Hepatic Superoxide Dismutase Research Articles

Golden bile powder prevents drunkenness and alcohol-induced liver injury in mice via the gut microbiota and metabolic modulation

BackgroundDrunkenness and alcoholic liver disease (ALD) are critical public health issues associated with significant morbidity and mortality due to chronic overconsumption of alcohol. Traditional remedies, such as bear bile powder, have been historically acclaimed for their hepatoprotective properties. This study assessed the efficacy of a biotransformed bear bile powder known as golden bile powder (GBP) in alleviating alcohol-induced drunkenness and ALD.MethodsA murine model was engineered to simulate alcohol drunkenness and acute hepatic injury through the administration of a 50% ethanol solution. Intervention with GBP and its effects on alcohol-related symptoms were scrutinized, by employing an integrative approach that encompasses serum metabolomics, network medicine, and gut microbiota profiling to elucidate the protective mechanisms of GBP.ResultsGBP administration significantly delayed the onset of drunkenness and decreased the duration of ethanol-induced inebriation in mice. Enhanced liver cell recovery was indicated by increased hepatic aldehyde dehydrogenase levels and superoxide dismutase activity, along with significant decreases in the serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, triglyceride, and total cholesterol levels (P < 0.05). These biochemical alterations suggest diminished hepatic damage and enhanced lipid homeostasis. Microbiota analysis via 16S rDNA sequencing revealed significant changes in gut microbial diversity and composition following alcohol exposure, and these changes were effectively reversed by GBP treatment. Metabolomic analyses demonstrated that GBP normalized the alcohol-induced perturbations in phospholipids, fatty acids, and bile acids. Correlation assessments linked distinct microbial genera to serum bile acid profiles, indicating that the protective efficacy of GBP may be attributable to modulatory effects on metabolism and the gut microbiota composition. Network medicine insights suggest the prominence of two active agents in GBP as critical for addressing drunkenness and ALD.ConclusionGBP is a potent intervention for alcohol-induced pathology and offers hepatoprotective benefits, at least in part, through the modulation of the gut microbiota and related metabolic cascades.

Selenomethionine Supplementation Mitigates Liver Dysfunction, Oxidative Injury and Apoptosis through Enhancing Antioxidant Capacity and Inhibiting JNK MAPK Pathway in Piglets Fed Deoxynivalenol-Contaminated Diets.

This research evaluated the impacts of selenomethionine (Se-Met) on hepatic functions, oxidative stress, mitochondrial function, and apoptosis of piglets fed deoxynivalenol (DON)-contaminated diets. Twenty-four piglets were allocated four dietary treatments (n = 6) in a 28-day feeding trial. The four treatments included the control group, which received 0.3 mg/kg of Se (as Se-Met) without DON treatment, and the DON treatment groups received 0, 0.3, or 0.5 mg/kg Se as Se-Met. A dietary addition of 0.5 mg/kg Se improved liver pathology and reduced serum aspartate aminotransferase and lactate dehydrogenase levels in piglets fed DON-contaminated diets. Furthermore, 0.5 mg/kg Se mitigated the oxidative stress and apoptosis of piglets fed DON-contaminated diets, as indicated by the decreased reactive oxygen species level, and the down-regulated mRNA levels of NRF-1, Bax, and CASP9 in the liver. Importantly, 0.5 mg/kg Se enhanced the hepatic antioxidant capacity, as evidenced by increased hepatic total antioxidant capacity, catalase, glutathione peroxidase, and total superoxide dismutase activities, as well as the up-regulated mRNA levels of Nrf2, Gclm, NQO1, SOD1, and GPX1 in the liver. Moreover, 0.5 mg/kg Se down-regulated the p-JNK protein level in the liver of piglets fed DON-contaminated diets. Collectively, Se-Met supplementation mitigated liver dysfunction, oxidative injury, and apoptosis through enhancing antioxidant capacity and inhibiting the JNK MAPK pathway in piglets fed DON-contaminated diets.

Effects of partial substitution of enzymatic hydrolysate of poultry by-product meal for fishmeal on the growth performance, hepatic health, antioxidant capacity, and immunity of juvenile largemouth bass (Micropterus salmoides)

