Liver Total Cholesterol Levels Research Articles

Ablation of Tas1r1 Reduces Lipid Accumulation Through Reducing the de Novo Lipid Synthesis and Improving Lipid Catabolism in Mice.

Amino acid sensing plays an important role in regulating lipid metabolism by sensing amino acid nutrient disturbance. T1R1 (umami taste receptor, type 1, member 1) is a membrane G protein-coupled receptor that senses amino acids. Tas1r1-knockout (KO) mice were used to explore the function of umami receptors in lipid metabolism. Compared with wild-type (WT) mice, Tas1r1-KO mice showed decreased fat mass (P < 0.05) and adipocyte size, lower liver triglyceride (7.835 ± 0.809 vs 12.463 ± 0.916 mg/g WT, P = 0.013) and total cholesterol levels (0.542 ± 0.109 vs 1.472 ± 0.044 mmol/g WT, P < 0.001), and reduced lipogenesis gene expressions in adipose and liver tissues. Targeted liver amino acid metabolomics showed that the amino acid content of Tas1r1-KO mice was significantly decreased, which was consistent with the branched-chain ketoacid dehydrogenase protein levels. Proteomics analysis showed that the upregulated proteins were enriched in lipid and steroid metabolism pathways, and parallel reaction monitoring results illustrated that Tas1r1 ablation promoted lipid catabolism through oxysterol 7 α-hydroxylase and insulin-like growth factor binding protein 2. In summary, Tas1r1 disruption in mice could reduce lipid accumulation by reducing de novo lipid synthesis and improving lipid catabolism.

Antihyperglycemic activity of verbenone and L-arginine in nicotinamide-streptozotocin-induced diabetic mice: in vitro and in vivo studies

BackgroundNatural products are utilized globally for the management of diseases such as diabetes mellitus. Carrot seeds are ethnobotanically used in the management of diabetes mellitus. This study investigated the in vitro and in vivo antihyperglycemic activities of verbenone and L-arginine, which are compounds found in carrot seed.ResultsVerbenone, L-arginine, and their ratios combination expressed significantly in vitro α-amylase inhibitory activity with IC50 of 13.00, 12.69, and 13.30 µg/mL respectively compared with acarbose (IC50 = 12.64 µg/mL) and significant in vitro α-glucosidases inhibitory activity with IC50 of 29.01, 23.76 and 30.11 µg/mL respectively compared with acarbose (IC50 = 16.80 µg/mL). Furthermore, the compounds improved glucose uptake in yeast cells and inhibited haemoglobin glycation in vitro. In the in vivo study, the compounds significantly reduced the levels of blood glucose, the levels of liver total cholesterol, and liver triacylglycerol, the calculated cardiovascular indices, whereas the level of plasma high density lipoprotein (HDL) cholesterol was significantly elevated in all diabetic treated mice.ConclusionThe data revealed the in vitro antidiabetic activity of verbenone and L-arginine. Also, the compounds ameliorated hyperglycemia, hyperlipidemia and other diabetic-induced biochemical alterations in NAD-STZ-induced diabetic mice model.

An fgf21-like gene from swamp eel (Monopterus albus): Recombinant expression and its potential roles in glucose and lipid homeostasis

Fibroblast growth factor 21 (FGF21) plays important roles in the regulation of glucose and lipid metabolism and energy balance in mammals. In this study, the full-length cDNA of swamp eel fgf21 was cloned. Sequence analysis showed that swamp eel FGF21 displayed high similarity with FGF21 of other vertebrates. Subsequently, a prokaryotic expression vector for swamp eel fgf21 was constructed, and recombinant FGF21 (rFGF21) was successfully induced and purified. To investigate the potential roles of swamp eel FGF21 in glucose and lipid metabolism, we examined the effects of rFGF21 on regulation of glucose and lipid homeostasis in type 1 diabetes mellitus (T1DM) mice as well as swamp eels under glucose stress. In T1DM mice, the levels of blood glucose, serum triglyceride (TG), liver TG, serum total cholesterol (TC), and liver TC were significantly downregulated after repeated daily injection of rFGF21 for 15 days. In addition, liver pathological section analysis indicated that rFGF21 alleviated the degree of damage to liver cells in T1DM mice. Furthermore, rFGF21 significantly upregulated the mRNA expression levels of peroxisome proliferators-activated receptor alpha (Pparα), β-Klotho, fibroblast growth factor receptor 1 (Fgfr1), phosphoenolpyruvate carboxykinase (Pepck), glucose transporter 1 (Glut1), and glucose transporter 4 (Glut4) in T1DM mouse livers. Moreover, in swamp eels, rFGF21 significantly decreased blood glucose and liver TC levels under glucose stress and upregulated the mRNA expression levels of fgf21, pparα, β-klotho, and fgfr1 in liver tissue. These results suggested that FGF21 plays important roles in the regulation of glucose and lipid homeostasis in swamp eel.

