Proanthocyanidins mitigate the toxic effects in loach (Misgurnus anguillicaudatus) exposed to phenanthrene via Nrf2/NF-κB signaling pathway.

Phenanthrene (PHE) is a typical polycyclic aromatic hydrocarbon compound that is ubiquitous in the environment and accumulates in aquatic products, thereby posing a risk to food safety. Oligomeric proanthocyanidins (OPC) is widely distributed powerful antioxidants with potent antioxidant and anti-inflammatory properties. This study aimed to evaluate the alleviating effects of dietary OPC on oxidative stress, inflammatory suppression, and tissue damage caused by PHE exposure in loach (Misgurnus anguillicaudatus). In the study, loach was continuously exposed to 2.36 mg/L PHE for 28 days, after which they were fed a basal diet supplemented with 0, 200, 400, or 800 mg/kg OPC. The results displayed that PHE exposure resulted in significantly increased levels of liver health parameters (AST, ALT, COR, LDH, and ADA) compared to the control group (P < 0.05). The PHE-exposed fish showed the lowest levels of antioxidant enzymes (CAT, SOD, GSH, GST, GSH-Px, and GR) and the greatest levels of oxidative stress parameters (ROS and MDA). PHE exposure resulted in down-regulation of nrf2, ho-1, gsh-px, gst, and nqo-1, and up-regulation of keap-1 gene expressions in loach (P < 0.05). Moreover, PHE-induced decreased the levels of immunity indicators (CRP, MPO, C3, C4, IgM, and LYS). An up-regulation of pro-inflammatory genes (nf-κb, il-1β, il-8, il-6, il-12, and tnf-α) and a down-regulation of anti-inflammatory gene il-10 were the consequences of the PHE exposure. In addition, tissues showed histopathological alterations including vacuolization (liver), displaced nuclei (liver), atrophy (gills), glomerular congestion (kidney), and inflammatory cell infiltration (spleen) caused by PHE. Notably, dietary supplementation of OPC augmented immuno-antioxidant parameters, including their key genes, reduced oxidative stress and immunosuppression, and ameliorated tissue damage compared to fish exposed to PHE. In summary, supplementation with 400 mg/kg OPC in the diets could effectively alleviate the oxidative damage and inflammatory response induced by PHE exposure in loach through the Nrf2/NF-κB signaling pathway and enhance the defense ability against toxic substances of loach.

Fang Q ，Li K ，Zhang X ，Liu X ，Jiao S ，Sun L ，Li M ，Wang G ，Kong Y ... -  《-》

Dietary Zanthoxylum bungeanum leaf powder improves growth performance and antioxidant capacity via Nrf2/HO-1 signaling pathway in broilers.

This study focused on the effects of dietary Zanthoxylum bungeanum leaves (ZBL) powder on the growth performance and antioxidant capacity via the Nrf2/HO-1 signaling pathway in broilers. The experiment adopted a single-factor completely random design, and 440 healthy 1-d-old Arbor Acres broiler chicks were randomly divided into 4 groups: the control group (CON) was fed a corn-soybean meal-based diet, the CZ1 group was fed a basic diet with 1% ZBL powder, the CZ2 group fed a basic diet with 2% ZBL powder, and the CZ3 group fed a basic diet with 3% ZBL powder. The experiment was divided into the starter period (1 to 21 d) and the grower period (22 to 42 d). There were 5 replicates per group in the starter period, with 22 chickens per replicate. The same grouping as in the starter period was used in the grower period, with 20 chickens per replicate. The results showed that the addition of ZBL powder to the diet had no adverse effects on the growth performance and morphological structure of the intestine of broiler chickens in the CZ1 and CZ2 groups (P > 0.05). Compared with the control group, the diet with 1% and 2% ZBL powder significantly increased the antioxidant indicators such as CAT, T-AOC, and T-SOD in the serum and liver tissue of broiler chickens, it upregulated the related gene expression of nuclear factor erythroid derived-2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway such as Nrf2, NQO1, HO-1, SOD1, and CAT in the jejunal mucosa and enhanced the expression of ZO-1 and OCLN genes in the jejunal mucosa (P < 0.05). In conclusion, dietary supplementation with 1% and 2% of ZBL powder in the daily diet can enhance the body's antioxidant capacity by elevating antioxidant levels in both serum and liver, upregulating the expression of genes associated with the Nrf2/HO-1 signaling pathway in the jejunal mucosa, and helps maintain the integrity of the intestinal mucosal barrier. The optimal addition level of ZBL powder in the diet was determined by quadratic regression analysis to be 1.36% to 1.60% during days 1 to 21 and 1.14% to 1.50% during days 22 to 42.

Hu Z ，Qiu Y ，Han J ，Feng F ，Chu Y ，Li Z ，Jiang L ，Sun Z ，Wang L ，Chen C ，Tang Z ... -  《-》

Potentials of bone marrow cells-derived from naïve or diabetic mice in autoimmune type 1 diabetes: immunomodulatory, anti-inflammatory, anti hyperglycemic, and antioxidative.

