inhibits lipid peroxidation and stimulates the antioxidant status of diabetic rats

Although melatonin has been established as a free radical scavenger and antioxidant, its effects in diabetes have not been thoroughly investigated. The purpose of this study, therefore, was to investigate the effects of melatonin administration on lipid peroxidation and antioxidant status in streptozotocin (STZ)-induced diabetes in rats. Concentrations of malondialdehyde (MDA) and reduced glutathione (GSH) in erythrocytes and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were compared in 3 groups of 10 rats each [control non-diabetic rats (group I), untreated diabetic rats (group II) and diabetic rats treated with melatonin (group III)]. In the study groups, diabetes developed 3 days after intraperitoneal (i.p.) administration of a single 60-mg/kg dose of STZ. Thereafter, while the rats in group II received no treatment, the rats in group III began to receive a 10-mg/kg i.p. dose of melatonin per day. After 6 wk, the rats in groups II and III had significantly lower body weights and significantly higher blood glucose levels than the rats of group I (P<0.001 and P<0.001, respectively). There were no significant differences in body weight or blood glucose levels between groups II and III. MDA levels in untreated diabetic rats were higher than those in control group rats and in diabetic rats treated with melatonin (P<0.01 and P<0.05, respectively). However, MDA levels in diabetic rats treated with melatonin were not different from those of the control group. The GSH, GSH-Px and SOD levels of untreated diabetic rats were significantly lower than those of the control group (P<0.02, P<0.002 and P<0.05, respectively). In group III, however, melatonin prevented decreases in the thiol antioxidant and the associated enzymes, and so these levels were not significantly different from those in the control group. These results confirm the presence of oxidative stress in STZ-induced experimental diabetes and indicate the beneficial free radical-scavenging and antioxidant properties of melatonin.     

Systemic markers of lipid peroxidation and antioxidants in patients with nonalcoholic Fatty liver disease

OBJECTIVES: The aim of the present study was to examine the systemic parameters of oxidative stress and antioxidants in patients with nonalcoholic fatty liver disease and investigate the relationship between these parameters and clinical and biochemical outcomes. METHODS: Fifty-one male patients with nonalcoholic fatty liver disease (group I), 30 age-matched and body mass index (BMI)-matched healthy male subjects, and 30 age-matched male patients with chronic viral hepatitis (group II) were enrolled in the study. RESULTS: Increased systemic levels of malondialdehyde and depletion of antioxidants such as coenzyme Q10, CuZn-superoxide dismutase, and catalase activity were observed in group I. Coenzyme Q10 and CuZn-superoxide dismutase correlated negatively with increasing necroinflammatory activity and fibrosis. Body fat was negatively associated with plasma coenzyme Q10 levels, while an inverse association was found between plasma catalase levels and TG. However, LDL was positively associated with plasma malondialdehyde levels. CuZn-superoxide dismutase levels were negatively associated with glucose, insulin, and HOMA-IR. In addition, the levels of CuZn-superoxide dismutase correlated significantly in a negative manner with BMI. CONCLUSIONS: Our results concerning correlations suggest that disturbances in BMI, body fat, and lipid metabolism may contribute to altered oxidative status in NAFLD, and insulin resistance may be related to decreased antioxidants in NAFLD as well as products of lipid peroxidation. However, although our results suggest interesting correlations, this different mostly "weak" relationships must be taken with caution.     

Serum biochemical responses under oxidative stress of aspartame in wistar albino rats

ObjectiveTo study whether the oral administration of aspartame (40 mg/kg body weight) for 15 d, 30 d and 90 d have any effect on marker enzymes, some selective liver and kidney function parameter, lipid peroxidation and antioxidant status in serum. To mimic human methanol metabolism, folate deficient animals were used.MethodAnimal weight, complete hemogram, marker enzyme in serum, some selected serum profile reflect liver and kidney function, plasma corticosterone level, and in serum, lipid peroxidation, nitric oxide, enzymatic and non-enzymatic antioxidant level was measured .ResultAfter 15 d of aspartame administration animals showed a significant change in marker enzymes, and antioxidant level. However, after repeated long term administration (30 d and 90 d) showed a significant change in some selected serum profile reflects liver and kidney function, along with marker enzymes, and antioxidant level.ConclusionsThis study concludes that oral administration of aspartame (40 mg/kg body weight) causes oxidative stress in Wistar albino rats by altering their oxidant/antioxidant balance.     

