Hepatic Superoxide Dismutase Activities Research Articles

Storage causes protein oxidation of soybean meal and affects antioxidant status, digestive performance and meat quality of broilers.

This study investigated the protein oxidation of soybean meal (SBM) stored in a warehouse and the effects of SBM on growth performance, antioxidant status, digestive performance, intestinal morphology, and breast muscle quality of broilers. In total, 160 one-day-old Arbor Acres Plus broilers (half male and half female) were randomly divided into two groups with ten replicates of eight birds each: The control group was served with a basal diet including SBM stored at -20°C (FSBM), and the experimental group was served with a basal diet including SBM stored in a warehouse at room temperature for 45 days (RSBM). Compared with FSBM, the protein carbonyl level in RSBM was increased, the free and total thiol levels and in vitro digestibility of protein were decreased. The RSBM decreased the serum glutathione (GSH) level and the hepatic total superoxide dismutase (T-SOD) activity at days 21 and 42 when compared with FSBM. Further, RSBM reduced the duodenal T-SOD activity, jejunal catalase (CAT), and T-SOD activities at day 21, and decreased the duodenal CAT and T-SOD activities, jejunal T-SOD activity, and ileal GSH level and T-SOD activity at days 21 and 42 when compared with FSBM. Besides, the trypsin activity and the ratio of villus height to crypt depth in small intestines of broilers at days 21 and 42 were reduced when fed with a RSBM-contained diet. Compared with FSBM, the 24-h drip loss, shear force, and 24- and 48-h cooking loss of breast muscle were increased of RSBM group, the opposite result was observed for muscle lightness at 48 h. Room temperature storage for 45 days led a protein oxidation and decreased in vitro digestibility in SBM, and fed RSBM impaired growth performance, antioxidant status, and meat quality, reduced trypsin activity, and affected the small intestine morphology in broilers.

Influence of dietary replacement of soybean meal with crawfish shell meals on the growth, skin coloration and muscle texture of Oujiang color common carp (Cyprinus carpio var. color)

An 8-week growth experiment was conducted to investigate the effects of different levels of crawfish shell meals (Procambarus clarkii, CSM) replacement of soybean meal (SM) on growth, feed utilization, antioxidant response, body color and muscle quality of Oujiang color common carp (3.0 ± 0.5g, Cyprinus carpio var. Color), and to assess the suitable range of CSM replacement of soybean meal and its effects on fish. Three isonitrogenous and isolipidic experimental diets were formulated to replace SM by equal proportion (1:1, w: w) of CSM at 0, 25, or 50% (designated as CSM0, CSM25, or CSM50, respectively). The results showed that weight gain (WG) as well as hepatic superoxide dismutase (SOD) activities were significantly (P < 0.05) higher in the CSM25group compared to the CSM0 group. In addition, there were no significant (P > 0.05) differences in growth performance, feed utilization, skin color, and muscle texture parameters between CSM50 and CSM0 groups, except for the overall ash content, which was significantly (P < 0.05) higher in CSM50 than CSM0 group. Therefore, it was feasible to replace 50% of SM with CSM in Oujiang color common carp diets without negative effects on serum biochemical indices, antioxidant and immune responses, skin color or muscle texture. These findings suggested that CSM could be a potential alternative protein source in diets of Oujiang color common carp.

Transcriptomic and physiological analyses reveal the response mechanism of the liver under acute ammonia stress in the Chinese soft-shelled turtle (Pelodiscus sinensis)

