Serum Alanine Aminotransferase Activity Research Articles

Dietary sugar kelp (Saccharina latissima) consumption did not attenuate atherosclerosis in low-density lipoprotein receptor knockout mice.

We previously demonstrated the beneficial effects of U.S.-grown sugar kelp (Saccharina latissima), a brown seaweed, on reducing serum triglycerides (TG) and total cholesterol (TC) and protecting against inflammation and fibrosis in the adipose tissue of diet-induced obesity mice. In this current study, we aimed to explore whether the dietary consumption of sugar kelp can prevent atherosclerosis using low-density lipoprotein receptor knockout (Ldlr KO) mice fed an atherogenic diet. Eight-week-old male Ldlr KO mice were fed either an atherogenic high-fat/high-cholesterol control (HF/HC) diet or a HF/HC diet supplemented with 6% (w/w) sugar kelp (HF/HC-SK) for 16 weeks. Consumption of sugar kelp significantly increased the body weight gain without altering fat mass and lean mass. Also, there were no significant differences in energy expenditure and physical activities between the groups. The two groups did not show significant differences in serum and hepatic TG and TC levels or the hepatic expression of genes involved in cholesterol and lipid metabolism. Although serum alanine aminotransferase (ALT) activity did not differ significantly between the two groups, there were significant increases in the expression of macrophage markers, including adhesion G protein-coupled receptor E1 and cluster of differentiation 68, as well as tumor necrosis factor alpha in the HF/HC-SK group compared to the HF/HC mice. The consumption of sugar kelp did not elicit a significant effect on the development of aortic lesions. Moreover, lipopolysaccharide-stimulated splenocytes isolated from HF/HC-SK-fed mice showed no significant changes in the mRNA levels of pro-inflammatory genes compared with those from the HF/HC mice. In summary, the consumption of dietary sugar kelp did not elicit anti-atherogenic and hepatoprotective effects in Ldlr KO mice.

Hepatoprotective effects and mechanisms of l-theanine and epigallocatechin gallate combined intervention in alcoholic fatty liver rats.

Chronic excessive alcohol consumption can lead to alcoholic fatty liver, posing substantial health risks. l-Theanine (LTA) and epigallocatechin gallate (EGCG) in tea exert antioxidant and hepatoprotective effects. However, the combined effects of LTA and EGCG on rats with alcoholic fatty liver, and the underlying mechanisms of such effects, remain unclear. In this study, Sprague Dawley (SD) rats were fed with alcohol for 6 weeks to induce alcoholic fatty liver. Subsequently, for another 6 weeks, the rats were administered LTA (200 mg kg-1 day-1), EGCG (200 mg kg-1 day-1), or a combination of LTA with EGCG (40 mg kg-1 day-1 l-Thea +160 mg kg-1 day-1 EGCG), respectively. The combined use of LTA and EGCG for alcoholic fatty liver disease had more significant effects than their individual administration. This combination reduced the activity of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as well as the levels of hepatic triglyceride (TG), malondialdehyde (MDA), and reactive oxygen species (ROS) in the rats. The combined intervention also increased hepatic superoxide dismutase (SOD) and glutathione peroxidase activity. Reductions in hepatic fat accumulation and inflammatory responses were observed. The mechanism underlying these effects primarily involved the inhibition of fatty acid synthesis and the alleviation of lipid peroxidation through the downregulation of the mRNA and protein expression of TNF-α, SREBP1c, and CYP2E1 and the upregulation of the mRNA and protein expression of ADH1, ALDH2, Lipin-1, PPARαPPARα, AMPK, and PGC-1α, thereby promoting the oxidative decomposition of fatty acids and reducing the synthesis of cholesterol and glucose. l-Theanine and EGCG appear to be able to alleviate alcoholic fatty liver by modulating lipid metabolism and ameliorating oxidative stress, indicating their potential as natural active ingredients in anti-alcoholic fatty liver food products. © 2024 Society of Chemical Industry.

The ameliorative effect of methanol extract of Ricinodendron heudelotii (Baill.) leaves on paracetamol-induced hepatotoxicity in Wistar rats

Plants are a rich source of antioxidants that are produced naturally. Therefore, this study was aimed to evaluate the effect of the plant Ricinodendron heudelotii (Baill.) in the attenuation of paracetamol (PCM) hepatotoxicity in Wistar rats. Twenty-four male albino Wistar rats weighing between 200 and 250 g were divided into four groups, with six rats each. Group 1 served as the control group, receiving just distilled water. Groups 2 and 3 received orally 250 mg/kg bwt/day PCM and 300 mg/kg bwt/day methanol extract of Ricinodendron heudelotii (Baill.) leaves for two weeks, respectively. For group 4, the Ricinodendron heudelotii (Baill.) leaf extract was pre-administered for 1 week before receiving 300 mg/kg bwt/day Ricinodendron heudelotii (Baill.) leaves extract and 250 mg/kg bwt/day PCM for 2 weeks. As a marker of liver damage, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. Liver tissue reduced glutathione (GSH) concentration, superoxide dismutase (SOD), glutathione-S-transferase (GST), and catalase activities were utilized to determine antioxidant state, while malondialdehyde (MDA) concentration was employed as a lipid peroxidation indicator. When compared to the control group, the activities of serum AST, ALT, SOD, and MDA levels were considerably (p < 0.05) higher in the PCM group, although GSH level and GST and catalase activities were significantly lower. In comparison to the PCM group, co-administration of PCM with Ricinodendron heudelotii (Baill.) extract decreased serum AST and ALT activities. This study shows that the leaf extracts of Ricinodendron heudelotii (Baill.) protects Wistar rats’ livers from PCM-induced oxidative stress by increasing antioxidant enzymes.