Therapeutic effects of tender coconut water on oxidative stress in fructose fed insulin resistant hypertensive rats

ObjectiveTo investigate whether tender coconut water (TCW) mitigates oxidative stress in fructose fed hypertensive rats.MethodsMale Sprague Dawley rats were fed with fructose rich diet and treated with TCW (4 mL/100 g of body weight) for 3 subsequent weeks. Systolic blood pressure was measured every three days using the indirect tail cuff method. At the end of the experimental period, plasma glucose and insulin, serum triglycerides and free fatty acids, lipid peroxidation markers (MDA, hydroperoxides and conjugated dienes) and the activities of antioxidant enzymes were analyzed in all the groups.ResultsTreatment with TCW significantly lowered the systolic blood pressure and reduced serum triglycerides and free fatty acids. Plasma glucose and insulin levels and lipid peroxidation markers such as MDA, hydroperoxides and conjugated dienes were significantly reduced in fructose fed rats treated with TCW. Activities of antioxidant enzymes are up regulated significantly in TCW treated rats. Histopathological analysis of liver showed that TCW treatment reduced the lipid accumulation and inflammatory infiltration without any significant hepatocellular damage.ConclusionsThe overall results suggest that, TCW treatment could prevent and reverse high blood pressure induced by high fructose diet probably by inhibition of lipid peroxidation, upregulation of antioxidant status and improved insulin sensitivity.     

Effect of aminoguanidine on lipid peroxidation in streptozotocin-induced diabetic rats.

Diabetes mellitus is postulated to be associated with increased lipid peroxidation, which may contribute to vascular complications. One potential mechanism of the increased lipid peroxidation in diabetes is lipid-linked advanced glycosylation and oxidation. Aminoguanidine (AMGN), the prototype inhibitor of advanced glycosylation end product (AGE) formation, has been recently shown to prevent oxidative modification of low-density lipoprotein (LDL) in vitro at a moderate concentration. It is unknown whether AMGN may act as an antioxidant against lipid peroxidation under hyperglycemia in vivo. To investigate the in vivo effect of AMGN on lipid peroxidation in diabetes, we administered AMGN (1 g/L in drinking water) or vitamin E (400 mg/d for 5 d/wk) to streptozotocin (STZ)-induced diabetic rats for 9 weeks and measured plasma lipid hydroperoxides by ferrous oxidation with xylenol orange II (FOX method) and red blood cell (RBC) membrane malondialdehyde (MDA) and related aldehydes as thiobarbituric acid-reactive substances (TBARS). Plasma lipid hydroperoxide was higher in STZ-induced diabetic rats versus control rats (mean +/- SD, 7.53 +/- 2.03 v 5.62 +/- 0.44 micromol/L, P < .05; n = 8 to 14). RBC membrane TBARS were also higher in STZ-induced diabetic rats than in control rats (2.67 +/- 0.46 v 1.81 +/- 0.19 nmol/mL, P < .05). Plasma lipid hydroperoxide was lower in AMGN-treated (6.23 +/- 0.59 micromol/L, P < .05) and vitamin E-treated (5.29 +/- 0.27 micromol/L, P < .05) diabetic rats than in untreated diabetic rats. RBC membrane TBARS were also lower in AMGN-treated (1.93 +/- 0.12 nmol/mL, P < .05) diabetic rats than in untreated diabetic rats. There was no significant difference in plasma glucose, cholesterol, and triglyceride levels among diabetic groups. Although the mechanism(s) of action of AMGN on lipid peroxidation in vivo should be studied further, these results suggest that AMGN may have an additional beneficial effect as an antioxidant against lipid peroxidation in a prevention trial for diabetic vascular complications.     

