As doenças que acometem bovinos na região Sul do Brasil foram analisadas através de um estudo dos protocolos de necropsia de 6.706 bovinos examinados pelo Laboratório de Patologia Veterinária da Universidade Federal de Santa (LPV-UFSM), Rio Grande do Sul, de 1964-2008. Desses, 20,9% foram necropsias realizadas no LPV-UFSM e 79,1% foram amostras de tecidos submetidos por veterinários de campo. Dos 6.706 exames, 62,9% tinham diagnóstico conclusivo. A autólise ou material insuficiente foram as principais razões para a ocorrência de casos com diagnóstico inconclusivo. A intoxicação por Senecio spp. foi a principal causa de morte de bovinos neste estudo. As plantas tóxicas e as toxiinfecções juntas, responderam por 22,8% dos casos com diagnóstico conclusivo. As doenças inflamatórias e as parasitoses juntas contribuíram com mais de 30% das doenças de bovinos e a tristeza parasitária bovina foi a principal doença nessa categoria. As demais categorias distribuíram-se na seguinte ordem: neoplasmas e lesões tumoriformes (13,87%), doenças causadas por agentes físicos (2,7%), doenças metabólicas e nutricionais (2,46%), distúrbios circulatórios (1,4%), doenças degenerativas (1,1%), distúrbios do desenvolvimento (0,54%), distúrbios iatrogênicos (0,16%), distúrbios imunogênicos (0,19%) e, outros distúrbios (0,21%). A alta prevalência de tumores em bovinos foi atribuída a ingestão crônica de Pteridium aquilinum, uma toxicose comum na região. As principais doenças de bovinos na região estudada estão relacionadas a fatores ambientais resultante do manejo característico de criação predominantemente extensiva adotado na região. The diseases affecting cattle in southern Brazil were studied through a review of the necropsy reports filed at the Laboratório de Patologia Veterinária of the Universidade Federal de Santa Maria (LPV-UFSM), Rio Grande do Sul, and pertaining to the examination of 6.076 cattle during 1964-2008. Of those exams 29.9% were necropsies performed at the LPV-UFSM and 79.1% were mailed-in organ fragments from necropsies performed at the field by veterinary practitioners. Autolysis and non-representative sampling o mailed in organs were the main reasons for non-conclusive diagnosis. Poisoning by Senecio spp. was the main cause of death in cattle in this study and poisonous plants together with toxi-infections accounted for 22.8% of the cases with conclusive diagnosis. Inflammatory diseases together with parasitic diseases accounted for more than 30% of cattle diseases and babesiosis and anaplasmosis were the main diseases in this category. Other categories were distributed in the following order: neoplasms and tumor-like lesions (13.87%), diseases caused by physical agents (2.7%), metabolic and nutritional diseases (2.46%), circulatory disturbances (1.4%), degenerative diseases (1.1%), developmental disorders (0.54%), iatrogenic diseases and sundry lesions. The high prevalence of tumors in cattle in this study was attributed to the chronic ingestion of Pteridium aquilinum, a common toxicosis in the region. The main diseases in cattle from the studied region are related to environmental factors associated to the predominantly husbandry practices adopted in the region

Casos de intoxicação por alcaloides pirrolizidínicos (APs) em ruminantes e equinos foram investigados retrospectivamente através do acesso aos arquivos de dois laboratórios de diagnóstico veterinário no Sul e Nordeste brasileiro. Os dados obtidos foram comparados com aqueles retirados da literatura concernentes a surtos dessa toxicose no Brasil, onde ela é associada com a ingestão de plantas que contêm APs dos gêneros Senecio, Crotalaria e Echium. Formas aguda e crônica da toxicose foram encontradas. A doença aguda foi observada em associação com a ingestão de Crotalaria retusa em ovinos e caprinos. C. retusa e Senecio spp. também foram responsáveis pela intoxicação crônica em bovinos, equinos e ovinos. A intoxicação por APs é uma importante causa de morte em animais pecuários no Brasil. Essa é a principal causa de morte em bovinos na região Central do Rio Grande do Sul e uma das principais causas de morte em equinos na Paraíba. A epidemiologia, os sinais clínicos, a patologia e a importância da intoxicação por APs são descritos e discutidos.

