Hepatic Malondialdehyde Levels Research Articles

Curcumin alleviates zearalenone-induced liver injury in mice by scavenging reactive oxygen species and inhibiting mitochondrial apoptosis pathway

Curcumin (CUR) is a compound extracted from turmeric that has a variety of functions including antioxidant and anti-inflammatory. As an estrogen-like mycotoxin, zearalenone (ZEN) not only attacks the reproductive system, but also has toxic effects on the liver. However, whether CUR can alleviate ZEN-induced liver injury remains unclear. This paper aims to investigate the protective effect of CUR against ZEN-induced liver injury in mice and explore the molecular mechanism involved. BALB/c mice were randomly divided into control (CON) group, CUR group (200 mg/kg b. w. CUR), ZEN group (40 mg/kg b. w. ZEN) and CUR+ZEN group (200 mg/kg b. w. CUR+40 mg/kg b. w. ZEN). 28 d after ZEN exposure and CUR treatment, blood and liver samples were collected for subsequent testing. The results showed that CUR reversed ZEN-induced hepatocyte swelling and necrosis in mice. It significantly reduced the serum alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in mice (p < 0.05). In addition, CUR significantly reduced hepatic ROS, malondialdehyde, hydrogen peroxide and apoptosis levels in mice (p < 0.05). Quantitative RT-PCR and Western blot results showed that CUR significantly reduced the expression of Bax and Caspase3, and reversed the increase of Nrf2, HO-1 and NQO1 expression in the liver of mice induced by ZEN (p < 0.05). In conclusion, CUR alleviated ZEN-induced liver injury in mice by scavenging ROS and inhibiting the mitochondrial apoptotic pathway.

Effect of an Airbag-selective Portal Vein Blood Arrester on the Liver after Hepatectomy: A New Technique for Selective Clamping of the Portal Vein.

A novel technique was explored using an airbag-selective portal vein blood arrester that circumvents the need for an intraoperative assessment of anatomical variations in patients with complex intrahepatic space-occupying lesions. Rabbits undergoing hepatectomy were randomly assigned to 4 groups: intermittent portal triad clamping (PTC), intermittent portal vein clamping (PVC), intermittent portal vein blocker with an airbag-selective portal vein blood arrester (APC), and without portal blood occlusion (control). Hepatic ischemia and reperfusion injury were assessed by measuring the 7-day survival rate, blood loss, liver function, hepatic pathology, hepatic inflammatory cytokine infiltration, hepatic malondialdehyde levels, and proliferating cell nuclear antigen levels. Liver damage was substantially reduced in the APC and PVC groups. The APC animals exhibited transaminase levels similar to or less oxidative stress damage and inflammatory hepatocellular injury compared to those exhibited by the PVC animals. Bleeding was significantly higher in the control group than in the other groups. The APC group had less bleeding than the PVC group because of the avoidance of portal vein skeletonization during hepatectomy. Thus, more operative time was saved in the APC group than in the PVC group. Moreover, the total 7-day survival rate in the APC group was higher than that in the PTC group. Airbag-selective portal vein blood arresters may help protect against hepatic ischemia and reperfusion injury in rabbits undergoing partial hepatectomy. This technique may also help prevent liver damage in patients requiring hepatectomy.

Prevotella and succinate treatments altered gut microbiota, increased laying performance, and suppressed hepatic lipid accumulation in laying hens

BackgroundThis work aimed to investigate the potential benefits of administering Prevotella and its primary metabolite succinate on performance, hepatic lipid accumulation and gut microbiota in laying hens.ResultsOne hundred and fifty 58-week-old Hyline Brown laying hens, with laying rate below 80% and plasma triglyceride (TG) exceeding 5 mmol/L, were used in this study. The hens were randomly allocated into 5 groups and subjected to one of the following treatments: fed with a basal diet (negative control, NC), oral gavage of 3 mL/hen saline every other day (positive control, PC), gavage of 3 mL/hen Prevotella melaninogenica (107 CFU/mL, PM) or 3 mL/hen Prevotella copri (107 CFU/mL, P. copri) every other day, and basal diet supplemented with 0.25% sodium succinate (Succinate). The results showed that PM and P. copri treatments significantly improved laying rate compared to the PC (P < 0.05). The amount of lipid droplet was notably decreased by PM, P. copri, and Succinate treatments at week 4 and decreased by P. copri at week 8 (P < 0.05). Correspondingly, the plasma TG level in Succinate group was lower than that of PC (P < 0.05). Hepatic TG content, however, was not significantly influenced at week 4 and 8 (P > 0.05). PM treatment increased (P < 0.05) the mRNA levels of genes PGC-1β and APB-5B at week 4, and ACC and CPT-1 at week 8. The results indicated enhanced antioxidant activities at week 8, as evidenced by reduced hepatic malondialdehyde (MDA) level and improved antioxidant enzymes activities in PM and Succinate groups (P < 0.05). Supplementing with Prevotella or succinate can alter the cecal microbiota. Specifically, the abundance of Prevotella in the Succinate group was significantly higher than that in the other 4 groups at the family and genus levels (P < 0.05).ConclusionsOral intake of Prevotella and dietary supplementation of succinate can ameliorate lipid metabolism of laying hens. The beneficial effect of Prevotella is consistent across different species. The finding highlights that succinate, the primary metabolite of Prevotella, represents a more feasible feed additive for alleviating fatty liver in laying hens.

