Mitigation of Diclofenac Sodium–Induced Hepatic Injury and Enteropathy in Rats by Vanillin

This study aimed to evaluate the potential protective effects of Vanillin (VA) against Diclofenac sodium (DFNa)-induced liver toxicity and enteropathy. A total of sixty male rats were divided into six groups; a control group received only saline, a DFNa-group received DFNa (9 mg/kg), 3rd, 4th, and 5th groups received DFNa along with escalated doses of VA (50, 100, 200 mg/kg). After five days of treatment, blood and tissue samples were collected for biochemical and histopathological analysis. According to our findings, administration of DFNa led to a substantial decrease in the final body weight and a considerable deterioration of hematologic parameters. Regarding biochemically, DFNa-induced a significant elevation in liver enzyme activities with a significant decrease in total protein and albumin levels, indicating liver intoxication. VA maintained normalized body weight and prevented DFNainduced adverse effects on hematologic and liver parameters. Additionally, histopathological examinations revealed that DFNa showed perivascular inflammation and cellular infiltration, along with congestion and dilation of the central vein and induction of both types of cell death (necrosis and apoptosis). In the intestinal sections, DFNa resulted in necrotic enteritis, desquamation, and sloughing of the mucosa, as well as considerable congestion and dilation of the blood vessels with prominent submucosal edema. It is intriguing to note that the VA-treated animals demonstrated a significant protective effect against the deleterious effects of the DFNa on the liver and intestine. As a result of our study, VA could be used as an adjuvant agent as part of various regimens containing DFNa

An in vitro evaluation of the inhibitory effects of an aqueous extract of Acacia nilotica on Eimeria tenella.

Eimeria tenella is one of the most important species of Eimeria that infect domestic fowl, causing coccidiosis in the poultry industry associated with drastic economic loss. Alternative treatment options are often necessary since anticoccidial drugs are prohibitively expensive, have serious side effects, or develop resistance. The role that herbal therapy plays in basic healthcare has been rediscovered worldwide. Consequently, our research assessed the in vitro inhibitory effect of escalated concentrations (6.25 mg, 12.5 mg, 25 mg, 50 mg, and 100 mg/ml) of Acacia nilotica aqueous extract (ANAE) on Eimeria tenella sporulation. Statistical analysis revealed that ANAE decreased the percentage of oocyst sporulation in a dose-dependent manner. Furthermore, ANAE showed abnormal sporulation and morphological deterioration of E. tenella oocytes. Area Under the Curve (AUC) calculation was used to determine the efficacy of ANAE and revealed that ANAE concentrations significantly reduced the coccidial score index. At 100 mg/ml, ANAE completely suppressed the sporulation of E. tenella oocysts, with obvious changes to their morphology and size. The phytochemical analysis of ANAE has shown that ANAE contains several active principles that possess anthelmintic activities. These compounds include tannins, saponins, flavonoids, terpenoids, and alkaloids, which can be attributed to the anticoccidial activity of ANAE. Considering our findings, we recommend that ANAE be used to prevent and control Eimeria

Hypoalbuminemia affects the spatio-temporal tissue distribution of ochratoxin A in liver and kidneys: consequences for organ toxicity

Hypoalbuminemia (HA) is frequently observed in systemic inflammatory diseases and in liver disease. However, the influence of HA on the pharmacokinetics and toxicity of compounds with high plasma albumin binding remained insufficiently studied. The ‘lack-of-delivery-concept’ postulates that HA leads to less carrier mediated uptake of albumin bound substances into hepatocytes and to less glomerular filtration; in contrast, the ‘concept-of-higher-free-fraction’ argues that increased concentrations of non-albumin bound compounds facilitate hepatocellular uptake and enhance glomerular filtration. To address this question, we performed intravital imaging on livers and kidneys of anesthetized mice to quantify the spatio-temporal tissue distribution of the mycotoxin ochratoxin A (OTA) based on its auto-fluorescence in albumin knockout and wild-type mice. HA strongly enhanced the uptake of OTA from the sinusoidal blood into hepatocytes, followed by faster secretion into bile canaliculi. These toxicokinetic changes were associated with increased hepatotoxicity in heterozygous albumin knockout mice for which serum albumin was reduced to a similar extent as in patients with severe hypoalbuminemia. HA also led to a shorter half-life of OTA in renal capillaries, increased glomerular filtration, and to enhanced uptake of OTA into tubular epithelial cells. In conclusion, the results favor the ‘concept-of-higher-free-fraction’ in HA; accordingly, HA causes an increased tissue uptake of compounds with high albumin binding and increased organ toxicity. It should be studied if this concept can be generalized to all compounds with high plasma albumin binding that are substrates of hepatocyte and renal tubular epithelial cell carriers

Spatio-Temporal Multiscale Analysis of Western Diet-Fed Mice Reveals a Translationally Relevant Sequence of Events during NAFLD Progression

Mouse models of non-alcoholic fatty liver disease (NAFLD) are required to define therapeutic targets, but detailed time-resolved studies to establish a sequence of events are lacking. Here, we fed male C57Bl/6N mice a Western or standard diet over 48 weeks. Multiscale time-resolved characterization was performed using RNA-seq, histopathology, immunohistochemistry, intravital imaging, and blood chemistry; the results were compared to human disease. Acetaminophen toxicity and ammonia metabolism were additionally analyzed as functional readouts. We identified a sequence of eight key events: formation of lipid droplets; inflammatory foci; lipogranulomas; zonal reorganization; cell death and replacement proliferation; ductular reaction; fibrogenesis; and hepatocellular cancer. Functional changes included resistance to acetaminophen and altered nitrogen metabolism. The transcriptomic landscape was characterized by two large clusters of monotonously increasing or decreasing genes, and a smaller number of ‘rest-and-jump genes’ that initially remained unaltered but became differentially expressed only at week 12 or later. Approximately 30% of the genes altered in human NAFLD are also altered in the present mouse model and an increasing overlap with genes altered in human HCC occurred at weeks 30–48. In conclusion, the observed sequence of events recapitulates many features of human disease and offers a basis for the identification of therapeutic targets