Plasma ALT Activities Research Articles

Acute and sub-acute toxicity study of aqueous and methanol root extract of Tetracera alnifolia in male albino rats

The aim of this study was to assess the acute and sub-acute toxicity of aqueous and methanol extracts of the root of Tetracera alnifolia as well as the effects on some biochemical parameters in albino rats as many plants used in traditional medicine lack scientific and clinical evidence to support a better understanding of their safety and efficacy. Phytochemical screening and proximate analysis of the pulverised root of Tetracera alnifolia was carried out using previously reported protocol. Sub-acute toxicity study of each extract was done for 28 days followed by organs function tests and histopathology studies of the liver, kidney and heart. Evaluation of lipid profile and oxidative stress marker to ascertain the effect of each extract on lipid peroxidation and their antioxidant property was done after administration of 200 mg/Kg body weight of each extract for a period of thirty-five days. Acute toxicity study of each extract gave oral LD50 (rat) of greater than 5000 mg/kg body weight with no signs of toxicity. Sub-acute toxicity study showed both extracts were non-toxic to the liver, kidney, heart and blood at doses between 200 and 3000 mg/Kg body weight assessed by the respective organ function tests, hematological parameters, and histopathology study. However, higher doses seem toxic to the liver particularly at 5000 mg/kg B. W due to increase in plasma AST, ALT and ALP activities accompanied with reduced protein and albumin concentrations. Effects of each extracts at 200 mg/Kg body weight on some biochemical parameters revealed no significant difference in lipid profile parameters and no lipid peroxidation. Each extract may possess antioxidant property due to increase in catalase activity. The result from this research may help validate the safety of the oral use of this plant in traditional medicine.

Influence of Varied Dietary Cholesterol Levels on Lipid Metabolism in Hamsters.

Syrian hamsters are valuable models for studying lipid metabolism due to their sensitivity to dietary cholesterol, yet the precise impact of varying cholesterol levels has not been comprehensively assessed. This study examined the impact of varying dietary cholesterol levels on lipid metabolism in Syrian hamsters. Diets ranging from 0% to 1% cholesterol were administered to assess lipid profiles and oxidative stress markers. Key findings indicate specific cholesterol thresholds for inducing distinct lipid profiles: below 0.13% for normal lipids, 0.97% for elevated LDL-C, 0.43% for increased VLDL-C, and above 0.85% for heightened hepatic lipid accumulation. A cholesterol supplementation of 0.43% induced hypercholesterolemia without adverse liver effects or abnormal lipoprotein expression. Furthermore, cholesterol supplementation significantly increased liver weight, plasma total cholesterol, LDL-C, and VLDL-C levels while reducing the HDL-C/LDL-C ratio. Fecal cholesterol excretion increased, with stable bile acid levels. High cholesterol diets correlated with elevated plasma ALT activities, reduced hepatic lipid peroxidation, and altered leptin and CETP levels. These findings underscore Syrian hamsters as robust models for hyperlipidemia research, offering insights into experimental methodologies. The identified cholesterol thresholds facilitate precise lipid profile manipulation, enhancing the hamster's utility in lipid metabolism studies and potentially informing clinical approaches to managing lipid disorders.

Sodium chloride alleviates oxidative stress and physiological responses induced by extreme winter cold in genetically improved farmed tilapia (GIFT; Oreochromis niloticus)

A 6-week trial was designed to investigate the effects of dietary sodium chloride supplementation on physiological, metabolic, and molecular stress response parameters. The findings showed that (1) there were no significant differences between sodium chloride supplementation groups (0.05S, 0.1S, and 0.15S) and the control group (P > 0.05), except for the 0.2S diet, which showed better final body weight, weight gain rate, specific growth rate, and feed conversion ratio than the control group (P < 0.05). (2) The hypothermic stress experiment results showed that the survival rates in the 0.1S and 0.15S diets were significantly higher than the control group (P < 0.05). (3) Transcription results showed that these enriched pathways in the gill were mainly energy metabolism and apoptosis pathways, while the major enrichment pathways in the liver were mainly amino acid metabolism and carbohydrate metabolism. (4) The plasma parameter results showed, compared to the control group, the 0.15S diet significantly increased the plasma GLU, TG contents, and Na+ and K+ concentrations and decreased the plasma ALT activity (P < 0.05). In addition, the 0.1S diet increased the plasma ALB content and Cl− concentration (P < 0.05). The gill Na+/K+-ATPase activity decreased markedly when the fish were fed the 0.1S and 0.15S diets (P < 0.05). The antioxidant enzyme activity results showed that the 0.1S and 0.15S diets significantly increased the T-SOD activities (P < 0.05). Gene expression results showed that compared to the control group, the 0.1S and 0.15S diets up-regulated the expression of gys, hsp70, mlcp, mlc, myosin, tnt mRNA, and down-regulated the akt, gk, and erk mRNA expression. Based on the regression analysis, the optimum dietary sodium chloride levels range from 0.10 % to 0.13 % of the diet, which could facilitate energy regulation, improve the immune response, and ultimately strengthen the cold resistance of GIFT.