Evening Primrose Oil Enriched with Gamma Linolenic Acid and D/L-Alpha Tocopherol Acetate Attenuated Carbon Tetrachloride-Induced Hepatic Injury Model in Male Rats via TNF-α, IL1 β and IL6 pathway.

The modulatory role of primrose oil (PO) supplementation enriched with γ-linolenic acid and D/L-alpha tocopherol acetate against a carbon tetrachloride (CCl4)-induced liver damage model was assessed in this study. Twenty male albino rats were divided into four groups. The control group received corn oil orally. The PO group received 10 mg/kg P O orally. The CCl4 group received 2 mL/kg CCl4 orally and PO/CCl4 group; received PO and 2 mL/kg CCl4 orally. The relative liver weight was recorded. Serum liver enzymes, hepatic malondialdehyde (MDA), hepatic reduced glutathione (GSH) and the expression of hepatic tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL1β), and interleukin 6 (IL6) were assessed. The binding affinities of γ-linolenic acid and D/L-alpha tocopherol constituents with IL1β, IL6 and TNF-α were investigated using molecular docking simulations. Histopathological and electron microscopic examinations of the liver were performed. The results indicated that CCl4 elevated serum liver enzyme and hepatic MDA levels, whereas GSH levels were diminished. The upregulation of IL1β, IL6, and TNF-α gene expressions were induced by CCl4 treatment. PO/CCl4 treated group showed amelioration of hepatic injury biomarkers and oxidative stress. Restoration of histopathological and ultrastructural alterations while downregulation the gene expressions of TNF-α, IL1 β and IL6 were observed. In conclusion, evening primrose oil enriched with γ-linolenic acid and D/L-alpha tocopherol acetate elicited a potential amelioration of CCl4-induced hepatic toxicity.

Low-dose Potassium bromate enhances ischemia-reperfusion-induced gastric ulcer healing in Thyroidectomised Rats.

Gastric ulcer healing is impaired in both hypothyroid and hyperthyroid conditions. Thyroid hormones regulate growth, energy metabolism and mitochondrial oxidative metabolism. Xenobiotics have been documented to negatively impact the thyroid gland at high doses but the redox and cellular interactions at low doses during wound healing process remains unclear. Potassium bromate has been documented to be toxic at high doses but there is dearth of information on its activities at a low dose in varied thyroid states which was evaluated in this study. 60 male Wistar rats (g, n=10) were randomised into 2 conditions: Normal, ulcerated untreated, ulcerated treated with 12.5mg/kg p.o KBrO3 and thyroidectomised groups: thyroidectomised ulcerated, thyroidectomised ulcer treated with KBrO3 and thyroidectomised treated with thyroxine (100µg/kg) Total thyroidectomy was used to model hypothyroidism, and ischaemia-reperfusion-induced gastric ulcers were monitored for healing. Daily body weights, Levels of thyroxine, Gastric mucin content, redox and sodium pump activity were examined alongside other markers of hepatic and haematological toxicity by days 3 and 7 post ulceration. Data were analysed using descriptive statistics and ANOVA α 0.05. The bromate-exposed hypothyroid rats showed increased gastric ulcer healing potential with reduced gastric epithelial oedema and inflammation; hepatic steatosis, and periportal inflammation. Haematological variables and markers of hepatic functions were normal. There were reduced levels of gastric and hepatic malondialdehyde levels. Thyroxine and potassium bromate treatment resolved the redox and cellular toxicity possibly via increasing catalase and sulfhydryl levels and increased Na+ K+ pump activity. We conclude that potassium bromate enhanced gastric ulcer healing in hypothyroid state, similar to thyroxine treatment.