The impact of chrysanthemi indici flos-enriched flavonoid part on the model of hyperuricemia based on inhibiting synthesis and promoting excretion of uric acid

Ethnopharmacological relevanceIn recent years, in addition to hypertension, hyperglycemia, and hyperlipidemia, the prevalence of hyperuricemia (HUA) has increased considerably. Being the fourth major health risk factor, HUA can affect the kidneys and cardiovascular system. Chrysanthemi Indici Flos is a flavonoid-containing traditional Chinese patent medicine that exhibits a uric acid (UA)-lowering effect. However, the mechanisms underlying Chrysanthemi Indici Flos-enriched flavonoid part (CYM.E) mediated alleviation of HUA remain unelucidated. Aim of the studyThis study aimed to elucidate the efficacy of CYM.E in preventing and treating HUA and its specific effects on UA-related transport proteins, to explore possible mechanism. MethodsThe buddleoside content in CYM.E was determined through high-performance liquid chromatography. HUA was induced in mice models using adenine and potassium oxonate. Subsequently, mice were administered 10 mg/kg allopurinol, and 30, 60, and 90 mg/kg CYM.E to evaluate the effects of CYM.E on the of HUA mice model. Herein, plasma uric acid (UA), creatinine (CR), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) contents, along with serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities were measured. Additionally, xanthine oxidase (XOD) and adenosine deaminase (ADA) activities in the liver were determined. The histomorphologies of the liver and kidney tissues were examined through hematoxylin and eosin staining. The messenger RNA (mRNA) expression of facilitated glucose transporter 9 (GLUT9), organic anion transporter (OAT)1, OAT3, and adenosine triphosphate binding cassette subfamily G2 (ABCG2) in the kidney was assessed by real-time quantitative polymerase chain reaction. Furthermore, the expression of urate transporter 1 (URAT1), GLUT9, OAT1, and OAT3 in the kidney, OAT4, and ABCG2 proteins was determined by immunohistochemistry and western blotting. ResultsThe buddleoside content in CYM.E was approximately 32.77%. CYM.E improved body weight and autonomous activity in HUA mice. Additionally, it reduced plasma UA, BUN, and CR levels and serum ALT and AST activities, thus improving hepatic and renal functions, which further reduced the plasma UA content. CYM.E reduced histopathological damage to the kidneys. Furthermore, it lowered plasma TC, TG, and LDL-c levels, thereby improving lipid metabolism disorder. CYM.E administration inhibited hepatic XOD and ADA activities and reduced the mRNA expression of renal GLUT9. CYM.E inhibited the protein expression of renal URAT1, GLUT9, and OAT4, and increased the mRNA and protein expression of renal OAT1, OAT3, and ABCG2. Altogether, these results show that CYM.E could inhibit the production and promote reabsorption of UA and its excretion.

Potential effects of Sargassum kjellmanianum as a dietary supplement on the growth performance, immunity response, antioxidant status, and ammonia resistance of yellow catfish (Pelteobagrus fulvidraco)

This study aimed to investigate the potential effects of seaweed Sargassum kjellmanianum (SK) as a dietary supplement on the growth performance, blood biochemistry, immunology, antioxidants, and ammonia stress resistance of yellow catfish, Pelteobagrus fulvidraco. Four diets containing 0 % SK (control), 2.5 % SK, 5 % SK, and 10 % SK were fed to fish for 8 weeks. After the feeding trial, the fish were exposed to ammonia for 72 h and their mortality was recorded. Compared with the control group, the growth performance was significantly increased in the 2.5 % and 5 % SK groups (P < 0.05). Serum albumin levels were significantly increased (P < 0.05), meanwhile serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels were significantly decreased in fish fed with 2.5 % and 5 % SK (P < 0.05). Interestingly, the serum AST and ALT activities were significantly increased in the 10 % SK group (P < 0.05). Additionally, serum lysozyme, acid phosphatase, and complement 4 levels were all significantly increased in all SK groups than those of the control group (P < 0.05). In addition, serum malondialdehyde levels were significantly decreased (P < 0.05). Meanwhile, the total antioxidant capacity, superoxide dismutase, and catalase levels were significantly increased in the 2.5 % and 5 % SK groups with relative to the control group (P < 0.05). Notably, the cumulative mortality rate was significantly higher (46.67 %) in the control fish than those fed the SK diets (35–38.33 %) (P < 0.05). Taken together, the results indicated that adding SK to the diet of yellow catfish can enhance growth performance, stimulate immune responses, improve antioxidant status, and increase resistance to ammonia stress. It is recommended to use concentrations between 2.5 % and 5.0 % in present study.

