Neuroprotection is a desirable process in many neurological disorders, yet complex mechanisms involved in this field are not completely understood. The pilocarpine epilepsy model causes potent, seizure-induced excitotoxicity cell death and mitochondria impairment. The present study is aimed at investigating the role of UCP2, a ROS negative regulator, in the neuroprotection after cholinergic insult. Our data demonstrated that UCP2 expression was augmented in the rat hippocampus 3 days after status epilepticus (SE), reaching a peak on the fifth day, then returning to basal levels. Concomitantly, phospho-AKT expression levels were higher in the hippocampus during the early silent phase (5 days after SE). Additionally, it was demonstrated that the blockade of UCP2 by antisense oligonucleotides (ASO) in SE rats successfully diminished both UCP2 mRNA and protein contents. SE ASO rats presented increased mitochondrial proapoptotic factor expression, caspase-3 activity, inflammatory cytokine expression, and ROS formation. Moreover, ASO treatment diminished p-AKT expression and antioxidant enzyme activities after pilocarpine insult. In conclusion, the present results highlight the neuroprotective actions of UCP2, acting in the inhibition of apoptotic factors and oxidative stress, to increase neuron survival after SE onset.

This study was designed to evaluate the lipid and oxidative stress profiles in diabetic rats that had undergone 15 days of myocardial infarction. Male Wistar rats were divided into control (C), diabetic (D), myocardial infarction (MI) and diabetic myocardial infarction (DMI). Left coronary artery occlusion was performed after 15 days of diabetes (STZ) and accompanied for more 15 days. The free fatty acids and triacylglycerol content and oxidative stress profile were determined by biochemical analysis in left ventricle. The free fatty acids were increased in DMI: 1.16±0.2 vs D: 0.45±0.09; MI: 0.72±0.1 and C: 0.4±0.05 mg/g of tissue, however the triacylglycerol was increased in D: 2.12±0.3 and decreased in DMI: 0.72±0.1 and MI: 1±0.2 vs C: 1.45±0.1 mg/g of tissue. The catalase activity was increased in DMI: 0.62±0.1; D: 0.56±0.09 vs C: 0.29±0.05 and MI: 0.35± 0.02 nmol/mg and glutathione peroxidase increased in DIM: 0.04±0.008 vs D: 0.02±0.003; MI: 0.02 ±0.0002 and C: 0.01±0.005 umol/min/mg. The superoxide anion and protein carbonylation were increased in MI group: 7±0.9 vs D:4±0.5; DIM:4±0.5 and C:4±0.4 O2‐mmoles/mg and MI:2.65 ± 0.36 vs D: 1.5 ± 0.24; DIM: 1.22 ± 0.2 and C: 1.45 ± 0.26 nmol/mg. These findings suggest that diabetic rats exposed to an ischemic injury showed an increase in the lipids utilization and an oxidative stress reduction, supporting previously published data of improvement of the cardiac function in these model. Grant Funding Source: Fapesp