The Hepatoprotective Effect of Omega-7 Against Paracetamol-Induced Hepatotoxicity in Male Rats

Abstract Paracetamol toxicity, whether accidental or not is a worldwide issue that leads to hepatotoxicity, acute liver failure, as well as irreversible liver injury requiring liver transplantation. Omega-7 is a monounsaturated fatty acid with a number of beneficial properties. The aim of the present study was to assess the potential protective role of omega-7 fatty acid against hepatotoxicity induced by paracetamol in male rats. Thirty male Rats were separated into five groups (six rats in each group) and received the following treatment: group 1 received liquid paraffin orally via gavage tube for seven days successively, group 2 received liquid paraffin orally via gavage tube for seven days successively, and on day eight, rats received a single intraperitoneal injection of paracetamol (500 mg/kg/day), group 3 received omega-7 (300 mg/kg/day) orally via gavage tube for seven days successively, group 4 received omega-7 (100 mg/kg/day) orally via gavage tube for seven days successively, and on day eight, rats received a single intraperitoneal injection of paracetamol (500 mg/kg/day), group 5 received omega-7 (300 mg/kg/day) orally via gavage tube for seven days successively, and on day eight, rats received a single intraperitoneal injection of paracetamol (500 mg/kg/day). On day nine, rats have been sacrificed by cervical dislocation and liver homogenate samples were collected for analysis. This study showed that there was a significant decrease in hepatic superoxide dismutase, catalase, glutathione-peroxidase and glutathione levels, accompanied with significant increase in hepatic malondialdehyde level in paracetamol group compared to the negative control group. However, administration of omega-7 resulted in significant increase in hepatic superoxide dismutase, catalase and glutathione levels and significant decrease in hepatic malondialdehyde level compared to paracetamol group. In conclusion, omega-7 has a protective effect on paracetamol-induced hepatotoxicity in rats. Keywords: Antioxidant, Hepatotoxicity, Omega-7, Oxidative stress, Paracetamol.

Hydrogen gas alleviates acute ethanol-induced hepatotoxicity in mice via modulating TLR4/9 innate immune signaling and pyroptosis

Alcoholic liver disease (ALD), which is induced by chronic heavy alcohol consumption, accompanies complicated pathological mechanisms, including oxidative stress, inflammation, cell death, epigenetic changes and acetaldehyde-mediated toxicity. Hydrogen (H2) is the lightest gas with multiple biological effects such as high selective anti-oxidation, anti-inflammation and anti-apoptosis. However, the dose effects and innate immune mechanisms of intraperitoneal injection of H2 on ALD are limited. Here, we used acute ethanol-induced hepatotoxicity mice models to estimate the actions of intraperitoneal injection of H2 on ALD. The effects of H2 on acute ethanol-induced liver damage were examined by hepatic oil red O staining, quantitative PCR (qPCR) for lipid metabolic genes, hepatic triglyceride (TG) and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Hepatic mitochondrial superoxide (MitoSOX), 3-nitrotyrosine (3-NT), malondialdehyde (MDA), and glutathione (GSH) levels were examined to evaluate oxidative stress. Immunoblot, and immunofluorescence staining were used to further confirm the innate immune molecular targets of H2. Our results showed that intraperitoneal injection of H2 improved acute ethanol-induced liver injury in mice in a dose dependent manner, as indicated by decreasing serum ALT and AST levels, hepatic TG levels, and increasing lipid export genes (Mttp and Apob) mRNA levels and reducing fatty acid uptake gene (CD36) mRNA levels. Mechanistically, H2 inhibited hepatic oxidative stress as indicated by reducing reactive oxygen species (ROS), 3-NT, and MDA levels in the liver, while increasing hepatic GSH levels; inhibited the overactived TLR4/9-NF-κB-TNF-α/IL-1β/IL-18 innate immune signaling; suppressed the canonical Caspase-1-GSDMD pyroptosis signaling, and the non-canonical pyroptosis signaling, such as Caspase-11-GSDMD, Caspase-8-GSDMD and Caspase-3-GSDME signaling. Therefore, our study highlights that intraperitoneal injection of H2 may represent a novel therapeutic and safe strategy for ALD via modulating oxidative stress, innate immunity and pyroptosis.

Dietary effects of microalga Tetraselmis suecica on growth, antioxidant-immune activity, inflammation cytokines,and resistance of Nile tilapia fingerlings to Aeromonas sobria infection.

