Lambs Fed Diets Containing By-Product from Coconut Processing: Histomorphometry Characteristics in the Digestive and Renal Systems

This study aimed to evaluate the histological characteristics in the digestive and renal systems of lambs fed diets containing coconut by-product (CB). A total of 35 male lambs with an initial weight of 16.9 ± 2.93 kg were distributed in a completely randomized design with five levels of CB in the diet (0; 4.8; 9.6; 14.4 and 19.2% in total dry matter). Samples of the liver, kidney, rumen, and intestine were histomorphometrically evaluated and the data were submitted to regression analysis, at a 5% error probability. The inclusion of CB linearly decreased the dry matter intake and caused a quadratic effect for the height of ruminal papillae, absorption area, epithelium thickness, as well as for average daily gain. The inclusion of CB linearly increased the mucous layer and reduced the submucosal layer, as well as promoted a decrease in goblet cells in the small intestine. The inclusion of BC did not influence hepatic glycogen, additionally, the histopathological examination did not reveal liver damage or congestion, vacuolization, and necrosis of the renal tissue. Therefore, our results indicate that CB can be included in lambs diet up to the level of 7.2% without causing changes in the histomorphometry characteristics of the gastrointestinal tract and changes in liver and kidney tissue that compromise animal performance.

N-Acetylcysteine Alleviated the Deltamethrin-Induced Oxidative Cascade and Apoptosis in Liver and Kidney Tissues

Deltamethrin (DLM) is a synthetic pyrethroid with anti-acaricide and insecticidal properties. It is commonly used in agriculture and veterinary medicine. Humans and animals are exposed to DLM through the ingestion of polluted food and water, resulting in severe health issues. N-acetylcysteine (NAC) is a prodrug of L-cysteine, the precursor to glutathione. It can restore the oxidant-antioxidant balance. Therefore, this research aimed to examine whether NAC may protect broiler chickens against oxidative stress, at the level of biochemical and molecular alterations caused by DLM intoxication. The indicators of liver and kidney injury in the serum of DLM-intoxicated and NAC-treated groups were examined. Furthermore, lipid peroxidation, antioxidant markers, superoxide dismutase activity, and apoptotic gene expressions (caspase-3 and Bcl-2) were investigated. All parameters were significantly altered in the DLM-intoxicated group, suggesting that DLM could induce oxidative damage and apoptosis in hepato-renal tissue. The majority of the changes in the studied parameters were reversed when NAC therapy was used. In conclusion, by virtue of its antioxidant and antiapoptotic properties, NAC enabled the provision of significant protection effects against DLM-induced hepato-renal injury.

Assessment of Hydroxyethyl Starch (6% HES 130/0.4) Kidney Storage in Critically Ill Dogs: A Post-mortem Prospective Study

Objective: Intravenous hydroxyethyl starch (HES) solutions are potentially nephrotoxic due to rapid renal tissue uptake, subsequent osmotic nephrosis, and long-lasting intracellular storage. This study aimed to investigate the severity of intracellular storage of HES in renal tissue samples from critically ill dogs receiving 6% HES 130/0.4.Materials and Methods: Fresh, post-mortem (<2 h after death) renal tissue samples were analyzed through histology, immunohistochemistry (HES 130/0.4-specific antibodies), and electron microscopy for the severity of renal tubular vacuolization (VAC), intravacuolar HES accumulation (ACC), and ultra-structure impairment. Moreover, we investigated the relationship between VAC or ACC grade and HES dose (mL/kg), duration of HES administration (h), and pre-HES plasma creatinine concentrations.Results: Histology revealed that 2/20 dogs (10%) had no, 11/20 dogs (55%) had mild, 5/20 dogs (25%) had moderate, and 2/20 dogs (10%) had severe VAC. Immunohistochemistry revealed that 5/20 dogs (25%) had no, 6/20 dogs (30%) had mild, 7/20 dogs (35%) had moderate, and 2/20 dogs (10%) had severe ACC. Both changes were predominantly found in the distal tubular epithelium of mild and moderate cases, and all tubular segments were affected in severe cases. Seven of 20 dogs (35%) had osmotic nephrosis (ON). On electron microscopy, large granules with an electron-dense content were repeatedly detected in individual cells, mainly in the distal tubules. No correlation was found between cumulative HES dose or duration of HES administration and VAC grade, ACC grade, or presence/absence of ON.Conclusion: A high percentage of dogs had renal tubular HES storage and one-third of dogs showed HES-induced ON. Short-term HES administration caused VAC and ACC, regardless of the dose or duration of administration. In contrast to previous studies, HES 130/0.4 deposits were mainly located in the renal distal tubule.

Generation of heterozygous PKD1 mutant pigs exhibiting early-onset renal cyst formation

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease, manifesting as the progressive development of fluid-filled renal cysts. In approximately half of all patients with ADPKD, end-stage renal disease results in decreased renal function. In this study, we used CRISPR-Cas9 and somatic cell cloning to produce pigs with the unique mutation c.152_153insG (PKD1insG/+). Pathological analysis of founder cloned animals and progeny revealed that PKD1insG/+ pigs developed many pathological conditions similar to those of patients with heterozygous mutations in PKD1. Pathological similarities included the formation of macroscopic renal cysts at the neonatal stage, number and cystogenic dynamics of the renal cysts formed, interstitial fibrosis of the renal tissue, and presence of a premature asymptomatic stage. Our findings demonstrate that PKD1insG/+ pigs recapitulate the characteristic symptoms of ADPKD.

