Differential vulnerability of substantia nigra and corpus striatum to oxidative insult induced by reduced dietary levels of essential fatty acids.

Oxidative stress (OS) has been implicated in the etiology of certain neurodegenerative disorders. Some of these disorders have been associated with unbalanced levels of essential fatty acids (EFA). The response of certain brain regions to OS, however, is not uniform and a selective vulnerability or resilience can occur. In our previous study on rat brains, we observed that a two-generation EFA dietary restriction reduced the number and size of dopaminergic neurons in the substantia nigra (SN) rostro-dorso-medial. To understand whether OS contributes to this effect, we assessed the status of lipid peroxidation (LP) and anti-oxidant markers in both SN and corpus striatum (CS) of rats submitted to this dietary treatment for one (F1) or two (F2) generations. Wistar rats were raised from conception on control or experimental diets containing adequate or reduced levels of linoleic and α-linolenic fatty acids, respectively. LP was measured using the thiobarbituric acid reaction method (TBARS) and the total superoxide dismutase (t-SOD) and catalase (CAT) enzymatic activities were assessed. The experimental diet significantly reduced the docosahexaenoic acid (DHA) levels of SN phospholipids in the F1 (~28%) and F2 (~50%) groups. In F1 adult animals of the experimental group there was no LP in both SN and CS. Consistently, there was a significant increase in the t-SOD activity (p < 0.01) in both regions. In EF2 young animals, degeneration in dopaminergic and non-dopaminergic neurons and a significant increase in LP (p < 0.01) and decrease in the CAT activity (p < 0.001) were detected in the SN, while no inter-group difference was found for these parameters in the CS. Conversely, a significant increase in t-SOD activity (p < 0.05) was detected in the CS of the experimental group compared to the control. The results show that unbalanced EFA dietary levels reduce the redox balance in the SN and reveal mechanisms of resilience in the CS under this stressful condition.

Fetal development and renal function in adult rats prenatally subjected to sodium overload.

The aims of this study were (1) to evaluate two factors that affect fetal development--placental oxidative stress (Ox) and plasma volume (PV)--in dams with sodium overload and (2) to correlate possible alterations in these factors with subsequent modifications in the renal function of adult offspring. Wistar dams were maintained on 0.17 M NaCl instead of water from 20 days before mating until either the twentieth pregnancy day/parturition or weaning. Colorimetric methods were used to measure Ox in maternal and offspring tissues, PV, 24-h urinary protein (U(Prot24 h)) and serum triacylglycerols (TG) and cholesterol (Chol). Renal hemodynamics was evaluated in the offspring at 90 days of age using a blood pressure transducer, a flow probe and inulin clearance to measure mean arterial pressure (MAP), renal blood flow and glomerular filtration rate (GFR), respectively. The number of nephrons (NN) was counted in kidney suspensions. Dams showed unchanged PV, placental Ox and fetal weight but increased U(Prot24 h) (150%, P < 0.05). Prenatally sodium-overloaded pups showed increased U(Prot24 h) (45%, P < 0.05) but unchanged MAP, renal hemodynamics, NN and kidney Ox. Prenatally and postnatally sodium-overloaded rats showed increased U(Prot24 h) (27%, P < 0.05) and kidney Ox (44%, P < 0.05), reduced GFR (12%, P < 0.05), increased PV (26%, P < 0.05) and unchanged MAP and NN. The TG increased in both groups of treated offspring (21%, P < 0.05), whereas Chol increased only in the postnatally sodium-overloaded group. We conclude that salt overload from the prenatal stage until weaning leads to alterations in lipid metabolism and in the renal function of the pups, which are additional to those alterations seen in rats only overloaded prenatally.

Placental oxidative stress in malnourished rats and changes in kidney proximal tubule sodium ATPases in offspring.

1. Intrauterine malnutrition has been linked to the development of adult cardiovascular and renal diseases, which are related to altered Na(+) balance. Here we investigated whether maternal malnutrition increases placental oxidative stress with subsequent impact on renal ATP-dependent Na(+) transporters in the offspring. 2. Maternal malnutrition was induced in rats during pregnancy by using a basic regional diet available in north-eastern Brazil. Placental oxidative stress was evaluated by measuring thiobarbituric acid-reactive substances, which were 35-40% higher in malnourished dams (MalN). Na(+) pumps were evaluated in control and prenatally malnourished rats (at 25 and 90 days of age). 3. Identical Na(+)/K(+)-ATPase activity was found in both groups at 25 days (approximately 150 nmol P(i)/mg per min). However, although Na(+)/K(+)-ATPase increased by 40% with growth in control rats, it remained constant in pups from MalN. 4. In juvenile rats, the activity of the ouabain-insensitive Na(+)-ATPase was higher in MalN than in controls (70 vs 25 nmol P(i)/mg per min). Nevertheless, activity did not increase with kidney and body growth: at 90 days, it was 50% lower in MalN than in controls. The maximal stimulation of the Na(+)-ATPase by angiotensin (Ang) II was 35% lower in MalN than in control rats and was attained only with a much higher concentration of the peptide (10(-10) mol/L) than in controls (10(-14) mol/L). 5. Protein kinase C activity, which mediates the effects of AngII on Na(+)-ATPase was only one-third of normal values in the MalN group. 6. These results indicate that placental oxidative stress may contribute to fetal undernutrition, which leads to later disturbances in Na(+) pumps from proximal tubule cells.