Mechanistic insight into the hepatoprotective effect of Moringa oleifera Lam leaf extract and telmisartan against carbon tetrachloride-induced liver fibrosis: plausible roles of TGF-β1/SMAD3/SMAD7 and HDAC2/NF-κB/PPARγ pathways

The increasing prevalence and limited therapeutic options for liver fibrosis necessitates more medical attention. Our study aims to investigate the potential molecular targets by which Moringa oleifera Lam leaf extract (Mor) and/or telmisartan (Telm) alleviate carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Liver fibrosis was induced in male Sprague-Dawley rats by intraperitoneal injection of 50% CCl4 (1 ml/kg) every 72 hours, for 8 weeks. Intoxicated rats with CCl4 were simultaneously orally administrated Mor (400 mg/kg/day for 8 weeks) and/or Telm (10 mg/kg/day for 8 weeks). Treatment of CCl4-intoxicated rats with Mor/Telm significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities compared to CCl4 intoxicated group (P < 0.001). Additionally, Mor/Telm treatment significantly reduced the level of hepatic inflammatory, profibrotic, and apoptotic markers including; nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), transforming growth factor-βeta1 (TGF-β1), and caspase-3. Interestingly, co-treatment of CCl4-intoxicated rats with Mor/Telm downregulated m-RNA expression of histone deacetylase 2 (HDAC2) (71.8%), and reduced protein expression of mothers against decapentaplegic homolog 3 (p-SMAD3) (70.6%) compared to untreated animals. Mor/Telm regimen also elevated p-SMAD7 protein expression as well as m-RNA expression of peroxisome proliferator-activated receptor γ (PPARγ) (3.6 and 3.1 fold, respectively p < 0.05) compared to CCl4 intoxicated group. Histopathological picture of the liver tissue intoxicated with CCl4 revealed marked improvement by Mor/Telm co-treatment. Conclusively, this study substantiated the hepatoprotective effect of Mor/Telm regimen against CCl4-induced liver fibrosis through suppression of TGF-β1/SMAD3, and HDAC2/NF-κB signaling pathways and up-regulation of SMAD7 and PPARγ expression.

Evaluation of capillary miR-122 as a prognostic biomarker of paracetamol-induced liver toxicity.

Paracetamol (acetaminophen) overdose is a leading cause of acute liver failure in many Western countries. Diagnostic tools for this poisoning may be suboptimal in some cases and new biomarkers have been investigated. We investigated the role of capillary microRNA-122 (miR-122) as a prognostic biomarker of liver injury in the clinical management of patients with paracetamol overdose. In a paracetamol overdose patient cohort, miR-122 was measured by quantitative polymerase chain reaction in a blood drop obtained by a finger prick at the end of an antidote cycle treatment with N-acetylcysteine treatment (12h). Liver injury was defined as serum alanine aminotransferase (ALT) activity > 100IU/L collected at 10 or 20h after the start of treatment. Pearson's correlation analyses were performed. In patients with paracetamol overdose, capillary miR-122 was positively correlated with ALT measured at 10h and at 20h (r = 0.83, P < 0.0001; r = 0.96, P < 0.0001, respectively). This work supports the potential use of capillary miR-122 as a prognostic biomarker of liver injury throughout clinical management of patients with paracetamol overdose. Capillary miR-122 can be measured in a blood drop collected by a finger prick, a minimally invasive diagnostic test for patient stratification.

Biomarkers in Detection of Hepatitis C Virus Infection.

The hepatitis C virus (HCV) infection affects 58 million people worldwide. In the United States, the incidence rate of acute hepatitis C has doubled since 2014; during 2021, this increased to 5% from 2020. Acute hepatitis C is defined by any symptom of acute viral hepatitis plus either jaundice or elevated serum alanine aminotransferase (ALT) activity with the detection of HCV RNA, the anti-HCV antibody, or hepatitis C virus antigen(s). However, most patients with acute infection are asymptomatic. In addition, ALT activity and HCV RNA levels can fluctuate, and a delayed detection of the anti-HCV antibody can occur among some immunocompromised persons with HCV infection. The detection of specific biomarkers can be of great value in the early detection of HCV infection at an asymptomatic stage. The high rate of HCV replication (which is approximately 1010 to 1012 virions per day) and the lack of proofreading by the viral RNA polymerase leads to enormous genetic diversity, creating a major challenge for the host immune response. This broad genetic diversity contributes to the likelihood of developing chronic infection, thus leading to the development of cirrhosis and liver cancer. Direct-acting antiviral (DAA) therapies for HCV infection are highly effective with a cure rate of up to 99%. At the same time, many patients with HCV infection are unaware of their infection status because of the mostly asymptomatic nature of hepatitis C, so they remain undiagnosed until the liver damage has advanced. Molecular mechanisms induced by HCV have been intensely investigated to find biomarkers for diagnosing the acute and chronic phases of the infection. However, there are no clinically verified biomarkers for patients with hepatitis C. In this review, we discuss the biomarkers that can differentiate acute from chronic hepatitis C, and we summarize the current state of the literature on the useful biomarkers that are detectable during acute and chronic HCV infection, liver fibrosis/cirrhosis, and hepatocellular carcinoma (HCC).