The dietary effects of the green microalga Tetraselmis suecica (TS) on the growth, digestive enzymes, immune and antioxidant responses, genes expression,and disease resistance of Nile tilapia (Oreochromis niloticus) fingerlings were investigated. This microalga was mixed with the diet'ingredients at doses of 0.0 (the control), 5, 10, 15,and 20 g/kg diet and then fed to fish daily for 84 days. After the feeding trial, fish were experimentally challenged with Aeromonas sobria, infection and fish mortalities were recorded for another 10days. Dietary TS significantly (p < 0.05) enhanced growth, digestive enzymes activities,and blood proteins, particularly at the level of 15 g/kg diet. Feeding the fish on 15 TS/kg feed exhibited highest mRNA expressions of GH and IGF-1 genes as well as SOD, CAT,and GPx genes compared to other TS groups. Moreover, highest levels of hepatic antioxidant and immune indices were found in the treatment of 15 g TS/kg feed. Significant downregulation of IL-1β and IL-8 genes expression and significant upregulation of IL-10 gene expression were observed in TS-fed fish, principally in fish groups fed on 15-20 g TS/kg feed. Conversely, hepatic malondialdehyde levels, blood glucose,and the activities of transaminases (ALT and AST) were significantly (p < 0.05) decreased in fish fed with 15-20 g TS/kg diet. Serum bactericidal activity against A. sobria was significantly higher in TS-fed fish groups, and its highest levels were found in treatments of 15-20 g/kg diet. Of interest, the survival rates of fish groups fed diets with 10-20 g TS/kg feed were higher after the challenge with A. sobria infection than the control group. Accordingly, we can conclude that supplementing fish diets with a 15 g TS/kg diet enhanced the growth, antioxidant and immune activities,and resistance of Nile tilapia fingerlings to possible A. sobria infection.

The Hepatic Antisteatosis Effect of Xanthohumol in High-Fat Diet-Fed Rats Entails Activation of AMPK as a Possible Protective Mechanism.

Obesity is the leading cause of non-alcoholic fatty liver disease by provoking hyperglycemia, hyperlipidemia, insulin resistance, oxidative stress, and inflammation. Low activity of AMP-activated protein kinase (AMPK) is linked to obesity, liver injury, and NAFLD. This study involves examining if the anti-steatosis effect of Xanthohumol (XH) in high-fat diet (HFD)-fed rats involves the regulation of AMPK. Adult male rats were divided into five groups (n = 8 each) as control (3.85 kcal/g); XH (control diet + 20 mg/kg), HFD (4.73 kcl/g), HFD + XH (20 mg/kg), and HFD + XH (30 mg/kg) + compound c (cc) (0.2 mg/kg). All treatments were conducted for 12 weeks. Treatment with XH attenuated the gain in body weight, fat pads, fasting glucose, and insulin in HFD rats. It also lowered serum leptin and free fatty acids (FFAs) and improved glucose and insulin tolerances in these rats. It also attenuated the increase in serum livers of liver marker enzymes and reduced serum and hepatic levels of triglycerides (TGs), cholesterol (CHOL), FFAs, as well as serum levels of low-density lipoproteins cholesterol (LDL-c) oxidized LDL-c. XH also reduced hepatic levels of malondialdehyde (MDA), nuclear accumulation of NF-κB, and the levels of tumor necrosis-factor-α (TNF-α) and interleukin-6 (IL-6) while stimulating the nuclear levels of Nrf2 and total levels of glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) in these HFD-fed rats. At the molecular levels, XH increased hepatic mRNA expression and phosphorylation of AMPK (Thr72) and reduced the expression of lipogenic genes SREBP1c and ACC-1. In concomitance, XH reduced hepatic liver droplet accumulation, reduced the number of apoptotic nuclei, and improved the structures of nuclei, mitochondria, and rough endoplasmic reticulum. Co-treatment with CC, an AMPK inhibitor, completely abolished all these effects of XH. In conclusion, XH attenuates obesity and HFD-mediated hepatic steatosis by activating hepatic AMPK.

Benefits of Chronic Administration of a Carbohydrate-Free Diet on Biochemical and Morphometric Parameters in a Rat Model of Diet-Induced Metabolic Syndrome.

Carbohydrate intake restriction positively affects markers related to metabolic syndrome (MS). However, the effects of long-term carbohydrate-free diets (CFD) have yet to be studied. The main objective of this study was to report the effects on biochemical and morphometric parameters in a rat model of MS. Male Wistar rats were initially divided into two groups: the standard diet group (SD, n = 20); and the MS group (n = 30) fed a high-glucose diet. Ten animals from each group were sacrificed after 20 weeks on their respective diets to verify MS development. The remaining MS animals were divided into two subgroups: one continued with the MS diet (n = 10); and the other transitioned to a carbohydrate-free diet (MS + CFD group, n = 10) for 20 more weeks. At week 40, parameters, including glucose, insulin, lipid profile, ketone bodies, C-reactive protein (CRP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, creatinine, liver and muscle glycogen, and serum, hepatic, renal, and pancreatic malondialdehyde (MDA) levels were assessed. Transitioning to CFD resulted in decreased caloric intake and body weight, with normalized parameters including MDA, insulin, lipid profile, ALT, liver glycogen, creatinine, and CRP levels. This shift effectively reversed the MS-induced alterations, except for glycemia and uremia, likely influenced by the diet's high protein content stimulating gluconeogenesis. This research underscores the potential benefits of long-term carbohydrate restriction in mitigating MS-related markers.