Protective and Therapeutic Effects of Orlistat on Metabolic Syndrome and Oxidative Stress in High-Fat Diet-Induced Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) in Rats: Role on Nrf2 Activation.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is an excessive buildup of liver lipids closely associated with various kinds of undesirable metabolic effects and oxidative stress. We aimed to investigate the protective and therapeutic effects of orlistat on metabolic syndrome and oxidative stress parameters in high-fat diet (HFD) induced-MAFLD rats. Twenty-four male Sprague-Dawley rats were randomly divided into four groups (n = 6/group), i.e., Normal control (N), HFD, HFD + orlistat (HFD + O) (10 mg/kg/day administered concomitantly for 12 weeks as a protective model), and obese+orlistat (OB + O) (10 mg/kg/day administered 6 weeks after induction of obesity as a therapeutic model) groups. After 12 weeks, the HFD group had significantly increased Lee obesity index, serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total cholesterol, triglyceride, low-density lipoprotein levels, liver total cholesterol and triglyceride levels, insulin resistance and non-alcoholic steatohepatitis (NASH) together with decreased serum high-density lipoprotein level. Additionally, the HFD group also showed increased Nrf2 translocation to the nucleus with high Keap1 expression and increased liver oxidative stress parameters. Orlistat significantly improved all these alterations in HFD rats. We demonstrated that orlistat might have protective and therapeutic effects against HFD-induced MAFLD rats by its activation on Nrf2 signaling pathway, which subsequently improved metabolic syndrome and oxidative stress parameters.

Dietary Protein From Different Sources Exerted a Great Impact on Lipid Metabolism and Mitochondrial Oxidative Phosphorylation in Rat Liver.

Associations between meat diets and human health have been widely considered. In this study, we focused on long-term effects of different sources of meat protein on liver metabolic enzymes. For 90 days, rats were fed with semisynthetic diets that differed only with protein source. Casein was used as a reference and isolated soybean, fish, chicken, pork, and beef proteins were compared. Changes in liver proteome were determined by isobaric tag for relative and absolute quantitation (iTRAQ) labeling and liquid chromatography electrospray ionization tandem mass spectrometry/mass spectrometry (LC–ESI–MS/MS). Fish and pork protein diets upregulated the gene expression involved in cholesterol synthesis and esterification, and pork protein diet also upregulated the gene expression of high-density lipoprotein receptor and low-density lipoprotein receptor. Chicken, pork, and beef protein diets upregulated the gene expression involved in cholesterol reverse transport and bile acid production, which increased the total cholesterol level in the fish protein diet group. Total cholesterol levels in liver were lower in the pork and beef protein diet groups. Triglyceride levels in liver were lower in chicken, pork, and beef protein diet groups. Peroxisomal proliferator-activated receptor-gamma coactivator-1 was upregulated by chicken, pork and beef protein diets, and promoted the degradation and metabolism of triglyceride, resulting in lower triglyceride in the three diet groups. Meat proteins at a recommended level could be more conducive to cholesterol degradation, triglyceride decomposition, and energy balance maintenance at a healthy level. The findings give a new insight into the associations between meat diet intake and human health.

Brassica juncea L. (Mustard) Extract Silver NanoParticles and Knocking off Oxidative Stress, ProInflammatory Cytokine and Reverse DNA Genotoxicity.

