Liensinine alleviates mouse intestinal injury induced by sepsis through inhibition of oxidative stress, inflammation, and cell apoptosis.

Sepsis is a clinical syndrome triggered by an imbalanced host response to pathogens that can lead to multiple organ dysfunction. The immune response and barrier function of the gut play an important role in the pathogenesis and progression of sepsis. This study aimed to explore the potential role of natural alkaloid Liensinine in the treatment of intestinal injury caused by sepsis and its possible molecular mechanism. In this study, a mouse model of sepsis was established by injecting LPS to explore the protective effect of Liensinine on intestinal injury in sepsis. The results showed that Liensinine could reduce the intestinal damage caused by LPS and increase the number of goblet cells. Furthermore, it decreased the release of inflammatory cytokines by inhibiting NF-kB phosphorylation and NLRP3 inflammasome synthesis. Liensinine also reduced the oxidative stress and ROS accumulation caused by LPS, and played an anti-oxidative stress role by regulating the Nrf2/keap1 signaling pathway. In addition, Liensinine alleviated the inhibition of intestinal autophagy caused by LPS by inhibiting the PI3K/Akt/mTOR pathway. And then it reduced the excessive apoptosis of intestinal cells. This study provides valuable insights for sepsis prevention and treatment, offering a potential therapeutic candidate to protect against intestinal injury and regulate the inflammatory response in sepsis.

Mitigation of avermectin exposure-induced brain tissue damage in carp by quercetin.

Avermectin is widely used as an important insecticide in agricultural production, but it also shows strong toxicity to non-target organisms. Quercetin is a natural flavonoid that is widely used due to its good anti-inflammatory and antioxidant effects. We believe that quercetin may have a potential therapeutic effect on avermectin poisoning. This experiment was proposed to observe the effect of quercetin on the toxic response to avermectin by observing the toxic response caused by avermectin in the brain of carp. In this project, 60 carp were studied as control group (Control), quercetin administration group (QUE), avermectin exposure group (AVM) and quercetin treatment avermectin exposure group (QUE + AVM) with different interventions to study the effect of quercetin on avermectin. The carp brain tissues were stained and simultaneously analyzed for blood-brain barrier (BBB), oxidative stress indicators, inflammatory factors, and apoptosis using qPCR technique. The results of the study indicate that avermectin exhibits a neurotoxic mechanism of action in fish by decreasing the transcript levels of tight junction protein-related genes, which in turn leads to the rupture of the BBB in the carp brain tissue. Avermectin induced apoptosis in carp brain tissue by increasing oxidative stress response and promoting inflammatory cell infiltration. Quercetin could reduce the accumulation of reactive oxygen species (ROS) in the brain tissue of carp caused by avermectin exposure toxicity, maintain redox homeostasis, reduce inflammatory response, and protect brain tissue cells from apoptosis. The present study confirmed the therapeutic and protective effects of quercetin on neurotoxicity in carp caused by avermectin exposure.

Difenoconazole disrupts carp intestinal physical barrier and causes inflammatory response via triggering oxidative stress and apoptosis.

As a common fungicide, difenoconazole (DFZ) is widespread in the natural environment and poses many potential threats. Carp makes up a significant proportion of China's freshwater aquaculture population and are vulnerable to the DFZ. Therefore, this study investigated the effects of DFZ (0.488 mg/L and 1.953 mg/L) exposure for 4 d on the intestinal tissues of carp and explored the mechanisms. Specifically, DFZ exposure caused pathological damage to the intestinal tissues of carp, reducing the expression levels of intestinal tight junction proteins, and leading to damage to the intestinal barrier. In addition, DFZ exposure activated the NF-κB signaling pathway, increasing the levels of pro-inflammatory factors (TNF-α, IL-1ß, IL-6) and decreasing the levels of anti-inflammatory factors (IL-10, TGF-ß1). As disruption of the intestinal barrier is closely linked to oxidative stress and apoptosis, we have conducted research in both areas for this reason. The results showed that DFZ exposure elevated reactive oxygen species in carp intestines, decreased antioxidant enzyme activity, and suppressed the expression of oxidative stress-related genes. TUNEL results showed that DFZ induced the onset of apoptosis. In addition, the expression levels of apoptosis-related genes and proteins were examined. Western blotting results showed that DFZ could upregulate the protein expression levels of Bax, Cytochrome C and downregulate the protein levels of Bcl-2. qPCR results showed that DFZ could upregulate the transcript levels of Bax, Caspase-3, Caspase-8 and Caspase-9 and downregulate the transcript levels of Bcl-2 transcript levels. This suggests that DFZ can induce apoptosis of mitochondrial pathway in carp intestine. In conclusion, DFZ can induce oxidative stress and apoptosis in carp intestine, leading to the destruction of intestinal physical barrier and the occurrence of inflammation. Our data support the idea that oxidative stress and apoptosis are important triggers of pesticide-induced inflammatory bowel illness.