Treatment and Prevention of Amebiasis
Roberto R. Kretschmer in Amebiasis: Infection and Disease by Entamoeba histolytica, 2020
Side-effects — The most important toxic reaction, mainly observed with clioquinol, is subacute myeloptic neuropathy. This disease, first described in Japan, appears to be restricted to that country because further cases have been rare in the rest of the world. It is noteworthy that clioquinol has been quite popular as self-medication for the treatment of “tourist-diarrhea” in many countries. A task force created in Japan for the study of the side-effects of clioquinol demonstrated a clear correlation between the use of this particular drug and the appearance of subacute optic myelopathy.44,45 In consequence, treatment with clioquinol was banned. Other side-effects of oxyquinoleins are iodine toxidermatitis, anal pruritus, and occasionally nausea and intestinal colic. Nevertheless, this drug is quite effective against exclusively intestinal amebiasis, particularly in its subacute and those claimed chronic forms and of course in the treatment of E. histolytica cyst carriers.
Alzheimer's Disease
Marc E. Agronin in Alzheimer's Disease and Other Dementias, 2014
Clioquinol (PBT1) and PBT2 are metal protein attenuating compounds that are believed to interfere with Ab42 aggregation and toxicity by removing extracellular copper and zinc that is coupled to it. Clioquinol has been shown to reduce Ab deposits in transgenic mice but also to induce myelinopathies in the central nervous system (Zhang et al., 2013). A small Phase II, placebo-controlled trial of clioquinol in 36 AD patients failed to show clinical improvement in cognition, and one patient developed impaired visual acuity and color vision likely due to the medication (Sampson, Jenagaratnam, & McShane, 2012). A similar study of PBT2 indicated that it was well tolerated in mild AD patients and appeared to benefit two tests of executive function, although not a larger outcome measure of cognition (Lannfelt et al., 2008). Additional studies of PBT2 are likely.
Confessions from an insider
Peter C. Gøtzsche, Richard Smith, Drummond Rennie in Deadly Medicines and Organised Crime, 2019
In 1966, two Swedish paediatricians studied a 3-year-old boy who had been treated with clioquinol and suffered severely impaired vision. They reported their findings in the medical literature and also informed Ciba that clioquinol was absorbed and could damage the optic nerve. These events, including the catastrophe in Japan, had no visible effect on the company that continued its marketing efforts worldwide. In 1976, clioquinol was still widely available as an over-the-counter drug for the prophylaxis and treatment of travellers’ diarrhoea despite the lack of evidence that it was effective.3 Package inserts from 35 countries showed wide variation in dosage, duration of treatment, contraindications for use, side effects and warnings; a complete mess.
Novel strategies for the fight of Alzheimer’s disease targeting amyloid-β protein
Published in Journal of Drug Targeting, 2022
Yang Xie, Yan Wang, Shangfei Jiang, Xiaohong Xiang, Jianhua Wang, Linhong Ning
In terms of the toxicity of Aβ aggregation state, Aβ-targeted agents have been mainly designed to restrain Aβ oligomerization or fibrillization, with plenty of such agents brought out successively (especially metal chelators and metal complexes), which have been reported as inhibitors interacting with Aβ species through various mechanisms [20,21]. For example, metal cations such as Cu2+ and Zn2+ is capable of coordinating with residues at the N-terminal of Aβ peptides, resulting in accelerated aggregation of Aβ and stabilised Aβ oligomers [22,23]. Hence, it has been proposed that metal-induced Aβ aggregation could be disaggregated by metal chelators, which is capable of capturing metal cations out of metal-Aβ aggregates and could be potential therapeutic agents of AD [24,25]. It has been reported that the chelation strategy designed to reduce amyloid pathology has plausibility in AD treatment [26]. In recent decades, improved cognition in Phase II clinical trials of the non-specific chelators (e.g. clioquinol (5-chloro-7-iodo-8-hydroxyquinoline)) encouraged a continued pursuit for therapeutic efficacy [27,28]. However, a quinoline derivative, PBT2, failed to show clinical benefit in a Phase 2a study in AD patients and was discontinued [29]. Besides, some kinds of natural compounds (e.g. gallic acid 30] and synthesised peptides [3]1 were proposed to have the ability of hampering Aβ pathologies through metal chelation and Aβ inhibition. The results of animal experiment demonstrated that a few metal chelating agents have exhibited therapeutic activities [32,33].