Nephroprotective effects of polyherbal extract via attenuation of the severity of kidney dysfunction and oxidative damage in the diabetic experimental model

In view of many complications of diabetes, kidney failure is considered as one of the main complications. The oxidative stress-induced due to persistent hyperglycemic conditions is the major cause of kidney disease. The present study was designed to explore the nephroprotective efficacy of polyherbal (PH) extract in a diabetic model induced by streptozotocin (STZ). STZ (55 mg/kg body weight, intraperitoneal) was injected in overnight fasting rats to develop the diabetic experimental model. Effect on kidney injury was evaluated by investigating biochemical and histological evidences in renal tissue after 56 days of treatment of PH extract. Results showed the high glucose level in STZ treated rats that suggested hyperglycemia persistence along with the successful establishment of nephropathy in diabetic rats with altered renal function, inflammatory cytokines level as well as oxidative and nitrosative stress. Administration of PH extract significantly improved the glycemic condition, glomerular function and proximal reabsorptive markers. Further, elevated pro-inflammatory cytokines levels and disturbed redox status were restored. Moreover, findings were fostered and substantiated by histopathological examinations. Our work strongly proposes that the nephroprotective effect of the PH extract on renal damage could be attributed due to its anti-inflammatory and antioxidant properties. Thus, PH extract could have potential as a pharmaceutical drug for diabetes mellitus (DM). Additional long-term study or clinical trial is required for further investigations.

Evaluation of the antitumor and antioxidant effects of jatobá (Hymenaea courbaril) extracts / Avaliação do efeito antitumoral e antioxidante de extratos do jatobá (Hymenaea courbaril)

Ethnobotanical surveys have revealed the use of jatobá for the treatment of several diseases. This study determined the effect of plant extracts on the development of Ehrlich carcinoma. Male Swiss mice (n=6) were subcutaneously inoculated with 106 tumor cells and intragastrically administered ethanol (2 mg·mL-1, 5 mg·mL-1, or 10 mg·mL-1) or aqueous extracts of jatobá seed or bark for 90 days. Tumor development did not significantly differ between the groups studied; however, animals treated with the aqueous extract of the seed (2.205 mg·mL-1) had a reduction in tumor size compared to those treated with the aqueous extract of the bark (1.7 mg·mL-1). The treatment was not found to influence the survival of the animals studied. A new group of animals (n=7), with or without the tumor, received the aqueous extract of jatobá seed for 7, 14, and 30 days to evaluate oxidative stress. The extract reduced the thiobarbituric acid reactive substances levels at 7 days in the liver and kidneys, and 14 days in brain and renal tissue. Protein carbonylation levels were also reduced at 7 days in the liver and brain tissue and 14 days in the liver. The reduced glutathione levels diminished in animals treated for 7 and 14 days. We conclude that treatment with the aqueous extract of the jatobá seed presents promising activity in the reduction of oxidative stress.

KIM-1 and GADDI-153 gene expression in paracetamol-induced acute kidney injury: effects of N-acetylcysteine, N-acetylmethionine, and N-acetylglucosamine

Objectives Acute kidney injury (AKI) is a critical clinical event characterized by a reduction in the excretory function of the kidneys. N-acetylcysteine (NAC), N-acetylmethionine (NAM) and N-acetylglucosamine (NAG) are antioxidants with scanty known genetic mechanisms. We aimed to assess both kidney injury molecule-1 (KIM-1) and growth-arrested DNA damage-inducible gene-153 (GADD-153) genes expression in paracetamol (PA) induced AKI. Also, to recognize whether NAC, NAM and/or NAG have roles in altering the expression of these genes for ameliorating the AKI induced by PA. Methods The present preliminary study achieved the AKI model by oral administration of PA therapeutic dose for 15 days in experimental male rats. Serum urea, creatinine, and renal oxidative stress parameters were analyzed. Genetic expression of KIM-1 and GADD-153 were determined using real time-PCR. Results Significant elevations of serum urea, creatinine and nitric oxide in renal tissue after PA administration; however, total thiol content was reduced. In addition, both KIM-1 and GADD-153 were upregulated. These biochemical alterations were improved after using NAC and partially after NAM; however, NAG had little effect. Conclusions Up-regulation of both KIM-1 and GADD-153 occur in AKI induced by PA, which was significantly reversed by NAC.

Renal Tissue miRNA Expression Profiles in ANCA-Associated Vasculitis—A Comparative Analysis

Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) comprises autoimmune disease entities that cause target organ damage due to relapsing-remitting small vessel necrotizing vasculitis, and which affects various vascular beds. The pathogenesis of AAV is incompletely understood, which translates to considerable disease- and treatment-related morbidity and mortality. Recent advances have implicated microRNAs (miRNAs) in AAV; however, their accurate characterization in renal tissue is lacking. The goal of this study was to identify the intrarenal miRNA expression profile in AAV relative to healthy, non-inflammatory and inflammatory controls to identify candidate-specific miRNAs. Formalin-fixed, paraffin-embedded renal biopsy tissue samples from 85 patients were obtained. Comprehensive miRNA expression profiles were performed using panels with 752 miRNAs and revealed 17 miRNA that differentiated AAV from both controls. Identified miRNAs were annotated to characterize their involvement in pathways and to define their targets. A considerable subset of differentially expressed miRNAs was related to macrophage and lymphocyte polarization and cytokines previously deemed important in AAV pathogenesis, lending credence to the obtained results. Interestingly, several members of the miR-30 family were detected. However, a validation study of these differentially expressed miRNAs in an independent, larger sample cohort is needed to establish their potential diagnostic utility.