The aim this study was to evaluate the effects on hemodynamic, autonomic and inflammatory profile in offspring (from birth to adulthood) of parents submitted to chronic fructose overload. The Fructose genitor group was formed by adult Wistar rats (males and females) that underwent a fructose overload (10%) in drinking water for 60 days. The Control genitor group was formed by adult Wistar rats who were only followed for the same period receiving a standard diet. Mating was carried out and the females continued to receive the same diet (fructose or standard) during all gestation and lactation. On the day of birth, the fructose (F) and control (C) offspring were submitted to an electrocardiogram to analyze heart rate variability (n = 10/group). On the day of weaning two groups were evaluated, the CW group (descendants of the control parents, n = 10) and the FW group (descendants of the fructose parents, n = 10). Another two groups were evaluated 30 days after weaning, group C30 (from control parents, n = 10) and the F30 group (from fructose parents, n = 10). During lifespan, all offspring received a standard diet without fructose. Arterial pressure (AP) were recorded directly. Baroreflex sensitivity was evaluated by increasing dosing of phenylephrine and sodium nitroprusside. Cardiovascular autonomic modulation was evaluated by spectral analysis. Inflammatory profile was measured by ELISA in cardiac tissue. Regarding the autonomic evaluations, the fructose groups presented an impairment from birth to adulthood evidenced by a sympathovagal imbalance (LF/HF) when compared to control groups (F: 0.71 ± 0.08; FW: 0.91 ± 0.08 and F30: 0.72 ± 0.09 vs. C: 0.37 ± 0.04; CW: 0.48 ± 0.07 and C30: 0.38 ± 0.04). Additionally, only the F30 group showed higher vascular sympathetic modulation among groups (4.7 ± 0.6 vs. C30: 2.8 ± 0.4; CW: 1.8 ± 0.4 and FW: 2.9 ± 0.4 mmHg2). Moreover, the fructose groups had a worse tachycardic response when compared to control groups at the same time (FW: −2.8 ± 0.3 and F30: −3.1 ± 0.2 vs. CW: −3.9 ± 0.4 and C30: −4.0 ± 0.1 bpm/mmHg). Finally, group F30 presented worse inflammatory profile compared to group C30, evidenced by the increase of IL‐6 (167.2 ± 9.5 vs C30: 104.9 ± 11.9 pg/ml) and decrease of the IL‐10/TNF alpha ratio (P<0.01). The mean, systolic and diastolic AP was increased only in group F30 when compared to the C30 group (mean AP, F30: 109 ± 1.9 vs. C30: 103 ± 1.3 mmHg). In conclusion, the offspring of parents submitted to fructose overload presented autonomic, hemodynamic and inflammatory cardiovascular dysfunctions. Moreover, the results suggest early autonomic dysfunctions, and these seem to precede hemodynamic and inflammatory changes. These findings suggest cardiovascular autonomic variability as a possible early marker of risk of developing disease in offspring of parents exposed to high fructose consumption. Support or Funding Information FAPESP (2018/17183‐4); CAPES.

Introduction: Thiazide diuretic is a classic drug used to treat elevated arterial pressure (AP). However, their neuroinflammatory effects are limited when compared with other therapies. Objective: To compare the effect of hydrochlorothiazide (HCTZ) alone or combined with concurrent exercise training (aerobic+resistance, CET) on mechanisms of AP control and on inflammatory and redox balance in hypertensive postmenopausal rats. Methods: Female spontaneously hypertensive rats were distributed into sedentary (S) and ovariectomized groups: sedentary (OS), sedentary treated with HCTZ (OSH), trained (OT) and trained treated with HCTZ (OTH). HCTZ treatment (30 mg/kg) and CET (40-60% maximal capacity, 3 days/wk) were conducted for 8wks. AP was directly recorded at rest and after vasopressor system blockade (vasopressin antagonist, losartan and hexamethonium). Inflammation and oxidative stress were evaluated in cardiac tissue. Results: Trained groups presented higher exercise tests performance. Systolic (OT:178±18 and OTH:178±17 vs. OS:205±15) and mean AP (mmHg) (OTH:153±17 vs. OS:176±16) were reduced in trained groups. CET promoted an increase in both bradycardic and tachycardic responses of baroreflex sensitivity and a reduction in AP variability indexes in relation to OS group. After sympathetic blockade, AP (mmHg) reduction was higher in OS group (-75.7±19.2 vs. S:-53.2±12.6 and OTH:-49.8±12.4). In addition, IL-10 (OTH vs. OS and OSH) and IL-10/TNF-alpha ratio (OTH vs. S, OS, OSH and OT) were higher in OTH group. OS group showed increased NAPDHoxidase and reduced catalase (vs. S); however, these changes were not observed in OTH group. Negative correlation was observed between sympathetic vascular modulation and IL/TNF-alpha ratio (p<0.001, r:-0.6). Conclusions: We concluded that CET alone or combined with HCTZ are more efficient approaches than HCTZ to reduce AP and improve AP control of circulation. Specifically, the combination HCTZ plus CET induces additional positive adaptations on physical, autonomic, inflammatory and redox balance. These results highlight the key role of exercise in the management of HTN, probably impacting on the quality of life and reducing the residual risk in post menopause. Grants: FAPESP (2019/06277-0).