A 95-day experiment was conducted to evaluate the feasibility of partially substituting fishmeal with enzymatic hydrolysate of poultry by-product meal (EHPB) as feed for juvenile largemouth bass (Micropterus salmoides). Five diets (EHPB0, EHPB3, EHPB6, EHPB9, and EHPB12) of fishmeal were 45% (0% EHPB, the control group), 41% (3.1% EHPB), 37% (6.2% EHPB), 33% (9.3% EHPB), and 29% (12.4% EHPB), respectively. The initial mean weigh of largemouth bass was 22.35 ± 0.08 g. There were no significant differences in growth performance among all EHPB groups compared with the control (P > 0.05). The growth performance of EHPB3 was significantly better than that of EHPB12 (P < 0.05). EHPB0 had the highest crude protein and moisture content (P < 0.05). Plasma total cholesterol (TC), triglyceride (TG), and lactate dehydrogenase (LDH) were significantly lower under EHPB9 and EHPB12 than the control (P < 0.05). Low-density lipoprotein (LDL) and alkaline phosphatase (ALP) were significantly lower under EHPB12 than the control (P < 0.05). High-density lipoprotein (HDL), total protein (TP), and albumin (ALB) did not significantly differ among diets (P > 0.05). Hepatic glutathione (GSH) content and glutathione peroxidase (GPx) activity were highest for the control (EHPB0). The hepatic superoxide dismutase (SOD) and catalase (CAT) activity levels were significantly lower for all treatments than the control except for EHPB3 (P < 0.05). Keap1 in the Nrf2 pathway was significantly upregulated and cat was significantly downregulated under all treatments compared with the control except for EHPB3 (P < 0.05). Jnk1/2, nf-κb, il-8/10, tnf-α, and traf2 were significantly upregulated under EHPB6 relative to the control (P < 0.05). The diet containing 29% basal fishmeal (12.4% EHPB) did not affect the growth performance of juvenile largemouth bass. However, the optimal levels of the genes related to antioxidant performance and immune function were attained under 3.1% EHPB (41% fishmeal).

Evaluation of the Antioxidant Effects of Berberine against Sodium Nitriteinduced Oxidative Injury in the Rat Liver.

Berberine is a plant derived alkaloid present in many plants that may has ameliorating potential influences against inflammatory and oxidative conditions. The current study aimed to evaluate the possible protective activity of berberine and investigate its probable mechanisms against sodium nitrite toxicity in the liver. Forty male rats were divided into five groups. Group one, as the control group, received normal saline, group two received berberine (100 mg.kg-1), and group three received sodium nitrite (80 mg.kg-1). Groups four and five received berberine in doses of 50 and 100 mg.kg-1, respectively, and sodium nitrite (80 mg.kg-1) was given orally. All the doses were orally administrated for two months. Then, at the end of the 60th day, the animals were sacrificed, and the liver homogenate was prepared. For evaluating the oxidative injury the levels of albumin (ALB) and aspartate transaminase (AST) in the serum and oxidative stress parameters in the liver were analyzed. Treatment of rats with sodium nitrite considerably increased the levels of serum AST and liver superoxide anion and significantly reduced the levels of serum ALB, hepatic superoxide dismutase (SOD), total antioxidant capacity (TAC), and catalase (CAT) activity in the liver tissue. Berberine treatment could ameliorate all these parameters dose dependently. Berberine at a dose of 100 mg.kg-1 had the best impact and reached the values of oxidative stress parameters to the normal level. Our results demonstrated that berberine in a dose-dependent manner offered protection against sodium nitrite-induced oxidative injury in liver, which possibly reflects the antioxidant abilities of this alkaloid.

Ameliorating the impairment of glucose utilization in a high-fat diet-induced obesity model through the consumption of Tucum-do-Cerrado (Bactris Setosa Mart.).

We evaluated the effect of Tucum-do-Cerrado on glucose metabolism homeostasis and its relationship with redox-inflammatory responses in a high-fat (HF) diet-induced obesity model. The HF diet increased energy intake, feed efficiency, body weight, muscle and hepatic glycogen, insulin, homeostatic model assessment of insulin resistance (HOMA IR) and beta (β)-cell function, and gut catalase (CAT) activity, and decreased food intake, hepatic glutathione reductase (GR), glutathione peroxidase (GPX), glutathione S-transferase (GST), and superoxide dismutase (SOD) activities, hepatic phosphoenolpyruvate carboxykinase 1 (Pck1), and intestinal solute carrier family 5 member 1 (Slc5a1) mRNA levels compared with the control diet. However, the HF diet with Tucum-do-Cerrado decreased hepatic glycogen, and increased hepatic GR activity, hepatic Slc2a2 mRNA levels and serum Tnfa compared with the HF diet. Tucum-do-Cerrado decreased muscle glycogen, intestinal CAT and GPX activities, muscle PFK-1 and HK activities, and increased hepatic protein (CARB) and intestinal lipid (MDA) oxidation, hepatic GST activity, serum antioxidant potential, hepatic phosphofructokinase-1 (PFK-1) activity, intestinal solute carrier family 2 member 2 (Slc2a2), tumor necrosis factor (Tnf), interleukin-1 beta (Il1b), muscle protein kinase AMP-activated alpha 1 (Prkaa1), solute carrier family 2 member 2 (Slc2a2) mRNA levels, and serum interleukin-6 (IL-6) levels, regardless of diet type. Tucum-do-Cerrado consumption may ameliorate impaired glucose utilization in a HF diet-induced obesity model by increasing liver and muscle glucose uptake and oxidation. These data suggest that Tucum-do-Cerrado consumption improves muscle glucose oxidation in non-obese and obese rats. This response may be related to the improvement in the total antioxidant capacity of rats.