Greenhouse intensive aquaculture is a common culture mode for juvenile Chinese soft-shelled turtles (CSST). Under this culture mode, the juvenile CSST are vulnerable to the stress of high ammonia‑nitrogen levels in the water, resulting in a suboptimal health state that may lead to disease susceptibility. However, few studies have reported the response mechanism of the CSST in the ammonia‑nitrogen environment. In this study, we detected the lethal range concentration of non-ionic ammonia‑nitrogen in CSST and examined the impact of acute ammonia nitrogen exposure for durations of 0 h, 12 h, 24 h, 48 h, 96 h, and 144 h on the blood indices and liver function in CSST. The results show that the lethal concentration range of non-ionic ammonia‑nitrogen is 23.0 mg/mL to 70.5 mg/mL. In the blood, blood ammonia, urea nitrogen and aspartate aminotransferase activity increased significantly, suggesting that the high ammonia‑nitrogen environment caused hyperammonemia, increased urea synthesis and liver damage in the CSST. The impact of acute ammonia nitrogen on the liver function of the CSST was assessed through analysis of liver histopathology, antioxidant defense, ammonia metabolism pathway, and transcriptome data. The results showed that the hepatic cord structure within the liver tissue of the CSST was destroyed, with the presence of vacuoles and edema. In addition, hepatic superoxide dismutase (SOD) and catalase (CAT) enzyme activities and Malondialdehyde (MDA) content were significantly increased, and the mRNA expression levels of Mn-SOD, Cu/Zn-SOD, and CAT were significantly increased, suggesting that the hepatic antioxidant system was activated to resist the environmental stresses caused by ammonia‑nitrogen. Moreover, there was a significant increase in the enzyme activity and expression levels of glutamate dehydrogenase (GDH), and a significant decrease in the enzyme activity and no significant change in the expression levels of glutamine synthetase (GS), suggesting that NH4+ is synthesized from glutamate by GDH in the liver to enter the urea metabolic cycle, and that glutamine is not synthesized for storage. Analysis of transcriptome data revealed potential effects on energy metabolism and lipid metabolism in response to short-term (48 h) ammonia‑nitrogen stress. In contrast, prolonged (96 h) exposure to ammonia nitrogen stress may increase the susceptibility of CSST to pathogens, and trigger the tissue repair mechanisms in the liver. These findings provide new insights into the potential risks and hazards of ammonia‑nitrogen to CSST and provide a scientific foundation for managing water quality in CSST aquaculture.

Effects of Taurine and Enzymatic Cottonseed Protein Concentrate Supplementation in Low-Fishmeal Diet on Growth, Liver Antioxidant Capacity, and Intestinal Health of Golden Pompano (Trachinotus ovatus)

This study was conducted to investigate the impacts of the dietary addition of taurine and enzymatic cottonseed protein concentrate (ECPC) in low-fishmeal diet on the growth performance, plasma biochemical indices, hepatic antioxidant capacity, intestinal anti-inflammatory capacity, intestinal microflora, and muscle quality of golden pompano (Trachinotus ovatus). A total of three isonitrogenous diets were given to 225 golden pompanos (5.6 ± 0.14 g). They were randomly divided into nine cages (1.0 m × 1.0 m × 1.5 m; three cages per treatment) with equal stocking numbers of twenty-five fish per cage. The results indicated that the CSM-TC group significantly increased the growth performance of juvenile T. ovatus (p &lt; 0.05). The results indicated that compared with other groups, the addition of 1% ECPC and 0.25% taurine has been found to enhance the WGR (weight gain rate), SGR (specific growth rate), and CF (condition factor). Compared with other groups, the relative expressions of GH, GHR1, GHR2, IGF1, IGF2, and MyoG were significantly higher in fish fed with CSM-TC. The results showed that CSM-TC significantly increased the activities of alkaline phosphatase, complement 3, and complement 4 enzymes (p &lt; 0.05). The results showed that dietary CSM-TC increased the activities of hepatic superoxide dismutase and total antioxidant capacity enzymes. Compared with other groups, the hepatic relative expressions of Nrf2, HO-1, and GSH-Px were significantly higher in fish fed with CSM-TC. The results showed that dietary CSM-TC increased the activities of intestinal chymotrypsin, lipase, and α-amylase enzymes. A CSM-TC diet significantly increased the relative expressions of IL-10, ZO-1, Occludin, Claudin-3, and Claudin-15 (p &lt; 0.05). The results showed that CSM-C significantly increased the index of Ace and Chao1 (p &lt; 0.05). In conclusion, a high-fermented cottonseed meal diet can have detrimental effects on physiological health in golden pompano, while adding 1% ECPC and 0.25% taurine can improve hepatic and intestinal health via attenuating inflammation and oxidative stress.

Methanolic stem-bark extracts of Adansonia digitata modulates haematological and antioxidant parameters in streptozotocin-induced diabetic rats

