Ajeel Mohammed Abdullah, Al-Robaiee Israa A
Department of Clinical Laboratory Science, College of Pharmacy, University of Mosul, Mosul, Iraq.
Department of Internal and Preventive Medicine, College of Veterinary Medicine, University of Mosul, Mosul, Iraq.
Open Vet J. 2024 Dec;14(12):3219-3231. doi: 10.5455/OVJ.2024.v14.i12.7. Epub 2024 Dec 31.
The gamma-aminobutyric acid (GABA) receptors are considered the main inhibitory neurotransmitter receptors in the mammalian brain and they have been proven to be existing in non-neuronal cells.
Lorazepam which is one of the benzodiazepines, drugs known for their effect of GABA receptors, has been used in this study as an enhancer to determine the impact of GABA activity enhancement on renal and liver functions, molecular and histological characteristics in male albino mice.
Male albino mice were divided into 3 groups (each has 7 animals) each group was treated with a different dose of lorazepam and 9 animals served as a control group. The molecular parameters included the usage of raped-polymerase chain reaction to detect any universal variations. The histological changes were detected using hematoxylin and eosin histopathological examination. Liver and kidney function tests were utilized to detect any functional changes.
The results of the functional parameters [serum urea, creatinine, glutamate-oxaloacetic transaminase, glutamate-pyruvic transaminase, gamma glutamyl enzyme (GGT)] and histopathological examination demonstrated that there was a significant change in treated groups compared to the control group. As for the molecular study, 7 primers out of 10 gave single and polymorphic bands using the random amplification of polymorphic DNA (RAPD) technique. The results revealed great changes in RAPD profiles of treated groups as normal bands lost and new bands appeared in comparison with the control group. The RAPD profiles of the treated and control samples gave 432 bands, 109 as control bands, 167 (loss of normal bands and appearance of new bands) as polymorphic bands, and 156 as homomorphic bands.
The marked changes in various biochemical, histopathological, and random amplified polymorphic DNA-polymerase chain reaction profiles indicate that lorazepam-mediated GABA modulation brings about widespread alterations in peripheral organ systems. Taken together, these data suggest caution in the use of lorazepam clinically and potentially represent an unmet need for safer therapeutic alternatives or strategies to limit benzodiazepine-induced organ toxicity.
γ-氨基丁酸（GABA）受体被认为是哺乳动物大脑中主要的抑制性神经递质受体，并且已被证实在非神经元细胞中也存在。
氯硝西泮是苯二氮䓬类药物之一，这类药物以其对GABA受体的作用而闻名，在本研究中被用作增强剂，以确定GABA活性增强对雄性白化小鼠的肾和肝功能、分子及组织学特征的影响。
将雄性白化小鼠分为3组（每组7只动物），每组用不同剂量的氯硝西泮进行处理，9只动物作为对照组。分子参数包括使用随机扩增多态性DNA（RAPD）技术检测任何普遍变异。使用苏木精和伊红组织病理学检查来检测组织学变化。利用肝肾功能测试来检测任何功能变化。
功能参数[血清尿素、肌酐、谷草转氨酶、谷丙转氨酶、γ-谷氨酰酶（GGT）]和组织病理学检查结果表明，与对照组相比，处理组有显著变化。至于分子研究，使用RAPD技术时，10个引物中有7个产生了单一条带和多态性条带。结果显示，与对照组相比，处理组的RAPD图谱有很大变化，正常条带丢失，新条带出现。处理组和对照组样本的RAPD图谱产生了432条带，其中109条为对照条带，167条（正常条带丢失和新条带出现）为多态性条带，156条为同形条带。
各种生化、组织病理学和随机扩增多态性DNA - 聚合酶链反应图谱的显著变化表明，氯硝西泮介导的GABA调节会导致外周器官系统发生广泛改变。综上所述，这些数据提示临床上使用氯硝西泮时需谨慎，并且可能代表了对更安全治疗替代方案或策略以限制苯二氮䓬类药物引起的器官毒性的未满足需求。
