Specific NOX4 Inhibition Preserves Mitochondrial Function and Dampens Kidney Dysfunction Following Ischemia-Reperfusion-Induced Kidney Injury.

Background: Acute kidney injury (AKI) is a sudden episode of kidney failure which is frequently observed at intensive care units and related to high morbidity/mortality. Although AKI can have many different causes, ischemia-reperfusion (IR) injury is the main cause of AKI. Mechanistically, NADPH oxidases (NOXs) are involved in the pathophysiology contributing to oxidative stress following IR. Previous reports have indicated that knockout of NOX4 may offer protection in cardiac and brain IR, but there is currently less knowledge about how this could be exploited therapeutically and whether this could have significant protection in IR-induced AKI. Aim: To investigate the hypothesis that a novel and specific NOX4 inhibitor (GLX7013114) may have therapeutic potential on kidney and mitochondrial function in a mouse model of IR-induced AKI. Methods: Kidneys of male C57BL/6J mice were clamped for 20 min, and the NOX4 inhibitor (GLX7013114) was administered via osmotic minipump during reperfusion. Following 3 days of reperfusion, kidney function (i.e., glomerular filtration rate, GFR) was calculated from FITC-inulin clearance and mitochondrial function was assessed by high-resolution respirometry. Renal histopathological evaluations (i.e., hematoxylin-eosin) and TUNEL staining were performed for apoptotic evaluation. Results: NOX4 inhibition during reperfusion significantly improved kidney function, as evidenced by a better-maintained GFR (p < 0.05) and lower levels of blood urea nitrogen (p < 0.05) compared to untreated IR animals. Moreover, IR caused significant tubular injuries that were attenuated by simultaneous NOX4 inhibition (p < 0.01). In addition, the level of renal apoptosis was significantly reduced in IR animals with NOX4 inhibition (p < 0.05). These favorable effects of the NOX4 inhibitor were accompanied by enhanced Nrf2 Ser40 phosphorylation and conserved mitochondrial function, as evidenced by the better-preserved activity of all mitochondrial complexes. Conclusion: Specific NOX4 inhibition, at the time of reperfusion, significantly preserves mitochondrial and kidney function. These novel findings may have clinical implications for future treatments aimed at preventing AKI and related adverse events, especially in high-risk hospitalized patients.

Antibacterial mouthwash alters gut microbiome, reducing nutrient absorption and fat accumulation in Western diet-fed mice.

Prolonged use of antibacterial mouthwash is linked to an increased risk of systemic disease. We aimed to investigate if disturbing the oral microbiota would impact the lower gut microbiome with functional effects in diet-induced obesity. Mice were exposed to oral chlorhexidine and fed a Western diet (WD). Food intake and weight gain were monitored, and metabolic function, blood pressure, and microbiota were analyzed. Chlorhexidine reduced the number of viable bacteria in the mouth and lowered species richness in the gut but with proportional enrichment of some bacteria linked to metabolic pathways. In mice fed a Western diet, chlorhexidine reduced weight gain, body fat, steatosis, and plasma insulin without changing caloric intake, while increasing colon triglycerides and proteins, suggesting reduced absorption of these nutrients. The mechanisms behind these effects as well as the link between the oral microbiome and small intestinal function need to be pinpointed. While the short-term effects of chlorhexidine in this model appear beneficial, potential long-term disruptions in the oral and gut microbiota and possible malabsorption should be considered.

External and digestive system morphology of the Tamandua tetradactyla.

Collared anteater is present throughout the Brazilian territory, but its morphology is little known. This study aimed to trace its external biometric profile and its digestive system. Six cadavers (4 ± 0.16 kg) from Paraíba, Brazil, were used. The thoracic limbs were more robust when compared to pelvic. The length of the tail is below that described in specimens from south-eastern Brazil, probably due to the greater use of the tail suspension function in the leafier forests in this region. The tongue had no papillae and had keratinized squamous epithelium. The oesophagus was tubular with keratinized squamous epithelium. The stomach was single-chambered with simple prismatic epithelium and presence of tubular glands in the lamina propria. The pyloric region was thicker and had larger folds of mucosa; the greater curvature was approximately three times greater than the smaller. The small intestine was larger than that found in other Xernathra species such as sloth, an herbivore animal; in the large intestine, the caecum was small. The colon was subdivided ascending, transverse and descending, with simple prismatic epithelium. This study is the first to bring the description of the external and digestive system morphometrics of collared anteater adult and pup. The anatomical characteristics of the digestive system show that the digestion of the anteaters, although not using the fermentation, is not as rapid as in other Xenarthras, probably due to the material of the exoskeleton of the insects by them consumed. The data generate subsidies for the clinic, surgery, preservation and nutrition of this species.