The scarcity of transplanted human islet tissue and the requirement for immunosuppressive drugs to prevent the rejection of allogeneic grafts have hindered the treatment of autoimmune type 1 diabetes mellitus (T1DM) through islet transplantation. However, there is hope in adoptively transferred bone marrow cells (BMCs) therapy, which has emerged as a propitious pathway for forthcoming medications. BMCs have the potential to significantly impact both replacement and regenerative therapies for a range of disorders, including diabetes mellitus, and have demonstrated anti-diabetic effects. The main goal of this study is to evaluate the effectiveness of adoptively transferred bone marrow cells derived from either naïve mice (nBMCs) or diabetic mice (dBMCs) in treating a T1DM mice model. Male Swiss albino mice were starved for 16 h and then injected with streptozotocin (STZ) at a dose of 40 mg/kg body weight for 5 consecutive days to induce T1DM. After 14 days, the diabetic mice were distributed into four groups. The first group served as a diabetic control treated with sodium citrate buffer, while the other three groups were treated for two weeks, respectively, with insulin (subcutaneously at a dose of 8 U/kg/day), nBMCs (intravenously at a dose of 1 × 106 cells/mouse/once), and dBMCs (intravenously at a dose of 1 × 106 cells/mouse/once). It is worth noting that administering adoptively transferred nBMCs or adoptively transferred dBMCs to STZ-induced T1DM mice resulted in a significant amelioration in glycemic condition, accompanied by a considerable reduction in the level of blood glucose and glycosylated hemoglobin % (HbA1C %), ultimately restoring serum insulin levels to their initial state in control mice. Administering nBMCs or dBMCs to STZ-induced T1DM mice led to a remarkable decrease in levels of inflammatory cytokine markers in the serum, including interferon-γ (INF-γ), tumor necrosis factor- α (TNF-α), tumor growth factor-β (TGF-β), interleukin-1 β (L-1β), interlekin-4 (IL-4), interleukin-6 (IL-6), and interleukin-10 (IL-10). Additionally, STZ-induced T1DM mice, when treated with nBMCs or dBMCs, experienced a notable rise in total immunoglobulin (Ig) level. Furthermore, there was a significant reduction in the levels of islet cell autoantibodies (ICA) and insulin autoantibodies (IAA). Furthermore, the serum of STZ-induced T1DM mice showed a significant increase in Zinc transporter 8 antigen protein (ZnT8), islet antigen 2 protein (IA-2), and glutamic acid decarboxylase antigen protein (GAD) levels. Interestingly, the administration of nBMCs or dBMCs resulted in a heightened expression of IA-2 protein in STZ-induced T1DM mice treated with nBMCs or dBMCs. Furthermore, the level of malondialdehyde (MDA) was increased, while the levels of catalase (CAT) and superoxide dismutase (SOD) were decreased in non-treated STZ-induced T1DM mice. However, when nBMCs or dBMCs were administered to STZ-induced T1DM mice, it had a significant impact on reducing oxidative stress. This was accomplished by reducing the levels of MDA in the serum and enhancing the activities of enzymatic antioxidants like CAT and SOD. STZ-induced T1DM mice displayed a significant elevation in the levels of liver enzymes ALT and AST, as well as heightened levels of creatinine and urea. Considering the crucial roles of the liver and kidney in metabolism and excretion, this research further examined the effects of administering nBMCs or dBMCs to STZ-induced T1DM mice. Notably, the administration of these cells alleviated the observed effects. The present study suggests that utilizing adoptively transferred nBMCs or adoptively transferred dBMCs in the treatment of T1DM led to noteworthy decreases in blood glucose levels, possibly attributed to their capacity to enhance insulin secretion and improve the performance of pancreatic islets. Additionally, BMCs may exert their beneficial effects on the pancreatic islets of diabetic mice through their immunomodulatory, antioxidant, anti-inflammatory, and anti-oxidative stress properties.

Gomaa S ，Nassef M ，Hafez A 《-》

Effect of vitamin supplementation and exposure-free break on hematological, Biochemical, and pathological parameters in male Wistar rats exposed to quinalphos.

