Background:To investigate the toxicity of N-n-butyl haloperidol iodide(F2),a quaternary ammonium salt derivative of haloperidol,in mice for potential therapeutic purposes.Methods:The acute median lethal dose(LD_(50))o...Background:To investigate the toxicity of N-n-butyl haloperidol iodide(F2),a quaternary ammonium salt derivative of haloperidol,in mice for potential therapeutic purposes.Methods:The acute median lethal dose(LD_(50))of F2 was determined using the Bliss method following intravenous administration in mice.Routine surface electrocardiograms(ECGs)and arterial blood pressures(aBPs)were recorded under general anesthesia in untreated and pharmacologically vagotomized mice injected with F2.Sublethal doses of F2 were tested for their effects on aBP,heart rate,and biochemical parameters such as lactate dehydrogenase(LDH),blood urea nitrogen(BUN),and serum lactate levels.Histopathological changes in the heart,lungs,liver,and kidneys were evaluated after F2 administration.Results:The acute LD_(50)of F2 was determined to be 5.11 mg/kg.A 10 mg/kg dose of F2 caused severe hypotension,second-degree atrioventricular block,progressive prolongation of Pmurr intervals,and death due to cardiac asystole.Similar ECG and aBP changes were observed in atropine-pretreated mice,indicating that cholinergic effects do not play a major role in F2-induced toxicity.Sublethal doses of F2(1.2 and 2.4 mg/kg)caused dose-dependent decreases in aBP and increases in heart rate.F2 induced significant,dose-dependent increases in LDH,BUN,and serum lactate levels.Histopathological analysis revealed acute lung lesions at 10 mg/kg,with no significant changes observed in the heart,liver,or kidneys.Conclusion:Acute intravenous injection of F2 exhibits dose-dependent cardiopulmonary toxicity,characterized by severe hypotension,arrhythmias,and biochemical changes.These findings highlight the potential risks of F2 and the need for further evaluation of its safety profile for therapeutic use.展开更多
双氟沙星(Difloxacin,DIF)作为水产养殖上常用的氟喹诺酮类(Fluorine quinolones,FQNS)药物之一,其对水产动物的急性毒性以及组织损伤情况等研究尚且不足。以异育银鲫(Carassais auratus gibebio)为研究对象,研究DIF对异育银鲫的急性毒...双氟沙星(Difloxacin,DIF)作为水产养殖上常用的氟喹诺酮类(Fluorine quinolones,FQNS)药物之一,其对水产动物的急性毒性以及组织损伤情况等研究尚且不足。以异育银鲫(Carassais auratus gibebio)为研究对象,研究DIF对异育银鲫的急性毒性,以及DIF在其96 h半数致死剂量(96 h LD_(50))剂量下的组织残留和损伤情况。结果显示,DIF对体质量为(60.04±5.02)g异育银鲫的96 h LD_(50)为2 840 mg/kg。另外,在其96 h LD_(50)剂量用药后,异育银鲫呈现胸鳍、腹鳍僵直、震颤等类似神经异常症状;同时其在肝脏、肾脏组织中的残留分别为(73.36±2.17)μg/g和(4.33±0.35)μg/g;另外组织切片结果显示,在DIF 96 h LD_(50)剂量下肝脏出现细胞核严重变形、核仁浓缩、破裂甚至溶解消失等病理变化;肾脏呈现血管球轻微皱缩,肾小管上皮细胞界线模糊、细胞核溶解等病理变化。以上结果表明,根据我国《生物技术检测规范(水环境部分)》将药物对水生动物毒性所分等级的相关规定,DIF对异育银鲫为低毒物质;但在其96 h LD_(50)剂量下,异育银鲫出现了严重的临床症状和组织损伤。展开更多
基金National Natural Science Foundation of China,Grant/Award Number:81903613。
文摘Background:To investigate the toxicity of N-n-butyl haloperidol iodide(F2),a quaternary ammonium salt derivative of haloperidol,in mice for potential therapeutic purposes.Methods:The acute median lethal dose(LD_(50))of F2 was determined using the Bliss method following intravenous administration in mice.Routine surface electrocardiograms(ECGs)and arterial blood pressures(aBPs)were recorded under general anesthesia in untreated and pharmacologically vagotomized mice injected with F2.Sublethal doses of F2 were tested for their effects on aBP,heart rate,and biochemical parameters such as lactate dehydrogenase(LDH),blood urea nitrogen(BUN),and serum lactate levels.Histopathological changes in the heart,lungs,liver,and kidneys were evaluated after F2 administration.Results:The acute LD_(50)of F2 was determined to be 5.11 mg/kg.A 10 mg/kg dose of F2 caused severe hypotension,second-degree atrioventricular block,progressive prolongation of Pmurr intervals,and death due to cardiac asystole.Similar ECG and aBP changes were observed in atropine-pretreated mice,indicating that cholinergic effects do not play a major role in F2-induced toxicity.Sublethal doses of F2(1.2 and 2.4 mg/kg)caused dose-dependent decreases in aBP and increases in heart rate.F2 induced significant,dose-dependent increases in LDH,BUN,and serum lactate levels.Histopathological analysis revealed acute lung lesions at 10 mg/kg,with no significant changes observed in the heart,liver,or kidneys.Conclusion:Acute intravenous injection of F2 exhibits dose-dependent cardiopulmonary toxicity,characterized by severe hypotension,arrhythmias,and biochemical changes.These findings highlight the potential risks of F2 and the need for further evaluation of its safety profile for therapeutic use.
文摘双氟沙星(Difloxacin,DIF)作为水产养殖上常用的氟喹诺酮类(Fluorine quinolones,FQNS)药物之一,其对水产动物的急性毒性以及组织损伤情况等研究尚且不足。以异育银鲫(Carassais auratus gibebio)为研究对象,研究DIF对异育银鲫的急性毒性,以及DIF在其96 h半数致死剂量(96 h LD_(50))剂量下的组织残留和损伤情况。结果显示,DIF对体质量为(60.04±5.02)g异育银鲫的96 h LD_(50)为2 840 mg/kg。另外,在其96 h LD_(50)剂量用药后,异育银鲫呈现胸鳍、腹鳍僵直、震颤等类似神经异常症状;同时其在肝脏、肾脏组织中的残留分别为(73.36±2.17)μg/g和(4.33±0.35)μg/g;另外组织切片结果显示,在DIF 96 h LD_(50)剂量下肝脏出现细胞核严重变形、核仁浓缩、破裂甚至溶解消失等病理变化;肾脏呈现血管球轻微皱缩,肾小管上皮细胞界线模糊、细胞核溶解等病理变化。以上结果表明,根据我国《生物技术检测规范(水环境部分)》将药物对水生动物毒性所分等级的相关规定,DIF对异育银鲫为低毒物质;但在其96 h LD_(50)剂量下,异育银鲫出现了严重的临床症状和组织损伤。
