Badar Ahmed, Ahmed Ayesha, Al-Tamimi Dalal M, Isab Anvarhusein A, Altaf Muhammad, Ahmed Sania
Department of Physiology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia.
Department of Pathology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia.
Pharmaceutics. 2021 Sep 23;13(10):1530. doi: 10.3390/pharmaceutics13101530.
Bipyridine gold (III) dithiocarbamate compounds are Gold-III complexes with promising cytotoxic properties. In this study, the subacute toxicity of a Gold (III) complex with dithiocarbamate ligand was evaluated. In the acute toxicity component, an initial LD (38.46 mg/kg) was calculated by the administration of 50, 100, 200, 400, and 800 mg/kg of the compound to five groups of rats, respectively ( = 4 each). The sixth group was the control. The sub-acute toxicity component comprised the control group A ( = 6) and the study groups B ( = 10) and C ( = 4), which were administered 1 mL distilled water, 1/10 LD (3.8 mg/kg), and 1/5 LD (7.6 mg/kg), respectively, daily for 6 weeks. The alive animals were then sacrificed. Autopsy; preservation of renal, hepatic and cardiac tissue in buffered formalin; histopathological processing; microscopic evaluation; and comparison with the controls were sequentially conducted. In the subacute toxicity study at dosages of 3.8 mg/kg and 7.6 mg/kg, the renal tubules remained unaffected with no necrosis or vacuolization. Mild to moderate renal interstitial, hepatic capsular, lobular and portal inflammation along with mild focal hepatic vacuolization were present. At 3.8 mg/kg, the cardiac muscle fibers were unremarkable in 80% ( = 8) of the specimens, with mild focal hyalinization in 20% ( = 2) of the specimens. The same was observed in 50% ( = 2) of the specimens at 7.6 mg/kg. Variable congestion was evident in all of the groups. In the subacute toxicity study, the absence of renal tubular necrosis or vacuolization, the presence of mild inflammatory hepatic and renal alterations, and predominantly unremarkable cardiac muscle fibers suggest that Bipyridine gold (III)-dithiocarbamate is safe in animal studies and is a potential candidate for clinical trials.
联吡啶金(III)二硫代氨基甲酸盐化合物是具有潜在细胞毒性特性的金(III)配合物。在本研究中,评估了一种含二硫代氨基甲酸盐配体的金(III)配合物的亚急性毒性。在急性毒性部分,通过分别给五组大鼠施用50、100、200、400和800mg/kg的该化合物来计算初始半数致死剂量(LD,38.46mg/kg)(每组n = 4)。第六组为对照组。亚急性毒性部分包括对照组A(n = 6)以及研究组B(n = 10)和C(n = 4),它们分别每天给予1mL蒸馏水、1/10 LD(3.8mg/kg)和1/5 LD(7.6mg/kg),持续6周。然后对存活的动物实施安乐死。依次进行尸检;将肾、肝和心脏组织保存在缓冲甲醛中;进行组织病理学处理;显微镜评估;以及与对照组进行比较。在3.8mg/kg和7.6mg/kg剂量的亚急性毒性研究中,肾小管未受影响,没有坏死或空泡化。存在轻度至中度的肾间质、肝包膜、小叶和门脉炎症以及轻度局灶性肝空泡化。在3.8mg/kg时,80%(n = 8)的标本中心肌纤维无明显异常,20%(n = 2)的标本中有轻度局灶性玻璃样变。在7.6mg/kg时,50%(n = 2)的标本中观察到同样情况。所有组中均可见不同程度的充血。在亚急性毒性研究中,肾小管无坏死或空泡化、存在轻度肝脏和肾脏炎症改变以及心肌纤维大多无明显异常,这表明联吡啶金(III)-二硫代氨基甲酸盐在动物研究中是安全的,是临床试验的潜在候选药物。