Detoxification is one of the main vital tasks performed by the liver. The purpose of this study was to investigate whether mustard in its normal or nanoparticles could confer a protective/therapeutic effect against TAA-induced acute liver failure in experimental animal models. Mustard ethanolic extract was analyzed by HPLC/MS. To induce liver failure, male rats were injected with 350 mg/kg bw TAA IP, then treated orally with a dose of 100 mg/kg for 15 d of mustard extract and its nanoform before and following induction. The levels of serum liver functions, total cholesterol (TCHo), total glyceride (TG), total bilirubin (TBIL), hepatic malonaldhyde (MDA) and nitric oxide (NO),glutathione (GSH), sodium oxide dismutase (SOD), as well as tumor necrosis factor (TNF-α,) and interleukin 6 (IL-6), were estimated. DNA genotoxicity and hepatic pathology, and immunohistologic (IHC) changes were assayed. The antioxidant content of Phenolic acids, flavonoids in mustard ethanolic extract substantially decreased the levels of ALT, AST, ALP and rehabilitated the histopathological alterations. In addition, nanoforms of mustard ethanol extract have notably increased the levels of GSH, SOD and significantly reduced the levels of MDA. The expression levels of TNF-α and IL-6 in serum and tissue were markedly downregulated. DNA genotoxicity was significantly reversed. Mustard introduced a protective and medicinal effect against TAA in both its forms.

Hepatic cholesterol synthesis and lipoprotein levels impaired by dietary fructose and saturated fatty acids in mice: Insight on PCSK9 and CD36.

The aim of this study was to investigate the uncertain effects of high saturated fatty acids (SFAs) or fructose intake on cholesterol and lipoproteins with an insight of proprotein convertase subtilisin/kexin type 9 (PCSK9)- and cluster of differentiation 36 (CD36)-induced mechanisms. Forty male C57 BL/6 mice (8 wks of age) were divided into four groups and fed ad libitum with standard chow or three isocaloric diets containing high SFAs (SFA group), monounsaturated fatty acids (MUFA group, vehicle), or fructose for 15 wks. Subsequently, mice were sacrificed and blood, liver, and heart were collected for further analysis. Consequently, fructose or SFA intake resulted in higher plasma and liver total cholesterol (TC) levels, plasma low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (HDL-C), apolipoprotein (Apo)-B levels, TC/HDL-C, and LDL-C/HDL-C ratios, and lower plasma levels of HDL-C and Apo-A1 (P < 0.05). Levels of 3-hydroxy-3-methylglutaryl-CoA reductase and acetyl-CoA acetyltransferase 1 enzymes in liver and CD36 levels in plasma were elevated by high SFAs and fructose intake (P < 0.05), whereas plasma PCSK9 levels were not significantly changed. Fructose and SFA intake increased PCSK9 and CD36 levels in the heart, along with increased CD36 levels in the liver (P < 0.05). Furthermore, plasma LDL-C was found to be positively correlated with liver PCSK9 (r=0.85, P=0.02), and CD36 (r=0.70, P=0.02) in the SFA and fructose groups. High intakes of dietary SFAs and fructose might induce dysregulations in the cholesterol synthesis and blood lipoprotein levels via proposed nutrient-sensitive biomarkers PCSK9 and CD36 in liver and extrahepatic tissues involved in cholesterol homeostasis.

The Effect of Rice Bran Extract on Arterial Blood Pressure, Hepatic Steatosis, and Inflammation in Mice Fed with a High-Fat Diet.

Background Inflammation and hypertension are primary mechanisms involving in obesity-associated adverse effects of a high-fat diet. The aim of this study was to evaluate the effects of rice bran extract (RBE) on arterial blood pressure, hepatic steatosis, inflammation, and oxidative stress in high-fat diet (HFD)-induced obese mice. Methods Male ICR mice were divided into four groups, including a normal-diet control group, a high-fat diet (HFD) (60% kcal from fat) group, an HFD group treated with RBE (220 mg/kg/day), and an HFD group treated with 1100 mg/kg/day for eight weeks. Besides body weight and arterial blood pressure, we determined liver values of total cholesterol, triglyceride, as well as percent body fat, tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), nuclear factor kappa-B (NF-κB), matrix metalloprotease-9 (MMP-9), cyclooxygenase-2 (COX-2), and mRNA endothelial nitric oxide synthase (eNOS). Results The HFD group had increased body weight, increased systolic and diastolic blood pressure, liver total cholesterol, triglyceride, NF-κB, COX-2 and MMP-9 protein levels, and decreased mRNA eNOS in the aorta. Mice of the HFD group receiving RBE had reduced diastolic blood pressure, as well as significantly decreased liver and serum TNF-α and MDA levels in the liver, and reduced NF-κB levels in both the liver and heart. Conclusions These results demonstrate that RBE decreases diastolic blood pressure, the liver lipid droplet accumulation, liver and myocardial NF-κB, myocardial COX-2 and MMP-9 protein levels, and oxidative stress. Moreover, RBE may improve endothelial function and may alleviate adverse health effects associated with obesity including obesity-associated hypertension.