Unveiling the Link: Exploring Mitochondrial Dysfunction as a Probable Mechanism of Hepatic Damage in Post-Traumatic Stress Syndrome.

PTSD is associated with disturbed hepatic morphology and metabolism. Neuronal mitochondrial dysfunction is considered a subcellular determinant of PTSD, but a link between hepatic mitochondrial dysfunction and hepatic damage in PTSD has not been demonstrated. Thus, the effects of experimental PTSD on the livers of high anxiety (HA) and low anxiety (LA) rats were compared, and mitochondrial determinants underlying the difference in their hepatic damage were investigated. Rats were exposed to predator stress for 10 days. Then, 14 days post-stress, the rats were evaluated with an elevated plus maze and assigned to HA and LA groups according to their anxiety index. Experimental PTSD caused dystrophic changes in hepatocytes of HA rats and hepatocellular damage evident by increased plasma ALT and AST activities. Mitochondrial dysfunction was evident as a predominance of small-size mitochondria in HA rats, which was positively correlated with anxiety index, activities of plasma transaminases, hepatic lipids, and negatively correlated with hepatic glycogen. In contrast, LA rats had a predominance of medium-sized mitochondria. Thus, we show links between mitochondrial dysfunction, hepatic damage, and heightened anxiety in PTSD rats. These results will provide a foundation for future research on the role of hepatic dysfunction in PTSD pathogenesis.

E Se tea extract ameliorates CCl4 induced liver fibrosis via regulating Nrf2/NF-κB/TGF-β1/Smad pathway

BackgroundLiver fibrosis is a crucial progress to deteriorate liver disease. E Se tea (ES) is an ethnic herbal tea in China that has various biological activities for human beings. However, the traditional application on the treatment of liver disease is not studied. PurposeThis study is firstly performed to explore the chemical constituents of ES extract together with its anti-hepatic fibrosis effect and potential mechanism on CCl4 treated mice. Study design and methodsThe chemical constituents of ethanol-aqueous extract from ES (ESE) were analyzed by UPLC-ESI-MS/MS. The anti-hepatic fibrosis effect of ESE was determined by measuring ALT and AST activities, antioxidative indexes, inflammatory cytokines and collagen protein levels on CCl4 treated mice. Moreover, H&E, Masson staining and immunohistochemical analysis were performed for evaluating the protective effect of ESE on histopathological changes of liver tissues. ResultsUHPLCHRESI-MS/MS analysis showed that the ESE was rich in flavonoids such as phlorizin, phloretin, quercetin and hyperoside. ESE could significantly reduce the plasma AST and ALT activities. The cytokines (IL-6, TNF-α, IL-1β) expressions were inhibited after ESE administration via suppressing NF-κB pathway. In addition, ESE could decrease MDA accumulation for alleviating CCl4 induced liver oxidative stress via regulating Nrf2 pathway to promote the expressions of antioxidant enzymes (SOD, HO-1, CAT and NQO1). Moreover, ESE could inhibit the expressions of TGF-β1, Smad2, α-SMA, and collagens Ⅰ and III proteins, thereby effectively alleviate the liver fibrosis. ConclusionThis study demonstrated that ESE could alleviate liver fibrosis through enhancing antioxidant and anti-inflammatory abilities by Nrf2/NF-κB pathway and reducing deposition of liver fibrosis via suppressing TGF-β/Smad pathway.

Acute, Sub-acute and Chronic Toxicity Evaluation of Aqueous Extract of the Aerial Parts of Leonurus cardiaca in Normal Non-pregnant Female Wistar Albino Rats per OECD 425 TG