Baseline and recurrent exposure to the standard dose of artemisinin-based combination therapies (ACTs) induces oxidative stress and liver damage in mice (BALB/c)

BackgroundIn malaria-endemic countries, repeated intake of artemisinin-based combination therapies (ACTs) is rampant and driven by drug resistance, improper usage, and easy accessibility. Stress effects and potential liver toxicity due to the frequent therapeutic use of ACTs have not been extensively studied. Here, we investigated the effects of repeated treatment with standard doses of the commonly used ACTs artemether/lumefantrine (A/L) and artesunate-amodiaquine (A/A) on oxidative stress and liver function markers in male mice (BALB/c).MethodsForty Five mice were divided into three groups: control, A/L, and A/A. The drugs were administered three days in a row per week, and the regimen was repeated every two weeks for a total of six cycles. The levels of oxidative stress and liver function markers were measured in both plasma and liver tissue after initial (baseline) and repeated exposures for the second, third, and sixth cycles.ResultsExposure to A/L or A/A caused a significant (p < 0.001) increase in plasma malondialdehyde (MDA) levels after the first and repeated exposure periods. However, Hepatic MDA levels increased significantly (p < 0.01) only after the sixth exposure to A/A. Following either single or repeated exposure to A/L or A/A, plasma and liver glutathione peroxidase (GPx) and catalase (CAT) activities, plasma aspartate and alanine transaminase, alkaline phosphatase activity, and bilirubin levels increased, whereas total plasma protein levels decreased significantly (p < 0.001). Varying degrees of hepatocyte degeneration and blood vessel congestion were observed in liver tissues after a single or repeated treatment period.ConclusionIrrespective of single or repeated exposure to therapeutic doses of A/L or A/A, plasma oxidative stress and liver damage were observed. However, long-term repeated A/A exposure can led to hepatic stress. Compensatory processes involving GPx and CAT activities may help reduce the observed stress.

Novel herbal beverage ameliorates exercise-induced fatigue in mice by modulating oxidative stress and reshaping the gut microbiota

With the demands of enhancing exercise performance, dietary supplements are widely used in the health management of athletes and who engaged in strenuous exercise. Based on the list of edible and medicinal materials approved by China's National Health Commission, we composed an herbal beverage formula named SRB, initially identified its chemical composition, and clarified its preventive effect on exercise-induced fatigue (EIF). SRB supplementation for four weeks significantly enhanced exercise performance in mice, as reflected by exhaustive swimming test and treadmill exercise test. In mice that underwent one single exhaustive exercise, SRB supplementation markedly reduced metabolite accumulation, increased glycogen contents in the liver and muscle, promoted anti-oxidative enzyme activities, decreased hepatic malondialdehyde (MDA) level, and protected quadriceps femoris morphology, respectively. Anti-oxidative stress effect of SRB may be relevant with increased gene expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2) and antioxidant response element (ARE)-dependent gene. Moreover, SRB treatment altered gut bacterial community structure, e.g., increased the relative abundance of short-chain fatty acids (SCFAs)-producing bacteria and decreased the relative abundance of sulfate-reducing bacteria. Altogether, we identified SRB as an effective anti-EIF dietary supplement with prebiotic effects in C57BL/6 mice.

Partial Replacement of Fishmeal with Poultry By-Product Meal in Diets for Coho Salmon (Oncorhynchus kisutch) Post-Smolts.

The present study evaluated the effects of partially substituting fish meal (FM) with poultry by-product meal (PBPM) on the growth, muscle composition, and tissue biochemical parameters of coho salmon (Oncorhynchus kisutch) post-smolts. Five isonitrogenous (7.45% nitrogen) and isoenergetic (18.61 MJ/kg gross energy) experimental diets were made by substituting 0%, 10%, 20%, 40%, and 60% FM protein with PBPM protein, which were designated accordingly as PBPM0 (the control), PBPM10, PBPM20, PBPM40, and PBPM60, respectively. Each diet was fed to triplicates of ten post-smolts (initial individual body weight, 180.13 ± 1.32 g) in three floating cages three times daily (6:50, 11:50, and 16:50) to apparent satiation for 84 days. Both specific growth rate (SGR) and protein efficiency ratio did not differ significantly (p > 0.05) among the control, PBPM10, and PBPM20 groups, which were remarkably (p < 0.05) higher than those of the PBPM40 and PBPM60 groups. Feed conversion ratio varied inversely with SGR. The PBPM replacement had no remarkable effects on the morphological indices and proximal muscle components. The control and PBPM10 groups led to significantly higher muscle contents of leucine, lysine, and methionine than groups of higher PBPM inclusion. The groups of PBPM40 and PBPM60 obtained significantly (p < 0.05) higher serum alanine aminotransferase and aspartate aminotransferase activities than the control and low PBPM inclusion groups. The control group had significantly higher albumin and total cholesterol contents than the groups with PBPM inclusion. The control group had significantly higher triglycerides content than the PBPM60 group. The PBPM60 group had significantly lower contents of high-density lipoprotein, low-density lipoprotein, and total protein than the control and PBPM10 groups. The high PBPM replacement level up to 40% and 60% had adverse effects on hepatic malondialdehyde levels. The catalase and superoxide dismutase activities were not affected by low PBPM inclusion, but significantly decreased in high-PBPM-inclusion groups. Based on broken-line regression analysis of SGR and PER, the optimum dietary PBPM replacing level was evaluated to be 16.63-17.50% of FM protein for coho salmon post-smolts.

