Hafida Merzouk

Oxidant and antioxidant status in mothers and their newborns according to birthweight.

OBJECTIVE The aim of this study is to determine the oxidant and antioxidant status in Algerian mothers and their newborns according to birth weight. STUDY DESIGN Subjects for the study were consecutively recruited from Tlemcen hospital. 139 pregnant women and their newborns were included. The plasma total antioxidant activity (ORAC), vitamins A, C, E, hydroperoxides, carbonyl proteins, and erythrocyte antioxidant enzyme activities (catalase, glutathione peroxidase, glutathione reductase and superoxide dismutase) were measured on mothers and their newborns. Lipid and lipoprotein parameters were also determined. The results were assessed in accordance with small for gestational age (SGA), appropriate (AGA) and large (LGA) birth weight of the newborn. RESULTS SGA newborns and their mothers had low ORAC, vitamin C and E values (P<0.01) and high plasma hydroperoxide and carbonyl protein levels (P<0.01) compared to AGA groups. The SGA group showed also altered erythrocyte antioxidant enzyme activities and several lipid and lipoprotein changes. In LGA compared to control newborns, hydroperoxide, carbonyl protein levels and SOD activity were enhanced while ORAC, vitamin A and E levels were reduced. However, oxidant and antioxidant status in their mothers was similar to that in control mothers. CONCLUSION Oxidative stress is present in both SGA and LGA newborns, with a concomitant alteration in maternal oxidant and antioxidant status only in intrauterine growth restriction.

Oxidative stress and maternal obesity: Feto-placental unit interaction

OBJECTIVE To determine oxidative stress markers in maternal obesity during pregnancy and to evaluate feto-placental unit interaction, especially predictors of fetal metabolic alterations. PATIENTS AND METHODS 40 obese pregnant women (prepregnancy BMI > 30 kg/m²) were compared to 50 control pregnant women. Maternal, cord blood and placenta samples were collected at delivery. Biochemical parameters (total cholesterol and triglycerides) and oxidative stress markers (malondialdehyde, carbonyl proteins, superoxide anion expressed as reduced Nitroblue Tetrazolium, nitric oxide expressed as nitrite, reduced glutathione, catalase, superoxide dismutase) were assayed by biochemical methods. RESULTS Maternal, fetal and placental triglyceride levels were increased in obese group compared to control. Maternal malondialdehyde, carbonyl proteins, nitric oxide and superoxide anion levels were high while reduced glutathione concentrations and superoxide dismutase activity were low in obesity. In the placenta and in newborns of these obese mothers, variations of redox balance were also observed indicating high oxidative stress. Maternal and placental interaction constituted a strong predictor of fetal redox variations in obese pregnancies. DISCUSSION Maternal obesity compromised placental metabolism and antioxidant status which strongly impacted fetal redox balance. Oxidative stress may be one of the key downstream mediators that initiate programming of the offspring. CONCLUSION Maternal obesity is associated with metabolic alterations and dysregulation of redox balance in the mother-placenta - fetus unit. These perturbations could lead to maternal and fetal complications and should be carefully considered.

Altered adipose tissue metabolism in offspring of dietary obese rat dams

To investigate further the mechanisms of developmental programming, we analysed the effects of maternal overnutrition and of postnatal high-fat feeding on adipose tissue metabolism in the offspring. Postnatal changes in serum adiponectin, leptin and TAG [triacylglycerol (triglyceride)] levels, adipose tissue TAGs, fatty acids and enzyme activities were determined in offspring of cafeteria-diet-fed dams during gestation and lactation, weaned on to standard chow or on to cafeteria diet. Obese rats showed higher adiposity (+35% to 85%) as well as a significant increase in serum glucose, insulin, leptin, adiponectin and TAG levels (P<0.01) and adipose tissue LPL (lipoprotein lipase) and GPDH (glycerol-3-phosphate dehydrogenase) activities (P<0.01), compared with control pups at weaning (day 21) and at adulthood (day 90). Adipose HSL (hormone-sensitive lipase) activity was increased only at day 90 (P<0.05), and FAS (fatty acid synthase) activity remained unchanged. The proportions of SFAs (saturated fatty acids) and MUFAs (mono-unsaturated fatty acids) and the Δ(9)-desaturation index were significantly increased (P<0.05), whereas PUFAs (polyunsaturated fatty acids) were decreased (P<0.01) in serum and adipose TAGs of obese pups compared with controls. The cafeteria diet at weaning induced more severe abnormalities in obese rats. In conclusion, maternal overnutrition induced permanent changes in adipose tissue metabolism of the offspring. These pre-existing alterations in offspring were worsened under a high-fat diet from weaning to adulthood. Consequently, adipose adipokines and enzymes could provide a potential therapeutic target, and new investigations in this field could constitute strategies to improve the impact of early-life overnutrition.

Modulation of lipid metabolism by n-3 polyunsaturated fatty acids in gestational diabetic rats and their macrosomic offspring.