Effects of supplementing coated methionine in a high plant-protein diet on growth, antioxidant capacity, digestive enzymes activity and expression of TOR signaling pathway associated genes in gibel carp, Carassius auratus gibelio.

This study explored the impacts of supplementation of different levels of coated methionine (Met) in a high-plant protein diet on growth, blood biochemistry, antioxidant capacity, digestive enzymes activity and expression of genes related to TOR signaling pathway in gibel carp (Carassius auratus gibeilo). A high-plant protein diet was formulated and used as a basal diet and supplemented with five different levels of coated Met at 0.15, 0.30, 0.45, 0.60 and 0.75%, corresponding to final analyzed Met levels of 0.34, 0.49, 0.64, 0.76, 0.92 and 1.06%. Three replicate groups of fish (initial mean weight, 11.37 ± 0.02g) (20 fish per replicate) were fed the test diets over a 10-week feeding period. The results indicated that with the increase of coated Met level, the final weight, weight gain (WG) and specific growth rate initially boosted and then suppressed, peaking at 0.76% Met level (P< 0.05). Increasing dietary Met level led to significantly increased muscle crude protein content (P< 0.05) and reduced serum alanine aminotransferase activity (P< 0.05). Using appropriate dietary Met level led to reduced malondialdehyde concentration in hepatopancreas (P< 0.05), improved superoxide dismutase activity (P< 0.05), and enhanced intestinal amylase and protease activities (P< 0.05). The expression levels of genes associated with muscle protein synthesis such as insulin-like growth factor-1, protein kinase B, target of rapamycin and eukaryotic initiation factor 4E binding protein-1 mRNA were significantly regulated, peaking at Met level of 0.76% (P< 0.05). In conclusion, supplementing optimal level of coated Met improved on fish growth, antioxidant capacity, and the expression of TOR pathway related genes in muscle. The optimal dietary Met level was determined to be 0.71% of the diet based on quadratic regression analysis of WG.

Hepatoprotective effect of jojoba oil against lead-induced toxicity in rats

Background Previous investigations showed that jojoba oil exhibited a protective effect against hepatotoxicity caused by different toxicants, however, to the best of our knowledge, no prior research has been done to determine the effectiveness of jojoba oil in protecting against lead toxicity. Objective This study assessed the hepatoprotective properties of jojoba oil against lead toxicity in rats. Materials and methods The study included four groups, each consisting of six Sprague Dawley male rats, and orally administered jojoba oil (JO group), lead acetate (LA group), and lead acetate plus jojoba oil (protective group) Results and conclusion The results showed that lead acetate-induced hepatotoxic effects were revealed by increased serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase activities with hepatic histomorphological changes. There was a significant increase in serum total cholesterol, triglycerides, and low-density lipoprotein-cholesterol, while levels of high-density lipoprotein-cholesterol significantly declined compared to normal rats. Additionally, lead acetate triggered oxidative damage of hepatocytes, evidenced by a significant increase of malondialdehyde levels and a decrease of reduced glutathione levels and activities of superoxide dismutase and glutathione S-transferase. Administration of lead was associated with a change in the distribution of cells over different cell cycle phases, characterized by a marked increase in the sub G1 cell population and a significant decrease in the G0/G1 cell population. Supplementation of jojoba oil with lead acetate relieved the toxic impacts of lead acetate with an enhancement of the liver enzyme activities, antioxidant status, lipid profile parameters, and histopathological alterations. In conclusion, jojoba oil might be an effective natural product that offers a promising preventive action towards lead-induced liver damage in rats.

Effects of Dietary Fish Meal Replaced by Cottonseed Protein Concentrate on Growth Performance, Antioxidant Capacity, and Liver and Intestinal Health of Juvenile Hybrid Culter

The objective of this study was to assess the impact of concentrated cottonseed protein (CPC) as a substitute for fishmeal (FM) in juvenile hybrid culter (Erythroculter ilishaeformis ♀ × Ancherythroculter nigrocauda ♂). A total of 360 fish with an initial body weight of 10.0 ± 0.5 g were randomly allocated into 12 indoor culture tanks, with each tank containing 30 fish. Four diets were formulated in which fish meal (FM) was replaced by CPC at different inclusion levels: 0% (T0), 15% (T15), 30% (T30), and 45% (T45). The corresponding amounts of CPC included were 0, 61, 122, and 182 g/kg, respectively. At the end of the 10-week feeding trial, the findings revealed an inverse correlation between the proportion of CPC replacing FM and both final body weight (FBW) and weight growth rate (WG) in hybrid culter. Specifically, the T30 and T45 groups exhibited significantly lower FBW and WG compared to the T0 group (p &lt; 0.05). No significant differences in crude protein and ash contents were observed among all groups (p &gt; 0.05). However, the crude lipid content was highest in hybrid culter fed the T45 diet and lowest in the T0 group (p &lt; 0.05). There were no significant differences in muscle amino acid composition among all treatment groups (p &gt; 0.05). The contents of total protein (TP) and albumin (ALB) declined slightly as the proportion of FM substituted by CPC increased, yet this decline did not reach statistical significance (p &gt; 0.05). Serum alanine aminotransferase (ALT) activity elevated with increasing dietary CPC, and the T45 group exhibited significantly higher ALT activity compared to the T0 group (p &lt; 0.05). The hepatic activities of superoxide dismutase (SOD) and catalase (CAT) were significantly lower in the T45 group than in the T0 and T15 groups (p &lt; 0.05). Furthermore, there was a decrease in intestinal villi length with an increasing replacement ratio of FM by CPC, and the villi length in the T45 group exhibited a significant reduction when compared to that in the T0 group (p &lt; 0.05). It is concluded that replacing 15% FM with CPC does not exert obviously detrimental effects on growth performance, serum biochemical indices, intestinal morphology, muscle amino acid profile, or antioxidant performance of juvenile hybrid culter.