Background and AimDiabetes mellitus is associated with haematological abnormalities and oxidative stress, contributing to disease progression and complications. Adansonia digitata, is a traditional medicinal plant well known for its potential therapeutic properties. This study investigates the effects of methanolic stem-bark extracts of Adansonia digitata on haematological and antioxidant status in streptozotocin-induced diabetic rats. Experimental ProcedureFourty-two wistar rats were distributed into 6 groups of 7 each. Group 1 served as normal control, group 2 to 6 animals were made diabetic by intraperitoneal administration of single dose of 50 mg kg-1 streptozotocin. Group 2 served as the negative control and did not receive treatment, group 3 served as the positive control and received 150 mg kg-1 metformin (Glucophage) (standard drug), while group 4, 5 and 6 received oral treatment of 100 mg kg-1, 200 mg kg-1 and 300 mg kg-1 of Adansonia digitata stem-bark methanolic extract respectively for 21days, after which the animals were sacrificed, and blood and liver were collected for haematological analysis including White Blood cell (WBC), red blood cell (RBC), haemoglobin (HGB), hematocrit (H CT), platelet (PLT), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), total bilirubin (TB), direct bilirubin(DB) and indirect bilirubin (IB) concentration and antioxidant parameters including antioxidant enzymes [catalase (CAT) and superoxide dismutase (SOD) activities] and oxidative stress marker [thiobarbituric acid reactive substance (TBARS)]. ResultsSTZ administration evoked a marked (p < 0.05) decline in the level of WBC, RBC, HGB, PLT, LYM and MCV in the diabetic rats when compared with the normal control. Howbeit, treatment with methanolic extracts of adansonia digitata stem-bark led to a profound (p < 0.05) increase in concentrations of these parameters close to the normal. In addition, STZ caused a non-significant (p > 0.05) decrease in MCH and MCHC. On the contrary, STZ caused an insignificant (p > 0.05) increase in the levels of TB and DB, but a significant (p > 0.05) increase IDB level in the diabetic control group when compared with the normal control group, while treatment with stem-bark extracts resulted in a marked (p > 0.05) fall in IDB level. Furthermore, there was a marked (P < 0.05) reduction in the activity of hepatic CAT and SOD and a considerable (P < 0.05) elevation in Malondialdehyde (MDA) level in the hepatic tissue of the diabetic control. Nonetheless, Adansonia digitata stem-bark extracts profoundly (P < 0.05) raised the activities of the enzymes and concomitantly counteracted MDA level. The extract elicited strong potency at 300 mg kg-1 which is comparable to metformin (Glucophage). ConclusionConsequently, this study advocates for the utility of Adansonia digitata extracts for the development of novel drugs for combating diabetes mellitus, associated hematological and oxidative stress complications and other ailments. Further research is needed to evaluate the clinical relevance of these effects in human subjects and to provide information on the sustained efficacy of the extracts in chronic models. Significant statementOxidative stress and hematological abnormalities are two of the consequences linked to diabetes mellitus. Anaemia and poor blood coagulation are two haematological changes that increase the risk of diabetes-related illness and death. Furthermore, oxidative stress is essential to the pathophysiology of diabetic complications such as nephropathy and cardiovascular disease. In addition, there are reports on hematological and biochemical alterations in diabetic subjects arising from the intake of synthetic antidiabetic medications.. Consequent to the safety, ease of use, efficacy, and lack of cytotoxic side effects of plants’ herbs, the study of Adansonia digitata's methanolic stem-bark extracts on haematological and antioxidant parameters in streptozotocin-induced diabetic rats is of paramount importance as the extracts' capacity to modify these parameters, will lead to the development of novel drugs that cures anemia, other blood abnormalities, and oxidative stress linked to diabetes as well as other ailments.

Interactive Effects of Dietary Probiotic and Succinic Acid on the Growth Performance, Digestive Enzyme Activities, Immunomodulation, Antioxidative Capacity, and Disease Resistance in Rainbow Trout (Oncorhynchus mykiss) Juveniles

Abstract The current study was carried out to explore the effects of lactofeed (LA) as a multi-strain probiotic and succinic acid (SA) on growth variables, gut lactic acid bacteria count, digestive enzymes, innate immune responses, antioxidant capacity, and resistance against yersinia ruckeri in rainbow trout juveniles (Oncorhynchus mykiss). Three hundred sixty healthy rainbow trout juveniles (13.21±0.41 g) were randomly divided into twelve tanks (300 L) as four experimental groups. They were fed with basal diet (Control; BD), FT1: BD + 1 g/kg LA, FT2: BD + 5 g/kg SA, and FT3: BD + 1 g/kg LA + 5 g/kg SA for eight weeks. According to the results, final weight (FW), weight gain (WG), protein efficiency rate (PER), and feed conversion rate (FCR) revealed a remarkable discrepancy compared to the control group. In addition, dietary inclusion of LA (FT1 and FT3) significantly increased the specific growth rate (SGR). Dietary supplementation of LA+SA (FT3) remarkably improved total bacteria count (TBC) and amylase activity compared to the unsupplemented group. Gut lactic acid bacteria (LAB) count and digestive protease activity in all supplemented fish were remarkably higher than in unsupplemented group. Blood immunological factors including white blood cell (WBC) count, total immunoglobulin content (Ig), and the activity of lysozyme (LYZ), alternative complement pathway (ACH50), and acid phosphatase (ACP) were significantly enhanced in the supplemented groups. Neutrophil (NEU) count, skin mucus Ig and hepatic glutathione peroxidase (GPX) increased in SA (FT2 and FT3) treatments. In addition, monocyte (MON) count and skin mucus LYZ activity were significantly elevated following feeding with the FT3 diet. Other immunological parameters of skin mucus including protease activity, alkaline phosphatase (ALP) activity, and ACH50 activity, as well as hepatic superoxide dismutase (SOD) and catalase (CAT) activities increased in fish fed with diets containing LA and/or SA. Malondialdehyde (MDA) value was remarkably decreased in all supplemented rainbow trout compared to the fish fed with BD. Disease resistance against Y. ruckeri in fish fed with supplemented diets significantly improved with respect to the results obtained in the control specimens. Overall, dietary LA+SA supplementation was beneficial to improve growth performance, gut LAB count, digestive enzyme activities, innate immune responses, antioxidant capacity, and disease resistance in rainbow trout. According to these findings, 1 g/kg LA + 5 g/kg SA is suggested for adding to rainbow trout diet.