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.

Effects of exogenous bile acids (BAs) on growth, lipid profile, digestive enzymes, and immune responses of thinlip mullet, Liza ramada

An eight-week trial was designed to explore the dietary effects of commercially purchased exogenous bile acids (BAs) on growth, whole-body composition, lipid profile, intestinal digestive enzymes, liver function enzymes, oxidative stress biomarkers, and serum immunity of thinlip mullet, Liza ramada. Four triplicate groups (10.50 ± 0.05 g) were fed four soybean meal (SBM)-based diets supplied with several BAs levels at 0 (control), 50, 130, or 350 mg/kg feed. Results indicated that the growth was significantly increased in groups fed BAs-based diets, especially at 130 mg/kg feed. The body composition analysis showed that feeding fish on diets supplied with BAs up to 130 mg/kg decreased moisture (%) alongside increased crude protein (%). However, the body composition of fish fed a diet with 350 mg BAs/kg had the lowest moisture (%) and the highest crude protein (%). Moreover, there were significant increases in the intestinal (protease, α-amylase, and lipase) enzyme activities in the groups supplied with BAs up to 130 mg BAs/kg. Liver function enzymes (aspartate aminotransferase and alanine aminotransferase enzyme activities) were significantly decreased in BAs-supplemented groups compared to those fed the BAs-free group. On the other hand, the control group had higher total cholesterol, triglycerides, and low-density lipoprotein alongside the lower high-density lipoprotein than BAs-supplemented groups, especially at 350 mg BAs/kg feed. BAs significantly decreased hepatic malondialdehyde concentrations and increased the activity of hepatic catalase, superoxide dismutase, and total antioxidant capacity compared with those reared on the control diet. Serum lysozyme, respiratory burst, and alternative complement activities were significantly increased in BAs-supplied groups, particularly in the group supplied with 130 mg BAs/kg compared to those fed on the control diet. Accordingly, our findings recommend that including 130 mg BAs/kg in an SBM-based diet enhanced the growth, digestive enzyme activities, and liver functions, alleviated oxidative stress, boosted serum immunity, and lowered lipid metabolites in thinlip mullet. These findings will be beneficial for improving the quality of feed prepared for feeding mullets and an effective alternative strategy to support mullet farming.

Effect of flavanone rich lemon peel extract on feed intake and growth of Labeo rohita (Hamilton, 1822) fingerlings reared at low temperature recirculatory aquaculture system

An 8-week experiment was conducted to study the effect of dietary lemon peel extract on feed intake and growth of Labeo rohita (rohu) fingerlings reared at low temperature (18 ± 1 °C). As a preliminary study, the antioxidant activity of lemon peel extract from water and ethanol was performed using DPPH, TPC, and FRAP assays, and found that the antioxidant activity in all three assays was higher for ethanol extract (25 mg L−1). Five isonitrogenous (300.0 g kg-1) and isocaloric (16.10 MJ kg−1) practical diets with varying levels of ethanol lemon peel extract viz, control (0.0 g kg−1 lemon peel extract), LPE2.5 (2.5 g kg−1 lemon peel extract), LPE5.0 (5.0 g kg−1 lemon peel extract), LPE10 (10.0 g kg−1 lemon peel extract), LPE20 (20.0 g kg−1 lemon peel extract) were prepared. The average initial body weight of the experimental animal was 10.30 ± 0.5 g, and the experiment was conducted in a low temperature (18 ± 1 °C) recirculatory aquaculture system (RAS) with a flow rate of 1.5 L min−1. The results showed that dietary lemon peel extract (LPE) supplementation increased the feed intake and growth performance in rohu fingerlings (p < 0.05). Fish fed with 5.0 g kg−1 LPE exhibited the best growth rates, thermal growth coefficient (TGC), and feed conversion (p < 0.05); however, TGC was similar in LPE5.0 and LPE10 fed groups (p > 0.05). Protease and aminotransferase enzyme activities positively correlated with growth rates (p < 0.05). Dietary LPE supplementation significantly augmented the hepatic malate dehydrogenase, citrate synthase, superoxide dismutase, and catalase activities (p < 0.05). From these results, it can be concluded that dietary supplementation of lemon peel extract at 5–10 g kg−1 level had positive effects on feed intake and metabolic activities of rohu reared at low temperature.