The time course of changes in lipid metabolism by dietary n-3 PUFAs (polyunsaturated fatty acids) in streptozotocin-induced diabetic rats during pregnancy (days 12 and 21) and their macrosomic offspring at birth (day 0) and through adulthood (days 60 and 90) was studied with respect to adipose tissue, liver and serum lipid concentrations, and fatty acid composition. Glucose and insulin levels were also assessed in order to characterize the diabetic state of macrosomic offspring. Pregnant diabetic and control rats were fed either an Isio-4 or EPAX diet (enriched with n-3 PUFA). The same diets were also consumed by pups at weaning. Compared with control rats, during pregnancy diabetic rats had a significant elevation in liver and serum triacylglycerol (triglyceride) and cholesterol concentrations. At birth, macrosomic pups had higher serum insulin and glucose levels than control pups. The macrosomic rats maintained accelerated postnatal growth combined with high adipose tissue weight and lipid content through the first 12 weeks of age. The macrosomic pups from diabetic rats fed the Isio-4 diet also showed a significant enhancement in liver and serum triacylglycerol and cholesterol levels at birth and during adulthood. Feeding the EPAX diet to diabetic mothers as well as their macrosomic pups increased serum and liver levels of EPA (eicospentaenoic acid) and DHA (docosahexaenoic acid) with a reduction in arachidonic acid. The EPAX diet induced a significant decrease in liver and serum triacylglycerol and cholesterol concentrations in mothers during pregnancy and in their macrosomic pups during adulthood. Since the EPAX diet improves lipid anomalies considerably in diabetic mothers and their macrosomic offspring, it may prevent long-term metabolic abnormalities associated with macrosomia.

Time course of changes in serum oxidant/antioxidant status in overfed obese rats and their offspring.

The aim of the present study was to determine the time course of changes in oxidant/antioxidant status, as well as serum glucose, insulin, leptin and lipid levels, liver adipose tissue and muscle lipid and protein contents, in cafeteria-diet-fed dams during gestation and lactation, and in their offspring throughout adulthood. Food intake was also evaluated. The cafeteria diet induced a significant increase in maternal body and relative adipose tissue weights, daily energy intake, and plasma glucose, insulin, leptin and lipid levels at parturition (day 0) and at the end of lactation (day 21). Plasma total antioxidant status [ORAC (oxygen radical absorbance capacity)], erythrocyte catalase and SOD (superoxide dismutase) activities were lower, whereas plasma hydroperoxide and carbonyl protein levels were higher in cafeteria-diet-fed mothers compared with control mothers at days 0 and 21. Pups from cafeteria-diet-fed dams, both males and females, also had consistently higher body and relative adipose tissue weights, and plasma glucose, insulin, leptin, triacylglycerol (triglyceride) and cholesterol levels at birth (day 0), weaning (day 21) and 3 months of age (day 90). These offspring had significantly lower ORAC and catalase activity, and higher plasma hydroperoxide and carbonyl protein levels and SOD activity at birth, at days 21 and 90 compared with control offspring. In conclusion, excessive maternal fat and energy intake can play an important role in the development of metabolic disorders in the offspring. Maternal oxidative stress may be among the responsible factors. Fetal oxidative stress may present an additional confounding influence and probably contributes to additional disorders, aggravating features of the metabolic syndrome. An improvement in maternal oxidant/antioxidant status during pregnancy and lactation, with adequate nutrition, could have beneficial effects on the progeny.

Implication of lipids in macrosomia of diabetic pregnancy: can n-3 polyunsaturated fatty acids exert beneficial effects?

Macrosomia or fetal obesity is a frequent complication of pregnancy in diabetes mellitus. Several alterations observed in carbohydrate and lipid metabolism in macrosomic infants of diabetic mothers are thought to be a consequence of maternal hyperglycaemia leading to fetal hyperinsulinaemia. Macrosomic infants of diabetic mothers are prone to the development of glucose intolerance, obesity and diabetes during childhood and adulthood. Furthermore, increasing evidence is accumulating regarding the importance of n -3 polyunsaturated fatty acids (PUFAs) in the reduction of plasma lipids and hyperglycaemia. In this review article, we shed light on the abnormalities in lipid metabolism in macrosomia. We also raise the question of the possible beneficial effects of n -3 PUFAs in diabetic pregnancy and in the prevention and treatment of long-term metabolic abnormalities associated with macrosomia.