Cymbopogon schoenanthus (L) extract ameliorates high fat diet-induced obesity and dyslipidemia via reducing expression of lipogenic and thermogenic proteins

Globally, obesity has become one of the major health problems. This study was conducted to evaluate the anti-obesity potential of Cymbopogon schoenanthus methanolic extract (CS) in rats. Fifty male Wistar rats of six to eight weeks old, 100–120 g body weight (BW) were randomly assigned into 5 groups (n = 10): The control group was fed a basal diet. CS-group was supplied with basal diet and orally given CS (200 mg/kg BW) for 12 weeks. HFD-group was fed a high-fat diet (HFD) for 18 weeks. HFD + CS-group was fed on HFD and CS HFD then CS-group was fed HFD for 12 weeks then shifted to basal diet and CS for another 6 weeks. Phytochemical analysis of CS indicated the presence of various terpenes and flavonoid compounds. Among the compounds characterized are quercetin, apigenin, luteolin, orientin, eudesmene, cymbopogonol, caffeic acid, coumaric acid, and linolenic acid. Supplementation of HFD significantly increased the body weight, levels of serum triacylglycerol, total cholesterol, very low-density lipoprotein, low-density lipo-protein (HDL), glucose, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. In addition, HFD up-regulated the protein expression of uncoupling protein (UCP)-1 in both brown and white adipose tissue; and the expression of hepatic mRNA of sterol regulatory element-binding protein (SREBP)-1c and SREBP-2. However, it decreased the serum level of HDL, and protein expression level of UCP-1 in both brown and white adipose tissue. Treatment of HFD-fed animals with CS extract either concurrently (HFD + CS-group), or after obesity induction (HFD then CS-group) significantly reversed all HFD-induced alterations in body weight; food intake; serum biochemical profile (including hyperglycemia, dyslipidemia); and tissue gene expressions. These results indicate that CS methanolic extract ameliorated HFD-induced obesity, serum biochemical, hepatic, and adipose tissue gene expression alterations. CS extract accomplished these effects mostly through its various identified bioactive compounds which have been proven to have anti-obesity and anti-diabetic activities.

Inhibiting apoptosis and GSDME-mediated pyroptosis attenuates hepatic injury in septic mice

BackgroundSepsis is characterized by severe inflammation and organ dysfunction resulting from a dysregulated organismal response to infection. Although pyroptosis has been presumably shown to be a major cause of multiple organ failure and septic death, whether gasdermin E (GSDME)-mediated pyroptosis occurs in septic liver injury and whether inhibiting apoptosis and GSDME-mediated pyroptosis can attenuate septic liver injury remain unclear. This study investigated the role of apoptosis and GSDME-mediated pyroptosis in septic liver injury. MethodsAdult male C57BL/6 mice were randomly divided into four groups: sham, cecal ligation puncture (CLP), CLP + Z-DEVD-FMK (a caspase-3 inhibitor, 5 mg/kg), and CLP + Ac-DMLD-CMK (a GSDME inhibitor, 5 mg/kg). Sepsis severity was assessed using the murine sepsis score (MSS). Hepatic tissue damage was observed by the hematoxylin-eosin staining method, the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the levels of malondialdehyde (MDA), the concentrations of interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were measured according to the related kits, and the changes in the hepatic tissue reactive oxygen species (ROS) levels were detected by immunofluorescence (IF). The protein expression levels of cleaved caspase-3, GSDME-N, IL-1β, B-cell lymphoma-2 (Bcl-2), cytochrome C (Cyt-c), and acetaldehyde dehydrogenase 2 (ALDH2) were detected using western blotting. GSDME expression was detected by immunohistochemistry. ResultsCompared with the Sham group, CLP mice showed high sepsis scores and obvious liver damage. However, in the CLP + Z-DEVD-FMK and CLP + Ac-DMLD-CMK groups, the sepsis scores were reduced and liver injury was alleviated. Compared with the Sham group, the serum ALT and AST activities, MDA and ROS levels, and IL-1β and TNF-α concentrations were increased in the CLP group, as well as the protein expression of cleaved caspase-3, GSDME-N, IL-1β, Cyt-c, and GSDME positive cells (P < 0.05). However, the expression levels of Bcl-2 and ALDH2 protein were decreased (P < 0.05). Compared with the CLP group, the CLP + Z-DEVD-FMK and CLP + Ac-DMLD-CMK groups showed low sepsis scores, ALT and AST activities, MDA and ROS levels, decreased IL-1β and TNF-α concentrations, and decreased expression of cleaved caspase-3, GSDME-N, IL-1β protein expression, and GSDME positive cells (P < 0.05). The expression levels of Bcl-2 and ALDH2 protein were increased (P < 0.05). ConclusionApoptosis and GSDME-mediated pyroptosis are involved in the development of sepsis-induced hepatic injury. Inhibition of apoptosis and GSDME-mediated pyroptosis attenuates injury. ALDH2 plays a protective role by inhibiting apoptosis and pyroptosis.