This study graded the acute, sub-acute, and chronic toxicity of aqueous extract of the aerial parts of Leonurus cardiaca in non-pregnant female wistar rats. Fifty wistar albino rats weighing between 180 and 200g were used for this study. The rats were grouped into 10 groups of five rats per group. Group 1 served as control while group 2-11 were orally administered aqueous extract of Leonurus cardiaca at 166, 250, and 500mg/kg for 7, 14, and 21 days. All haematological and biochemical parameters were determined based on standard methods. The plasma RBC, Hb, MCV, and WBC of the control were 5.33±0.01 x 1012/L, 13.54±0.01 g/dl, 42.16±0.01 fl, and 1.83±0.01 X 109/L respectively. The plasma RBC, Hb, MCV, and WBC of the rats treated with 500mg/kg of the extract for 21 days were 10.93±0.01x 1012/L, 19.24±0.01g/dl, 28.33±0.01fl, and 1.41±0.01 x 109/L respectively and were significantly different from the control at p≤0.05. The plasma Na+, K+ , Cl-, HCO3 , creatinine, and urea levels treated with extract at 500mg/kg for 21 days were 167.97±0.01 01mmol/l, 7.85±0.0101mmol/l, 164.24±0.0101mmol/l, 40.84±0.0101mmol/l, 1.16±0.0101mmol/l, and 5.68±0.02 01mmol/l respectively, were significantly different from the control at p≤0.05. The plasma ALT, ALP, and AST activities treated with extract at 500mg/kg for 21 days were 146.24±0.02U/L, 77.33±0.01U/L, and 168.71±0.01U/L respectively, were significantly different from the control at p≤0.05. Enhancement on architecture of the heart, kidney and liver tissues occurred after treatment with 500mg/kg of the extract for 21 days in comparison to the control. The significantly improved effects observed on all assayed parameters were expressive that the extract of the aerial parts of Leonurus cardiaca is safe at 500 mg/Kg.

Dietary camellia seed oil attenuates liver injury in mice chronically exposed to alcohol.

Dietary fat composition is closely associated with the pathological development of alcoholic liver disease (ALD). Fat enriched with saturated fatty acids protects whereas with polyunsaturated fatty acids aggravates alcohol-induced liver injury. However, limited study has addressed how monounsaturated fatty acids (MUFAs) determines the pathological process of ALD. Our study was conducted to evaluate the effect of MUFAs-enriched-camellia seed oil (CSO) on alcohol-induced liver injury. The ALD model was established by feeding C57BL/6 mice with Lieber-DeCarli diet, and with either CSO or polyunsaturated fatty acids (PUFAs)-enriched-corn oil (CO) as fat source. After 4-week-intervention, CSO-feed rescued alcohol-induced liver injury compared to CO-feed, evidenced by measurements of plasma ALT activity, H&E stain, and hepatic cleaved-Caspase-3 expression. Besides, CSO-feed alleviated alcohol-induced oxidative stress, associated with NRF2 and Hif-1α expressions improvement. The reduction of F4/80 immunostaining and the decreased expressions of hepatic TNF-α and IL-6 suggested CSO-feed improved alcohol-induced inflammation. The mechanistic analysis showed that the inhibition of ASK1 and MAPKs might contribute to CSO-protected liver injury. Notably, we observed CSO-feed relieved the gut microbiota disturbance with the decreased Firmicutes and Turicibater, and the increased Bacteroidota, Alloprevotella, and Bacteroides, and reduced circulatory endotoxin level and lipolysis of adipose tissue, which are the known pathogenic factors in alcohol-induced liver injury. Unexpectedly, CSO induced more hepatic steatosis than CO-feed. In conclusion, CSO attenuated chronic alcohol consumption-induced liver injury but enhanced hepatic steatosis. CSO could be a potential dietary choice for alcoholic individuals with liver injury.

Dietary Supplementation with Eucommia ulmoides Leaf Extract Improved the Intestinal Antioxidant Capacity, Immune Response, and Disease Resistance against Streptococcus agalactiae in Genetically Improved Farmed Tilapia (GIFT; Oreochromis niloticus).

A 7-week rearing trial was designed to investigate the effects of Eucommia ulmoides leaf extract (ELE) on growth performance, body composition, antioxidant capacity, immune response, and disease susceptibility of diet-fed GIFT. The results showed that dietary ELE did not affect growth performance or whole-body composition (p > 0.05). Compared with the control group, plasma ALB contents increased in the 0.06% dietary ELE group (p < 0.05), and plasma ALT and AST activities decreased in the 0.08% dietary ELE group (p < 0.05). In terms of antioxidants, compared with GIFT fed the control diet, 0.06% dietary ELE upregulated the mRNA expression levels of Nrf2 pathway-related antioxidant genes, including CAT and SOD (p < 0.05), and 0.06% and 0.08% dietary ELE upregulated the mRNA levels of Hsp70 (p < 0.05). In terms of immunity, 0.06% dietary ELE suppressed intestinal TLR2, MyD88, and NF-κB mRNA levels (p < 0.05). Moreover, the mRNA levels of the anti-inflammatory cytokines TGF-β and IL-10 were upregulated by supplementation with 0.04% and 0.06% dietary ELE (p < 0.05). In terms of apoptosis, 0.06% and 0.08% ELE significantly downregulated the expression levels of FADD mRNA (p < 0.05). Finally, the challenge experiment with S. agalactiae showed that 0.06% dietary ELE could inhibit bacterial infection, and significantly improve the survival rate of GIFT (p < 0.05). This study demonstrated that the supplementation of 0.04–0.06% ELE in diet could promote intestinal antioxidant capacity, enhance the immune response and ultimately improve the disease resistance of GIFT against Streptococcus agalactiae.