Sanguisorba officinalis L. Ameliorates Hepatic Steatosis and Fibrosis by Modulating Oxidative Stress, Fatty Acid Oxidation, and Gut Microbiota in CDAHFD-Induced Mice.

Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver diseases and encompasses non-alcoholic steatosis, steatohepatitis, and fibrosis. Sanguisorba officinalis L. (SO) roots have traditionally been used for their antioxidant properties and have beneficial effects on metabolic disorders, including diabetes and obesity. However, its effects on hepatic steatosis and fibrosis remain unclear. In this study, we explored the effects of a 95% ethanolic SO extract (SOEE) on NAFLD and fibrosis in vivo and in vitro. The SOEE was orally administered to C57BL/6J mice fed a choline-deficient, L-amino-acid-defined, high-fat diet for 10 weeks. The SOEE inhibited hepatic steatosis by modulating hepatic malondialdehyde levels and the expression of oxidative stress-associated genes, regulating fatty-acid-oxidation-related genes, and inhibiting the expression of genes that are responsible for fibrosis. The SOEE suppressed the deposition of extracellular matrix hydroxyproline and mRNA expression of fibrosis-associated genes. The SOEE decreased the expression of fibrosis-related genes in vitro by inhibiting SMAD2/3 phosphorylation. Furthermore, the SOEE restored the gut microbial diversity and modulated specific bacterial genera associated with NAFLD and fibrosis. This study suggests that SOEE might be the potential candidate for inhibiting hepatic steatosis and fibrosis by modulating oxidative stress, fatty acid oxidation, and gut microbiota composition.

Effect of dietary supplementation of betaine and organic minerals on growth performance, serum biochemical parameters, nutrients digestibility, and growth-related genes in broilers under heat stress

Global warming and climate changes have a detrimental impact on poultry production, causing substantial economic losses. This study investigated the effects of incorporating dietary betaine (BT) and organic minerals (OMs) on broilers’ performance as well as their potential to mitigate the negative impacts of heat stress (HS). Six hundred 1-day-old Ross 308 chicks were randomly allocated to 12 experimental treatments with 5 replicates of 10 birds each (5 male + 5 female). The birds were provided with diets containing BT (0 and 2,000 ppm) and OMs (0, 250, and 500 ppm), either individually or in combination, under both thermoneutral and HS-inducing temperatures. The HS conditions involved exposing the birds to cyclic periods of elevated temperature (35°C ± 2°C) for 6 h daily, from 10:00 am to 4:00 pm, starting from d 10 and continuing until d 35. The exposure to HS deteriorated birds’ growth performance; however, dietary BT and OMs inclusion improved the growth performance parameters bringing them close to normal levels. Carcass traits were not affected by dietary supplementation of BT, OMs, HS, or their interaction. Interestingly, while HS led to increased (P < 0.05) levels of total cholesterol, LDL-cholesterol, and hepatic malondialdehyde (MDA), these adverse effects were mitigated (P < 0.05) by the addition of BT and OMs. Moreover, dietary BT supplementation led to elevated serum total protein and globulin concentrations. Cyclic HS did not alter Mn, Zn, and Cu contents in the pectoral muscle. However, the incorporation of OMs at both levels increased concentrations of these minerals. Notably, the combination of 500 ppm OMs and 2,000 ppm BT improved Mn, Zn, Cu, and Fe digestibility, which has been compromised under HS conditions. Cyclic HS upregulated gene expression of interleukin-1β, heat shock protein 70, and Toll-like receptor-4 while downregulated the expression of claudin-1, uncoupling protein, growth hormone receptor, superoxide dismutase 1, glutathione peroxidase 1 and insulin-like growth factor 1. The aforementioned gene expressions were reversed by the combination of higher dietary levels of BT and OMs. In conclusion, the dietary supplementation of 500 ppm OMs along with 2,000 ppm BT yielded significant improvements in growth performance and mineral digestibility among broiler chickens, regardless of thermal conditions. Moreover, this combination effectively restored the expression of growth-related genes even under heat-stress conditions.

