Silybin protected from avermectin-induced carp (Cyprinus carpio) nephrotoxicity by regulating PPAR-γ-involved inflammation, oxidative stress, ferroptosis and autophagy.

Avermectin, a widely used deworming drug, poses a significant threat to fisheries. Silybin is recognized for its antioxidant and anti-inflammatory properties. The kidney, being crucial for fish survival, plays a vital role in maintaining ion balance, nitrogen metabolism, and hormone regulation. While residual avermectin in water could pose a risk to carp (Cyprinus carpio), it remains unclear whether silybin can alleviate the renal tissue toxicity induced by avermectin in this species. In current study, we developed a model of long-term exposure of carp to avermectin to investigate the potential protective effect of silybin against avermectin-induced nephrotoxicity. The results indicated that avermectin induced renal inflammation, oxidative stress, ferroptosis, and autophagy in carp. Silybin suppressed the mRNA transcript levels of pro-inflammatory factors, increased catalase (CAT) activity, reduced glutathione (GSH) activity, diminished reactive oxygen species (ROS) accumulation in renal tissues, and promoted the activation of the Nrf2-Keap1 signaling pathway. Furthermore, the transcript levels of ferroptosis-associated proteins, including gpx4 and slc7a11, were significantly reduced, while those of cox2, ftl, and ncoa4 were elevated. The transcript levels of autophagy-related genes, including p62 and atg5, were also regulated. Network pharmacological analysis revealed that silybin inhibited ROS accumulation and mitigated avermectin-induced renal inflammation, oxidative stress, ferroptosis, and autophagy in carp through the involvement of PPAR-γ. Silybin exerted its anti-inflammatory effect through the NF-κB pathway and antioxidant effect through the Nrf2-Keap1 pathway, induced renal cell iron efflux through the SLC7A11/GSH/GPX4, and suppressed autophagy initiation via the PI3K/AKT pathway. This study provides evidence of the protective effect of silybin against avermectin-induced nephrotoxicity in carp, highlighting its potential as a therapeutic agent to alleviate the adverse effects of avermectin exposure in fish.

Effect of montelukast on the expression of CD4+CD25+ regulatory T cells in children with acute bronchial asthma.

The aim of this study was to investigate the effect of montelukast on the expression of CD4+CD25+ regulatory T cells in children with acute bronchial asthma. Fifty-six child patients with acute bronchial asthma treated in the Department of Pneumology at the Shangluo Central Hospital were selected and randomly divided into the control group (n=28) and treatment group (n=28). The control group was treated with the conventional therapy of bronchial asthma, while the treatment group received montelukast on the basis of the control group for 7 days. The clinical symptoms, lung function and proportion of CD4+CD25+ regulatory T cells in peripheral T lymphocyte subsets in patients in the two groups were observed. Moreover, the levels of inflammatory factors and immunoglobulin E (IgE) in peripheral blood in both groups were detected. The effective treatment rate in the treatment group was significantly higher than that in the control group (P<0.05), and the forced expiratory volume in 1 sec/forced vital capacity (FEV1/FVC), peak expiratory flow (PEF) and 25% peak expiratory flow (PEF25) in the treatment group were significantly higher than those in the control group (P<0.05). The proportions of CD4+CD25+ regulatory T cells in the two groups after drug therapy were significantly increased. The proportion and content per unit volume of peripheral CD4+CD25+ regulatory T cells in the treatment group were obviously higher than those in the control group (P<0.01). After treatment, the levels of interleukin-4 (IL-4), IL-5 and IL-6 in peripheral blood in the two groups were significantly decreased. However, the levels of transferrin-γ (TFN-γ) and IL-10 were significantly increased (P<0.01). The IgE level in the treatment group was also significantly higher than that in the control group (P<0.01). In conclusion, montelukast can regulate the T helper 1 (Th1)/Th2 balance, increase the expression of CD4+CD25+ regulatory T cells, and improve the airway inflammation caused by acute bronchial asthma and the clinical symptoms and lung function of patients with acute bronchial asthma.