Phytochemical Composition and Hepatoprotective Potential of Ethanolic Root Extract of Jatropha curcas in Acetaminophen-Induced Toxicity in Albino Wistar Rats

This study evaluated the phytochemical composition and hepatoprotective potential of ethanolic root extract of Jatropha curcas in acetaminophen-induced toxicity in wistar albino rats. The phytochemical screening and composition were determined using gas chromatography. Thirty albino rats weighing between 170 and 200 g were used, were separated into 5 groups. Group one was administered distilled water, 2 was administered 1000 mg/kg AC only, 3, 4 and 5 were administered 1000 mg/kg acetaminophen + 200 mg/kg extract, 1000 mg/kg acetaminophen + 400 mg/kg extract, 1000 mg/kg AC + 100 mg/kg Silymarin. Phytochemical composition of root of the plant showed saponin (55.7079 µg/g) lunamarine (34.3976 µg/g), kaempferol (32.7107 µg/g), rutin (20.7399 µg/g), sapogenin (11.2644 µg/g), phenol (4.1557 µg/g), anthocyanin (1.1946 µg/g), epicatechin (0.8303 µg/g) and catechin (0.1883 µg/g). The plasma ALP, AST, ALT and GGT activities of the negative control were 151.50±14.11 U/L, 48.00±7.19 U/L, 79.50 ± 2.14 U/L and 3.50± 0.45 U/L respectively. The plasma ALP, AST, ALT and GGT activities of group 3 were 78.50± 4.75 U/L, 23.00± 2.35 U/L, 49.00± 3.65 and 2.95 ± 0.17 U/L respectively, were significantly decreased when compared with the controls. The plasma total protein, albumin and total bilirubin levels of the negative control were 57.00± 0.86 g/l, 32.00 ± 0.86 g/l, 20.35 ± 0.83 µmol. The plasma total protein, albumin and total bilirubin levels of group 3 were 61.50± 2.14 g/l, 33.00± 0.86 g/l 11.15 ± 0.98 µmol respectively and were significantly increased when compared the controls. The significant improvement observed on the liver markers is suggestive of the hepatoprotective properties of Jatropha curcas.

Dietary Protein Modifies Hepatic Glycolipid Metabolism, Intestinal Immune Response, and Resistance to Streptococcus agalactiae of Genetically Improved Farmed Tilapia (GIFT: Oreochromis niloticus) Exposed to High Temperature

The present study investigates the effects of dietary protein levels on glucolipid metabolism, immune function, and resistance to Streptococcus agalactiae of genetically improved farmed tilapia (GIFT) exposed to high temperature. Six practical diets were prepared to feed 360 fish (initial weight 43.78 ± 0.12 g) with graded protein levels (26.45%, 29.28%, 31.69%, 33.68%, 36.18%, and 38.75% dry matter). The results showed that 26.45% dietary protein significantly improved glycolysis by increasing PK mRNA levels, while the 29.28% and 31.69% dietary protein levels promoted gluconeogenesis by increasing PEPCK and G6Pase mRNA levels. For lipid metabolism, 26.45% dietary protein enhanced lipid synthesis by increasing PPAR-γ, SREBP1c, and FAS mRNA levels, while 31.69% dietary protein enhanced the level of lipolysis by increasing the PPAR-α and CPT1 mRNA levels. The highest plasma TG and TC contents were observed in the 29.28% and 31.69% dietary protein groups, respectively. In terms of antioxidants and immunity, the 31.69% dietary protein level activated the expression levels of HSP90 mRNA, thus increasing the expression levels of antioxidant-related genes (CAT, SOD, and GPx), and upregulating the anti-inflammatory factor IL-10 mRNA levels. In addition, regarding the antioxidant enzymes, the highest GSH content was found in the 29.28% dietary protein group, while the 31.69% dietary protein group had the maximum GSH-Px activity. The lowest plasma ALT and AST activities were observed in the 31.69% dietary protein group. Ultimately, the survival rate of juvenile GIFT fed 31.69% dietary protein was highest after a Streptococcus agalactiae challenge. Overall, 29.28–31.69% dietary protein was recommended in the diet of GIFT in a high-temperature environment.

