Oxidative stress represents one of the principal inductors of lifestyle-related and genetic diseases. Among them, inherited retinal dystrophies, such as age-related macular degeneration and retinitis pigmentosa, are well known to be susceptible to oxidative stress. To better understand how high reactive oxygen species levels may be involved in retinal dystrophies onset and progression, we performed a whole RNA-Seq experiment. It consisted of a comparison of transcriptomes' profiles among human retinal pigment epithelium cells exposed to the oxidant agent N-retinylidene-N-retinylethanolamine (A2E), considering two time points (3h and 6h) after the basal one. The treatment with A2E determined relevant differences in gene expression and splicing events, involving several new pathways probably related to retinal degeneration. We found 10 different clusters of pathways involving differentially expressed and differentially alternative spliced genes and highlighted the sub- pathways which could depict a more detailed scenario determined by the oxidative-stress-induced condition. In particular, regulation and/or alterations of angiogenesis, extracellular matrix integrity, isoprenoid-mediated reactions, physiological or pathological autophagy, cell-death induction and retinal cell rescue represented the most dysregulated pathways. Our results could represent an important step towards discovery of unclear molecular mechanisms linking oxidative stress and etiopathogenesis of retinal dystrophies.

Maternal obesity is associated with obesity and metabolic disorders in offspring. However, there remains a paucity of data on strategies to reverse the effects of maternal obesity on maternal and offspring health. With maternal undernutrition, taurine supplementation improves outcomes in offspring mediated in part via improved glucose-insulin homeostasis. The efficacy of taurine supplementation in the setting of maternal obesity on health and well-being of offspring is unknown. We examined the effects of taurine supplementation on outcomes related to growth and metabolism in offspring in a rat model of maternal obesity.

Wistar rats were randomised to: 1) control diet during pregnancy and lactation (CON); 2) CON with 1.5% taurine in drinking water (CT); 3) maternal obesogenic diet (MO); or 4) MO with taurine (MOT). Offspring were weaned onto the control diet for the remainder of the study.

At day 150, offspring body weights and adipose tissue weights were increased in MO groups compared to CON. Adipose tissue weights were reduced in MOT versus MO males but not females. Plasma fasting leptin and insulin were increased in MO offspring groups but were not altered by maternal taurine supplementation. Plasma homocysteine concentrations were reduced in all maternal taurine-supplemented offspring groups. There were significant interactions across maternal diet, taurine supplementation and sex for response to an oral glucose tolerance test , a high-fat dietary preference test and pubertal onset in offspring.

These results demonstrate that maternal taurine supplementation can partially ameliorate adverse developmental programming effects in offspring in a sex-specific manner.

This study tests the hypothesis that perinatal taurine supplementation prevents diabetes mellitus and hypertension in adult offspring of maternal diabetic rats. Female Wistar rats were fed normal rat chow and tap water with (Diabetes group) or without diabetic induction by intraperitoneal streptozotocin injection (Control group) before pregnancy. Then, they were supplemented with 3% taurine in water (Control+T and Diabetes+T groups) or water alone from conception to weaning. After weaning, both male and female offspring were fed normal rat chow and tap water throughout the study. Blood chemistry and cardiovascular parameters were studied in 16-week old rats. Body, heart, and kidney weights were not significantly different among the eight groups. Further, lipid profiles except triglyceride were not significantly different among male and female groups, while male Diabetes displayed increased fasting blood glucose, decreased plasma insulin, and increased plasma triglyceride compared to other groups. Compared to Control, mean arterial pressures significantly increased and baroreflex control of heart rate decreased in both male and female Diabetes, while heart rates significantly decreased in male but increased in female Diabetes group. Although perinatal taurine supplementation did not affect any measured parameters in Control groups, it abolished the adverse effects of maternal diabetes on fasting blood glucose, plasma insulin, lipid profiles, mean arterial pressure, heart rate, and baroreflex sensitivity in adult male and female offspring. The present study indicates that maternal diabetes mellitus induces metabolic and cardiovascular defects more in male than female adult offspring, and these adverse effects can be prevented by perinatal taurine supplementation.