Hepatic and very low-density lipoprotein fatty acids in obese offspring of overfed dams

The combined effects of developmental programming and high-fat feeding at weaning on fatty acid metabolism of the offspring are not well known. In the present study, we aim at characterizing the influence of maternal and offsprings own diets on liver and very low-density lipoprotein (VLDL) lipids; fatty acid profiles of VLDL and liver phospholipids, triglycerides, and cholesteryl esters; and hepatic enzyme activities. Twenty obese male rats born to cafeteria diet-fed dams and 20 control rats born to control diet-fed dams were selected. At weaning, 10 rats of each group were fed control or cafeteria diet. Obese rats had a significant increase in serum glucose, insulin, leptin, VLDL apolipoprotein B100 and lipid levels, and hepatic fatty acid synthase and a reduction in acyl-coenzyme A oxidase and dehydrogenase activities compared with control pups at day 21 and day 90. Hepatic steatosis was apparent only at day 90. The proportions of saturated fatty acids and monounsaturated fatty acids and the oleic to stearic acid ratio were significantly increased, whereas polyunsaturated fatty acids and the arachidonic to linoleic acid ratio were decreased, in liver and VLDL lipids of obese pups compared with controls. The cafeteria diet at weaning induced more severe abnormalities in obese rats. In conclusion, maternal cafeteria diet induced a permanent reduction in hepatic β-oxidation and an increase in hepatic lipogenesis that caused liver steatosis and VLDL and fatty acid alterations in adult offspring. These preexisting alterations in offspring were worsened under a high-fat diet from weaning to adulthood. Nutritional recommendations in obesity must then target maternal and postnatal nutrition, especially fatty acid composition.

In Vitro Antioxidant versus Metal Ion Chelating Properties of Flavonoids: A Structure-Activity Investigation

Natural flavonoids such as quercetin, (+)catechin and rutin as well as four methoxylated derivatives of quercetin used as models were investigated to elucidate their impact on the oxidant and antioxidant status of human red blood cells (RBCs). The impact of these compounds against metal toxicity was studied as well as their antiradical activities with DPPH assay. Antihemolytic experiments were conducted on quercetin, (+)catechin and rutin with excess of Fe, Cu and Zn (400 μM), and the oxidant (malondialdehyde, carbonyl proteins) and antioxidant (reduced glutathione, catalase activity) markers were evaluated. The results showed that Fe and Zn have the highest prooxidant effect (37 and 33% of hemolysis, respectively). Quercetin, rutin and (+)catechin exhibited strong antioxidant properties toward Fe, but this effect was decreased with respect to Zn ions. However, the Cu showed a weak antioxidant effect at the highest flavonoid concentration (200 μM), while a prooxidant effect was observed at the lowest flavonoid concentration (100 μM). These results are in agreement with the physico-chemical and antiradical data which demonstrated that binding of the metal ions (for FeNTA: (+)Catechin, KLFeNTA = 1.6(1) × 106 M-1 > Rutin, KLFeNTA = 2.0(9) × 105 M-1 > Quercetin, KLFeNTA = 1.0(7) × 105 M-1 > Q35OH, KLFeNTA = 6.3(8.7) × 104 M-1 > Quercetin3’4’OH and Quercetin 3OH, KLFeNTA ~ 2 × 104 M-1) reflects the (anti)oxidant status of the RBCs. This study reveals that flavonoids have both prooxidant and antioxidant activity depending on the nature and concentration of the flavonoids and metal ions.

Impaired lipoprotein metabolism in obese offspring of streptozotocin-induced diabetic rats.

The time course of changes in lipoprotein metabolism of obese offspring of mildly diabetic rats was studied with respect to serum lipoprotein composition as well as LCAT and tissue lipoprotein lipase (LPL) activities. Mild hyperglycemia in pregnant rats was induced by intraperitoneal injection of streptozotocin on day 5 of gestation. Control pregnant rats were injected with citrate buffer. At birth, obese pups had higher serum glucose, insulin, and lipoprotein (VLDL, LDL-HDL1, HDL2–3) levels than control pups. After 1 mon of life, all of these parameters in obese rats became similar to those of controls. However, LCAT, adipose tissue LPL, and hepatic triacylglycerol lipase activities were high. At 2 mon of age, VLDL-TAG levels were higher in obese females than in controls. By the age of 3 mon, obese offspring had developed insulin resistance with hyperglycemia, hyperinsulinemia, and higher serum lipoprotein concentrations. Indeed, qualitative abnormalities of lipoproteins were seen and were typical of obese and diabetic human beings. Fetal hyperinsulinemia should be considered as a risk factor for later metabolic diseases, including dyslipoproteinemia.

The effects of alpha-cypermethrin exposure on biochemical and redox parameters in pregnant rats and their newborns

Pyrethroid insecticides are extensively used in agriculture and in household activities. During pregnancy, they might affect maternal metabolic status and there after fetal development. In this work, we studied metabolic and redox effects of low dose alpha-cypermethrin exposure in pregnant rats and their offspring. The diet containing alpha cypermethrin at 0.02mg/kg/day was consumed during the entire gestation. Plasma biochemical parameters as well as liver lipid and oxidative stress markers were determined. Our results showed that alpha-cypermethrin induced an increase in body weight and in plasma glucose and lipid levels, as well as in plasma aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase activities in pregnant rats and their newborns. Pregnant rats showed cellular oxidative stress and altered oxidant-antioxidant status when treated by the insecticide and these disturbances were also seen in their newborns. In conclusion, low dose alpha-cypermethrin exposure induced several metabolic and redox alterations leading to maternal physiological impairments and to fetal metabolic changes. Alpha-cypermethrin should be used with caution especially during pregnancy.