India is a land of agriculture, where the economy is based on cash crop cultivation. The wide and chronic use of pesticides for agriculture, domestic, and industrial purposes without protective measures has led to subsequent adverse health effects and further evaluation. It has become a major concern of public health due to its usage throughout the year among pesticide industrial workers, distributors and retail shopkeepers, agricultural field workers, and sprayers. Among the different types of pesticides (organochlorines, organophosphorus, carbamates, and pyrethroid compounds) used, quinalphos is the most common organophosphorus compound used in South India. These compounds were known to produce oxidative damage in the liver, kidney, bone marrow, brain, and intestine. Nonenzymatic antioxidants like vitamin C and E were found to alleviate the oxidative damage imposed by these pesticides. Thus, the present study aims to evaluate the effect of oral supplementation of vitamin E and vitamin C in comparison to exposure-free days on complete blood count, antioxidant enzymes, liver enzymes, and histopathological changes in the liver following exposure of male Wistar rats to quinalphos. This experimental study was done at XXXX after getting scientific and ethical committee clearance. A total of 24 adult male Wistar rats were divided randomly into four groups, with six in each group. Group A consists of animals not exposed to quinalphos for 60 days (control group), group B exposed to quinalphos for 60 days, group C exposed to quinalphos orally only for the first 30 days with exposure-free days for the next 30 days, and group D exposed to quinalphos orally for 60 days along with vitamin E and vitamin C oral supplementation. During exposure, quinalphos was administered at the dose of 3 mg/kg/day mixed with drinking water through oral gavage. Animals were sacrificed at the end of 60 days. Blood was collected by direct cardiac puncture, and the liver tissue was used for histopathological investigation. Data were analyzed with one-way ANOVA and post hoc Turkey's test for intergroup comparison using SPSS 21.0 software. RBC count (P = 0.011), Hb % (P = 0.000), and hematocrit (P = 0.000) were significantly reduced, whereas WBC count (P = 0.005) and neutrophil % (P = 0.001) significantly increased in the quinalphos-exposed group (group B) compared to other three groups. Liver enzymes, SGPT (P = 0.028) and SGOT (P = 0.343), were elevated, and the antioxidants catalase (P = 0.000) and glutathione peroxidase (P = 0.000) were significantly reduced in the quinalphos-exposed group when compared to the control and exposure free group. Histopathology of the liver showed diffuse necrosis of the hepatocytes with central venous congestion in quinalphos-exposed (group B) compared to the other three groups. The exposure-free group (group C) has shown better histopathological changes when compared to quinalphos exposure with (group D) and without (group B) vitamin C and E supplementation group. Quinalphos exposure orally results in anemia, leucocytosis with neutrophilia, liver damage, and oxidative stress. As evidenced by liver histopathology and altered antioxidant enzymes in the supplementation group compared to the group with exposure-free days, the toxic effects of quinalphos were less during exposure-free days. Thus, people occupationally exposed to quinalphos can alleviate the ill effects by having exposure-free days as interval breaks to remove the toxic accumulation of organophosphorus compounds.

Udayakumar KP ，Priyatharshini M ，Adhimoolam M ，Ukkirapandian K ，Theresa M ，Murugesan SB ... -  《-》

Effects of Kalimeris indica on alcohol-induced liver injury through storing Nrf2/HO-1 pathway and gut microbiota.

Kalimeris indica (L.) Sch. Bip., (K. indica) is a plant classified under the genus Kalimeris within the Asteraceae family. The herb of K. indica has been historically utilized as a traditional medicine. The consumption of excessive amounts of alcohol represents a lifestyle choice that can induce tissue damage and contribute to the development of various health conditions. The HPLC-MS method was used to reveal the chemical composition of K. indica extract. HepG2 cells were used to test the in vitro oxidative stress. C57BL/6 mice were used to construct the in vivo alcohol-induced liver injury. H/E staining and serum ALT and AST levels were tested to assess the in vivo protective effect of ML (50 and 200 mg/kg). GSH, SOD, and CAT levels along with byproduct MDA levels were used to evaluate the in vivo oxidative stress. Immunohistochemical experiments were used to examine the in vivo Nrf2 and HO-1 levels. 16S rRNA gene-based profiling method was used to test the alteration in gut microbiota. 16 compounds were identified from K. indica extract. K. indica treatment reduced oxidative stress in HepG2 cells treated with 5% alcohol. H/E staining results showed that K. indica (50 and 200 mg/kg) alleviated liver injury caused by alcohol administration, eliciting a similar protective effect to the positive drug silymarin. Serum ALT and AST examination gave a consistent result, showing that ML could restore serum ALT and AST levels in mice treated with alcohol. Furthermore, K. indica could also restore GSH, SOD, CAT, and MDA levels in alcohol-treated mice, showing a potent effect on oxidative stress alleviation. Immunohistochemical experiments indicated that K. indica showed the liver protective effect through Nrf2/HO-1 pathway. 16S rRNA gene-based profiling revealed that alcohol treatment caused the alteration in gut microbiota, while K. indica treatment could result in a significantly richer variety of microbial communities compared to the alcohol group. K. indica (ML) has a protective effect on liver injury caused by alcohol administration. The Nrf2/HO-1 pathway and gut microbiota regulation were involved in the ML-induced liver protection. All the results indicate that K. indica has a potential in the treatment of alcohol-induced liver injury.

Wang MF ，Sun T ，Chen SY ，Wang X ，Li H ，Wang JQ ... -  《-》