Effects of Alkalinity Stress on Amino Acid Metabolism Profiles and Oxidative-Stress-Mediated Apoptosis/Ferroptosis in Hybrid Sturgeon (Huso dauricus ♀ × Acipenser schrenckii ♂) Livers

Alkaline water is toxic to cultured aquatic animals that frequently live in pH-neutral freshwater. Overfishing and habitat destruction have contributed to the decline in the wild sturgeon population; consequently, the domestic hybrid sturgeon has become an increasingly important commercial species in China. Hybrid sturgeons are widely cultured in alkaline water, but little is known about the effects of alkalinity stress on hybrid sturgeon liver tissues. We exposed hybrid sturgeons to four alkaline concentrations (3.14 ± 0.02 mmol/L, 7.57 ± 0.08 mmol/L, 11.78 ± 0.24 mmol/L and 15.46 ± 0.48 mmol/L). Histopathology, biochemical index assessment, gene expression level detection and metabolomics analysis were used to investigate the negative effects on liver functions following exposure to NaHCO3. Livers exposed to alkaline stress exhibited severe tissue injury and clear apoptotic characteristics. With increased exposure concentrations, the hepatic superoxide dismutase, catalase, glutathione peroxidase and alkaline phosphatase activities significantly decreased in a dose-dependent manner. NaHCO3 exposure up-regulated the transcriptional levels of apoptosis/ferroptosis-related genes in livers. Similarly, the expression trends of interleukin-1β and heat shock protein genes also increased in high-alkalinity environments. However, the expression levels of complement protein 3 significantly decreased (p &lt; 0.05). Hepatic untargeted metabolomics revealed the alteration conditions of various metabolites associated with the antioxidant response, the ferroptosis process and amino acid metabolism (such as beta-alanine metabolism; alanine, aspartate and glutamate metabolism; and glycine, serine and threonine metabolism). These data provided evidence that NaHCO3 impaired immune functions and the integrity of hybrid sturgeon liver tissues by mediating oxidative-stress-mediated apoptosis and ferroptosis. Our results shed light on the breeding welfare of domestic hybrid sturgeons and promote the economic development of fisheries in China.

Growth performance, fatty acid profile, antioxidant capacity, liver and gut histopathology in Asian seabass (Lates calcarifer) fed various levels of oxidized fish oil and vitamin E