Effects of Lycium barbarum polysaccharides supplemented to high soybean meal diet on immunity and hepatic health of spotted sea bass Lateolabrax maculatus.

High soybean meal diet (HSBMD) decreased the immunity and damaged the liver health of spotted sea bass; in this study, Lycium barbarum polysaccharides (LBP) was added to HSBMD to explore its effects on the immunity and liver health. The diet with 44% fish meal content was designed as a blank control. On this basis, soybean meal was used to replace 50% fish meal as HSBMD, and LBP was added in HSBMD in gradient (1.0, 1.5, 2.0 g/kg) as the experimental diet. 225-tailed spotted sea bass with initial body weight of 44.52 ± 0.24 g were randomly divided into 5 groups and fed the corresponding diet for 52 days, respectively. The results show that: after ingestion of HSBMD, the immunity of spotted sea bass decreased slightly and hepatic tissue was severely damaged. And the addition of LBP significantly improved the immune capacity and protected the hepatic health. Specifically, the activities of serum lysozyme (LZM), immunoglobulin M (IgM), liver acid phosphatase (ACP) and alkaline phosphatase (AKP) were increased, and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were significantly decreased, and hepatic morphology was improved. In the analysis of transcriptome results, it was found that toll-like receptor 3 (TLR3) and toll-like receptor 5 (TLR5) were down-regulated in toll-like receptor signaling pathway. And LBP may protect hepatic health by regulating Glycolysis/Gluconeogenesis, Insulin signaling pathway, Steroid biosynthesis and other glucolipid-related pathways. In conclusion, the addition of LBP in HSBMD can improve the immunity and protect the hepatic health of spotted sea bass, and its mechanism may be related to glucose and lipid metabolism.

Hepatoprotective effect of the flavonoid fustin in a rat model of paracetamol-induced acute liver damage

Paracetamol (PCM)-induced toxicity is a well-established pharmacological model. Cotinus coggygria is a medicinal plant rich in polyphenols, including the flavonoid fustin. The aim of the present study was to evaluate the effects of the flavonoid fustin isolated from Cotinus coggygria heartwood in a model of PCM-induced liver damage. Male Wistar rats (n=48) were allocated to four groups: Control, PCM, F5+PCM, F10+PCM. The rodents were treated daily orally for nine consecutive days as follows: groups F5+PCM and F10+PCM – with fustin (suspended in a vehicle) at doses of 5 and 10 mg/kg, respectively; groups Control and PCM – with the vehicle. PCM was injected intraperitoneally (1.0 g/kg) on day 7. At the end of the experiment, serum and liver samples were prepared. PCM caused a severe liver damage confirmed by histopathological, immunohistochemical and biochemical indices. Compared to PCM group, in F5+PCM and F10+PCM groups, the hepatic necrosis, steatosis, ballooning degeneration, inflammation and expression of NF-κB were significantly reduced. Fustin treatment resulted in a significant reduction of serum activities of alanine aminotransferase and gamma-glutamyl transferase to levels that did not differ from the control values. The present study demonstrated a hepatoprotective effect of the flavonoid fustin in a rat model of acute paracetamol-induced toxicity.