Impact Of Continuous Treatment With Propylthiouracil On Renal And Hepatic Functions In Rabbits

This study was designed to investigate the effect of continuous treatment with the anti-thyroid drug, propylthiouracil (PTU), on renal and hepatic functions in rabbits as an experimental animal model. Animals were randomly divided into four different isolated groups (n = 10); Group I received normal saline. Group II, III, and IV were daily administrated with PTU in oral dosing of 50, 75, and 150 mg/kg, BWT, respectively, for three successive weeks. Serum T3 and T4 levels were measured in all groups. Increased serum creatinine and blood urea nitrogen levels (P<0.05) were also associated. Moreover, liver enzymes levels, aspartate aminotransferase, alanine aminotransferase, and total serum cholesterol levels showed a significant increase in a dose and time decedent manner. Thyroid glands of PTU-treated rabbits showed variable sized-follicles lined by multiple layers of follicular cells, which displayed signs of hyperactivity as the average follicular cell height. The diameter of its width was significantly increased compared with that in the control group. Besides, follicles were filled with a variable quantity of low-dense vacuolated colloids. Kidneys of such animals showed tubulointerstitial nephritis, glomerular atrophy, and multiple focal areas of mononuclear cell reaction. While the observed hepatic lesions were in the form of severe congestion in central vein and hepatic artery, hepatocellular necrosis, and granulocytic lymphoid cellular responses around portal areas associated with peri-portal fibrosis. Such lesions were dependent on doses of PTU. This study referred to that continuous treatment with an antithyroid drug PTU induced a hypothyroid state that was associated with impaired renal and hepatic functions in rabbits.

Effect of cefepime on hematological, immunological and oxidant/antioxidant parameters in rats experimentally infected with E. coli ATCC 25922

Objective: To evaluate the effect of cefepime on hematological changes, immunological disorders and hepatic oxidative damage in rats experimentally infected with E.coli ATCC 25922. Design: Randomized controlled experimental study. Animals: Thirty-two adult male albino rats weighting150-200 g. Procedures: Rats used for this study were randomly assigned into 4 equal groups: the control one, E.coli infected group (1×108CFU/I/P/once), the cefepime treated group (45 mg/kg bw/I/M/day) for 5 days and the E.coli infected group that treated with cefepime 24h after bacterial inoculation as previously described. Hematological and immunological parameters, liver function biomarkers and hepatic oxidative stress and antioxidant markers were determined. Results: Our result revealed that E.coli infection induced a significant elevation in the erythrocytes count, hemoglobin concentration, PCV% and total leukocytic count (TLC) (P &lt; 0.05). In the same respect, liver function biomarkers, serum glucose, total cholesterol, and triglyceride levels as well hepatic malondialdehyde (MDA), nitric oxide (NO), TNF-α, IL-10, and lysozyme activity were significantly increased compared to the control rats (P &lt; 0.05). In contrast, hepatic reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were decreased significantly (P &lt; 0.05). Cefepime treatment in E.coli + CFPM group reduced the elevated eythrogram, TLC and liver function biomarkers. Cefepime also ameliorated the oxidative damage and inflammatory response induced by E.coli infection. Conclusion and clinical relevance: Cefepime is safe when administered in a fixed-dose and possess antioxidant that contributes to improve efficacy against adverse effect induced by E.coli ATCC 25922 infection.

Impact of cefepime on hematological, immunological and oxidant/antioxidant parameters in rats experimentally infected with E. coli ATCC 25922