This study has examined the role of supplementing a treatment of diabetic rats with captopril (CAP), metformin (MET) or CAP-MET with the antioxidant amino acid taurine (TAU) on biochemical indices of diabetes-induced metabolic changes, oxidative stress and nephropathy. To this end, groups of 6 male Sprague-Dawley rats (250-375 g) were made diabetic with a single, 60 mg/kg, intraperitoneal dose of streptozotocin (STZ) in 10 mM citrate buffer pH 4.5 and, after 14 days, treated daily for up to 42 days with either a single oral dose of CAP (0.15 mM/kg), MET (2.4 mM/kg) or TAU (2.4 mM/kg), or with a binary or tertiary combination of these agents. Rats receiving only 10 mM citrate buffer pH 4.5 or only STZ served as negative and positive controls, respectively. All rats were sacrificed by decapitation on day 57 and their blood and kidneys collected. In addition, a 24 h urine sample was collected starting on day 56. Compared to normal rats, untreated diabetic ones exhibited frank hyperglycemia (+313%), hypoinsulinemia (-76%) and elevation of the glycated hemoglobin value (HbA1c, +207%). Also they showed increased plasma levels of Na+ (+35%), K+ (+56%), creatinine (+232%), urea nitrogen (+158%), total protein (-53%) and transforming growth factor-β1 (TGF-β1, 12.4-fold) values. These changes were accompanied by increases in the renal levels of malondialdehyde (MDA, +42%), by decreases in the renal glutathione redox state (-71%), and activities of catalase (-70%), glutathione peroxidase (-71%) and superoxide dismutase (-85%), and by moderate decreases of the urine Na+ (-33%) and K+ (-39%) values. Following monotherapy, MET generally showed a greater attenuating effect than CAP or TAU on the changes in circulating glucose, insulin and HbA1c levels, urine total protein, and renal SOD activity; and CAP appeared more potent than TAU and MET, in that order, in antagonizing the changes in plasma creatinine and urea nitrogen levels. On the other hand, TAU generally provided a greater protection against changes in glutathione redox state and in CAT and GPx activities, with other actions falling in potency between those of CAP and MET. Adding TAU to a treatment with CAP, but not to one with MET, led to an increase in protective action relative to a treatment with drug alone. On the other hand, the actions of CAP-MET, which were about equipotent with those of MET, became enhanced in the presence of TAU, particularly against the changes of the glutathione redox state and activities of antioxidant enzymes. In short, the present results suggest that the addition of TAU to a treatment of diabetes with CAP or CAP-MET, and sometimes to one with MET, will lead to a gain in protective potency against changes in indices of glucose metabolism and of renal functional impairment and oxidative stress.

This study tests the hypothesis that taurine supplementation reduces sugar-induced increases in renal sympathetic nerve activity related to renin release in adult male rats. After weaning, male rats were fed normal rat chow and drank water containing 5% glucose (CG) or water alone (CW) throughout the experiment. At 6-7 weeks of age, each group was supplemented with or without 3% taurine in drinking water until the end of experiment. At 7-8 weeks of age, blood chemistry and renal nerve activity were measured in anesthetized rats. Body weights slightly and significantly increased in CG compared to CW groups but were not significantly affected by taurine supplementation. Plasma electrolytes except bicarbonate, plasma creatinine, and blood urea nitrogen were not significantly different among the four groups. Mean arterial pressure significantly increased in both taurine treated groups compared to CW, while heart rates were not significantly different among the four groups. Further, all groups displayed similar renal nerve firing frequencies at rest and renal nerve responses to sodium nitroprusside and phenylephrine infusion. However, compared to CW group, CG significantly increased the power density of renin release-related frequency component, decreased that of sodium excretion-related frequency component, and decreased that of renal blood flow-related frequency component. Taurine supplementation completely abolished the effect of high sugar intake on renal sympathetic activity patterns. These data indicate that in adult male rats, high sugar intake alters the pattern but not firing frequency of sympathetic nerve activity to control renal function, and this effect can be improved by taurine supplementation.