Anesthetics efficacy and physiological response of MS222 and clove oil in spotted knifejaw Oplegnathus punctatus

Anesthesia prevents mechanical injuries and manipulation stress during fish farming. The efficacy of the clove oil and tricaine methanesulfonate (MS222) and their effects on respiratory frequency, the proportion of the secondary lamellae available for gas exchange (PAGE), gill histological alteration, biochemical (cortisol, glucose, lactate, aspartate aminotransferase [AST], alanine aminotransferase [ALT]), hematological (white blood cells [WBC], red blood cells [RBC], hemoglobin [Hb], hematocrit [Hct]) and hepatic antioxidative parameters (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GSH-Px], malondialdehyde [MDA]) during anesthesia and recovery were determined to illustrate their underlying physiological response mechanisms in spotted knifejaw. Results showed that the anesthetic induction and recovery under clove oil (10, 20, 30, 35, 40 mg/L) and MS222 (50, 60, 70, 80, 90, 100 mg/L) treatment exhibited time-dose dependent manner for fish (206 g). The minimum concentrations of clove oil and MS222 producing desirable anesthetic properties were 35 mg/L and 80 mg/L, respectively. Rapid induction and recovery were observed in the fish with 16–839 g average body weight (BW) upon exposure to 35 mg/L clove oil and 80 mg/L MS222, while 30 min exposure cause the death of fish with 16 g average BW. The survival rate of the fish with the average BW of 102–839 g was more than 90 % after expose to 80 mg/L MS222 for 30 min. However, 35 mg/L clove oil treatment for 30 min induced significantly lower survival rate than 80 mg/L MS222. Meanwhile, 35 mg/L clove oil significantly increased PAGE, caused higher percentage of lamellar clubbing and hypertrophy compared with 80 mg/L MS222. Plasma glucose, lactate contents, AST and ALT activities, WBC and RBC counts, Hb and Hct levels exhibited similar results. These parameters recovered to nearly normal levels after the fish returned to normal active swimming for 6 h. Hepatic SOD, GSH-Px, and CAT activities and MDA levels were significantly stimulated by 35 mg/L clove oil but were not affected by 80 mg/L MS222 during anesthesia and recovery. These results suggest that compared with clove oil, MS222 exhibits advantages in different scenarios and its dose of 80 mg/L is recommended for use in spotted knifejaw.

Diet-Induced Mouse Model of Nonalcoholic Steatohepatitis That Replicates the Human Disease

ObjectivesDeveloping a mouse model of nonalcoholic steatohepatitis (NASH) with obesity and fibrosis. MethodsWe fed agouti yellow male mice, which are hyperphagic, a western diet and water containing high fructose corn syrup for either 16 weeks or a year. We measured body weight and composition; we evaluated the development of NASH by histopathology and analyzed changes in gene expression by RNASeq. ResultsAfter 16 weeks, the mice had higher body weight and fat mass. The mice developed NASH with activity scores 5-6; this was confirmed by higher liver triacylglycerol content, elevated plasma ALT and AST activities, and greater hepatic infiltration by CD45-expressing leukocytes. The mice developed liver fibrosis, which was stage 1 after 16 weeks, and stage 3 after a year. Liver gene expression analysis showed increases in lipogenesis-, inflammation-, and fibrosis-related genes. Gene set enrichment analysis showed that 90% of the pathways were similarly upregulated or downregulated in the livers of mice and in human patients with NASH. ConclusionsIn this mouse model, NASH is induced with a diet similar to the average US diet, without nutritional deficiencies or hepatotoxins. NASH replicates the human disease, including the development of advanced fibrosis and very similar changes in gene expression. These similarities make this model useful for the study the pathophysiology of NASH and for preclinical studies of new drugs. Funding SourcesNIH, NSFC.

Hepatoprotective Effects of Glycyrrhetinic Acid on Lithocholic Acid-Induced Cholestatic Liver Injury Through Choleretic and Anti-Inflammatory Mechanisms.

Cholestasis is a clinical syndrome triggered by the accumulation and aggregation of bile acids by subsequent inflammatory responses. The present study investigated the protective effect of glycyrrhetinic acid (GA) on the cholestatic liver injury induced by lithocholic acid (LCA) from both anti-inflammatory and choleretic mechanistic standpoints. Male C57BL/6 mice were treated with LCA twice daily for 4 days to induce intrahepatic cholestasis. GA (50 mg/kg) and pregnenolone 16α-carbonitrile (PCN, 45 mg/kg) were intraperitoneally injected 3 days before and throughout the administration of LCA, respectively. Plasma biochemical indexes were determined by assay kits, and hepatic bile acids were quantified by LC-MS/MS. Hematoxylin and eosin staining of liver sections was performed for pathological examination. Protein expression of the TLRs/NF-κB pathway and the mRNA levels of inflammatory cytokines and chemokines were examined by Western blotting and PCR, respectively. Finally, the hepatic expression of pregnane X receptor (PXR) and farnesoid X receptor (FXR) and their target genes encoding metabolic enzymes and transporters was evaluated. GA significantly reversed liver necrosis and decreased plasma ALT and ALP activity. Plasma total bile acids, total bilirubin, and hepatic bile acids were also remarkably preserved. More importantly, the recruitment of inflammatory cells to hepatic sinusoids was alleviated. Additionally, the protein expression of TLR2, TLR4, and p-NF-κBp65 and the mRNA expression of CCL2, CXCL2, IL-1β, IL-6, and TNF-α were significantly decreased. Moreover, GA significantly increased the expression of hepatic FXR and its target genes, including BSEP, MRP3, and MRP4. In conclusion, GA protects against LCA-induced cholestatic liver injury by inhibiting the TLR2/NF-κB pathway and upregulating hepatic FXR expression.