Lippia javanica (Burm. F.) Herbal Tea: Modulation of Hepatoprotective Effects in Chang Liver Cells via Mitigation of Redox Imbalance and Modulation of Perturbed Metabolic Activities.

Introduction: Hepatic oxidative injury is one of the pathological mechanisms that significantly contributes to the development of several liver diseases. In the present study, the hepatoprotective effect of Lippia javanica herbal tea was investigated in Fe2+- mediated hepatic oxidative injury. Methods: Using an in vitro experimental approach, hepatic oxidative injury was induced by co-incubating 7mM FeSO4 with Chang liver cells that have been pre-incubated with or without different concentrations (15-240μg/mL) of L. javanica infusion. Gallic acid and ascorbic acid served as the standard antioxidants. Results: The infusion displayed a reducing antioxidant activity in ferric-reducing antioxidant power (FRAP) assay and a potent scavenging activity on 2,2-diphenyl-2- picrylhydrazyl (DPPH) radical. Pretreatment with L. javanica infusion significantly elevated the levels of reduced glutathione and non-protein thiol, and the activities of superoxide dismutase (SOD) and catalase, with concomitant decrease in hepatic malondialdehyde levels, acetylcholinesterase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glycogen phosphorylase and lipase activities. The infusion showed the presence of phytoconstituents such as phenolic compounds, tannins, phenolic glycosides and terpenoids when subjected to liquid chromatography-mass spectrometry analysis. Molecular docking revealed a strong binding affinity of dihydroroseoside and obacunone with both SOD and catalase compared to other phytoconstituents. Conclusion: These results portray a potent antioxidant and hepatoprotective effect of L. javanica, which may support the local usage of the herbal tea as a prospective therapeutic agent for oxidative stress-related liver diseases.

Icariin Supplementation Suppresses the Markers of Ferroptosis and Attenuates the Progression of Nonalcoholic Steatohepatitis in Mice Fed a Methionine Choline-Deficient Diet.

Icariin, a flavonoid abundant in the herb Epimedium, exhibits anti-ferroptotic activity. However, its impact on nonalcoholic steatohepatitis (NASH) development remains unclear. This study aimed to investigate the potential role of icariin in mitigating methionine choline-deficient (MCD) diet-induced NASH in C57BL/6J mice. The results showed that icariin treatment significantly reduced serum alanine aminotrasferase and aspartate aminotransferase activities while improving steatosis, inflammation, ballooning, and fibrosis in the liver tissues of mice fed the MCD diet. These improvements were accompanied by a substantial reduction in the hepatic iron contents and levels of malondialdehyde and 4-hydroxynonenal, as well as an increase in the activities of catalase and superoxide dismutase. Notably, icariin treatment suppressed the hepatic protein levels of ferroptosis markers such as acyl-CoA synthetase long-chain family member 4 and arachidonate 12-lipoxygenase, which were induced by the MCD diet. Furthermore, transmission electron microscopy confirmed the restoration of morphological changes in the mitochondria, a hallmark characteristic of ferroptosis, by icariin. Additionally, icariin treatment significantly increased the protein levels of Nrf2, a cystine/glutamate transporter (xCT), and glutathione peroxidase 4 (GPX4). In conclusion, our study suggests that icariin has the potential to attenuate NASH, possibly by suppressing ferroptosis via the Nrf2-xCT/GPX4 pathway.

Sophoricoside attenuates autoimmune‑mediated liver injury through the regulation of oxidative stress and the NF‑κB signaling pathway.