Objective: To evaluate the effect of cefepime on hematological changes, immunological disorders and hepatic oxidative damage in rats experimentally infected with E.coli ATCC 25922. Design: Randomized controlled experimental study. Animals: Thirty-two adult male albino rats weighting150-200 g. Procedures: Rats used for this study were randomly assigned into 4 equal groups: the control one, E.coli infected group (1×108CFU/I/P/once), the cefepime treated group (45 mg/kg bw/I/M/day) for 5 days and the E.coli infected group that treated with cefepime 24h after bacterial inoculation as previously described. Hematological and immunological parameters, liver function biomarkers and hepatic oxidative stress and antioxidant markers were determined. Results: Our result revealed that E.coli infection induced a significant elevation in the erythrocytes count, hemoglobin concentration, PCV% and total leukocytic count (TLC) (P &lt; 0.05). In the same respect, liver function biomarkers, serum glucose, total cholesterol, and triglyceride levels as well hepatic malondialdehyde (MDA), nitric oxide (NO), TNF-α, IL-10, and lysozyme activity were significantly increased compared to the control rats (P &lt; 0.05). In contrast, hepatic reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were decreased significantly (P &lt; 0.05). Cefepime treatment in E.coli + CFPM group reduced the elevated eythrogram, TLC and liver function biomarkers. Cefepime also ameliorated the oxidative damage and inflammatory response induced by E.coli infection. Conclusion and clinical relevance: Cefepime is safe when administered in a fixed-dose and possess antioxidant that contributes to improve efficacy against adverse effect induced by E.coli ATCC 25922 infection.

Impact of cefepime on hematological, immunological and oxidant/antioxidant parameters in rats experimentally infected with E. coli ATCC 25922

Objective: To evaluate the effect of cefepime on hematological changes, immunological disorders and hepatic oxidative damage in rats experimentally infected with E.coli ATCC 25922. Design: Randomized controlled experimental study. Animals: Thirty-two adult male albino rats weighting150-200 g. Procedures: Rats used for this study were randomly assigned into 4 equal groups: the control one, E.coli infected group (1×108CFU/I/P/once), the cefepime treated group (45 mg/kg bw/I/M/day) for 5 days and the E.coli infected group that treated with cefepime 24h after bacterial inoculation as previously described. Hematological and immunological parameters, liver function biomarkers and hepatic oxidative stress and antioxidant markers were determined. Results: Our result revealed that E.coli infection induced a significant elevation in the erythrocytes count, hemoglobin concentration, PCV% and total leukocytic count (TLC) (P &lt; 0.05). In the same respect, liver function biomarkers, serum glucose, total cholesterol, and triglyceride levels as well hepatic malondialdehyde (MDA), nitric oxide (NO), TNF-α, IL-10, and lysozyme activity were significantly increased compared to the control rats (P &lt; 0.05). In contrast, hepatic reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were decreased significantly (P &lt; 0.05). Cefepime treatment in E.coli + CFPM group reduced the elevated eythrogram, TLC and liver function biomarkers. Cefepime also ameliorated the oxidative damage and inflammatory response induced by E.coli infection. Conclusion and clinical relevance: Cefepime is safe when administered in a fixed-dose and possess antioxidant that contributes to improve efficacy against adverse effect induced by E.coli ATCC 25922 infection.

Impact of cefepime on hematological, immunological and oxidant/antioxidant parameters in rats experimentally infected with E. coli ATCC 25922

Objective: To evaluate the effect of cefepime on hematological changes, immunological disorders and hepatic oxidative damage in rats experimentally infected with E.coli ATCC 25922. Design: Randomized controlled experimental study. Animals: Thirty-two adult male albino rats weighting150-200 g. Procedures: Rats used for this study were randomly assigned into 4 equal groups: the control one, E.coli infected group (1×108CFU/I/P/once), the cefepime treated group (45 mg/kg bw/I/M/day) for 5 days and the E.coli infected group that treated with cefepime 24h after bacterial inoculation as previously described. Hematological and immunological parameters, liver function biomarkers and hepatic oxidative stress and antioxidant markers were determined. Results: Our result revealed that E.coli infection induced a significant elevation in the erythrocytes count, hemoglobin concentration, PCV% and total leukocytic count (TLC) (P &lt; 0.05). In the same respect, liver function biomarkers, serum glucose, total cholesterol, and triglyceride levels as well hepatic malondialdehyde (MDA), nitric oxide (NO), TNF-α, IL-10, and lysozyme activity were significantly increased compared to the control rats (P &lt; 0.05). In contrast, hepatic reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were decreased significantly (P &lt; 0.05). Cefepime treatment in E.coli + CFPM group reduced the elevated eythrogram, TLC and liver function biomarkers. Cefepime also ameliorated the oxidative damage and inflammatory response induced by E.coli infection. Conclusion and clinical relevance: Cefepime is safe when administered in a fixed-dose and possess antioxidant that contributes to improve efficacy against adverse effect induced by E.coli ATCC 25922 infection.