Determination of the effect of Quercetinon oxidant- antioxidant parameters in the blood and liver tissues of rats given sodium fluoride experimentally

AimThe purpose of the study is to research the effect of quercetin, which has a good antioxidant characteristic in rats exposed to sodium fluoride (NaF) toxication, on oxidant and antioxidant activity in liver tissue and erythrocyte. Material and method40 Swiss albino male rats with a weight of approximately 20–25 gr were used in the study. The rats were separated into 4 equal groups (n = 10). The first group, the control group, was given normal drinking water; the second group was given 12 mg/kg/day NaF; the third group was given 40 mg/kg/day quercetin; the fourth group was given 12 mg/kg/day NaF+40 mg/kg/day quercetin orally for 30 days. As a result of the experiment, plasma AST and ALT activities were found. Total oxidant capacity (TOC) and total antioxidant capacity (TAC) analyses were made in liver tissue and erythrocyte hemogenisate. Histopathological analyses of the liver tissue were conducted. ResultsNo changes were found in plasma ALT activities between groups. Increases were found in AST activity of all groups. While erythrocyte TAC level was found to increase in fluorine and fluorine + quercetin group when compared with the control group, erythrocyte TOC level was found to increase in all groups when compared with the control group. No significant change was found in TOC and TAC levels in the liver tissue. In liver tissue histopathology, while hydropic degeneration and cellular necrosis were found in vena centralis area in fluorine group, hydropic degeneration was found in heptocytes in centrilobular area in the quercetin group. In the fourth group, hydropic degeneration and centrilobular necrosis were more severe. It was found that in rats which are given NaF experimentally, fluorine and quercetin caused histopathological degenerations in the liver tissue during this time. ConclusionWhile no changes were found in TOC and TAC levels of liver tissue, antioxidant capacity was found to be stimulated in fluorine groups in erythrocyte.

Human Beta Defensin 2 Ameliorated Alcohol-Associated Liver Disease in Mice.

Alcohol-associated liver disease (ALD) is a prevalent liver disorder and significant global healthcare burden with limited effective therapeutic options. The gut-liver axis is a critical factor contributing to susceptibility to liver injury due to alcohol consumption. In the current study, we tested whether human beta defensin-2 (hBD-2), a small anti-microbial peptide, attenuates experimental chronic ALD. Male C57Bl/6J mice were fed an ethanol (EtOH)-containing diet for 6 weeks with daily administration of hBD-2 (1.2 mg/kg) by oral gavage during the final week. Two independent cohorts of mice with distinct baseline gut microbiota were used. Oral hBD-2 administration attenuated liver injury in both cohorts as determined by decreased plasma ALT activity. Notably, the degree of hBD-2-mediated reduction of EtOH-associated liver steatosis, hepatocellular death, and inflammation was different between cohorts, suggesting microbiota-specific mechanisms underlying the beneficial effects of hBD-2. Indeed, we observed differential mechanisms of hBD-2 between cohorts, which included an induction of hepatic and small intestinal IL-17A and IL-22, as well as an increase in T regulatory cell abundance in the gut and mesenteric lymph nodes. Lastly, hBD-2 modulated the gut microbiota composition in EtOH-fed mice in both cohorts, with significant decreases in multiple genera including Barnesiella, Parabacteroides, Akkermansia, and Alistipes, as well as altered abundance of several bacteria within the family Ruminococcaceae. Collectively, our results demonstrated a protective effect of hBD-2 in experimental ALD associated with immunomodulation and microbiota alteration. These data suggest that while the beneficial effects of hBD-2 on liver injury are uniform, the specific mechanisms of action are associated with baseline microbiota.

Effect of Aqueous Extract of the Aerial Parts of Leonurus cardiaca On Cisplatin-induced Hepato-renal Damage in Wistar Albino Rats

