Activation of endogenous angiotensin converting enzyme 2 prevents early injuries induced by hyperglycemia in rat retina

Diabetic retinopathy (DR) is a serious complication of diabetes mellitus that may result in blindness. We evaluated the effects of activation of endogenous angiotensin converting enzyme (ACE) 2 on the early stages of DR. Rats were administered an intravenous injection of streptozotocin to induce hyperglycemia. The ACE2 activator 1-[[2-(dimethylamino) ethyl] amino]-4-(hydroxymethyl)-7-[[(4-methylphenyl) sulfonyl] oxy]-9H-xanthone 9 (XNT) was administered by daily gavage. The death of retinal ganglion cells (RGC) was evaluated in histological sections, and retinal ACE2, caspase-3, and vascular endothelial growth factor (VEGF) expressions were analyzed by immunohistochemistry. XNT treatment increased ACE2 expression in retinas of hyperglycemic (HG) rats (control: 13.81±2.71 area%; HG: 14.29±4.30 area%; HG+XNT: 26.87±1.86 area%; P0.05). Altogether, these findings indicate that activation of ACE2 reduced the death of retinal ganglion cells by apoptosis in HG rats

Probiotic Therapy Reduces Periodontal Tissue Destruction and Improves the Intestinal Morphology in Rats With Ligature-Induced Periodontitis

Background: With increase in the incidence of resistance to antibiotics, probiotics are emerging as a promising adjunctive periodontal therapy. The authors of this study evaluate the influence of probiotic (PROB) supplementation on ligature-induced periodontitis (LIP) and intestinal morphology in rats.Methods: Thirty-two rats were randomly divided into four groups: control (C), LIP, PROB, and LIP/PROB. In groups PROB and LIP/PROB, the PROB was administered orally by addition to the drinking water of the animals for 44 days. In groups LIP and LIP/PROB, the mandibular right first molar of the animals received a cotton ligature that was left in the same position for 14 days. All animals were euthanized 44 days after the start of the PROB supplementation. The jaws were resected and histomorphometric analyses were performed. The measurements included evaluation of attachment loss (AL) and alveolar bone level (ABL) on the distal root of the mandibular first molar. Samples of the duodenum, jejunum, and ileum were also dissected from each animal to evaluate the villous height (VH) and crypt depth (CD). The data obtained were subjected to statistical analyses (analysis of variance, Tukey; P <0.05).Results: Mean values of AL and ABL were significantly higher in group LIP compared with group LIP/PROB (AL: 3.05 +/- 0.57 mm and 1.78 +/- 0.63 mm, respectively; ABL: 4.21 +/- 0.42 mm and 3.38 +/- 0.17 mm, respectively). In group LIP/PROB, the mean values of VH and CD of the jejunum were significantly higher than the ones from group LIP (VH: 672.1 +/- 83.3 mu m and 528.0 +/- 51.7 mu m, respectively; CD: 463.8 +/- 100.9 mu m and 269.0 +/- 48.4 mu m, respectively).Conclusions: It can be concluded that PROB supplementation 1) reduces AL and alveolar bone loss in rats with LIP and 2) can protect the small intestine from reactive changes induced by LIP.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Antiglaucomatous Effects of the Activation of Intrinsic Angiotensin-Converting Enzyme 2

PURPOSE. To evaluate the effects of the activation of endogenous angiotensin-converting enzyme 2 (ACE2) using the compound diminazene aceturate (DIZE) in an experimental model of glaucoma in Wistar rats. METHODS. DIZE (1 mg/kg) was administered daily, either systemically or topically, and the IOP was measured weekly. To examine the role of the Mas receptor in the effects of DIZE, the Ang-(1-7) antagonist A-779 was co-administered. Drainage of the aqueous humor was evaluated by using scintigraphy. The analysis of ACE2 expression by immunohistochemistry and the counting of retinal ganglion cells (RGCs) were performed in histologic sections. Additionally, the nerve fiber structure was evaluated by transmission electron microscopy. RESULTS. The systemic administration and topical administration (in the form of eye drops) of DIZE increased the ACE2 expression in the eyes and significantly decreased the IOP of glaucomatous rats without changing the blood pressure. Importantly, this IOP-lowering action of DIZE was similar to the effects of dorzolamide. The antiglaucomatous effects of DIZE were blocked by A-779. Histologic analysis revealed that the reduction in the number of RGCs and the increase in the expression of caspase-3 in the RGC layer in glaucomatous animals were prevented by DIZE. This compound also prevented alterations in the cytoplasm of axons in glaucomatous rats. In addition to these neuroprotective effects, DIZE facilitated the drainage of the aqueous humor. CONCLUSIONS. Our results evidence the pathophysiologic relevance of the ocular ACE2/Ang-(1-7)/Mas axis of the renin-angiotensin system and, importantly, indicate that the activation of intrinsic ACE2 is a potential therapeutic strategy to treat glaucoma

Therapeutic treatment of Zika virus infection using a brain-penetrating antiviral peptide

Zika virus is a mosquito-borne virus that is associated with neurodegenerative diseases, including Guillain-Barre syndrome' and congenital Zika syndrome(2). As Zika virus targets the nervous system, there is an urgent need to develop therapeutic strategies that inhibit Zika virus infection in the brain. Here, we have engineered a brain-penetrating peptide that works against Zika virus and other mosquito-borne viruses. We evaluated the therapeutic efficacy of the peptide in a lethal Zika virus mouse model exhibiting systemic and brain infection. Therapeutic treatment protected against mortality and markedly reduced clinical symptoms, viral loads and neuroinflammation, as well as mitigated microgliosis, neurodegeneration and brain damage. In addition to controlling systemic infection, the peptide crossed the blood-brain barrier to reduce viral loads in the brain and protected against Zikavirus-induced blood-brain barrier injury. Our findings demonstrate how engineering strategies can be applied to develop peptide therapeutics and support the potential of a brain-penetrating peptide to treat neurotropic viral infections