Effects of proanthocyanidin on oxidative stress biomarkers and adipokines in army cadets: a placebo-controlled, double-blind study.

PURPOSE: The relatively recent advent of polyphenol supplement for exercise studies has been tested in a variety of forms and doses. However, the dose-response on adipokines and oxidative stress biomarker effect remains unknown. The aim of the present study was to assess the effect of intense, long-duration (48-h) exercise, and a single dose of proanthocyanidin, on plasma leptin, adiponectin, and electronegative low-density lipoprotein (LDL(-)) concentrations. METHODS: Fifty-four healthy male army cadets (22 ± 2 years) participated in a double-blind, randomized, placebo-controlled study and were distributed between control (CG; n = 27) and supplemented groups (SG; n = 27). Immediately before the start of the exercise, both CG and SG groups received a capsule containing starch (200 mg) or proanthocyanidin (dry Vitis vinifera extract, 200 mg), respectively. Following a 12-h fasting period, the plasma adiponectin, leptin, and LDL(-) concentrations were measured prior to the start of the exercise after 24 and 48 h of military training, and after 24 h of rest. The effects of the proanthocyanidin (supplement), exercise (time), and their interaction were investigated using factorial two-way ANOVA. RESULTS: Plasma leptin concentration was only influenced by exercise (p = 0.001). Plasma adiponectin concentration was influenced by exercise (p = 0.037), and by the exercise x supplement interaction (p = 0.033). LDL(-) was influenced by the supplement (p = 0.001), exercise (p = 0.001), and their interaction (p = 0.001). CONCLUSIONS: A single dose of proanthocyanidin (200 mg) was able to reduce LDL(-) concentration and increase plasma adiponectin concentration after 24 h of rest in SG group, indicating its potential protective action.

Aerobic Conditioning Might Protect Against Liver and Muscle Injury Caused by Short-Term Military Training.

This study aimed to compare the biochemical markers of muscle and liver injury and total antioxidant capacity in army cadets after a traditional army physical training program and to correlate these effects with aerobic conditioning. Male army cadets (n = 87; age, 20 ± 2 years) were evaluated 12 hours before the start of training (T0), 12 hours after a 30-km march (T1), and 48 hours after military training (T2). Creatine kinase (CK), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) serum levels were measured using an autoanalyzer. Total antioxidant capacity was determined by 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity (Sc%). Seventy-four percent of army cadets were classified as having excellent aerobic conditioning (53.9 ± 3.0 ml · kg(-) · min(-1) predicted VO2max from the Cooper test). The median serum concentration of all enzymes increased 12 hours after marching (T1: CK 675%; ALT 59%; AST 336%; AST/ALT ratio 85%; p = 0.001) and 48 hours after the end of training (T2: CK 878%; ALT 256%; AST 418%; AST/ALT ratio 180%; p = 0.001). Sc% was higher in T2 (31.1 ± 9.8%; p = 0.01) than in T0 (3.4% change). Maximal oxygen consumption (ml · kg(-1) · min(-1)) correlated negatively with CK (r = -0.25; p = 0.009) and ALT (r = -0.21; p = 0.03) serum levels, and positively with the change in Sc% (r = 0.22; p = 0.04) at T2. The results indicate that intense military training can cause liver and muscle injury and that aerobic conditioning can be considered as a protective factor for these injuries.

Resveratrol attenuates oxidative stress and prevents steatosis and hypertension in obese rats programmed by early weaning.