OUTCOME OF AZITHROMYCIN AND MONOSODIUM GLUTAMATE ON HISTOLOGIC AND BIOCHEMICAL ALTERATIONS IN RATS’ LIVER

Background: Monosodium glutamate (MSG), a commonly used flavouring, mediated hepatotoxic and pro-inflammatory responses. Azithromycin (AZT), an antibiotic with anti-inflammatory activity, may be co-consumed with MSG to present unknown outcomes on the liver, a major organ for the detoxification of xenobiotics. Aim: This study evaluated the effect of AZT and MSG on histologic and biochemical changes in rats’ liver. Methods: Thirty rats in five groups were for seven successive days orally exposed to groups 1, (distilled water 1 mL Kg−1), 2, (MSG 8000 mg/kg), 3, overdose AZT, OAZT (AZT 412.5 mg Kg−1), 4, therapeutic concentration AZT, TAZT, (AZT 82.5mg Kg−1), and 5, (TAZT 82.5 mg Kg−1 + MSG 8000 mg Kg−1). Liver function markers in therats’ serum and liver tissue, and changes in the liver histologic were assessed by acceptable protocols. The mean of numeric data were tested for significance at p value less than 0.05 by analysis of variance (ANOVA). Results: MSG treatment significantly (p&lt;0.05) increased hepatic and serum alanine aminotransferase activity (ALT), aspartate aminotransferase activity (AST), alkaline phosphatase activity (ALP), total bilirubin concentration (T-BIL), and direct bilirubin concentration (D-BIL) but decreased albumin concentration (ALB) compared to control and others. TAZT treatment caused a significant (p&lt;0.05) decrease in these effects unlike MSG and OATZ treatments while TAZT + MSG co-treatment significantly (p&lt;0.05) reversed these effects compared to MSG-treated rats. Rats’ liver sections for rats in groups 2 and 3 showed severe hepatocellular degeneration and necrosis compared to others while those in group 4 (TAZT) showed the normal hepatic histo-architecture comparable to those in group 1 (control). Those in group 5 showed marked cellular swelling and leukocytic infiltration in only the centrilobular areas, suggesting active restorative responses. Conclusion: Thus, TAZT significantly mitigated the compromised histologic and biochemical integrities of liver function due to MSG treatment in rats via probable normalization of their enzymatic and non-enzymatic indicators of liver function. This suggests that TAZT could be useful in managing histologic and biochemical malfunction of rats’ liver due to MSG assault. Peer Review History: Received: 12 October 2023; Revised: 9 November; Accepted: 13 December, Available online: 15 January 2024 Academic Editor: Dr. Marwa A. A. Fayed, University of Sadat City, Egypt, maafayed@gmail.com Received file: Reviewer's Comments: Average Peer review marks at initial stage: 6.0/10 Average Peer review marks at publication stage: 7.0/10 Reviewers: Idoko Alexander, Caritas University, Enugu, Nigeria, idokoalexander1@gmail.com Dr. Dennis Amaechi, MrsFoluBabade Mini Estate, Flat 5 by Old Soldiers Quarter, Sabongari/Bwari, Abuja- Federal Capital Territory, Nigeria. amaechitoexcel@yahoo.com

Effects of quercetin and hydroxytyrosol supplementation in a high-fat diet on growth, lipid metabolism, and mitochondrial function in spotted seabass (Lateolabrax maculatus)

Endoplasmic reticulum (ER) stress and mitochondrial impairment commonly occur during the progression of fatty liver disease. There is a close connection and crosstalk between mitochondria and ER. The potential positive influence of mitigating ER stress (ERS) and mitochondrial damage in the context of preventing and treating fatty liver was explored in spotted seabass (Lateolabrax maculatus) as a susceptible model to fatty liver. A normal-fat diet (11% fat, NFD) and a high-fat diet (17% fat, HFD) were formulated and three additional diets were prepared by supplementation of quercetin (QUE) (0.1%), hydroxytyrosol (HT) (0.02%) or their combination (0.1% QUE + 0.02% HT) to the HFD (HFD + QUE HFD + HT and HFD + QUE + HT diets).Three replicate groups of fish (25 ± 0.02 g) were fed the test diets to visual satiety for 8 weeks. The results revealed the deterioration of growth, feed intake and feed utilization in HFD group compared to the NFD group whereas QUE and HT application improved their values and the optimum results were achieved for the HFD + QUE + HT group. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, and both serum and hepatic triglyceride (TG), total cholesterol (T-CHO) and non-esterified free fatty acids (NEFA) concentrations were enhanced in HFD group, and their values decreased by QUE and HT, particularly their combined supplementation. The results of oil red O staining exhibited a remarkable reduction in number of lipid droplets in the liver of fish from HFD + QUE + HT group compared to the HFD group. Whole-body and muscle fat contents and abdominal fat index decreased by QUE and HT application. Expression of lipid metabolism related genes (srebp-1c, fas, acc) were down-regulated by QUE and HT treatment. Co-supplementation of QUE and HT down-regulated the expression of ERS-related genes (grp78, chop, perk, atf6, ire1), improved ER ultrastructure, and enhanced the coupling between mitochondria and ER. Moreover, expression of genes associated with hepatic mitochondrial biogenesis (pgc1-α, pgc1-β, nrf1) and mitophagy (pink1, atg5, mul1) was up-regulated in HFD + QUE, HFD + HT and HFD + QUE + HT groups. These data suggest that combined supplementation of QUE and HT in HFD for spotted seabass can improve growth and feed utilization, reduce hepatic damage and fat accumulation, and alleviate HFD induced ERS and mitochondrial dysfunction.

Melhora dos parâmetros clínicos e laboratoriais em um cão com hepatite idiopática crônica após transplante de células mesenquimais alogênicas derivadas da medula óssea - relato de caso

ABSTRACT Chronic hepatitis (CH) is characterized by the replacement of hepatocytes for fibrotic tissue after injury, and treatment is not curative. Stem cell therapy has shown potential to reduce liver fibrosis. This report describes the management of a dog with CH with a mesenchymal cell-based approach. A 13-year old dog was presented with weight loss, vomiting, diarrhea, and lethargy. She was previously diagnosed with CH. Blood analysis showed hypoalbuminemia, increased serum activities of alanine aminotransferase (ALT) and alkaline phosphatase (ALP), and anemia. Three 2.5x106 bone marrow-derived mesenchymal cells transplantations were performed. After the first transplantation, the owner reported an improvement in clinical signs. Biochemistry evidenced a reduction in ALP activity. After the second administration, serum biochemistry showed a decrease in serum ALT and ALP activities, which kept falling after the third transplantation. There was an increase in albumin and total plasmatic proteins concentration. After six months, the dog came back for control and further improvement in clinical signs, new decrease in ALT activity and a mild increase in ALP concentration was observed. Increase in total and plasmatic protein were also observed. Stem cell-based therapy may be considered a promising alternative for liver diseases. It was safe and showed efficacy in this report.

