Lipid Profile, Haematological Assay and Tissue Histology of Alloxan Induced Diabetic Wistar Rats Administered Extracts of Vernomia amygdalina (Bitter leaf) and Gnetum africanum (okazi leaf)

Diabetes mellitus is predominant in numerous nations of the world with millions of deaths directly linked to it. The utilization of plants in providing answers to this pandemic has expanded over the years. This study investigated changes in some haematological parameters and tissue histology of alloxan induced diabetic Wistar rats administered combined leaf extracts (CLE) of vernonia amygdalina (bitter leaf (BI)) and gnetum africanum (okazi leaf (OK)). Aqueous extracts of bitter leaf and okazi leaf were prepared using the conventional method. Forty Wistar rats were grouped into eight of five rats each. Groups A and B were normal and diabetic control respectively, groups C to G (diabetic groups) were treated with varied mixtures of extracts of vernomia amygdalina and gnetum africanum at (10:90BI/OK), (30:70BI/OK), (50:50BI/OK), (70:30 BI/OK) and (90:10% BI/OK) ratios respectively. Group H, the diabetic control was administered the standard drug (Metformin). The animals were sacrificed on the 28th day, blood samples and liver tissue were collected for biochemical analysis and histological examination. There was a significant (p<0.05) reduction in the lipid profile of the diabetic groups (C-G) especially in triglycerides with the highest reduction in (50:50 BI/OK) combination (0.70±0.07) while the least reduction was seen in (30:70 BI/OK) combination (1.37±0.08). There were time and ratio-dependent variations in the haematological indices. Hepatic histology showed evidence of varying levels of restoration of cellular structural integrity by the combined extracts. These results suggest that the combined extracts of vernomia amygdalina and gnetum africanum could be used to manage diabetes mellitus.

Expression of Jejunal Taste Receptors in Women with Morbid Obesity

Nutrient sensing plays important roles in promoting satiety and maintaining good homeostatic control. Taste receptors (TAS) are located through the gastrointestinal tract, and recent studies have shown they have a relationship with metabolic disorders. The aim of this study was to analyze the jejunal expression of TAS1R2, TAS1R3, TAS2R14 and TAS2R38 in women with morbid obesity, first classified according to metabolic syndrome presence (MetS; n = 24) or absence (non-MetS; n = 45) and then classified according to hepatic histology as normal liver (n = 28) or nonalcoholic fatty liver disease (n = 41). Regarding MetS, we found decreased expression of TAS2R14 in MetS patients. However, when we subclassified patients according to liver histology, we did not find differences between groups. We found negative correlations between glucose levels, triglycerides and MetS with TAS1R3 expression. Moreover, TAS2R14 jejunal expression correlated negatively with the presence of MetS and ghrelin levels and positively with the jejunal Toll-like receptor (TLR)4, peroxisome proliferator-activated receptor (PPAR)-γ, and interleukin (IL)-10 levels. Furthermore, TAS2R38 expression correlated negatively with TLR9 jejunal expression and IL-6 levels and positively with TLR4 levels. Our findings suggest that metabolic dysfunctions such as MetS trigger downregulation of the intestinal TASs. Therefore, taste receptors modulation could be a possible therapeutic target for metabolic disorders.

ZINC40099027 Promotes Gastric Mucosal Repair in Ongoing Aspirin-Associated Gastric Injury by Activating Focal Adhesion Kinase

Nonsteroidal anti-inflammatory drugs cause gastric ulcers and gastritis. No drug that treats GI injury directly stimulates mucosal healing. ZINC40099027 (ZN27) activates focal adhesion kinase (FAK) and heals acute indomethacin-induced small bowel injury. We investigated the efficacy of ZN27 in rat and human gastric epithelial cells and ongoing aspirin-associated gastric injury. ZN27 (10 nM) stimulated FAK activation and wound closure in rat and human gastric cell lines. C57BL/6J mice were treated with 300 mg/kg/day aspirin for five days to induce ongoing gastric injury. One day after the initial injury, mice received 900 µg/kg/6 h ZN27, 10 mg/kg/day omeprazole, or 900 µg/kg/6 h ZN27 plus 10 mg/kg/day omeprazole. Like omeprazole, ZN27 reduced gastric injury vs. vehicle controls. ZN27-treated mice displayed better gastric architecture, with thicker mucosa and less hyperemia, inflammation, and submucosal edema, and lost less weight than vehicle controls. Gastric pH, serum creatinine, serum alanine aminotransferase (ALT), and renal and hepatic histology were unaffected by ZN27. Blinded scoring of pFAK-Y-397 immunoreactivity at the edge of ZN27-treated lesions demonstrated increased FAK activation, compared to vehicle-treated lesions, confirming target activation in vivo. These results suggest that ZN27 ameliorates ongoing aspirin-associated gastric mucosal injury by a pathway involving FAK activation. ZN27-derivatives may be useful to promote gastric mucosal repair.