Impact of cefepime on hematological, immunological and oxidant/antioxidant parameters in rats experimentally infected with E. coli ATCC 25922

Objective: To evaluate the effect of cefepime on hematological changes, immunological disorders and hepatic oxidative damage in rats experimentally infected with E.coli ATCC 25922. Design: Randomized controlled experimental study. Animals: Thirty-two adult male albino rats weighting150-200 g. Procedures: Rats used for this study were randomly assigned into 4 equal groups: the control one, E.coli infected group (1×108CFU/I/P/once), the cefepime treated group (45 mg/kg bw/I/M/day) for 5 days and the E.coli infected group that treated with cefepime 24h after bacterial inoculation as previously described. Hematological and immunological parameters, liver function biomarkers and hepatic oxidative stress and antioxidant markers were determined. Results: Our result revealed that E.coli infection induced a significant elevation in the erythrocytes count, hemoglobin concentration, PCV% and total leukocytic count (TLC) (P &lt; 0.05). In the same respect, liver function biomarkers, serum glucose, total cholesterol, and triglyceride levels as well hepatic malondialdehyde (MDA), nitric oxide (NO), TNF-α, IL-10, and lysozyme activity were significantly increased compared to the control rats (P &lt; 0.05). In contrast, hepatic reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were decreased significantly (P &lt; 0.05). Cefepime treatment in E.coli + CFPM group reduced the elevated eythrogram, TLC and liver function biomarkers. Cefepime also ameliorated the oxidative damage and inflammatory response induced by E.coli infection. Conclusion and clinical relevance: Cefepime is safe when administered in a fixed-dose and possess antioxidant that contributes to improve efficacy against adverse effect induced by E.coli ATCC 25922 infection.

Effect of cefepime on hematological, immunological and oxidant/antioxidant parameters in rats experimentally infected with E. coli ATCC 25922

Objective: To evaluate the effect of cefepime on hematological changes, immunological disorders and hepatic oxidative damage in rats experimentally infected with E.coli ATCC 25922. Design: Randomized controlled experimental study. Animals: Thirty-two adult male albino rats weighting150-200 g. Procedures: Rats used for this study were randomly assigned into 4 equal groups: the control one, E.coli infected group (1×108CFU/I/P/once), the cefepime treated group (45 mg/kg bw/I/M/day) for 5 days and the E.coli infected group that treated with cefepime 24h after bacterial inoculation as previously described. Hematological and immunological parameters, liver function biomarkers and hepatic oxidative stress and antioxidant markers were determined. Results: Our result revealed that E.coli infection induced a significant elevation in the erythrocytes count, hemoglobin concentration, PCV% and total leukocytic count (TLC) (P < 0.05). In the same respect, liver function biomarkers, serum glucose, total cholesterol, and triglyceride levels as well hepatic malondialdehyde (MDA), nitric oxide (NO), TNF-α, IL-10, and lysozyme activity were significantly increased compared to the control rats (P < 0.05). In contrast, hepatic reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were decreased significantly (P < 0.05). Cefepime treatment in E.coli + CFPM group reduced the elevated eythrogram, TLC and liver function biomarkers. Cefepime also ameliorated the oxidative damage and inflammatory response induced by E.coli infection. Conclusion and clinical relevance: Cefepime is safe when administered in a fixed-dose and possess antioxidant that contributes to improve efficacy against adverse effect induced by E.coli ATCC 25922 infection.

Antioxidant status and hepato-protective role of Anchomanes difformis in streptozotocin-induced diabetes in male Wistar rats

