Mostafa Dalia G, Ahmed Salwa Fares, Hussein Ola A
a Department of Medical Physiology, Faculty of Medicine , Assiut University , Assiut , Egypt.
b Department of Medical Physiology, College of Medicine , King Khalid University , Abha , Saudi Arabia.
Ultrastruct Pathol. 2018 Nov-Dec;42(6):516-531. doi: 10.1080/01913123.2018.1559566. Epub 2018 Dec 29.
Cadmium (Cd) has been recognized as one of the most important environmental and industrial pollutants. This study investigated the impact of acute exposure to Cd on oxidative stress and the inflammatory marker interleukin-6 (IL-6) in the plasma of rats and the histological picture of liver and kidney, as well as to examine the potential protective effect of tetrahydrobiopterin (BH4).
Rats were divided into control group, Cd group that received a single intraperitoneal (i.p.) dose of 4 mg/kg b.w. of CdCl2 and BH4+ Cd group that received a single dose of BH4 (20 mg/kg, i.p.) and subsequently exposed to a single dose of Cd 24 h after the BH4 treatment.
Cd increased the plasma levels of hepatic enzymes (ALT and AST), urea, creatinine, malondialdehyde (MDA), and IL-6 and decreased the superoxide dismutase (SOD) activity. Also, it induced histopathological alterations in the liver with severe degeneration, especially in centrilobular zones. Renal tubular epithelium showed vacuolated cytoplasm and dense nuclei. VEGF expression was mild. Ultrastuctural changes were seen in some renal tubules. The nuclei appeared distorted with electron dense chromatin. Mitochondria with destructed cristae were observed. BH4 pretreatment had protective effects, since it significantly reduced the levels of IL-6 and ameliorated the alteration in oxidative status biomarkers induced by Cd. Improvement of histopathological alterations was observed in Cd-groups. The nuclei were vesicular euchromatic, intact mitochondria and normal appearance of the filtration membrane. Moderate expression of VEGF was noted.
This study has provided clear evidence for the protective efficacy of BH4 against experimental Cd toxicity.
镉（Cd）已被公认为最重要的环境和工业污染物之一。本研究调查了急性镉暴露对大鼠血浆氧化应激和炎症标志物白细胞介素-6（IL-6）的影响以及肝脏和肾脏的组织学情况，并检测了四氢生物蝶呤（BH4）的潜在保护作用。
将大鼠分为对照组、接受单次腹腔注射4mg/kg体重CdCl2的镉组以及接受单次BH4（20mg/kg，腹腔注射）剂量并在BH4处理24小时后随后暴露于单次镉剂量的BH4+镉组。
镉增加了肝酶（ALT和AST）、尿素、肌酐、丙二醛（MDA）和IL-6的血浆水平，并降低了超氧化物歧化酶（SOD）活性。此外，它还在肝脏中诱导了组织病理学改变，伴有严重变性，尤其是在小叶中心区。肾小管上皮细胞显示细胞质空泡化和细胞核致密。VEGF表达轻微。在一些肾小管中观察到超微结构变化。细胞核出现扭曲，染色质电子密度高。观察到线粒体嵴破坏。BH4预处理具有保护作用，因为它显著降低了IL-6水平，并改善了镉诱导的氧化状态生物标志物的改变。在镉组中观察到组织病理学改变有所改善。细胞核呈泡状常染色质，线粒体完整，滤过膜外观正常。注意到VEGF有中度表达。
本研究为BH4对实验性镉毒性的保护效果提供了明确证据。
