The administration of Glycyrrhiza polysaccharides mitigates liver injury in mice caused by mancozeb via the Keap1-Nrf2/NF-κB pathway.

The extensive utilization of mancozeb (MCZ) poses environmental pollution risks, threatens human health, particularly hepatotoxicity. Glycyrrhiza polysaccharides (GP) exhibit antioxidant, anti-inflammatory and other biological activities. The aim of this study is to explore the mechanism of liver injury in mice exposed to MCZ and the protective effect of GP on alleviating MCZ induced liver injury. Initially, 70 female mice were divided into 7 groups, and the optimal dose of MCZ induced liver injury in mice was screened by oral administration different doses of MCZ (0, 50, 100, 150, 200, 250 and 300 mg/kg MCZ). The results demonstrated that, compared to the blank control group, as the concentration of MCZ increased, several physiological and biochemical parameters were significantly affected. Specifically, body weight and liver index significantly decreased, while the activities of SOD and CAT also decreased. Additionally, the content of ROS increased, the levels of Keap1 and Nrf2 proteins increased, the mRNA levels of Gpx2 and HO-1decreased, and the mRNA levels of Gstt2, GcLc and NQO1 were upregulated. Based on the test data, select 100 mg/kg MCZ as the optimal modeling dose for experimental animals. Sixty female mice were divided into six groups and orally administered: control group A (0.2 mL deionized water), model group B (100 mg/kg MCZ), positive control group F (100 mg/kg MCZ+100 mg/kg VC), the high-dose GP group C (100mg/kgMCZ+200mg/kgGP), the medium-dose GP group D (100 mg/kg MCZ+150mg/kgGP) and the low-dose GP group E (100 mg/kg MCZ+100mg/kgGP). The results showed that compared to the model group, adding GP alleviated the effects of MCZ on body weight, liver index, CAT and SOD activity, MDA content, HO-1, TNF-α, and IL-1β. Additionally, the addition of GP decreased the expression of Keap1, Nrf2, NF-kB, and NQO1, GcLc, and Gstt2 mRNA. GP ameliorated liver vacuolar degeneration, steatosis and nuclear pyknosis ameliorate by MCZ. The results show that MCZ triggers hepatotoxicity via the activation of the Keap1/Nrf2 signaling pathway, whereas GP has the potential to mitigate liver damage caused by MCZ exposure by inhibiting this pathway.

Gao N ，Li Y ，Zhang L ，Zhang Y ，Wang X ... -  《-》

[Sulforaphane alleviates acute liver injury induced by diquat in mice by activating Keap1/Nrf2 signaling pathway].

Wang J ，Peng L ，Wu L ，Huang S ，He G ，Shen P ，Liang J ，Huang T ，Huang J ，Zhong H ，Zhou M ... -  《-》

[Protective effect of astaxanthin on acute liver injury induced by α-amanitin in mice].

Luo YP ，Zhong JJ ，Yao QM ，Geng ZX ，Chen CG ，Yu CM ... -  《-》

Hepatoprotective effects of olive leaf extract against carbon tetrachloride-induced oxidative stress: in vivo and in-silico insights into the Nrf2-NFκB pathway.

Olive Leaves Extract (OLE) holds therapeutic potential, traditionally used to treat hepatic ailments, though its molecular mechanisms remain unclear. This study evaluated the efficacy of ethanolic OLE against Carbon Tetrachloride (CCl4)-induced oxidative stress in a rat model. Phytochemical analysis was performed using High Performance Liquid Chromatography (HPLC). For this porous, thirty rats were divided into six groups (n = 5): Group 1 (negative control) received a standard diet, while Groups 2-6 were subjected to CCl4-induced toxicity. Group 2 served as the disease control, and Group 3 was treated with silymarin (100 mg/kg). Groups 4, 5, and 6 received OLE at 100 mg/kg, 200 mg/kg, and 300 mg/kg, respectively, for 21 days. OLE significantly modulated hepatic biomarkers (ALT, AST, ALP), increased Total Antioxidant Capacity (TAC), decreased Total Oxidation Capacity (TOC), and restored levels of SOD, GSH, and CAT compared to the CCl4 group. Malondialdehyde (MDA) levels, elevated in the disease group, however downregulated by OLE, particularly at 300 mg/kg. Histological examination revealed normal liver integrity in the OLE-treated groups. Additionally, OLE modulated the mRNA expression of IL-1β, IL-6, TNF-α, NF-kB, Bcl2, and p-53. Apoptotic markers such as Nrf2, HO-1, Cytochrome c, caspase 3, caspase 7, and Bax were normalized with OLE treatment. The inhibition of KEAP1-NRF2 protein-protein interaction showed OLE's superior efficacy compared to silymarin, with a better docking score. These findings suggest that OLE exerts significant hepatoprotective effects against CCl4-induced oxidative stress and inflammation via the Nrf2-NFκB pathway.

Buzdar JA ，Shah QA ，Khan MZ ，Zaheer A ，Shah T ，Ataya FS ，Fouad D ... -  《-》

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 ... -  《-》