Sodium para‐aminosalicylic acid attenuates combined manganese/iron‐induced cortical synaptic damage in rats

• Published in: Basic & clinical pharmacology & toxicology Vol. 135; no. 1; pp. 81 - 97
• Main Authors: Song, Han‐Xiao, Xie, Yu‐Han, Fang, Yuan‐Yuan, Lin, Jun‐Jie, Wang, Lei‐Lei, Gan, Cui‐liu, Aschner, Michael, Jiang, Yue‐Ming
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.07.2024
• Subjects: Aminosalicylic Acid - pharmacology; Animal models; Animals; Cell death; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Cerebral Cortex - pathology; Cognitive ability; cognitive dysfunction; Damage; Disease Models, Animal; Exposure; Ferromanganese; Gene expression; In vivo methods and tests; Iron; Iron - metabolism; Learning; Male; Manganese; Manganese - toxicity; Maze Learning - drug effects; Memory; Neuroprotective Agents - pharmacology; Neurotoxicity; Neurotoxicity Syndromes - etiology; Neurotoxicity Syndromes - pathology; Neurotoxicity Syndromes - prevention & control; PC12 Cells; Pheochromocytoma cells; Polymerase chain reaction; Presynapse; Rats; Rats, Sprague-Dawley; Reverse transcription; Sodium; sodium para‐aminosalicylate acid; Synapses - drug effects; synaptic damage; Synergistic effect; iron; synaptic damage; cognitive dysfunction; manganese; sodium para‐aminosalicylate acid
• ISSN: 1742-7835; 1742-7843; 1742-7843
• DOI: 10.1111/bcpt.14033

We established experimental models of manganese (Mn) and iron (Fe) exposure in vitro and in vivo, and addressed the effects of manganese and iron combined exposure on the synaptic function of pheochromocytoma derived cell line 12 (PC12) cells and rat cortex, respectively. We investigated the protective effect of sodium para‐aminosalicylate (PAS‐Na) on manganese and iron combined neurotoxicity, providing a scientific basis for the prevention and treatment of ferromanganese combined neurotoxicity. Western blot and reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) were performed to detect the expression levels of protein and mRNA related to synaptic damage. Y‐maze novelty test and balance beam test were used to evaluate the motor and cognitive function of rats. Haematoxylin and eosin (H&E) and Nissl staining were performed to observe the cortical damage of rats. The results showed that the combined exposure of Mn and Fe in rats led to a synergistic effect, attenuating growth and development, and altering learning and memory as well as motor function. The combination of Mn and Fe also caused damage to the synaptic structure of PC12 cells, which is manifested as swelling of dendrites and axon terminals, and even lead to cell death. PAS‐Na displayed some antagonistic effects against the Mn‐ and Fe‐induced synaptic structural damage, growth, learning and memory impairment.