Lead (Pb) is a toxic heavy metal and environmental pollutant that adversely affects the nervous system. However, effective therapeutic drugs for Pb-induced neurotoxicity have yet to be developed. In the present study, we investigated the ameliorative effect of sodium para-aminosalicylic acid (PAS-Na) on Pb-induced neurotoxicity. Male Sprague–Dawley rats were treated with (CH₃COO)₂ Pb•4H₂O (6 mg/kg) for 4 weeks, followed by 3 weeks of PAS-Na (100, 200, and 300 mg/kg). The results showed that subacute Pb exposure significantly decreased rats body-weight gains and increased liver coefficient, and impaired spatial learning and memory. HE staining showed that Pb damaged the structure of the hippocampus. Moreover, Pb activated the ERK1/2-p90^RSK/ NF-κB pathway concomitant with increased inflammatory cytokine IL-1β levels in rat hippocampus. PAS-Na reversed the Pb-induced increase in the liver coefficient as well as the learning and memory deficits. In addition, PAS-Na reduced the phosphorylation of ERK1/2, p90^RSK and NF-κB p65, decreasing IL-1β levels in hippocampus. Our findings indicated that PAS-Na showed efficacy in reversing Pb-induced rats cognitive deficits and triggered an anti-inflammatory response. Thus, PAS-Na may be a promising therapy for treating Pb-induced neurotoxicity.

铅 (Pb) 是一种有毒重金属和环境污染物，会对神经系统产生不利影响。然而，尚未开发出针对铅诱导的神经毒性的有效治疗药物。在本研究中，我们研究了对氨基水杨酸钠 (PAS-Na) 对铅诱导的神经毒性的改善作用。雄性 Sprague-Dawley 大鼠用 (CH ₃ COO) ₂ Pb•4H ₂ O (6 mg/kg) 处理 4 周，然后用 PAS-Na（100、200 和 300 mg/kg）处理 3 周。结果表明，亚急性铅暴露显着降低大鼠体重增加和肝系数增加，并损害空间学习和记忆。HE染色显示Pb破坏了海马结构。此外，Pb 激活了 ERK1/2-p90 ^RSK/ NF-κB 通路伴随大鼠海马中炎症细胞因子 IL-1β 水平升高。PAS-Na 逆转了铅诱导的肝系数增加以及学习和记忆缺陷。此外，PAS-Na 降低了 ERK1/2、p90 ^RSK和 NF-κB p65 的磷酸化，降低了海马中的 IL-1β 水平。我们的研究结果表明，PAS-Na 在逆转铅诱导的大鼠认知缺陷方面显示出功效，并引发了抗炎反应。因此，PAS-Na 可能是治疗 Pb 诱导的神经毒性的一种有前途的疗法。