Protective effects of chlorogenic acid against cyclophosphamide induced liver injury in mice

ABSTRACT We investigated possible protective effects of chlorogenic acid (CGA) against cyclophosphamide (CP) induced hepatic injury in mice. We measured aminotransferase alanine transaminase (ALT) and aspartate transaminase (AST) levels in the serum. We assayed catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in hepatic tissue. We assessed expression of nuclear transcription factor 2 (Nrf2) and Kelch sample related protein-1 (keap1) proteins in hepatic tissues using immunohistochemistry. The relative mRNA expression levels of heme oxygenase-1 (HO-1), NADH quinone oxidoreductase 1 (NQO1), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Hematoxylin & eosin staining was used to assess liver histopathology. We found that administration of CGA prior to induction of injury by CP decreased serum ALT, AST and MDA expressions in hepatic tissue, while CAT, SOD, GSH and GSH-Px concentrations were increased. We found that hepatocytes of animals administered CGA gradually returned to normal morphology. CGA increased the protein expression of Nrf2 in murine hepatic tissue. Administration of CGA up-regulated mRNA expression levels of HO-1, NQO1, TNF-α and IL-6 in hepatic tissue. CGA exhibited a marked protective effect on CP induced liver injury in mice.

Protecting deleterious effects of high stocking density of Nile tilapia, Oreochromis niloticus using dietary microalgae Golenkinia longispicula: Growth, immune-oxidative markers and associated gene expression

Microalgae have been capably used as additive to boost the fish performance and welfare because of their unique nutritional properties and functional bioactive compounds. Thus, factorial experimental design (4 × 2) investigated the effect of dietary dried Golenkinia. longispicula (0.0, 5, 10 and 15 g kg−1 diets) supplementation used in Nile tilapia, Oreochromis niloticus on growth, feed efficiency, hematological, biochemical parameters, antioxidant activity, immunity, and associated gene expression reared under two stoking densities 100 fish m3 (SD100) and 200 fish m3 (SD200). Fingerlings (initial weight of 3.29 ± 0.16 g) were randomly assigned into twenty-four fiberglass tanks (0.5 m3; 250 L volume of water) in triplicate for each treatment at two stocking density SD100 and SD200 for 90-days. Three times per day at 9:00 a.m., 11:00 a.m., and 2:00 p.m., four isonitrogenous (32.89 g kg−1 CP) and isocaloric (17.86 MJ kg−1 GE) diets were given to experimental fish. After 90 days of the feeding trial, the results demonstrated final body weight (FBW), weight gain (WG), specific growth rate (SGR), and feed conversion ratio (FCR) were significantly (P < 0.05) improved by a diet contained 15 g kg−1 G. longispicula reared under SD100. The highest hematocrit (Hct), hemoglobin (Hb), red blood cells (RBCs) levels were detected in the fish-fed diet that had 15 g of G. longispicula kg−1 under SD100 or SD200. No significant differences (P < 0.05) were found in alanine amino transferase (ALT) and aspartate amino transferase (AST) among treatment groups. While adding G. longispicula at SD200 had a substantial (P < 0.05) impact on total protein (TP), Albumin, or growth hormone. The values of immunoglobulin M (IgM), complement component 4 (C4), complement component 3 (C3) and growth hormone (GH) was higher in fish fed a diet that included 15 g kg−1 G. longispicula kg−1 diet under SD100. The maximum activity of glutathione (GSH), glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase (CAT) was found in a fish-fed diet supplemented with 15 g G. longispicula kg−1 diet under SD100 (P < 0.05) as well as the related hepatic gene expression superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase (GPX). The malondialdehyde (MDA) value was lowest when fish were stocked at SD100 or SD200 and 10 g of G. longispicula kg−1 was added to their diet. Fish raised at SD100 or SD200 and fed diets containing 15 g kg−1 G. longispicula were substantially up-regulated the gene expression of the interleukin-1β (IL-1β) and interleukin-8 (IL-8) (P < 0.05). Based on these conclusions, adding G. longispicula up to 10 or 15 g kg−1 to a basal diet ameliorates and enhances growth performance, feed efficiency, immune responses, hepatic antioxidant enzyme, and related immune-antioxidant genes expression and imparts resistance to SD200 stress in Nile tilapia.