This study investigated the effect of aqueous extract of the aerial parts of Leonurus cardiaca on cisplatin-induced hepato-renal damage in male Wistar albino rats. Sixty male wistar albino rats weighing between 180 and 220g were used for this study. The rats were grouped into 12 groups, five rats per group. Group 1 served as normal control, group 2 received 5mg/kg weight of cisplatin, serving as negative control while group 3 received 5mg/kg b.w of cisplatin and treated with 25mg/kg weight of hydrochlorothiazide and served as positive control. Group 4-12 rats were cisplatin-induced cardiovascular damage treated with Leonurus cardiaca extract at 166, 250, and 500mg/kg for 7, 14, and 21 days. Biochemical assays were determined using standard methods and procedures. The Na+, Cl-, HCO3-, creatinine, and urea levels of kidney homogenate of group 7 treated rats with the extract at 250mg/kg b.w for 7 days were 123.05±0.01mmol/l, 1.07±0.01mmol/l, 27.27±0.01mmol/l, 13.63±0.01mmol/l, 0.68±0.02mmol/l, and 1.14±0.01mmol/l respectively and were significantly increased when compared to the negative and normal control groups. Similar increases occurred for 14 and 21 days treatments. The kidney homogenate Na+, Cl-, HCO3, creatinine, and urea of group 7 treated rats with the extract at 500mg/kg b.w for 7 days were 158.05±0.01mmol/l, 3.03±0.01mmol/l, 31.13±0.01mmol/l, 19.46±0.01mmol/l, 2.06±0.00mmol/l, and 2.03±0.01mmol/l respectively. Values were significantly increased (p&lt;0.05) in comparison to the normal and negative control groups. Similar increases were observed for 14 and 21 days treatments. The plasma ALT, ALP, and AST activities were 187.35±0.00U/L, 98.03±0.01U/L, 185.64±40.81U/L respectively, were significantly decreased (p&lt;0.05) in comparison to negative control treated with the extract at 250mg/kg b.w for 14 days. The plasma ALT, ALP, and AST activities of group 10 rats treated with the extract at 500mg/kg b.w for 7 days were 164.24±0.01U/L, 87.02±0.01U/L, and 183.74±0.01U/L respectively and were significantly decreased (p&lt;0.05) in comparison to negative control. The hepato-renal curative potential of Leonurus cardiaca could be attributed in part to its ability in enhancing liver and kidney regeneration.

Synbiotics Alleviate Hepatic Damage, Intestinal Injury and Muscular Beclin-1 Elevation in Rats after Chronic Ethanol Administration.

The purpose of this study was to investigate the beneficial effects of synbiotics on liver damage, intestinal health, and muscle loss, and their relevance in rats with chronic ethanol feeding. Thirty Wistar rats fed with a control liquid diet were divided into control and synbiotics groups, which were respectively provided with water or synbiotics solution (1.5 g/kg body weight/day) for 2 weeks. From the 3rd to 8th week, the control group was divided into a C group (control liquid diet + water) and an E group (ethanol liquid diet + water). The synbiotics group was separated in to three groups, SC, ASE, and PSE. The SC group was given a control liquid diet with synbiotics solution; the ASE group was given ethanol liquid diet with synbiotics solution, and the PSE group was given ethanol liquid diet and water. As the results, the E group exhibited liver damage, including increased AST and ALT activities, hepatic fatty changes, and higher CYP2E1 expression. Intestinal mRNA expressions of occludin and claudin-1 were significantly decreased and the plasma endotoxin level was significantly higher in the E group. In muscles, beclin-1 was significantly increased in the E group. Compared to the E group, the PSE and ASE groups had lower plasma ALT activities, hepatic fatty changes, and CYP2E1 expression. The PSE and ASE groups had significantly higher intestinal occludin and claudin-1 mRNA expressions and lower muscular beclin-1 expression when compared to the E group. In conclusion, synbiotics supplementation might reduce protein expression of muscle protein degradation biomarkers such as beclin-1 in rats with chronic ethanol feeding, which is speculated to be linked to the improvement of intestinal tight junction and the reduction of liver damage.

Protective Role of Plasminogen Deficiency in Non-Alcoholic Fatty Liver Disease and Glucose Dysmetabolism

Obesity is global health problem with 40% of the world population being classified as overweight (BMI > 25) and 13% as obese (BMI > 30). Obesity drives chronic metabolic inflammation leading to metabolic syndrome, cardiovascular disease, fatty liver disease, Type II diabetes, and certain cancers. A documented clinical manifestation of obesity is perturbed and dysregulated hemostatic system leading to a procoagulant and anti-fibrinolytic state that ultimately results in an increased risk of thrombosis.Previous work suggested that clotting system components thrombin and fibrin engage in reciprocal mechanisms and contribute to the development of obesity. Specifically, we have shown that fibrin accumulates within obese adipose tissue and liver of obesity patients and mice challenged with a high fat diet (HFD) and colocalizes with macrophages, a key driver of inflammation in obesity. Despite the fact that obesity is known to be linked to an impaired fibrinolytic system, a potential functional contribution of fibrinolytic proteases to the development of obesity and associated downstream diseases has been understudied.Here, we tested the hypothesis that elimination of the fibrinolytic protease plasminogen would increase HFD-driven fibrin deposition and exacerbate macrophage accumulation and subsequent weight gain and obesity-associated pathologies. Contrary to our hypothesis, plasminogen-deficient (Plg-) mice gained as much weight as the Plg+ mice after 20 weeks on HFD. However, whereas the liver mass of HFD-challenged Plg+ mice was significantly higher than that of low fat diet (LFD)-fed mice, the livers of HFD-fed Plg- mice had a mass comparable to LFD-fed mice. HFD-fed Plg- mice had reduced hepatocellular damage, measured by plasma ALT activity, as well as reduced hepatosteatosis, measured by hepatic triglyceride content and liver histology, compared to HFD-fed Plg+ mice. Circulating cholesterol levels in HFD-fed Plg -/- mice were comparable to LFD-fed Plg- mice, while it was significantly elevated in HFD-fed Plg+ mice. While the epididymal white adipose tissue mass was higher in HFD-fed Plg- mice compared to HFD-fed Plg+ mice, the brown adipose tissue mass was comparable. However, there was an upregulation of uncoupling protein-1 (UCP-1) expression BAT of HFD-fed Plg- mice. Glucose clearance was more efficient in HFD-fed Plg- mice compared to HFD-fed Plg+ mice in a glucose tolerance test. Collectively, our data suggest that plasmin(ogen) contributes to HFD-induced fatty liver disease and glucose dysmetabolism. DisclosuresNo relevant conflicts of interest to declare.