Hepatic Histopathology Among Excessive Drinkers Without Advanced Liver Disease

AimsAlcohol-associated liver disease represents a spectrum of histopathological changes from steatosis to advanced fibrosis and cirrhosis. The major goals of this retrospective study were to characterize the histologic features in patients with excessive alcohol use who presented with an abnormal hepatic panel and/or abnormal radiographic imaging and did not meet the clinical diagnosis of alcoholic hepatitis or cirrhosis.MethodsWe performed a retrospective study to describe hepatic histology of 62 and 83 excessive drinkers with normal and abnormal serum aspartate transaminase, respectively. The types of inflammatory cells in the liver were characterized by immunohistochemistry for CD4, CD8, CD20, CD68 and myeloperoxidase.ResultsAmong 62 patients with aspartate aminotransferase (AST) ≤ 50 U/L, 37% had histological evidence of steatosis. Of these, we found evidence of hepatocyte ballooning (21%), lobular inflammation (50%), portal inflammation (52%) and fibrosis (14%). For those with AST &gt; 50 U/L, the presence of hepatic steatosis, lobular inflammation and portal inflammation was observed in 29, 60 and 69% of patients, respectively. Fibrosis was found in 33%, four with bridging fibrosis, and one with cirrhosis. We observed the aggregation of CD68+ macrophages, rather than normally distributed with minimal neutrophilic infiltration. Lobular and portal lymphocytic infiltrations are primarily CD8+ T cells.ConclusionAbnormal hepatic histopathology occurs in excessive drinkers with normal transaminase activity. Future studies to determine the diagnostic modalities to detect such abnormalities and to better understand its clinical implications and long-term outcome are needed.

Growth response, flock uniformity, organ weight, abdominal fat, carcass yield and hepatic histology of finisher broiler chicken fed toasted pigeon pea seed meal

Three hundred (300) 21d old (Arbor-acre) broiler chicks apportioned to five (5) dietary groups of sixty (60) birds each, further replicated six (6) times were fed graded levels of toasted pigeon pea seed meal (TPSM) to assess the performance, flock uniformity, organ weights, carcass yield and hepatic histology at the finisher phase. A maize-full-fat soybean meal diet served as the control diet (I). The TPSM was incorporated to replace full-fat soybean meal at 12.5%, 25.0%, 37.5% and 50.0% in diets II, III, IV and V, respectively. Toasting improved the protein content, ether extract, fibre content, metabolizable energy and reduced the anti-nutrients except for oxalate. The final weight, total weight change, average weight gain, feed conversion ratio, eviscerated weight, breast yield and thigh yield were significantly influenced (P<0.05), especially depressed at 50% replacement, unlike the average feed intake, mortality and flock uniformity (P>0.05). The kidney and abdominal fat were also influenced (P<0.05). There were varying levels of hepatic degeneration, which increased in intensity as the level of inclusion increased. They ranged from mild sinusoidal congestion and cellular infiltration to necrosis of the cells in the liver. Up to 37.5% TPSM toasted pigeon pea seed meal replacement for soybean meal supported optimum growth, breast and thigh yield, and mild to moderate hepatic disruptions.

Effects of Iron Deficiency on Serum Metabolome, Hepatic Histology, and Function in Neonatal Piglets

Few studies focused on the effects of iron on characterizing alterations of metabolic processes in neonatal piglets. In the present study, 16 neonatal piglets were randomly assigned to two groups. In the first group piglets were given an intramuscularly injection of iron dextran at 150 mg as a positive control (CON) and the second group were not supplemented with iron as a negative control for iron deficiency (ID). At day 8, iron status, serum biochemical parameters, serum metabolome, hepatic histology, and hepatic expression of genes for the metabolism were analyzed. Results indicated that piglets without iron supplementation had significantly reduced iron values and increased blood urea nitrogen concentrations at day 8 (p < 0.05). Analysis of serum metabolome revealed that concentrations of serum lysine, leucine, tyrosine, methionine, and cholesterol were significantly decreased while concentrations of 3-Methyldioxyindole, chenodeoxycholate acid, indoleacetic acid, icosadienoic acid, phenylpyruvic acid, pantothenic acid, ursocholic acid, and cholic acid were significantly increased in iron deficient piglets (p < 0.05). Furthermore, expressions of cyp7a1 and the urea cycle enzyme (ornithinetranscarbamoylase and argininosuccinate synthetase) were significantly increased in iron deficient pigs (p < 0.05). The present experimental results indicated that neonatal piglets without iron supplementation drop to borderline anemia within 8 days after birth. Iron deficiency led to a series of metabolic changes involved in tyrosine metabolism, phenylalanine metabolism, bile secretion, primary bile acid biosynthesis, steroid biosynthesis, and upregulated activities of the urea cycle enzymes in the liver of neonatal piglets, suggesting early effects on metabolic health of neonatal piglets.