Gallic acid rescues uranyl acetate induced-hepatic dysfunction in rats by its antioxidant and cytoprotective potentials

BackgroundThe liver was identified as a primary target organ for the chemo-radiological effects of uranyl acetate (UA). Although the anti-oxidant and anti-apoptotic properties of gallic acid (GA) make it a promising phytochemical to resist its hazards, there is no available data in this area of research.MethodsTo address this issue, eighteen rats were randomly and equally divided into three groups. One group was received carboxymethyl cellulose (vehicle of GA) and kept as a control. The UA group was injected intraperitoneally with UA at a single dose of 5 mg/kg body weight. The third group (GA + UA group) was treated with GA orally at a dose of 100 mg/kg body weight for 14 days before UA exposure. UA was injected on the 15th day of the experiment in either the UA group or the GA + UA group. The biochemical, histological, and immunohistochemical findings in the GA + UA group were compared to both control and UA groups.ResultsThe results showed that UA exposure led to a range of adverse effects. These included elevated plasma levels of aspartate aminotransferase, lactate dehydrogenase, total protein, globulin, glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and very-low-density lipoprotein and decreased plasma levels of high-density lipoprotein cholesterol. The exposure also disrupted the redox balance, evident through decreased plasma total antioxidant capacity and hepatic nitric oxide, superoxide dismutase, reduced glutathione, glutathione-S-transferase, glutathione reductase, and glutathione peroxidase and increased hepatic oxidized glutathione and malondialdehyde. Plasma levels of albumin and alanine aminotransferase did not significantly change in all groups. Histopathological analysis revealed damage to liver tissue, characterized by deteriorations in tissue structure, excessive collagen accumulation, and depletion of glycogen. Furthermore, UA exposure up-regulated the immuno-expression of cleaved caspase-3 and down-regulated the immuno-expression of nuclear factor-erythroid-2-related factor 2 in hepatic tissues, indicating an induction of apoptosis and oxidative stress response. However, the pre-treatment with GA proved to be effective in mitigating these negative effects induced by UA exposure, except for the disturbances in the lipid profile.ConclusionsThe study suggests that GA has the potential to act as a protective agent against the adverse effects of UA exposure on the liver. Its ability to restore redox balance and inhibit apoptosis makes it a promising candidate for countering the harmful effects of chemo-radiological agents such as UA.

Insights into the interaction between stocking density and feeding rate in fish Megalobrama ambylcephala based on growth performance, innate immunity, antioxidant activity, and the GH-IGF1 axis

The interaction between stocking density and feeding rate was investigated in juvenile blunt snout bream (Megalobrama ambylcephala) (11.94 ± 0.04 g) based on growth performance and health status. A 2 × 4 factorial design was adopted, containing two stocking densities (10 and 20 fish/m3) and four feeding rates (3%, 4%, 5% and 6% body weight/day). After the 12-weeks feeding trial, high stocking density (20 fish/m3) significantly (P < 0.05) reduced weight gain rate (WGR), feed intake (FI), protein efficiency ratio (PER), nitrogen and energy retention efficiency (NRE and ERE), plasma immunoglobulin M (IgM) level, plasma lysozyme (LZM), myeloperoxidase (MPO) and alkaline phosphatase (AKP) activities, as well as hepatic superoxide dismutase (SOD) and catalase (CAT) activities, while the opposite was observed in feed conversion rate (FCR), condition factor (CF) and plasma complement 4 (C4) level. The highest feeding rate (6%) significantly (P < 0.05) increased WGR, FI, FCR, CF, the intraperitoneal fat ratio and the protein expression of growth hormone receptor, but significantly (P < 0.001) decreased PER, NRE and ERE. Moderate feeding rates (4%–5%) significantly (P < 0.05) increased body lipid and energy contents, the activities of SOD, CAT, glutathione peroxidase, LZM, MPO, AKP and acid phosphatase, the levels of complement 3 and 4 (C3 and C4), and the transcriptions and protein levels of growth hormone and insulin-like growth factor 1, while the opposite was noted in the malondialdehyde content. Furthermore, an interactive effect between stocking density and feeding rate was also noted in WGR, FI, plasma ACP, AKP and MPO activities, and liver malondialdehyde content. In summary, stocking density and feeding rate interactively affect the growth performance and health status of blunt snout bream. The optimum feeding rate of this species increased when cultured under high-density conditions.

Stimulatory effects of seaweed Laminaria digitata polysaccharides additives on growth, immune-antioxidant potency and related genes induction in Rohu carp (Labeo rohita) during Flavobacterium columnare infection