Summary Introduction: The liver is involved in the metabolism of xenobiotics and their metabolites and it is vulnerable to oxidative damage. Hyperglycaemia is highly implicated in the progression of diabetes mellitus, and adversely affects the liver. Though, conventional hypoglycaemic drugs may be effective in reducing blood glucose, they do not appear to be effective in attenuating the progression of diabetes and its complications. Objective: This study evaluated the ameliorative effects of Anchomanes difformis on hyperglycaemia and hepatic injuries in type 2 diabetes. Methods: Type 2 diabetes was induced in male Wistar rats with a single intraperitoneal injection of streptozotocin (40 mg/kg BW) after two weeks of fructose (10%) administration. Aqueous extract of A. difformis (200 and 400 mg/kg BW) and glibenclamide (5 mg/kg BW) were administered orally for six weeks. Blood glucose concentrations were measured. Serum levels of liver dysfunction markers (ALT, AST, and ALP), total cholesterol, triglycerides, HDL- and LDL-cholesterol were investigated. Total protein, albumin, and globulin were also assessed. Antioxidant parameters: ORAC, GSH, GSSG, SOD, CAT and FRAP were evaluated in the liver while ORAC, FRAP and lipid peroxidation were determined in the serum. Histological examination of the liver tissue was carried out. Results: Treatment with aqueous extract of A. difformis significantly (p&lt;0.05) reduced blood glucose and reversed steatosis in the diabetic-treated rats. The antioxidant status of diabetic-treated rats was significantly (p&lt;0.05) improved. Serum levels of liver dysfunction markers were significantly (p&lt;0.05) reduced in diabetic-treated rats. Conclusion: The findings in this study revealed that 400 mg/kgBW Anchomanes difformis was more effective than 200 mg/kg BW in ameliorating diabetes-induced hepatopathy, however, both doses of Anchomanes difformis demonstrated more antidiabetic ability than glibenclamide. Anchomanes difformis may be a novel and potential therapeutic agent in the management of diabetes and resulted hepatic injuries.

Effect of probiotics Lactobacillus paracasei GKS6, L. plantarum GKM3, and L. rhamnosus GKLC1 on alleviating alcohol-induced alcoholic liver disease in a mouse model.

BACKGROUND/OBJECTIVESHeavy alcohol consumption causes the development of alcoholic liver disease (ALD), a neglected but important public health problem. Many studies have pointed out that probiotics could improve gut health, which is also considered to be a cause of ALD. Therefore, this study screened the probiotics, Lactobacillus casei GKC1 (GKC1), L. fermentum GKF3 (GKF3), Bifidobacterium lactis GKK2 (GKK2), L. rhamnosus GKLC1 (GKLC1), L. paracasei GKS6 (GKS6), and L. plantarum GKM3 (GKM3), for their potential benefits in alleviating ALD for applications to disease prevention.SUBJECTS/METHODSC57BL/6N mice were divided into 8 groups (n = 6 in each): normal control, positive control (alcohol-diet fed), and treatments of feeding probiotics GKC1, GKF3, GKK2, GKLC1, GKS6, and GKM3 under an oral dose 0.82 g/kg B.W. per day by oral gavage. The experiment was conducted for 8 weeks, and the concentrations of alanine aminotransferase (ALT), aspartate aminotransferase, triglyceride (TG), and total cholesterol (TC) in mice were measured. The glutathione (GSH), catalase (CAT), and histology were analyzed after sacrifice.RESULTSThe results showed a decrease in the serum ALT, liver TG, and liver TC levels in the GKS6, GKM3, and GKLC1 groups compared to the positive control. In addition, the decreasing GSH and CAT levels were inhibited in the GKS6 and GKM3 groups. The histopathological results showed that all probiotics could reduce the accumulation of liver fat. Furthermore, there was a significant difference in GKLC1 with lower stomach damage compared to the alcohol-fed mice without any addition of probiotics.CONCLUSIONSGKLC1, GKS6, and GKM3 can be used as supplements for alleviating the development of ALD.

Metabolomics of the Protective Effect of Ampelopsis grossedentata and Its Major Active Compound Dihydromyricetin on the Liver of High‐Fat Diet Hamster

The flavonoid dihydromyricetin (DMY) is the main component of Ampelopsis grossedentata (Hand-Mazz) W. T. Wang (AG), a daily beverage and folk medicine used in Southern China to treat jaundice hepatitis, cold fever, and sore throat. Recently, DMY and AG were shown to have a beneficial effect on lipid metabolism disorder. However, the mechanisms of how DMY and AG protect the liver during lipid metabolism disorder remain unclear. In this study, we first analyzed the chemical compounds of AG by HPLC-DAD-ESI-IT-TOF-MSn. Of the 31 compounds detected, 29 were identified based on previous results. Then, the effects of DMY and AG on high-fat diet hamster livers were studied and the metabolite levels and metabolic pathway activity of the liver were explored by 1H NMR metabolomics. Compared to the high-fat diet group, supplementation of AG and DMY attenuated the high-fat-induced increase in body weight, liver lipid deposition, serum triglycerides and total cholesterol levels, and normalized endogenous metabolite concentrations. PCA and PLS-DA score plots demonstrated that while the metabolic profiles of hamsters fed a high-fat diet supplemented with DMY or AG were both far from those of hamsters fed a normal diet or a high-fat diet alone, they were similar to each other. Our data suggest that the underlying mechanism of the protective effect of DMY and AG might be related to an attenuation of the deleterious effect of high-fat diet-induced hyperlipidemia on multiple metabolic pathways including amino acid metabolism, ketone body metabolism, energy metabolism, tricarboxylic acid cycle, and enhanced fatty acid oxidation.