A 60-day research was carried out to investigate interactive effects of dietary oxidized fish oil (OXFO) and vitamin E (Vit E) interaction effects on the growth, body composition and health indices in Asian seabass juveniles (Lates calcarifer, 21.9 ± 0.1 g). Fresh fish oil (FFO) and two levels of OXFO (50 and 100 % dietary inclusion level) along with three levels of Vit E (125, 250 and 500 mg) were used to design a 3 × 3 factorial research trial. Accordingly, nine experimental diets were formulated, including FFO+125 (FFO + 125 mg Vit E), FFO+250 (FFO + 250 mg Vit E), FFO+500 (FFO + 500 mg Vit E), 50 %OXFO+125 (blends (1:1) of FFO + OXFO +125 mg Vit E), 50 %OXFO+250 (blends (1:1) of FFO + OXFO +250 mg Vit E), 50 %OXFO+500 (blends (1:1) of FFO + OXFO +500 mg Vit E), 100 %OXFO+125 (OXFO +125 mg Vit E), 100 %OXFO+250 (OXFO +250 mg Vit E) and 100 %OXFO+500 (OXFO +500 mg Vit E). Four hundred five L. calcarifer juveniles were stocked into twenty-seven 300-L circular tanks (15 fish/tank), in a flow through system. The greatest and least final weights were recorded in fish fed 50 %OXFO+250 and 100 %OXFO+125 diets (129.4 vs. 114.8 g final weight) diets, respectively. Whole body lipid content in fish fed FFO+125 increased compared to the other treatments. Fish oil oxidation significantly reduced Vit E concentration in the liver, meanwhile supplementing diet with 500 mg Vit E enhanced Vit E contents of the liver and muscle (P < 0.05). Eicosapentaenoic acid and long chain polyunsaturated fatty acids (LC-PUFA) contents of fillet increased with increasing dietary OXFO content to 50 %, and supplementing diet with 250 mg Vit E enhanced LC-PUFA content of fillet. Hepatic catalase, superoxide dismutase and glutathione peroxidase activities reduced by supplementing diets with Vit E. Sever pathological alterations occurred in liver and gut of L. calcarifer by dietary inclusion of OXFO or high Vit E concentration (500 mg). In summary, supplementing OXFO containing diets with moderate levels of Vit E (250 mg) could improve growth performance and feed utilization by ameliorating oxidative stress indices, improving antioxidant capacity, and increasing body LC-PUFA content in L. calcarifer.

Sexual dimorphism in physiological responses of turbot (Scophthalmus maximus L) under acute hypoxia and reoxygenation

Dissolved oxygen (DO) is a crucial factor throughout fish life cycle. In this study, the hematology, hepatic antioxidant levels, histomorphology of the liver and gill were determined in both female and male turbot under acute hypoxia to evaluated the underlying mechanisms and potential sexual dimorphism difference. Results showed that acute hypoxia stress treatment for 3 h significantly increased plasma cortisol, glucose, hemoglobin (HGB), cholesterol (CHO), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and hepatic malondialdehyde (MDA) contents, red blood cell count (RBC) number, hepatic superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), alanine-aminotransferase (ALT) and aspartate-aminotransferase (AST) activity in both male and female turbot. Male obtained higher plasma CHO, TG and LDL contents, GSH-Px and SOD activity than female under hypoxia. Meanwhile, hypoxia increased gill respiratory frequency, secondary lamellar length, secondary lamellar width, perimeter, lamellar surface area and gill surface area and decreased interlamellar distance. Acute hypoxia induced clubbing, hyperplasia, hypertrophy of gill filaments and hepatic vacuolization in both male and female turbot. The aforementioned parameters were recovered to normal levels after reoxygenation for 12 h. In conclusion, sex dimorphism difference of turbot hematological (RBC, HGB) and biochemical (glucose, CAT, GSH-Px, MDA) parameters were observed under hypoxia stress, while male demonstrated more hypoxia tolerance than female. These results help understand turbot hypoxia tolerance mechanisms and provide more data for management in captivity.

Delayed treatment with hydro-ethanolic extract of Khaya grandifoliola protects mice from acetaminophen-hepatotoxicity through inhibition of c-Jun N-terminal kinase phosphorylation and mitochondrial dysfunction

The use of N-acetylcysteine against acetaminophen(APAP)-induced hepatotoxicity, a leading cause of liver injury, has several drawbacks, including short therapeutic windows. Khaya grandifoliola (Meliaceae) has been traditionally used to manage liver-related diseases, and many reports have confirmed its hepatoprotective properties. However, its therapeutic potential as an antidote against APAP-induced hepatotoxicity has yet to be proven in a clinically relevant model. This study aimed to verify the efficacy of delayed treatment with the hydroethanolic extract of K. grandifoliola (KgE) in suppressing the early injury phase of APAP pathophysiology. KgE was analyzed using HPLC/UV. Acute oral toxicity tests were conducted in mice to determine the therapeutic dose of KgE. Mice were treated with 300 ​mg/kg APAP; 1h and 12h later, they were treated with either predetermined doses of KgE or 20 ​mg/kg c-Jun N-Terminal Kinase (JNK) inhibitor SP600125, which served as a reference antidote. At 6h and 24h after APAP treatment, the parameters of liver damage and mitochondrial dysfunction, phosphorylation of JNK, and mitochondrial translocation were assessed. KgE at a dose of 5000 ​mg/kg was safe for mice. Accordingly, 100, 200, and 400 ​mg/kg were selected as curative treatments. Delayed administration of KgE reversed the histopathological changes in the liver, inhibited serum levels of alanine aminotransferase, reduced the liver content of nitric oxide and malondialdehyde, and restored hepatic glutathione pools and superoxide dismutase and catalase activities in APAP-intoxicated mice. Moreover, KgE prevented APAP-induced JNK phosphorylation and p-JNK mitochondrial translocation and rescued the activities of mitochondrial enzyme complexes II and V. HPLC/UV analysis revealed the presence of gallic acid, Quercetin and Silibinin, with retention times of 3.77, 11.63 and 11.95 ​min as the major active ingredients present in KgE. Our findings demonstrate that post-treatment with KgE protects the mouse liver from APAP-hepatotoxicity through the inhibition of JNK activation and mitochondrial dysfunction.