Renal fibrosis, associated with oxidative stress and nitric oxide (NO) deficiency, contributes to the development of chronic kidney disease and renal failure. As major energy source in maintaining renal physiological functions, tubular epithelial cells with decreased fatty acid oxidation play a key role in renal fibrosis development. Inorganic nitrate, found in high levels in certain vegetables, can increase the formation and signaling by bioactive nitrogen species, including NO, and dampen oxidative stress. In this study, we evaluated the therapeutic value of inorganic nitrate treatment on development of kidney fibrosis and investigated underlying mechanisms including regulation of lipid metabolism in tubular epithelial cells. Inorganic nitrate was supplemented in a mouse model of complete unilateral ureteral obstruction (UUO)-induced fibrosis. Inorganic nitrite was applied in transforming growth factor β-induced pro-fibrotic cells in vitro. Metformin was administrated as a positive control. Fibrosis, oxidative stress and lipid metabolism were evaluated. Nitrate treatment boosted the nitrate-nitrite-NO pathway, which ameliorated UUO-induced renal dysfunction and fibrosis in mice, represented by improved glomerular filtration and morphological structure and decreased renal collagen deposition, pro-fibrotic marker expression, and inflammation. In human proximal tubule epithelial cells (HK-2), inorganic nitrite treatment prevented transforming growth factor β-induced pro-fibrotic changes. Mechanistically, boosting the nitrate-nitrite-NO pathway promoted AMP-activated protein kinase (AMPK) phosphorylation, improved AKT-mediated peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC1α) activity and restored mitochondrial function. Accordingly, treatment with nitrate (in vivo) or nitrite (in vitro) decreased lipid accumulation, which was associated with dampened NADPH oxidase activity and mitochondria-derived oxidative stress. Our findings indicate that inorganic nitrate and nitrite treatment attenuates the development of kidney fibrosis by targeting oxidative stress and lipid metabolism. Underlying mechanisms include modulation of AMPK and AKT-PGC1α pathways.

Renal ischemia-reperfusion (IR) injury is a common cause of acute kidney injury (AKI), which is associated with oxidative stress and reduced nitric oxide (NO) bioactivity and increased risk of developing chronic kidney disease (CKD) and cardiovascular disease (CVD). New strategies that restore redox balance may have therapeutic implications during AKI and associated complications. To investigate the therapeutic value of boosting the nitrate-nitrite-NO pathway during development of IR-induced renal and cardiovascular dysfunction. Male C57BL/6 J mice were given sodium nitrate (10 mg/kg, i. p) or vehicle 2 h prior to warm ischemia of the left kidney (45 min) followed by sodium nitrate supplementation in the drinking water (1 mmol/kg/day) for the following 2 weeks. Blood pressure and glomerular filtration rate were measured and blood and kidneys were collected and used for biochemical and histological analyses as well as renal vessel reactivity studies. Glomerular endothelial cells exposed to hypoxia-reoxygenation, with or without angiotensin II, were used for mechanistic studies. IR was associated with reduced renal function and slightly elevated blood pressure, in combination with renal injuries, inflammation, endothelial dysfunction, increased Ang II levels and Ang II-mediated vasoreactivity, which were all ameliorated by nitrate. Moreover, treatment with nitrate (in vivo) and nitrite (in vitro) restored NO bioactivity and reduced mitochondrial oxidative stress and injuries. Acute treatment with inorganic nitrate prior to renal ischemia may serve as a novel therapeutic approach to prevent AKI and CKD and associated risk of developing cardiovascular dysfunction.