Anti-tumour activity of zinc ionophore pyrithione in human ovarian cancer cells through inhibition of proliferation and migration and promotion of lysosome-mitochondrial apoptosis
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2020
Mengge Chen, Yanpeng Ding, Yuan Ke, Yifei Zeng, Nuomin Liu, Yahua Zhong, Xinying Hua, Zheng Li, Yudi Xiong, Chaoyan Wu, Haijun Yu
Our previous studies have proved that clioquinol could transfer Zinc into cancer cells focussing on lysosome [17,18]. Then we further demonstrated that clioquinol combined with Zinc could inhibit NF-kB activity and leading cancer cells apoptosis [19]. The recent studies found that transferring Zinc into cells could also increase the radiosensitivity of nasopharyngeal cancer stem-like cells [20,21]. However, there were rarely studies to explore the influence of overloaded Zinc on ovarian cancer and the drug-resistant cells. Therefore, we researched the anti-cancer effects of ZPT combined with Zinc in this study. We emphasised the inhibiting effect of overloaded Zinc on the malignancy tumour behaviours and provided a considerable treatment strategy for ovarian cancer.
Zinc regulates reactive oxygen species generation in platelets
Published in Platelets, 2021
M.E. Lopes-Pires, N. S. Ahmed, D. Vara, J. M. Gibbins, G. Pula, N. Pugh
Zn2+-dependent activation of nucleated cells by Zn2+ is associated with concurrent MAPK activation [47,48]. To assess the effect of [Zn2+]i on MAPK- dependent signaling in platelets, we employed immunoblotting to quantify Erk1/2 (Thr202/Tyr204) and JNK (Thr183/Tyr185) phosphorylation, in response to ionophore treatment. Incubation of platelets with clioquinol (100 µM) resulted in increases of phosphorylation of both Erk1/2 and JNK (Figure 5). Quantification of immunoblots showed that clioquinol treatment resulted in increases in phosphorylation of Erk1/2 from 1.0 ± 0.07AU to 2.5 ± 0.34AU, whilst JNK phosphorylation increased from 1.97 ± 0.29AU to 3.8 ± 0.17AU relative to vehicle control (Figure 5a, p < .05). A23187 treatment (100 µM) did not significantly change the levels of phosphorylation of either Erk1/2 or JNK (Figure 5a). Further experiments were performed to investigate the role of Zn2+ in agonist-evoked phosphorylation events. Stimulation of platelets with thrombin (1 U/mL) resulted increases in phosphorylation of Erk1/2 and JNK respectively. Phosphorylation of Erk1/2 increased from 2.0 ± 0.2AU to 4.26 ± 0.24AU, whilst JNK increased from 1.6 ± 0.52AU to 5.33 ± 0.33AU, (Figure 5b, p < .05). Agonist-evoked phosphorylation was abrogated in TPEN treated platelets (Erk1/2 phosphorylation was reduced to 4.26 ± 0.24AU, and JNK to 2.89 ± 0.49AU in TPEN pre-treatment platelets). Stimulation with CRP-XL (1 μg/mL) did not result in phosphorylation of either kinase. These data indicate a specific signaling response leading to Erk1/2 and JNK phosphorylation that is dependent on Zn2+, and independent of Ca2+
Related Knowledge Centers
- Antifungal
- Dientamoeba Fragilis
- Entamoeba Histolytica
- Ionophore
- Shigella
- Virus
- Antiprotozoal
- Neurotoxicity
- 8-Hydroxyquinoline
- Subacute Myelo-Optic Neuropathy