Metabolic effects of physical exercise on zebrafish (Danio rerio) fed a high-fat diet.

The present study aimed to establish zebrafish as an experimental model for investigations into obesity and physical exercise, as well as to assess the effects of these factors on metabolism. The experiment spanned twelve weeks, comprising a feeding trial during which the last four weeks incorporated a physical exercise protocol. This protocol involved placing fifteen animals in a five-liter aquarium, where they were subjected to swimming at an approximate speed of 0.08m/s for 30min daily. Throughout the experiment, histological analyses of visceral, subcutaneous, and hepatic adipose tissues were conducted, along with biochemical analyses of total cholesterol and its fractions, triglycerides, glucose, lactate, and alanine aminotransferase (ALT) levels. Additionally, oxidative stress markers, such as reactive oxygen species (ROS) levels, superoxide dismutase (SOD) activity, and catalase activity and the formation of thiobarbituric acid-reactive substances, were investigated. The results revealed that the group fed a high-fat diet exhibited an increase in ROS production and SOD activity. In contrast, the group administered the high-fat diet and subjected to physical exercise demonstrated a notable reduction in visceral adipocyte area, hepatic steatosis levels, ALT levels, and SOD activity. These findings indicate that physical exercise has a positive effect on obesity and oxidative stress in zebrafish, providing promising evidence for future investigations in this field.

The protective role of two oxindole derivatives is mediated by modulating NLRP3/caspase-1 and PI3K/AKT pathways in a preclinical animal model of hepatic ischemia reperfusion injury

AimHepatic ischemia reperfusion injury (HIRI) is a leading cause of mortality post liver transplantation, hypovolemic shock and trauma. In this study, we tested, on molecular bases, the possible protective role of two different derivatives of 2-oxindole in a preclinical model of HIRI in rats. Main methodsHIRI was operated in male Wistar albino rats and prophylactic treatment with oxindole-curcumin (Coxi) or oxindole-vanillin (Voxi) was carried out before the operation. The biochemical and histopathological investigations, in addition to the mechanistic characterizations of the effect of the tested drugs were performed. Key findingsHIRI was assured with elevated liver enzymes and marked changes in histopathological features, inflammatory response and oxidative stress. Pretreatment with Coxi and Voxi improved the hepatic histopathological alterations, reduced the elevated serum liver enzymes level and hepatic Malondialdehyde (MDA) content, increased the hepatic Superoxide Dismutase (SOD) activity and reduced Glutathione (GSH) content, downregulated the expression of TNF-α, IL-6, Nod-Like Receptor p3 (NLRP3), Cleaved caspase1, Cleaved caspase 3 proteins, alongside the expression level of IL-1β, ICAM-1, VCAM-1 and BAX genes, attenuated NF-кB p-P65 Ser536 and Myeloperoxidase (MPO)-positive neutrophils, and activated the PI3K/AKT pathway. SignificanceCoxi and Voxi have promising hepatoprotective activity against HIRI in rats through ameliorating the biochemical and histopathological alterations, attenuating inflammatory and oxidative stress status by modulating the inflammatory TNF-α/ICAM-1, the pyroptosis NLRP3/Caspase-1, and the antioxidant PI3K/AKT pathways.

