Diet enriched in saturated fatty acids induces liver oxidative stress and elicits inflammatory pathways prior to metabolic disruption in perinatal protein undernutrition.

The impact of diets high in saturated fatty acids in individuals who have undergone maternal protein restriction is not clear. Here, we tested the hypothesis that a saturated fatty acid-enriched hyperlipidic diet (HL) affects liver expression of genes of the redox balance and inflammatory pathway in postweaning rat offspring subjected to maternal protein restriction. Pregnant Wistar rats received either a control (C; 19% protein) or low protein (LP; 8% protein) diet during gestation and lactation. At weaning, pups received either C or HL diets up to 90 days of life. The LP+HL group showed an upregulation of transcription of peroxisome proliferator-activated receptor γ (+48%) and peroxisome proliferator-activated receptor γ coactivator α (+96%) compared with the LP+C group (P < .05), respectively. Similarly, gene expression of the markers of inflammation, nuclear factor-kappa B1 (+194%) and tumor necrosis factor-α (+192%), was enhanced (P < .05). Although other antioxidant enzymes were not modified in gene expression, catalase (CAT) was 66% higher in LP+HL compared with LP+C. In contrast, CAT protein content in the liver was 50% lower in LP groups compared with C, and superoxide dismutase 2 (SOD2) was twice as high in LP groups compared with C. Postweaning HL after maternal protein restriction induces hepatic metabolic adaptation characterized by enhanced oxidative stress, unbalanced expression in the antioxidant enzymes SOD1, SOD2 and CAT, and activation of inflammatory pathways but does not impact circulating markers of lipid metabolism and liver function.

Oxidative injuries induced by maternal low-protein diet in female brainstem.

Many studies have shown that a maternal low-protein diet increases the susceptibility of offspring to cardiovascular disease in later-life. Moreover, a lower incidence of cardiovascular disease in females than in males is understood to be largely due to the protective effect of high levels of estrogens throughout a woman's reproductive life. However, to our knowledge, the role of estradiol in moderating the later-life susceptibility of offspring of nutrient-deprived mothers to cardiovascular disease is not fully understood. The present study is aimed at investigating whether oxidative stress in the brainstem caused by a maternal low-protein diet administered during a critical period of fetal/neonatal brain development (i.e during gestation and lactation) is affected by estradiol levels. Female Wistar rat offspring were divided into four groups according to their mothers' diets and to the serum estradiol levels of the offspring at the time of testing: (1) 22 days of age/control diet: (2) 22 days of age/low-protein diet; (3) 122 days of age/control diet: (4) 122 days of age/low-protein diet. Undernutrition in the context of low serum estradiol compared to undernutrition in a higher estradiol context resulted in increased levels of oxidative stress biomarkers and a reduction in enzymatic and non-enzymatic antioxidant defenses. Total global oxy-score showed oxidative damage in 22-day-old rats whose mothers had received a low-protein diet. In the 122-day-old group, we observed a decrease in oxidative stress biomarkers, increased enzymatic antioxidant activity, and a positive oxy-score when compared to control. We conclude from these results that following a protein deficiency in the maternal diet during early development of the offspring, estrogens present at high levels at reproductive age may confer resistance to the oxidative damage in the brainstem that is very apparent in pre-pubertal rats.

Moderate physical training counterbalances harmful effects of low-protein diet on heart: metabolic, oxidative and morphological parameters

Aims: Maternal low-protein diet induces several impairments on cardiac system. Conversely, moderate exercise has been widely recommended to health improvement due to its effects on heart function. Thus, we investigated whether the moderate physical training is capable to offset the lasting injuries of a maternal protein restriction on the hearts of male adult rats. Methods: Pregnant rats were divided into two groups: Control (C=17% casein) and undernutrition (U=8% casein). Offspring from the undernutrition group, at 60 days of life, were subdivided into undernutrition (U) and undernutrition+exercise (UT) groups. Treadmill exercise was performed: (8 weeks, 5 days/week, 60 min/day at 70% of VO2máx). 48 hours after last exercise session, tissues were collected for morphological and biochemical analysis. Results Despite the deleterious effect induced by low-protein diet, physical training was able to restore morphological parameters to similar levels to the control group. Additionally, oxidative stress index was also improved in UT group, due to the increase in antioxidant enzymatic defense. In metabolic enzymes, maternal low-protein diet induced a change in metabolism, and moderate physical training improved oxidative metabolism. Conclusion: We demonstrated that moderate physical training can offset the cardiac metabolism in adult rats that were exposed to a maternal low-protein diet.(AU)

Protective effects of l-carnitine and piracetam against mitochondrial permeability transition and PC3 cell necrosis induced by simvastatin.

Mitochondrial oxidative stress followed by membrane permeability transition (MPT) has been considered as a possible mechanism for statins cytotoxicity. Statins use has been associated with reduced risk of cancer incidence, especially prostate cancer. Here we investigated the pathways leading to simvastatin-induced prostate cancer cell death as well as the mechanisms of cell death protection by l-carnitine or piracetam. These compounds are known to prevent and/or protect against cell death mediated by oxidative mitochondrial damage induced by a variety of conditions, either in vivo or in vitro. The results provide evidence that simvastatin induced MPT and cell necrosis were sensitive to either l-carnitine or piracetam in a dose-dependent fashion and mediated by additive mechanisms. When combined, l-carnitine and piracetam acted at concentrations significantly lower than they act individually. These results shed new light into both the cytotoxic mechanisms of statins and the mechanisms underlying the protection against MPT and cell death by the compounds l-carnitine and piracetam.