We hypothesized that resveratrol, a natural phytoalexin found in grapes, can prevent oxidative stress, obesity and its related disturbances in obese rats programmed by early weaning. Lactating Wistar rats were separated into two groups: early weaning (EW) - dams who were wrapped with a bandage to interrupt the lactation in the last 3 days of lactation; control - dams whose pups had free access to milk during all lactation. At the 150th day, EW offspring were randomly subdivided into EW+resveratrol (EW+Res) - resveratrol (30 mg/kg/day); EW+vehicle (EW) - rats that received 0.5% (w/v) aqueous methylcellulose. The control group received vehicle. Rats were treated by gavage daily for 30 days. EW offspring developed hyperphagia, higher body weight, visceral obesity, higher systolic (SBP) and diastolic blood pressure (DBP) (+15% and +20%, respectively; P<.05) and higher serum triglycerides (TG) and low-density lipoprotein but lower high-density lipoprotein (+55%, +33% and -13%, respectively; P<.05). Resveratrol normalized food intake, SBP and DBP and prevented obesity and dyslipidemia in EW+Res. EW rats had higher plasma and liver thiobarbituric-acid-reactive substances (TBARS) and lower plasma superoxide dismutase (SOD) and liver glutathione peroxidase activities (+51%, +18%, -58%, -31%, respectively; P<.05), and resveratrol normalized both plasma and liver TBARS and increased the activity of SOD and catalase in plasma. EW rats presented liver steatosis and higher liver TG, and resveratrol prevented these hepatic alterations. In conclusion, this study demonstrated a potential therapeutic use of resveratrol in preventing obesity and oxidative stress and reducing the risk of hypertension, dyslipidemia and steatosis in adult rats programmed by early weaning.

Oxidative stress programming in a rat model of postnatal early overnutrition--role of insulin resistance.

Postnatal early overfeeding (EO) is related to later development of overweight and other metabolic disorders. As oxidative stress is implicated in most human diseases, as obesity and diabetes, we decided to study some parameters related to oxidative stress and insulin signaling in liver from EO animals in adult life. To induce EO, litter size was reduced to three pups per litter (SL: small litter) and groups with normal litter size (NL:10 pups per litter) were used as control. After weaning, rats had free access to standard diet and water. Body weight and food intake were monitored daily and offspring were killed at 180 days-old. Significant differences had P<.05 or less. As expected, SL rats had hyperphagia, higher body weight and higher visceral fat mass at weaning and adulthood. In liver, postnatal EO programmed for lower catalase (-42%), superoxide dismutase (-45%) and glutathione peroxidase (-65%) activities. The evaluation of liver injury in adult SL group showed lower nitrite content (-10%), higher liver and plasma malondialdehyde content (+25% and 1.1-fold increase, respectively). No changes of total protein bound carbonyl or Cu/Zn superoxide dismutase protein expression in liver were detected between the groups. Regarding insulin signaling pathway in liver, SL offspring showed lower IRß (-66%), IRS1 (-50%), phospho-IRS1 (-73%), PI3-K (-30%) and Akt1 (-58%). Indeed, morphological analysis showed that SL rats presented focal areas of inflammatory cell infiltrate and lipid drops in their cytoplasm characterizing a microsteatosis. Thus, we evidenced that postnatal EO can program the oxidative stress in liver, maybe contributing for impairment of the insulin signaling.

Maternal prolactin inhibition at the end of lactation affects learning/memory and anxiety-like behaviors but not novelty-seeking in adult rat progeny.

Maternal hypoprolactinemia at the end of lactation in rats reduces milk production and is associated with offspring's malnutrition. Since malnutrition during development is also known to have long lasting effects on cognition and emotion, in the present study we tested the hypothesis that maternal hypoprolactinemia, induced by bromocriptine treatment, at the end of the lactating period affects memory/learning, novelty-seeking and anxiety-like behaviors in adult male Wistar rats using, respectively, the radial arm water maze (RAWM), the hole board (HB) arena and the elevated plus-maze (EPM). We also analyzed serum corticosterone and thyroid hormone levels at postnatal day (PN) 21. Lactating dams were treated with bromocriptine (BRO, 1mg twice a day, inhibiting prolactin) or saline from PN19 to 21 (the last 3 days of lactation). BRO offspring had hypercorticosteronemia and hypothyroidism at PN21. In the RAWM, reductions in latency observed in CON rats were initially more accentuated than in BRO ones. By the end of the testing period, latencies became similar between groups. No difference was observed between groups regarding the number of nose-pokes in the HB. In the EPM, BRO rats stayed less time in and had fewer entries into the open-arms than CON ones. This pattern of results indicates that maternal bromocriptine treatment at the end of the lactating period results in poorer memory/learning performance and in higher levels of anxiety-like behavior in the adult offspring, demonstrating that even a relatively short period of malnutrition during development can have long lasting detrimental effects regarding cognition and emotion.