The Hepatoprotective Effect of a Newly Synthesized 5-Mercapto-1,2,4-Triazole Derivative based on Nalidixic Acid Against Ccl4 induced Oxidative Stress in Mice

Background: Oxidative stress plays a key role in the development of a wide range of diseases, including diabetes and cancer. Recent studies reported that the derivatives of triazole compounds have a potent antioxidant activity. Therefore, this study was designed to investigate the hepatoprotective effect of a novel newly synthesized 5-mercapto-1,2,4-triazole based on nalidixic acid [1-ethyl-3-(5-mercapto-4-(p-tolyl)-4H-1,2,4-triazol-3-yl)-7-methyl-1,8-naphthyridin] (MTTN) 3 compound against CCl4 induced oxidative stress in mice. Materials and Methods: The MTTN compound was synthesized through the interaction and then cyclization of p-tolylisothiocyanate with nalidixic acid hydrazide. By using 1 H-NMR, 13C-NMR, IR, and elemental analyses, the structure of the newly synthesized MTTN compound was identified. To investigate the hepatoprotective effect of this compound, forty BALB/c mice were divided into four groups (n=10) as follows: the control group, the oxidative stress-induced group, which was intraperitoneally injected with 10% CCl4 (2 mL/kg), one pre-treatment group, which was treated orally with 200 mg/kg of MTTN compound for 8 days before being treated with CCl4 at day 8, and one post-treatment group, which was treated orally with 200 mg/kg of MTTN compound for 8 days simultaneously with CCl4 co-administration at days 3 and 5. At day 9, animals were scarified and serum and liver samples were collected. Results: CCl4 administration caused significant hepatotoxicity as evidenced by marked elevation in the serum activity of the liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and high blood cholesterol levels. Furthermore, the hepatic malondialdehyde (MDA) level, a marker of lipid peroxidation, was increased with CCl4 administration that was associated with a decrease in the hepatic superoxide dismutase (SOD) and catalase (CAT) activities (p &lt; 0.05). However, pre and post-treatment with the new newly synthesized MTTN compound significantly reduced the serum levels of AST, ALT, and cholesterol and reduced hepatic oxidative stress as indicated by the decrease in the hepatic MDA level and the increases in the SOD and CAT activities (p &lt; 0.05). Conclusion: This study suggests that the newly synthesized MTTN compound has a potent antioxidant property and can protect against CCl4-induced liver injury. Thus, with more clinical studies, this compound may be used as effective therapeutic agents against oxidative stress related diseases.

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.

Physiological Response of European Sea Bass (Dicentrarchus labrax) Juveniles to an Acute Stress Challenge: The Impact of Partial and Total Dietary Fishmeal Replacement by an Insect Meal

This study aimed to explore the effect of FM substitution by defatted Tenebrio molitor larvae meal (dTM) on the response of European seabass to an acute stress challenge. An FM-based diet was used as a control and two other isoproteic/isoenergetic diets were formulated to replace 50 and 100% of FM by dTM. Each diet was tested in quadruplicate groups of 15 fish (69 ± 5 g) fed until visual satiety for 16 weeks. After the feeding trial, fish were subjected to 1 min air exposure followed by 1 h of recovery before sampling. The haematological profile, plasma metabolites, and humoral immunity biomarkers, as well as hepatic oxidative stress and antioxidant capacity, were analysed. A clear response to acute stress was observed by a significant increase in haemoglobin, haematocrit, red blood cells, and almost all evaluated plasma metabolites and humoral parameters, regardless of dietary treatment. The obtained results demonstrated that partial substitution of FM by IM did not affect the stress response of seabass. However, total FM replacement increased the hepatic activity of total peroxidase and superoxide dismutase in fish fed TM100.

Arbutin abrogates cisplatin-induced hepatotoxicity via upregulating Nrf2/HO-1 and suppressing genotoxicity, NF-κB/iNOS/TNF-α and caspase-3/Bax/Bcl2 signaling pathways in rats.

Cisplatin is a potent anticancer agent widely employed in chemotherapy. However, cisplatin leads to toxicity on non-targeted healthy organs, including the liver. We investigated the hepatoprotective mechanism of arbutin (ARB), a glycosylated hydroquinone, against cisplatin-induced hepatotoxicity. Rats were orally administered with ARB (ARB1=50mg/kg; ARB2=100mg/kg) for 14 consecutive days against hepatotoxicity induced by a single dose of cisplatin (10mg/kg) on day 15. Three days after the intraperitoneal cisplatin injection, serum and liver tissue were collected for subsequent analyses. Cisplatin triggered marked increases in serum AST, ALT, and ALP activities, hepatic malondialdehyde (MDA) and reactive oxygen species (ROS) coupled with a considerable diminution in hepatic activities of superoxide dismutase (SOD), catalase (CAT) and the concentration of reduced glutathione (GSH). The gene expressions of interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), and IL-6 were notably increased. The pre-administration of ARB1 and ARB2 reduced AST, ALT and ALP in serum and restored SOD, CAT, GSH, ROS, MDA and cytokine levels which was also evidenced by alleviated hepatic lesions. Further, cisplatin-induced prominent alterations in the gene expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), iNOS, NF-κB, Bax, Bcl-2, caspase-3 and 8-OHdG in the liver. Interestingly, ARB protected the liver and mitigated the cisplatin-induced alterations in serum AST, ALT, ALP, and reduced hepatic redox markers, 8-OdG, inflammatory markers and gene expressions. The findings demonstrate that ARB is a potential protective adjuvant against cisplatin-induced hepatotoxicity via inhibition of hepatic oxidative stress, inflammation, and apoptosis.