Combination of Probiotics and Salvia miltiorrhiza Polysaccharide Alleviates Hepatic Steatosis via Gut Microbiota Modulation and Insulin Resistance Improvement in High Fat-Induced NAFLD Mice.

BackgroundNonalcoholic fatty liver disease (NAFLD) increases the risk of hepatocellular carcinoma, which is currently the leading cause of obesity-related cancer deaths in middle-aged men.MethodsProbiotics with lipid-lowering function were screened from the fecal microbiota of healthy adults. Polysaccharide from different sources was screened for improving insulin resistance. The combination of probiotics and Salvia miltiorrhiza polysaccharide (LBM) was investigated for alleviating hepatic steatosis.ResultsFirst, Bifidobacterium bifidum V (BbV) and Lactobacillus plantarum X (LpX) were obtained from the fecal microbiota of healthy adults. Second, to improve insulin resistance, a Salvia miltiorrhiza Bunge polysaccharide showing good performance in reducing insulin resistance was obtained. The liver total cholesterol (TC) and total triglyceride (TG) levels and the serum levels of free fatty acid, alanine transaminase, aspartate transaminase, low density lipoprotein cholesterol, TG, and TC can be significantly reduced through supplementation with LpX-BbV (LB) in NAFLD mice. Interestingly, the function of the probiotic LB can be enhanced by S. miltiorrhiza Bunge polysaccharide. Furthermore, the gut microbiota was modulated by LpX-BbV+S. miltiorrhiza Bunge polysaccharide (LBM). The lipopolysaccharide concentration of the LBM group was decreased by 73.6% compared to the NAFLD group. Ultimately, the mRNA concentrations of the proinflammatory cytokines (tumor necrosis factor α, interleukin 1β [IL-1β], and IL-6) decreased with LB and LBM treatment.ConclusionThe results of this this study indicate that the LBM combination can be used as a therapeutic for ameliorating NAFLD via modulating the gut microbiota and improving insulin resistance.

Yunpi Heluo decoction attenuates insulin resistance by regulating liver miR-29a-3p in Zucker diabetic fatty rats

Background and objectiveYunpiheluo (YPHL) decoction is a Chinese herbal formula with unique advantages for the treatment of type 2 diabetes mellitus (T2DM). The aim of the present study was to investigate changes in miRNA expression and downstream gene expression in Zucker diabetic fatty (ZDF) rats treated with YPHL to determine whether YPHL could be used as an adjuvant treatment of T2DM. MethodsSerum and liver total cholesterol (TC) and triglycerides (TG) levels, insulin resistance index (IR) and differentially expressed miRNAs were detected in a T2DM ZDF rat model. miRNA target prediction was based on bioinformatic algorithms and dual luciferase reporter assay. Protein expression of genes in the insulin receptor signaling pathway was detected by Western blot. The IR cell model was established and the effects of lyophilized YPHL powder on the protein expressions were observed by transfecting specific miRNA mimics and inhibitors. ResultsThe miR-29a-3p expression level was significantly increased in the liver of ZDF rats. Insulin receptor substrate 1 (IRS1) was the target gene of miR-29a-3p. IRS1 mRNA and protein expressions of IRS1, IRS1 (phospho S307), protein kinase B (Akt), Akt (phosphor ser473) and pyruvate dehydrogenase lipoamide kinase isozyme 1 (PDK1) were decreased significantly. miR-29a-3p over-expression decrease IRS1 and the others protein expressions in the HepG2 IR cell model while anti-miR-29a-3p showed the opposite result. The miR-29a-3p level was decreased, and the expressions of IRS1 mRNA and the above proteins were all increased after YPHL treatment. ConclusionmiR-29a-3p played a functional role in insulin receptor signaling in the liver of ZDF rats. YPHL decoction attenuated IR in T2DM probably by down-regulating or maintaining the miR-29a-3p level, increasing the expression of IRS1 mRNA and its phosphorylated proteins, and regulating the expression of insulin receptor signaling-related proteins. YPHL may prove to be an alternative treatment for T2DM.