Neonatal nicotine exposure causes insulin and leptin resistance and inhibits hypothalamic leptin signaling in adult rat offspring.

Maternal nicotine (NIC) exposure during lactation leads to overweight, hyperleptinemia, and hypothyroidism in adult rat offspring. In this model, we analyzed adipocyte morphology, glucose homeostasis (serum insulin and adiponectin; liver and muscle glycogen), serum lipid, and the leptin signaling pathway. After birth, osmotic minipumps were implanted in lactating rats, which were divided into the groups NIC (6 mg/kg per day s.c. for 14 days) and control (C, saline). NIC and C offspring were killed at the age of 180 days. Adult NIC rats showed higher total body fat (+10%, P<0.05), visceral fat mass (+12%, P<0.05), and cross-sectional area of adipocytes (epididymal: +12% and inguinal: +43%, P<0.05). Serum lipid profile showed no alteration except for apolipoprotein AI, which was lower. We detected a lower adiponectin:fat mass ratio (-24%, P<0.05) and higher insulinemia (+56%, P<0.05), insulin resistance index (+43%, P<0.05), leptinemia (+113%, P<0.05), and leptin:adiponectin ratio (+98%, P<0.05) in the adult NIC group. These rats presented lower hypothalamic contents of the proteins of the leptin signaling pathway (leptin receptor (OB-R): -61%, janus tyrosine kinase 2: -41%, and p-signal transducer and activator of transcription 3: -56%, P<0.05), but higher suppressor of cytokine signaling 3 (+81%, P<0.05). Therefore, NIC exposure only during lactation programs rats for adipocyte hypertrophy in adult life, as well as for leptin and insulin resistance. Through the effects of NIC, perinatal maternal cigarette smoking may be responsible for the future development of some components of the metabolic syndrome in the offspring.

Effects of maternal hyperleptinaemia during lactation on short-term memory/learning, anxiety-like and novelty-seeking behavioral traits of adult male rats.

The objective of the present study was to evaluate whether maternal hyperleptinaemia programs anxiety-like and novelty-seeking behaviors as well as short-term memory/learning in adult male Wistar rats. During the first 10 days of lactation dams were s.c. injected with either murine leptin (LEP) or saline (CON). Adult LEP offspring displayed less anxiety-like behavior and had better memory performance than CON ones, indicating that maternal hyperleptinaemia has specific long lasting behavioral effects at adulthood.

Neonatal hyperleptinaemia programmes anxiety-like and novelty seeking behaviours but not memory/learning in adult rats.

Leptin treatment during lactation programmes for leptin resistance at adulthood, evidenced by hyperleptinaemia, hyperphagia and overweight. Since leptin is known to affect stress response, emotional behaviour and memory/learning performance, the objective of the present study was to evaluate whether neonatal hyperleptinaemia programmes anxiety-like and novelty-seeking behaviours as well as memory/learning in adult male rats. During the first 10 days of lactation (from PN1 to PN10), pups were s.c. injected once per day with either 50 microL of saline (SAL) or murine leptin (LEP - 8 microg/100 g of body mass, saline diluted). Serum leptin was assessed at PN10 and at PN150. Two separate experiments were carried out: 1) experiment one: at PN137, 29 SAL and 30 LEP rats were tested in the elevated plus-maze (EPM) and, at PN142, their behaviour was assessed in the hole board (HB) arena; 2) experiment two: at PN140, a different group of rats consisting of 53 SAL and 56 LEP animals were tested in the radial arm water maze (RAWM). Serum leptin concentration was higher in the LEP group at PN10 and at PN150. LEP animals spent significantly less time in the open arms of the EPM. Furthermore, the number of nose-pokes in the HB arena was higher in LEP rats. There were no differences between groups regarding latency to find the hidden platform in the RAWM. Our results suggests that a central mechanism of leptin resistance at adulthood, caused by neonatal hyperleptinaemia, is associated with an increased level of anxiety and also that it intensifies novelty seeking-behaviour.