Dietary arginine regulates the growth performance, antioxidant capacity, and immune response in Culter alburnus.

Culter alburnus is sensitive to stressors. Arginine is a precursor of nitric oxide, which can effectively relieve the level of oxidative stress and improve the antioxidant and immune capacity of fish. The effect of different arginine levels on topmouth culter (Culter alburnus) fry development performance, liver antioxidant capacity, and immune parameters were investigated in this study. Five diets (1.96%, ARG1, control group; 2.28%, ARG2; 2.52%, ARG3; 2.81%, ARG4; 3.09%, ARG5) were used to feed fry (initial weight 0.31 ± 0.01g) for 8weeks. The data showed that the final weight (FW), weight gain rate (WGR), and specific growth rate (SGR) of the ARG3 and ARG4 groups were significantly improved, while the feed conversion ratio (FCR) reduced significantly. Compared with the ARG1 group, all groups remarkably reduced the crude ash content of the whole body. The activity of hepatic superoxide dismutase (SOD) and the content of hepatic glutathione (GSH) were significantly increased in the ARG3 and ARG4 groups, while the malondialdehyde (MDA) content was significantly decreased. Compared with the ARG1 group, arginine levels in ARG2, ARG3, and ARG4 groups up-regulated the expression levels of Nrf2, down-regulated the gene expression level of Keap1 in the liver. And the expression of Nrf2/Keap1 pathway downstream genes Mn-SOD and CAT was up-regulated in ARG2 and ARG3 groups. Furthermore, the expression levels of MyD88 and IL-1β were down-regulated, and the anti-inflammatory gene TGF-β expression levels were up-regulated in the ARG2, ARG3, and ARG4 groups. Additionally, compared to the ARG1 group, there was a significant increase in the relative expression levels of the C3 and C4 genes in the ARG4 group. In conclusion, 2.28-2.81% dietary arginine levels improved the growth performance, promoted antioxidant capacity, and enhance immune response. The optimal level of arginine was determined by the quadratic regression analysis of SGR and FCR to be 2.55% of diet (5.43% of dietary protein) and 2.53% of diet (5.38% of dietary protein), accordingly.

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.

Chrysophyllum albidum (African star apple) Fruit-Skin Attenuates Hyperglycemia-Mediated Oxidative Stress in Experimental Diabetic Rats

Diabetes mellitus, a chronic metabolic disturbance characterized by hyperglycemia has become a health problem affecting millions of people worldwide. Hyperglycemia mediated oxidative stress performs a key role in diabetic complications. The fruit-skin of Chrysophyllum albidum (African star apple) has been reported to have anti-hyperglycemic, hypolipidemic and in vitro antioxidant properties, but its effect on oxidative damage in diabetic animals has not been well investigated. This study investigated the effect of Chrysophyllum albidum fruit-skin (CAFS) in mitigating hyperglycemia induced oxidative stress in diabetic rats. Oxidative stress markers included superoxide dismutase (SOD) and catalase (CAT), lipidperoxidation status using malondialdehyde and non-enzymatic antioxidants in serum, hepatic and pancreatic tissues. Non-diabetic and streptozotocin-diabetic rats were compared after 4 weeks of treatment. The diabetic untreated group showed significant (p&lt; 0.05) elevation of malondialdehyde and depression of non-enzymatic antioxidants levels, while suppressing SOD and CAT activities in serum, hepatic and pancreatic tissues when compared to normal rats. CAFS supplemented diet treatment ameliorated these metabolic disturbances and increased the activities of hepatic and pancreatic SOD from 0.28±0.25 to 0.61±0.13 Unit/mg protein and 0.08±0.01 to 0.15±0.01 Unit/mg protein respectively and CAT from 0.21±0.06 to 0.81±0.17 Unit/mg protein and 0.07±0.01 to 0.50±0.15 Unit/mg protein respectively. The findings suggest that CAFS treatment in diabetic rats exerts a protective effect via attenuation of oxidative stress mediated by hyperglycemia and improves the antioxidant status.&#x0D;

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.