Peroxidative events in stored platelet concentrates

Changes in metabolic and functional activity of platelets stored as platelet concentrates in plastic bags highly permeable to gases were investigated. The following parameters were measured daily: pH, pO2, pCO2, HCO3, glucose, lactic acid, lactic dehydrogenase, cellular ATP and platelet aggregation induced by different agents (collagen and ADP). As indexes of lipid peroxidative damage, the cellular levels of conjugated dienes, malonyldialdehyde and some antioxidant molecules such as coenzyme Q10 and vitamin E were determined. A marked increase in pO2, conjugated dienes, malonyldialdehyde, lactic acid and lactic dehydrogenase activity was observed during the preservation. Platelet ATP content was unmodified and a remarkable decrease in platelet aggregability was found. pCO2, cyclooxygenase activity, vitamin E, coenzyme Q10, bicarbonate and glucose showed a rapid fall. Our data seem to indicate a preservation of platelet metabolic activity and a correlation between increased lipid peroxidation and functional impairement.     

Moderate exercise with a dietary vitamin C and e combination protects against streptozotocin-induced oxidative damage to the kidney and lens in pregnant rats.

Moderate exercise and vitamin C and E (VCE) supplementation can be beneficial to diabetes due to reducing free radical production in lens and kidney of diabetic pregnant rats. We investigated the effect of VCE supplementation and moderate exercise on lipid peroxidation (MDA) and scavenging enzyme activity in the kidneys and lens of STZ-induced diabetic pregnant rats. Fifty female Wistar rats were used and were randomly divided into five groups. First and second were used as the control and pregnant control group. Third group was the pregnant diabetic group. The fourth group was the diabetic-pregnant-exercise group. VCE-supplemented feed was given to pregnant-diabetic-exercise rats constituting the fifth group. Animals in the exercised groups were moderately exercised daily on a treadmill (16.1 m/min, 45 min/d) for three weeks (five days a week). Diabetes was induced on day zero of the study. Plasma, lens, and kidney samples were taken from all animals on day 20. Exercise and administration of VCE to pregnant diabetic rats resulted in significant decrease in the albumin and total protein values and the elevated MDA, plasma creatinine, and urea levels as an indicator of oxidative stress and renal functional parameters. Exercise and VCE supplementation also increased glutathione peroxidase (GSH-Px), reduced glutathione (GSH), vitamin E, and beta-carotene levels in the kidney, GSH-Px and GSH in the lens, the albumin and total protein values in plasma. In the diabetic pregnant animals, the decreased vitamins A and E concentration and GSH levels in kidney, creatinine, and urea values in plasma did not improve through exercise only although their concentrations were increased by VCE supplementation. Kidney weight did not also affect either by exercise or VCE supplementation. In conclusion, these results suggest that exercise plus VCE affects antioxidant metabolism and reduces lipid peroxidation, thereby improving the damage caused by oxidative stress involved in the pathogenesis of lens and kidney in diabetic pregnant rats. Moderate exercise with dietary VCE may play a role in preventing nephropathy and cataract formation in diabetic pregnant rat.     

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.     

Safranal ameliorates antioxidant enzymes and suppresses lipid peroxidation and nitric oxide formation in aged male rat liver

Free radical production and oxidative stress are known to increase in liver during aging, and may contribute to oxidative damage. The objective of this study was to observe the changes in activities of antioxidant enzymes (superoxide dismutase, glutathione-S-transferase, catalase), lipid peroxidation levels and serum nitric oxide occurring in livers of rats of 2, 10 and 20 months old, and to see whether these changes are restored to those of the two month old control levels rats after administration of safranal. The aged rats (10 and 20 months) were given intraperitoneal injections of safranal (0.5 mg/kg day) daily for one month. The results obtained in the present work revealed that normal aging was associated with a significant decrease in the activities of antioxidant enzymes, and an increase in lipid peroxidation in livers and nitric oxide content in serum of aging rats. The results of the present study demonstrate that safranal could be a candidate to suppress the development of age-induced damage by protecting against oxidative stress and increasing antioxidant defenses. A likely mode of action of safranal can be its activity as a hormetin by inducing mild oxidative damage which leads to the activation of antioxidative enzymes.     