Creolin® administered by different pathways in rats experimentally poisoned with Bothrops jararaca venom / Creolina ® administrada por diferentes vias em ratos envenenados experimentalmente com veneno de Bothrops jararaca

ABSTRACT: This study aimed to evaluate the effects of Creolin® when administered by different pathways in rats experimentally poisoned with Bothrops jararaca venom. In female Wistar rats, the Bothropic venom was inoculated intramuscularly, and then the rats were either treated with Creolin® (administered orally, topically, or intramuscularly), or with amixture of venom + Creolin® intramuscularly. Animals that received Creolin®, apart from the venom, by oral, topical, or intramuscular routes developed local symptoms and showed laboratory findings similar to those animals that received only the venom. Conversely, animals inoculated with the venom incubated with Creolin® showed no signs of local venom toxicity (necrosis or hemorrhage) and displayed hematological parameters within the normal range for the species. These results suggest that Creolin® exhibited an antiophidian effect only when it is mixed with the venom and administered intramuscularly.

RESUMO: Esse estudo objetivou avaliar os efeitos da Creolina® quando administrada por diferentes vias de acesso em ratos experimentalmente envenenados pela peçonha de Bothrops jararaca. Em ratas Wistar fêmeas foi inoculada a peçonha botrópica por via intramuscular, e em seguida as ratas foram tratadas com Creolina® (administrada oralmente, topicamente e intramuscularmente) ou a mistura de veneno + Creolina®. Os animais que receberam a Creolina®, além do veneno, por via oral, tópica e muscular desenvolveram a sintomatologia local e achados laboratoriais semelhantes ao grupo que recebeu apenas o veneno. De forma controversa, os animais inoculados com o veneno misturado a Creolina® não apresentaram sinais característicos da ação local do veneno (necrose, hemorragia) e apresentaram parâmetros hematológicos dentro da normalidade para espécie. Esses resultados sugerem que a Creolina® apresentou efeito antiofídico apenas quando misturada ao veneno e administrada intramuscularmente.

Intoxicação por Portulaca elatior (Portulacaceae) em bovinos / Portulaca elatior (Portulacaceae) poisoning in cattle

Descreve-se um surto de intoxicação aguda em bovinos causado pela ingestão de Portulaca elatior na região nordeste do Brasil. O surto resultou da ingestão a partir da administração da planta no cocho pelo criador para os bovinos. Quatro de cinco bovinos foram intoxicados e dois morreram. Os sinais clínicos incluíram dor abdominal, tremores musculares, intensa salivação, timpanismo moderado e desidratação. O curso clínico da doença variou de 10 a 18 horas. Os achados macroscópicos incluíram desidratação, avermelhamento das mucosas dos pré-estômagos, abomaso e intestinos, além de ulceração da mucosa ruminal. Nos dois casos foi notada a presença de fragmentos de Portulaca no interior do rúmen. Os achados histológicos foram de degeneração e necrose das camadas superficiais do epitélio dos pré-estômagos, necrose e inflamação da mucosa intestinal e necrose linfoide. As atividades de AST e GGT estavam dentro dos valores de normalidade. O diagnóstico de intoxicação associado à ingestão de P. elatior foi baseado na epidemiologia, sinais clínicos e lesões. A ausência de informação sobre a toxicidade de P. elatior foi a principal causa para a ocorrência da intoxicação acidental.(AU)

An outbreak of acute poisoning in cattle caused by the ingestion of Portulaca elatior occurred in the northeastern Brazil. The outbreak resulted from ingestion of the plant provided by the farmer. Four out of five cattle were poisoned and two died. Clinical signs included abdominal pain, muscle trembling, intense salivation, mild bloat and dehydration. The course of the disease ranged from 10 to 18 hours. Gross findings included dehydration, reddening of the mucosa of forestomachs, abomasum, and intestine, with ulcerations of the ruminal mucosa. The presence of Portulaca leaves in the rumen was noted in both cases. The main histologic lesions were superficial to full thickness degeneration and necrosis of the stratified epithelium lining the forestomachs, necrosis and inflammation of the intestinal mucosa, and lymphoid necrosis. The serum activities of AST and GGT and serum were within normal ranges. The diagnosis of poisoning associated with ingestion of P. elatior was based on the epidemiology, clinical signs and lesions. The lack of information about the toxicity of P. elatior was the main cause for the accident of poisoning.(AU)