Von Willebrand factor exerts hepatoprotective effects in acute but not chronic cholestatic liver injury in mice

Acute and chronic liver disease are associated with substantial alterations in the hemostatic system, including elevated levels of the platelet-adhesive protein von Willebrand factor (VWF). Carbon tetrachloride-induced liver fibrosis is reduced in VWF-deficient mice, but it is unclear if VWF plays a pathologic role in all settings of liver fibrosis. Indeed, several studies suggest an anti-fibrotic role for components of the hemostatic system, including platelets, in experimental settings of bile duct fibrosis. However, the role of VWF in this specific pathology has not been examined. We tested the hypothesis that VWF exerts hepatoprotective effects in experimental bile duct injury. Wild-type and VWF-deficient (VWF−/−) mice were challenged with the bile duct toxicant alpha-naphthylisothiocyanate (ANIT) and the impact of VWF deficiency on acute cholestatic liver injury and chronic liver fibrosis was determined. Acute ANIT (60 mg/kg, po)-induced cholestatic liver injury was associated with increased VWF plasma antigen and activity levels. VWF deficiency enhanced ANIT-induced hepatocellular injury, evidenced by increased plasma ALT activity and area of hepatocellular necrosis. Surprisingly, platelet accumulation within necrotic areas was increased in ANIT-challenged VWF−/− mice compared to wild-type mice. Compared to acute ANIT challenge, hepatic platelet accumulation was modest and appeared to be VWF-dependent in mice exposed to ANIT diet (0.05 %) for 6 weeks. However, contrasting the role of VWF after acute ANIT challenge, VWF deficiency did not impact biliary fibrosis induced by chronic ANIT exposure. The results suggest that VWF plays dichotomous roles in experimental acute and chronic ANIT-induced cholestatic liver injury.

Benfotiamine ameliorates high‐carbohydrate diet‐induced hepatic oxidative stress, inflammation and apoptosis in Megalobrama amblycephala

A 12-week nutritional research was conducted to evaluate the influences of benfotiamine on the growth performance, oxidative stress, inflammation and apoptosis in Megalobrama amblycephala (45.25 ± 0.34 g) fed high-carbohydrate (HC) diets. Six diets were prepared, containing the control diet (30% carbohydrate, C), the HC diet (43% carbohydrate) and the HC diet supplemented with four benfotiamine levels (0.7125 (HCB1), 1.425 (HCB2), 2.85 (HCB3) and 5.7 (HCB4) mg/kg). HC diet remarkably decreased DGC, GRMBW, liver T-AOC, SOD and CAT activities, SIRT1 protein expression as well as the mRNA levels of SIRT1, Nrf2, CAT, Mn-SOD and IL10 in liver compared with the C group, but the opposite trend was found in plasma activities of AST and ALT, and contents of IL1β and IL6, liver contents of MDA and mRNA levels of Keap1, NF-κB, TNF α, IL1β, IL6, Bax, caspase 3, caspase 9 and P53. As for benfotiamine supplementation, HCB2 diet remarkably increased DGC, GRMBW, liver T-AOC, SOD and CAT activities, SIRT1 protein expression as well as liver mRNA levels of SIRT1, Nrf2, CAT, Mn-SOD, IL10 and Bcl2, while the opposite was true for plasma AST and ALT activities, and IL1β and IL6 contents, liver MDA contents as well as mRNA levels of Keap1, NF-κB, TNF α, IL1β, IL6, Bax, caspase 3, caspase 9 and P53. In summary, benfotiamine (1.425 mg/kg) promoted the growth, and alleviated the oxidative stress, inflammation and apoptosis of M. amblycephala fed HC diets through the SIRT1-mediated signaling pathway.