金糖宁胶囊的抗糖尿病作用药效研究

目的探讨具有α-糖苷酶抑制活性的金糖宁胶囊提取物（MC）在动物模型中的抗糖尿病作用。方法比较MC对正常小鼠及四氧嘧啶高血糖小鼠蔗糖、淀粉及葡萄糖负荷后糖耐量的影响。测定给药4周后MC对四氧嘧啶高血糖大鼠一般状况、尿糖、空腹血糖、餐后血糖、血脂、血清果糖胺、血清NAG酶活性、晶状体和坐骨神经中山梨醇含量及肾脏病理变化等的影响。结果MC能显著降低正常小鼠和高血糖小鼠蔗糖或淀粉负荷后的血糖峰值及血糖曲线下面积（AUC）,并使血糖峰值后移,但对葡萄糖耐量无影响;MC给药组与阿卡波糖组的血糖AUC减小及血糖峰值后移趋势基本一致。在长期实验中,MC可明显改善高血糖大鼠的三多症状,降低空腹血糖、餐后血糖、血清果糖胺浓度、尿糖、血脂、血清NAG酶活性、坐骨神经中山梨醇含量,增加红细胞中GSH含量,改善肾脏肥大及肾小管上皮细胞大量糖元沉积等糖尿病早期肾脏病理改变。结论金糖宁胶囊提取物具有α-糖苷酶活性抑制作用,可改善糖尿病动物的糖、脂代谢异常,并有益于糖尿病慢性并发症的防治。     

Serum concentration of lipoprotein(a) decreases on treatment with hydrosoluble coenzyme Q10 in patients with coronary artery disease: discovery of a new role

OBJECTIVE: To examine the effect of coenzyme Q10 supplementation on serum lipoprotein(a) in patients with acute coronary disease. STUDY DESIGN: Randomized double blind placebo controlled trial. SUBJECTS AND METHODS: Subjects with clinical diagnosis of acute myocardial infarction, unstable angina, angina pectoris (based on WHO criteria) with moderately raised lipoprotein(a) were randomized to either coenzyme Q10 as Q-Gel (60 mg twice daily) (coenzyme Q10 group, n=25) or placebo (placebo group, n=22) for a period of 28 days. RESULTS: Serum lipoprotein(a) showed significant reduction in the coenzyme Q10 group compared with the placebo group (31.0% vs 8.2% P<0.001) with a net reduction of 22.6% attributed to coenzyme Q10. HDL cholesterol showed a significant increase in the intervention group without affecting total cholesterol, LDL cholesterol, and blood glucose showed a significant reduction in the coenzyme Q10 group. Coenzyme Q10 supplementation was also associated with significant reductions in thiobarbituric acid reactive substances, malon/dialdehyde and diene conjugates, indicating an overall decrease in oxidative stress. CONCLUSION: Supplementation with hydrosoluble coenzyme Q10 (Q-Gel) decreases lipoprotein(a) concentration in patients with acute coronary disease.     

Effect of Cogent db,a herbal drug,on serum and tissue lipid metabolism in experimental hyperglycaemic rats

Aims:   We have previously reported the antidiabetic effect of Cogent db. The present study with alloxan-induced hyperglycaemic rats is focused on the mechanism of action, specifically on the activity of hepatic lipogenic enzymes, serum and tissue lipids.
Methods:   Male Wistar rats body weight of 180–200 g (six normal and 18 diabetic rats) were used in this study. The rats were divided into four groups after the induction of alloxan diabetes: normal rats; diabetic control; diabetic rats given Cogent db (0.45 g/kg body weight); diabetic rats given glibenclamide (600 µg/kg body weight). After 40 days treatment, fasting blood glucose, plasma insulin, activities of hepatic lipogenic enzymes, serum and tissue lipids were determined in normal and experimental animals.
Results:   Oral administration of Cogent db for 40 days resulted in significant reduction in blood glucose, serum and tissue (liver and kidney) lipids, whereas the level of plasma insulin and the activity of hepatic lipogenic enzymes were significantly increased in alloxan diabetic rats. Similar studies using glibenclamide have been conducted to compare the mode of action of these two drugs.
Conclusions:   Thus our study shows that Cogent db exhibits a strong antihyperlipidaemic effect, which could exert a beneficial action against macrovascular complications (cardiovascular disease) associated with diabetes mellitus.     

