This study investigated the effects of subchronic arsenic exposure on behavior, neurological function, and hippocampal damage in rats. Thirty-two male Wistar rats were divided into four groups and exposed to different concentrations of arsenic in their drinking water for 12 weeks, while weekly water intake and body weight were recorded. Various neurobehavioral tests were conducted, evaluating overall activity levels, exploratory behavior, short-term memory, spatial learning and memory, anxiety-like behavior, and depressive-like states. Arsenic levels in urine, serum, and brain tissue were measured, and histopathological analysis assessed hippocampal damage using hematoxylin and eosin staining. The results demonstrated that arsenic exposure did not significantly affect overall activity or exploratory behavior. However, it impaired short-term memory and spatial learning and memory functions. Arsenic-exposed rats exhibited increased anxiety-like behavior and a depressive-like state. Arsenic levels increased dose-dependently in urine, serum, and brain tissue. The histopathological examinations revealed significant hippocampal damage, including neuronal shrinkage, cell proliferation, irregular structure, disordered arrangement, and vacuolation. These findings emphasize the importance of understanding the impact of arsenic exposure on behavior and brain health, highlighting its potential neurological consequences.

Background: Hesperetin, a flavonoid derived from citrus fruits, exhibits potent antioxidant and anti-inflammatory activities and has been implicated in cartilage protection. However, its effectiveness against T-2 toxin-induced knee cartilage damage remains unclear. Methods: In this study, high-throughput sequencing analysis was employed to identify the key signaling pathways involved in T-2 toxin-induced articular cartilage damage in rats. Animal models were divided into the following groups: control, low-dose T-2 toxin, high-dose T-2 toxin, T-2 toxin + hesperetin, hesperetin, and vehicle. Pathological staining and immunohistochemistry were used to assess pathological changes, as well as the expression levels of the cartilage matrix-related proteins MMP13 and collagen II, along with the activation of the p38 MAPK signaling pathway. Additionally, primary rat chondrocytes were cultured to establish an in vitro model for investigating the underlying mechanism. Results: High-throughput sequencing analysis revealed the involvement of the MAPK signaling pathway in T-2 toxin-induced articular cartilage damage in rats. Hesperetin intervention in T-2 toxin-exposed rats attenuated pathological cartilage damage. Immunohistochemistry results demonstrated a significant reduction in collagen II protein expression in the high-dose T-2 toxin group (p < 0.01), accompanied by a significant increase in MMP13 protein expression (p < 0.01). In both the articular cartilage and the epiphyseal plate, the T-2 toxin + hesperetin group exhibited significantly higher collagen II protein expression than the high-dose T-2 toxin group (p < 0.05), along with significantly lower MMP13 protein expression (p < 0.05). Hesperetin inhibited the over-activation of the p38/MEF2C signaling axis induced by T-2 toxin in primary rat chondrocytes. Compared to the T-2 toxin group, the T-2 toxin + hesperetin group showed significantly reduced phosphorylation levels of p38 and protein expression levels of MEF2C (p < 0.001 or p < 0.05). Moreover, the T-2 toxin + hesperetin group exhibited a significant decrease in MMP13 protein expression (p < 0.05) and a significant increase in collagen II protein expression (p < 0.01) compared to the T-2 toxin group. Conclusions: T-2 toxin activates the p38 MAPK signaling pathway, causing knee cartilage damage in rats. Treatment with hesperetin inhibits the p38/MEF2C signaling axis, regulates collagen II and MMP13 protein expression, and reduces cartilage injury significantly.

Arsenic is a natural toxin which is widely distributed in the environment, incurring diverse toxicities and health problems. Previous studies have shown that long non-coding RNAs (LncRNAs) are also reported to contribute to As-induced adverse effects. LncRNAs are involved in the development of nerve injury, generally acting as sponges for microRNAs (miRNAs). This study aimed to investigate the competitive endogenous RNA (ceRNA) regulatory networks associated with arsenic-induced nerve damage. A total of 40 male Wistar rats were exposed to different doses of arsenic for 12 weeks, and samples were collected for pathological observation and high-throughput sequencing. The ceRNA network was constructed using Cytoscape, and key genes were identified through the PPI network and CytoHubba methods. A real-time quantitative PCR assay was performed to validate gene expression levels. The results showed that subchronic exposure to arsenic in drinking water resulted in pathological and ultrastructural damage to the hippocampal tissue, including changes in neuron morphology, mitochondria, and synapses. Exposure to arsenic results in the dysregulation of LncRNA and mRNA expression in the hippocampal tissues of rats. These molecules participated in multiple ceRNA axes and formed a network of ceRNAs associated with nerve injury. This study also verified key molecules within the ceRNA network and provided preliminary evidence implicating the ENRNOT-00000022622-miR-206-3p-Bdnf axis in the mechanism of neural damage induced by arsenic in rats. These findings provide novel insights into the underlying mechanism of nervous system damage induced by arsenic exposure.