Kadry Mai O, Abdel Megeed Rehab M
National Research Center, Therapeutic Chemistry Department, Al Bhoouth Street, Cairo, Egypt.
National Research Center, Therapeutic Chemistry Department, Al Bhoouth Street, Cairo, Egypt.
J Trace Elem Med Biol. 2022 Dec;74:127058. doi: 10.1016/j.jtemb.2022.127058. Epub 2022 Aug 5.
Mercuric chloride (HgCl3) is categorized as class II B hazardous metal that is present in many occupational and environmental conditions. In the meantime, Hg exists in the environment in such an abundant manner, it is virtually impossible for humans to avoid exposure to different forms of Hg. In addition to environmental exposure, individuals may be exposed to Hg from dental amalgams, medicinal treatments and dietary sources. Nevertheless, Liposomal drug delivery system is a promising era in the field of Nano-medicine and have the advantageous of increasing drug bioavailability and retention phenomena in addition to targeting organ for all mentioned the present study was designed to investigate the hypothesis that messenger RNA gene expression of Signal transducer and activator of transcription- 5 A (STAT-5A), Phosphatase and tensin homolog (PTEN), phosphoinositol kinase (PI3K) and alpha serine/threonine-protein kinase (AKT) can trigger HgCl3 induced nephrotoxicity post Ubidecarenone and liposomal Ubidecarenone therapy.
HgCl3 toxicity was induced in rats via a dose of 5 mg/kg BW for one week followed by Ubidecarenone and liposomal Ubidecarenone therapy in a dose of 10 & 3 mg/kg BW for one month, respectively. Then kidney function tests, Glutathione and gene expression for PI3K, AKT, PTEN and STAT-5A was investigated.
HgCl3 intoxication significantly up regulated PI3K, AKT, PTEN and STAT-5A signaling pathways meanwhile, Ubidecarenone and liposomal- Ubidecarenone treatment significantly reduced PI3K, AKT, PTEN and STAT-5A gene expression post HgCl3 intoxication with the liposomal regimen revealing the most significant impact. Furthermore, renal toxicity was confirmed via monitoring urea and creatinine which were modulated post Ubidecarenone and liposomal-Ubidecarenone treatment. Wide evidence declared that mercuric S-conjugates of small endogenous thiols (such as Hcy, NAC and Cys) are probably the main transportable forms of Hg to the kidneys thus reduced glutathione was investigated which reflected a significant down regulation post Hgcl3 toxicity.
liposomal drug delivery system including liposomal-Ubidecarenone can be considered as a prospective candidate for treating HgCl3 renal toxicity via modulating STAT-5A, PTEN, PI3K and AKT signaling pathways and via increasing retention time, bioavailability, shielding from macrophage recognition and targeting organs.
氯化汞（HgCl₂）被归类为II B类有害金属，存在于许多职业和环境条件中。与此同时，汞在环境中大量存在，人类几乎不可能避免接触不同形式的汞。除环境暴露外，个体还可能通过牙科汞合金、药物治疗和饮食来源接触汞。然而，脂质体药物递送系统是纳米医学领域一个有前景的时代，除了靶向器官外，还具有提高药物生物利用度和滞留现象的优势。本研究旨在探讨以下假设：在泛癸利酮和脂质体泛癸利酮治疗后，信号转导和转录激活因子-5A（STAT-5A）、磷酸酶和张力蛋白同源物（PTEN）、磷酸肌醇激酶（PI3K）和α丝氨酸/苏氨酸蛋白激酶（AKT）的信使RNA基因表达可引发HgCl₂诱导的肾毒性。
通过5mg/kg体重的剂量给大鼠诱导HgCl₂毒性一周，然后分别以10mg/kg体重和3mg/kg体重的剂量进行泛癸利酮和脂质体泛癸利酮治疗一个月。然后进行肾功能测试、谷胱甘肽以及PI3K、AKT、PTEN和STAT-5A的基因表达研究。
HgCl₂中毒显著上调PI3K、AKT、PTEN和STAT-5A信号通路，同时，泛癸利酮和脂质体泛癸利酮治疗在HgCl₂中毒后显著降低PI3K、AKT、PTEN和STAT-5A基因表达，脂质体方案显示出最显著的影响。此外，通过监测尿素和肌酐证实了肾毒性，泛癸利酮和脂质体泛癸利酮治疗后其得到了调节。大量证据表明，小内源性硫醇（如Hcy、NAC和Cys）的汞S-缀合物可能是汞向肾脏运输的主要可运输形式，因此对还原型谷胱甘肽进行了研究，其反映了HgCl₂毒性后显著下调。
包括脂质体泛癸利酮在内的脂质体药物递送系统可被视为通过调节STAT-5A、PTEN、PI3K和AKT信号通路以及通过增加滞留时间、生物利用度、避免巨噬细胞识别和靶向器官来治疗HgCl₂肾毒性的潜在候选物。