The influence of breed's difference on the hemogram and biochemistry profile of goats raised in Libya during winter.

In Libya, goats are considered as one of the most important livestock in which there are many breeds of goats such as Kurdi, Hegazi, Cyprus, Shami, and Mahali. A little hematological and biochemical information is known on these goat breeds raised in Libya. The main purpose was to verify the effect of breed variations on the hematological and biochemical parameters of goat breeds raised in Libya. The blood samples were collected in the winter season from 70 clinically healthy animals of different breeds for hematology and biochemical analysis. Regarding the effect of breeds on blood hematology, significantly higher number (p < 0.01) of Mid cells were found in Hegazi (3.12 ± 1.30 × 103/µl) and Cyprus (2.41 ± 1.69 × 103/µl) when compared to other goat's breeds including Kurdi (2.28 ± 0.95 × 103/µl), Shami (1.90 ± 0.84 × 103/µl), and Mahali (1.37 ± 0.88 × 103/µl). Moreover, the percentage of Mid cells was highest in Hegazi (22.34% ± 9.40%), 11.40% ± 4.34%), followed by Kurdi (17.71% ± 8.16%), Cyprus (15.84% ± 8.33%), Shami (13.38% ± 5.76%), and lowest in Mahali (11.40% ± 4.34%). There are significant differences (p < 0. 01) in hemoglobin (Hb), red blood cells (RBCs), hematocrit (HCT), mean corpuscular hemoglobin (MCH), red cell width distribution-coefficient of variation (RDW-CV, %), and red cell distribution width-standard deviation (RDW-SD, fl) values among all different breeds of Libyan goats. The results of biochemistry displayed significant changes among the studied goats' breeds, where the highest serum alanine aminotransferase (ALT, U/L) activity was observed in Cyprus (17.81 ± 7.95) and Shami (17.27 ± 1.15) compared with Hegazi (15.31 ± 6.13) and Mahali (14.60 ± 0.46), while Kurdi breed (11.68 ± 7.95) showed the lowest ALT activity. Moreover, significant differences (p < 0.01) in serum lactate dehydrogenase (LDH, U/l), total and direct bilirubin, glucose (GLU), creatinine, lipid profile, and electrolyte levels were recorded among different breeds used in this study. On the other hand, non-significant variations (p >0. 05) are reported in aspartate aminotransferase (U/l), alkaline phosphatase (U/l), total protein (g/dl), albumin (g/dl), urea and magnesium (Mg, mg/dl) levels. These results showed a significant difference between some blood parameters of goat breeds raised in Libya. This could aid veterinarians in interpreting laboratory data properly in order to improve the management and conservation of those breeds.

Evaluation of the Optimum Dietary Arachidonic Acid Level and Its Essentiality for Black Seabream (Acanthopagrus schlegelii): Based on Growth and Lipid Metabolism.

The aim of this study was to investigate how dietary arachidonic acid (ARA) level affects growth performance and lipid metabolism in juvenile black seabream (Acanthopagrus schlegelii). A feeding trial was conducted for 8 weeks, during which the fish (0.99 ± 0.10 g) were fed six isonitrogenous and isolipidic diets with varying ARA levels of 0.1%, 0.59%, 1.04%, 1.42%, 1.94%, and 2.42%. Fish fed the diet with 1.42% ARA had significantly higher weight gain (WG) and specific growth rate (SGR) than the other groups (p < 0.05), except for the ARA1.04. As the ARA level increased, the liver and muscle effectively accumulated n-6 polyunsaturated fatty acids (n-6 PUFAs; p < 0.05). However, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and n-3 PUFA contents of liver and muscle significantly decreased by increasing dietary ARA level (p < 0.05). Results of liver histology showed dramatically increased vacuolar fat droplets leading to hepatic fat pathological changes in fish fed diets with ARA levels of 1.94% and 2.42% (p < 0.05). Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities increased with increasing dietary ARA level which was accompanied with elevated liver lipid content (p < 0.05). Consistently, triglyceride (TG) and nonesterified fatty acid (NEFA) concentrations of serum and liver, and serum cholesterol (CHO) concentration increased (p < 0.05). As the level of dietary ARA increased, the indicators of lipid metabolism such as sirtuin 1 (sirt1) and peroxisome proliferator-activated receptor α (pparα) also increased (p < 0.05). However, after reaching their peak in ARA1.04 group, the level of these indicators declined (p < 0.05). The same trend was observed for the expression of genes related to the downstream pathways. While the mRNA levels of sterol regulatory element-binding protein-1 (srebp-1) and its downstream genes were markedly increased with the increase of dietary ARA level (p < 0.05). In conclusion, these data suggested that the optimum dietary ARA requirement of A. schlegelii is 1.03% of diet based on the WG. The study revealed that a diet containing 1.04% ARA can activate the expression levels of sirt1 and pparα leading to promoted lipolysis. However, dietary ARA levels of ≥1.42% induced lipid accumulation in the liver, as they suppressed the mRNA levels of sirt1 and pparα, while elevating the expression level of genes related to lipogenesis.