Stimulatory effects of dietary supplementation of large brown alga, Laminaria digitata polysaccharides (LDPs) at doses of 0, 100, 200, and 300 mg/kg diets were assessed on growth, hemato-biochemical, and antioxidant-immune variables as well as related genes expression in Indian rohu carp (Labeo rohita) during Flavobacterium columnare infection. Fish growth indices were significantly (P < 0.05) influenced by dietary LDPs and bacterial infection but not their interaction. However, growth indices of rohu carp in normal unchallenged (NuC) increased pointedly at treatments of 200 or 300 mg/kg diets with no significant difference between them. In normal challenged bacterial (NbC) groups, highest fish growth was observed at the treatment of 300 mg LDPs/kg diets. Feed intake and FCR values were significantly (P < 0.05) affected by dietary LDPs, bacterial infection, and their interaction. The highest feed intake accompanied with lowest FCR value was observed in the treatment of 200 mg LDPs/kg diets. No mortality was seen in NuC groups but lowest fish survival was observed in NbC groups fed with 0.0 and 100 mg LDPs/kg diets. Highest values of white blood cell, total protein, albumin, and globulin found in NuC fish groups administrated with 200 or 300 mg/kg diets with no differences between them. Feeding NbC fish groups on 300 mg LDPs/kg diet recovered the adverse effects of bacterial infection. It is noted that levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH) were significantly (P < 0.05) affected by dietary LDPs, bacterial infection, and their interaction. The values of antioxidant indices were significantly (P < 0.05) higher in NuC fish groups received 200 or 300 mg LDPs/kg diets with no significant (P > 0.05) differences between them. In NbC fish groups, values of antioxidant indices were significantly (P < 0.05) lower that those in NuC fish groups. Malondialdehyde (MDA) was significantly influenced by dietary LDPs alone and its lowest values were observed in both NuC and NbC fish groups fed with 200 or 300 mg/kg diets with no differences between them. Phagocytic activity, alternate complement pathway, lysozyme, respiratory burst, peroxidase, complement C3, and immunoglobulin M values improved significantly (P < 0.05) in both NuC and NbC fish groups fed with 200 or 300 mg/kg diets with no differences between them. The mRNA manifestation of hepatic SOD, CAT, and GPx genes were significantly (P < 0.05) upregulated in both NuC fish groups fed on 200 and 300 mg LDPs/kg diets but feeding NbC fish on 300 mg LDPs/kg diets enhanced their mRNA expression. The HSP70, HSP90, TNF-α, IL-1β, and IL-8 mRNA expression in the NuC fish groups showed no significant (P > 0.05) differences due to dietary supplementation of LDPs to ruho carp, but their expressions were significantly (P < 0.05) higher in NbC fish groups; particularly at the treatment of 100 mg LDPs/kg diets. The mRNA expression of IL-10, IgM, hepcidin, and Mx1 genes were significantly (P < 0.05) upregulated in NuC fish group fed with 200 or 300 mg LDPs/kg diets. The bacterial infection downregulated their expressions but the dietary LDPs recovered the adverse effects of bacterial infection especially at 200 or 300 mg LDPs/kg diets. These results shown that the use of LDPs (200 or 300 mg/kg diets) has a valuable role in enhancing the growth, antioxidant-immune status, and inflammatory responses in rohu carp during F. columnare infection.

The implication of LPS/TLR4 and FXR receptors in hepatoprotective efficacy of indole-3-acetic acid and chenodeoxycholic acid

AimValproic acid (VPA) belongs to the first-generation antiepileptic drugs, yet its prolonged use can cause life-threatening liver damage. The importance of our study is to investigate the protective effect of indole-3-acetic acid (IAA), chenodeoxycholic acid (CDCA) and their combination on VPA-induced liver injury focusing on lipopolysaccharides (LPS)/toll-like receptor 4 (TLR4) pathway and farnesoid X receptor (FXR). MethodsThirty rats were randomly assigned into five groups, normal control group, VPA group received 500 mg/kg of VPA intraperitoneally. The remaining groups were orally treated with either 40 mg/kg of IAA, 90 mg/kg of CDCA, or a combination of both, along with VPA. All treatments were administered one hour after the administration of VPA for three weeks. Key findingsVPA group showed significant elevations in the liver weight/body weight ratio, serum aminotransferases, triglyceride, and total cholesterol levels. Hepatic glutathione (GSH) level and superoxide dismutase (SOD) activity were significantly decreased, while malondialdehyde (MDA) level, tumor necrosis factor-α (TNF-α), interleukin-1beta (IL-1β), lipopolysaccharide (LPS) and caspase 3 were significantly increased. Likewise, immunohistochemical analysis revealed that TLR4 expression was elevated, whereas FXR expression was downregulated in hepatocytes. IAA substantially ameliorated all previously altered parameters, whereas CDCA treatment showed a partial improvement compared to IAA. Surprisingly, combination therapy of IAA with CDCA showed an additive effect only in the hepatic expression of TLR4 and FXR proteins. SignificanceIAA could be a promising protective agent against VPA-induced liver injury.