The prevalence of autoimmune hepatitis (AIH) is increasing, yet specific pharmacotherapies remain to be explored. The present study aimed to investigate the effects of sophoricoside (SOP), a bioactive component of medical herbs, on AIH and to elucidate the underlying mechanisms. Bioinformatic approaches were used to predict the potential targets and underlying regulatory mechanisms of SOP on AIH. The effects of SOP on AIH were evaluated by determining the expression levels of inflammatory cytokines, histological liver injury and hepatic fibrosis in an improved chronic cytochrome P450 2D6 (CYP2D6)‑AIH mouse model and in a model of concanavalin‑A (ConA)‑induced acute immune‑mediated liver injury. The antioxidant activity of SOP was detected in invivo and invitro experiments. The selected signal targeted by SOP in AIH was further confirmed using western blot analysis and immunofluorescence staining. The results of bioinformatic analysis revealed that the targets of SOP in AIH were related to oxidative stress and the NF‑κB gene set. The NF‑κB transcription factor family is a key player that controls both innate and adaptive immunity. The activation of the NF‑κB signaling pathway is often associated with autoimmune disorders. In the animal experiments, SOP attenuated CYP2D6/ConA‑induced AIH, as evidenced by a significant reduction in the levels of hepatic enzymes in serum, inflammatory cytokine expression and histological lesions in the liver. The oxidative response in AIH was also significantly inhibited by SOP, as evidenced by a decrease in the levels of hepatic malondialdehyde, and elevations in the total antioxidant capacity and glutathione peroxidase levels. The results of the invivo and invitro experiments revealed that SOP significantly reduced the enhanced expression and nuclear translocation of phosphorylated p65 NF‑κB in the livers of mice with AIH and in lipopolysaccharide‑stimulated AML12 cells. On the whole, the present study demonstrates the protective role of SOP in AIH, which may be mediated by limiting the oxidative response and the activation of the NF‑κB signaling pathway in hepatocytes.

Liposomal Glutathione Supplementation Mitigates Extrapulmonary Tuberculosis in the Liver and Spleen.

Extrapulmonary tuberculosis (EPTB) accounts for a fifth of all Mycobacterium tuberculosis (M. tb) infections worldwide. The rise of multidrug resistance in M. tb alongside the hepatotoxicity associated with antibiotics presents challenges in managing and treating tuberculosis (TB), thereby prompting a need for new therapeutic approaches. Administration of liposomal glutathione (L-GSH) has previously been shown to lower oxidative stress, enhance a granulomatous response, and reduce the burden of M. tb in the lungs of M. tb-infected mice. However, the effects of L-GSH supplementation during active EPTB in the liver and spleen have yet to be explored. In this study, we evaluated hepatic glutathione (GSH) and malondialdehyde (MDA) levels, and the cytokine profiles of untreated and L-GSH-treated M. tb-infected wild type (WT) mice. Additionally, the hepatic and splenic M. tb burdens and tissue pathologies were also assessed. L-GSH supplementation increased total hepatic levels and reduced GSH. A decrease in the levels of MDA, oxidized GSH, and interleukin (IL)-6 was also detected following L-GSH treatment. Furthermore, L-GSH supplementation was observed to increase interferon-gamma (IFN-γ) and tumor necrosis factor (TNF)-α production and decrease IL-10 levels. M. tb survival was significantly reduced in the liver and spleen following L-GSH supplementation. L-GSH treatment also provided a host-protective effect in the liver and spleen of M. tb-infected mice. Overall, L-GSH supplementation elevated the levels of total and reduced forms of GSH in the liver and reduced the burden of M. tb by decreasing oxidative stress, enhancing the production of immunosupportive cytokines, and reducing the levels of immunosuppressive cytokines. These observed benefits highlight the potential of L-GSH supplementation during active EPTB and provide insight into novel therapeutic interventions against M. tb infections.

The Gut Microbiota Contributes to Systemic Responses and Liver Injury in Gut-Derived Sepsis.

The gut microbiota, as a major source of opportunistic pathogens, poses a great threat to systemic infection, whereas the role of the gut microbiota in sepsis is underestimated. Here, we aimed to explore the effects of different gut microbiota patterns (namely, enterotypes) in cecal ligation and puncture (CLP)-induced murine sepsis. To achieve this purpose, we built four kinds of enterotypes by exposing mice to different types of antibiotics (azithromycin, amoxicillin, metronidazole, and levofloxacin). The results showed that antibiotic exposure induced different enterotypes, which, in turn, led to varying levels of systemic inflammation in septic mice, with amoxicillin-associated enterotypes exhibiting the most severe inflammation, followed by metronidazole, azithromycin, and levofloxacin. Specifically, the amoxicillin-associated enterotype was characterized by an abundance of intestinal opportunistic pathogens, including Enterobacteriaceae, Sutterellaceae, and Morganellaceae. This enterotype played a significant role in promoting the pathogenic potential of the gut microbiota, ultimately contributing to the development of severe systemic inflammation. Furthermore, the amoxicillin-associated enterotype exaggerated the sepsis-related liver injury, as evidenced by higher levels of alanine aminotransferase, aspartate transaminase, and hepatic malondialdehyde. The results of the RNA sequencing and the fecal suspension intraperitoneal injection sepsis model indicated that the amoxicillin-associated enterotype provoked acute hepatic immune responses and led to more significant metabolic compensation in the event of sepsis. Collectively, we concluded that the gut microbiota was one crucial factor for heterogeneity in sepsis, where the modulated gut microbiota likely prevented or reduced the serious consequences of sepsis, at least in gut-derived sepsis.