A Comparative Analysis of In Vitro Toxicity of Synthetic Zeolites on IMR-90 Human Lung Fibroblast Cells.

Broad industrial application of zeolites increases the opportunity of inhalation. However, the potential impact of different types and compositions of zeolite on cytotoxicity is still unknown. Four types of synthetic zeolites have been prepared for assessing the effect on lung fibroblast: two zeolite L (LTL-R and LTL-D), ZSM-5 (MFI-S), and faujasite (FAU-S). The cytotoxicity of zeolites on human lung fibroblast (IMR-90) was assessed using WST1 cell proliferation assay, mitochondrial function, membrane leakage of lactate dehydrogenase, reduced glutathione levels, and mitochondrial membrane potential were assessed under control. Intracellular changes were examined using transmission electron microscopy (TEM). Toxicity-related gene expressions were evaluated by PCR array. The result showed significantly higher toxicity in IMR-90 cells with FAU-S than LTL-R, LTL-D and MFI-S exposure. TEM showed FAU-S, spheroidal zeolite with a low Si/Al ratio, was readily internalized forming numerous phagosomes in IMR-90 cells, while the largest and disc-shaped zeolites showed the lowest toxicity and were located in submembranous phagosomes in IMR-90 cells. Differential expression of TNF related genes was detected using PCR arrays and confirmed using qRT-PCR analysis of selected genes. Collectively, the exposure of different zeolites shows different toxicity on IMR-90 cells.

Hydroxycitrate: a potential new therapy for calcium urolithiasis.

Alkali supplements are used to treat calcium kidney stones owing to their ability to increase urine citrate excretion which lowers stone risk by inhibiting crystallization and complexing calcium. However, alkali increases urine pH, which may reduce effectiveness for patients with calcium phosphate stones and alkaline urine. Hydroxycitrate is a structural analog of citrate, widely available as an over-the-counter supplement for weight reduction. In vitro studies show hydroxycitrate has the capacity to complex calcium equivalent to that of citrate and that it is an effective inhibitor of calcium oxalate monohydrate crystallization. In fact, hydroxycitrate was shown to dissolve calcium oxalate crystals in supersaturated solution in vitro. Hydroxycitrate is not known to be metabolized by humans, so it would not be expected to alter urine pH, as opposed to citrate therapy. Preliminary studies have shown orally ingested hydroxycitrate is excreted in urine, making it an excellent candidate as a stone therapeutic. In this article, we detail the crystal inhibition activity of hydroxycitrate, review the current knowledge of hydroxycitrate use in humans, and identify gaps in knowledge that require appropriate research studies before hydroxycitrate can be recommended as a therapy for kidney stones.

Antimalarials inhibit hematin crystallization by unique drug-surface site interactions.

In malaria pathophysiology, divergent hypotheses on the inhibition of hematin crystallization posit that drugs act either by the sequestration of soluble hematin or their interaction with crystal surfaces. We use physiologically relevant, time-resolved in situ surface observations and show that quinoline antimalarials inhibit ß-hematin crystal surfaces by three distinct modes of action: step pinning, kink blocking, and step bunch induction. Detailed experimental evidence of kink blocking validates classical theory and demonstrates that this mechanism is not the most effective inhibition pathway. Quinolines also form various complexes with soluble hematin, but complexation is insufficient to suppress heme detoxification and is a poor indicator of drug specificity. Collectively, our findings reveal the significance of drug-crystal interactions and open avenues for rationally designing antimalarial compounds.