Diets with soybean oil and l-carnitine alter lipid metabolism and improve the growth and reproduction of Rhamdia quelen females

This study aimed to evaluate the reproduction, growth, biochemical parameters of blood, hepatic and gonadal redox parameters, hepatic and gonadal histology, and lipid metabolism of silver catfish females (Rhamdia quelen) fed diets containing l-carnitine and different lipid sources. Females were fed for 223 days with eight (08) isoproteic (282 g of digestible protein kg of ration−1) and isoenergetic (13.34 MJ of digestible energy kg of ration−1) diets, containing 0.00, 0.15, 0.45, and 0.75 g l-carnitine kg−1 of feed, and soybean or marine fish oils. Feeding the females diets containing l-carnitine and the different oils resulted in an interactive effect (p < 0.05) that improved the growth and reproduction of the fish. Females fed soybean oil and 0.45 g l-carnitine kg−1 had the highest growth rates, the largest ovaries, and produced the most fertile oocytes, which resulted in the highest hatching rates. These females also showed higher levels of total cholesterol and high-density lipoprotein (HDL) cholesterol, and alterations in the levels of alanine aminotransferase in the blood, in addition to greater activity of hepatic superoxide dismutase and a greater amount of saturated fatty acids in the liver. The ovaries of these females also had the highest amount of docosahexaenoic fatty acid (DHA), highest amount of polyunsaturated fatty acids and fatty acids from the n-3 and n-6 series, and the lowest crude protein content. The interaction between l-carnitine and the lipid source of the diets promoted hepatic protection and regulated lipid metabolism and the fatty acid profile in the liver and ovaries of silver catfish females. The benefits of these interactions improved the growth and reproduction of females fed diets containing soybean oil and 0.45 g l-carnitine kg−1.

Hepatoprotective effects of Alpinia officinarum rhizome extract on cisplatin-induced hepatotoxicity in rats: A biochemical, histopathological and immunohistochemical study

BackgroundAlpinia officinarum is a member of the ginger family (Zingiberaceae), which is widely cultivated in Asia and traditionally used for its anti-inflammatory, antimicrobial, and antihyperlipidemic qualities. This study aimed to evaluate the effect of Alpinia officinarum rhizome extract (AORE) on cisplatin (CP)-induced hepatotoxicity in rats. MethodsForty-four male rats were divided into six groups including the control group, AORE control group, CP control group, and three groups of CP (7 mg/kg dose, on the 10th day) with AORE (at concentrations of 100, 200 and 400 mg/kg, daily for 14 days). After 14 days, the rats' livers were removed and their liver function was assessed using biochemical marker enzymes including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) activities and albumin, total protein, and total bilirubin (T. bilirubin). Oxidative stress was assessed by evaluating malondialdehyde concentration and hepatic superoxide dismutase activity, histopathological and immunohistochemical tests were also conducted. ResultsResults demonstrated that treatment with AORE reduced the toxicity in levels of the hepatic biomarkers in cp-induced groups. AORE treatment decreased oxidative stress and improved histopathological indexes. Furthermore, immunohistochemical (IHC) investigation showed the B-cell lymphoma 2 (Bcl-2) upsurging and p53 downregulating expression exhibiting the recovery following AORE administration. ConclusionThe founding suggested that AORE administration has positive biochemical, histopathological, and immunohistochemical impacts on the ameliorating of hepatotoxicity in CP-induced rats.

Carbon nanofibers caused oxidative stress and disrupted anti-predator responses in common spiny loach

Carbon nanofibers, recently recognized pollutants, have been heavily used among the nanomaterials in many industries. Due to the poor suspension-stability, carbon nanofibers tend to sediment at the bottom of waterbodies and hence can be consumed by the bottom-dwellers. The current investigation evaluates the impact of carbon nanofibers at concentrations between 0.1 and 10 mg L−1 on the common bottom dweller spiny loach Lepidocephalichthys thermalis inhabiting Indian rivers. Carbon nanofiber exposure elevated the activities of the hepatic antioxidant enzymes superoxide dismutase, catalase, peroxidase and glutathione S-transferase, as oxidative stress markers. The fish behaviour patterns were examined by testing the effect of carbon nanofibers on predator recognition ability using kairomones, conspecific alarm cues, and dietary cues. The carbon nanofiber-exposed fish showed a loss of predator-recognition abilities. The results collectively demonstrated the carbon nanofiber driven hepatic oxidative damage and impaired predator-recognition ability in L. thermalis. The investigation, first of its kind, highlights the toxic potential of the carbon nanofibers on benthic fishes.