Pharmacologic treatment of hyperlipidemia reduces glomerular injury in rat 5/6 nephrectomy model of chronic renal failure

The role of lipid abnormalities in the pathogenesis of focal glomerulosclerosis was investigated in the rat remnant kidney model of chronic renal failure. Rats subjected to right nephrectomy and two-thirds segmental infarction of the left kidney (5/6 nephrectomy) were treated for 10 weeks with the lipid-lowering agent clofibric acid. Both serum cholesterol and urine albumin excretion were significantly reduced by clofibric acid. At 10 weeks, the percent of glomeruli with focal glomerulosclerosis was 5 +/- 2% in clofibric acid-treated and 24 +/- 5% in untreated 5/6 nephrectomy rats (p less than 0.01). Inulin clearance was greater in clofibric acid-treated than in untreated 5/6 nephrectomy rats (0.28 +/- 0.02 versus 0.22 +/- 0.02 ml/min 100 g body wt, p less than 0.05). Body weight, kidney weight, and systemic blood pressure were not significantly altered by clofibric acid. Micropuncture studies, performed in separate groups of clofibric acid-treated and untreated 5/6 nephrectomy rats, demonstrated elevated single nephron glomerular filtration rates and glomerular capillary pressures 4 weeks after surgery. However, clofibric acid did not significantly alter single nephron glomerular filtration rates (95 +/- 2.1 nl/min in treated versus 97.0 +/- 6.2 nl/min in untreated, p greater than 0.05) or glomerular capillary pressures (56.6 +/- 1.5 mm Hg in treated versus 57.8 +/- 0.8 mm Hg in untreated, p greater than 0.05) in 5/6 nephrectomy rats. In a separate set of experiments, 5/6 nephrectomy rats were treated with the specific cholesterol synthesis inhibitor, mevinolin. Mevinolin improved serum lipid levels and reduced albuminuria in 5/6 nephrectomy rats without causing significant alterations in blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dietary polyunsaturated fatty acid prevents hyperlipidemia and hepatic oxidant status in pregnant diabetic rats and their macrosomic offspring

A considerable amount of clinical and experimental evidence now exists and suggests the involvement of fatty acids and free radical-mediated oxidative processes in the pathogenesis of diabetic complications. Fetuses from diabetic mothers are at increased risk of developing neonatal macrosomia and oxidative stress. We investigated the modulation of antioxidant status and liver biochemical parameters in normal and diabetic pregnant rats and their offspring. Animals were randomly allocated into three groups of six rats each: a control group, a diabetic group and diabetic rats fed with flax and sesame seeds mixture group. The time course of changes in lipid metabolism and antioxidant status by dietary rich in ω3- and ω6-polyunsaturated fatty acids in alloxan-induced diabetic pregnant rats and their macrosomic offspring was studied. Glucose and insulin levels were also assessed in order to characterize the diabetic state of dams and their offspring. The diabetic rats presented a significant increase in glycemia, plasma and liver lipid parameters compared with those of control group. In addition, liver malonaldialdehyde levels significantly increased. Antioxidant enzyme activities such as catalase and superoxide dismutase and reduced glutathione levels significantly decreased in the liver of diabetic rats when compared with controls. Diet supplemented with flax and sesame seeds mixture in pregnant diabetic rats ameliorated lipid parameters, antioxidant enzyme activities, level of reduced glutathione and significantly decreased malonaldialdehyde levels. These ameliorations were also observed in pups whose pregnant diabetic mothers were fed seeds mixture. Our results suggested that flax and sesame seeds mixture supplemented to diet of pregnant diabetic rats might be helpful in preventing diabetic complications in adult dams and their offspring.