Metformin alleviates sodium arsenite‐induced hepatotoxicity and glucose intolerance in mice by suppressing oxidative stress, inflammation, and apoptosis

BackgroundEpidemiological studies have shown that exposure to sodium arsenite (NaAsO2) causes diabetes and hepatotoxicity. Metformin (MET), an oral hypoglycemic agent, has long been used in diabetes therapy. In addition, MET has been shown to have hepatoprotective effects. In this study, we investigated the effects of MET on NaAsO2-induced hepatotoxicity and glucose intolerance in mice. MethodsMice were divided into four groups: Groups I and II received distilled water and NaAsO2 (10 mg/kg, p.o.) for five weeks, respectively. Groups III and IV were treated with NaAsO2 (10 mg/kg, p.o.) for three weeks, followed by MET (125 and 250 mg/kg, p.o.) for the last two weeks before NaAsO2. A glucose tolerance test was performed on day 35. The serum and tissue parameters were also evaluated. ResultsHistopathological examination revealed NaAsO2-induced liver and pancreatic damage. NaAsO2 caused hyperglycemia, glucose intolerance, and a significant increase in liver function enzymes. Administration of NaAsO2 significantly reduced hepatic superoxide dismutase, catalase, glutathione peroxidase, and total thiol levels and increased the content of reactive thiobarbituric acid substances. In addition, it led to an increase in liver nitric oxide levels and protein expression of tumor necrosis factor-α, nuclear factor kappa B, and cysteine-aspartic proteases-3. In contrast, treatment with MET (250 mg/kg) significantly improved NaAsO2-induced biochemical and histopathological changes. ConclusionOur findings suggest that the significant effects of MET against NaAsO2-induced hepatotoxicity and glucose intolerance may be exerted via the regulation of oxidative stress, followed by suppression of inflammation and apoptosis.

Erythropoietin Suppresses the Hepatic Fibrosis Caused by Thioacetamide: Role of the PI3K/Akt and TLR4 Signaling Pathways.

Erythropoietin (EPO) is recognized for its function in erythropoiesis; however, its potential antifibrotic effect against liver fibrosis remains unknown. This study examined whether EPO affects thioacetamide (TAA)-induced liver fibrosis by concentrating on the Toll-like receptor 4 (TLR4) cascade and the phosphatidylinositol 3-kinase (PI3K)/Akt pathway as possible pathways. Male Wistar rats were randomized into four groups, which included: the negative control group, the TAA group (intraperitoneal; TAA 100 mg/kg three times per week for 2 weeks), and EPO-treated groups (150 and 300 IU/kg, i.p.) for 2 weeks after TAA injections. EPO attenuated hepatic fibrosis in a dosage-dependent way, as manifested by the diminution in serum alanine aminotransferase and aspartate aminotransferase activities, as well as the increase in albumin level. EPO inhibited the increase in tissue levels of tumor necrosis factors-α, interleukin-1β, transforming growth factor-β1, and TLR4 and raised tissue levels of PI3K and p-PI3K. EPO antioxidant properties were demonstrated by restoring hepatic glutathione and superoxide dismutase by preventing the accumulation of hepatic malondialdehyde. Further, EPO increased the protein expression of PI3K and Akt and decreased TLR4 protein expression. Immunohistochemically, EPO treatment altered tissue histology and downregulated mitogen-activated protein kinase protein expression. Overall, the research suggested that EPO could prevent TAA-induced hepatic fibrosis through upregulating the PI3K/Akt signaling cascade and downregulation the TLR4 downstream axis.

Molecular mechanisms of hepatoprotective effect of tectorigenin against ANIT-induced cholestatic liver injury: Role of FXR and Nrf2 pathways.

Cholestatic liver injury is caused by toxic action or allergic reaction, resulting in abnormality of bile formation and excretion. Few effective therapies have become available for the treatment of cholestasis. Herein, we found that tectorigenin (TG), a natural isoflavone, showed definite protective effects on alpha-naphthylisothiocyanate (ANIT)-induced cholestatic liver injury, significantly reversing the abnormality of plasma alanine/aspartate aminotransferase, total/direct bilirubin and alkaline phosphatase, as well as hepatic reactive oxygen species, catalase and superoxide dismutase. Importantly, the targeted metabolomic determination found that BA homeostasis could be well maintained in TG-treated cholestatic mice, especially the levels of glycocholic acid, tauromuricholic acid, taurocholic acid, taurolithocholic acid, tauroursodeoxycholic acid and taurodeoxycholic acid. Overall, primary/secondary and amidated/unamidated bile acid (BA) levels were significantly altered upon ANIT stimulation but could be restored by TG intervention to certain extents. In addition, TG boosted the expression of farnesoid x receptor (FXR), which in turn upregulated multidrug resistance protein 2 (MRP2) and bile salt export pump (BSEP) to accelerate the excretion of BA. Meanwhile, TG enhanced the expression of Nrf2 and its upstream genes PI3K/Akt and downstream target genes HO-1, NQO1, GCLC and GCLM to strengthen the antioxidant capacity. Taken together, TG plays a vital role in maintaining BA homeostasis and ameliorating cholestatic liver injury through regulating FXR-mediated BA efflux and Nrf2-mediated antioxidative pathways.