Alterations in mitochondrial Ca2+ flux by the antibiotic X-537A (lasalocid-A)

Antônio, Regina Vasconcellos; Silva, Lúcia Pereira da; Vercesi, Anı́bal E.

doi:10.1016/s0005-2728(05)80056-8

Cited by 21 publications

(5 citation statements)

References 28 publications

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“…These results are in accordance with other study on mitochondria in different rat cultures, both primary cells and cell lines (Antonio et al 1991, Bolkent and Zierold 2002, Radko et al 2007, 2011. The cytotoxic mechanism of lasalocid action is associated with an impaired flow of ions (monovalent and divalent) through cellular membranes (Antonio et al 1991). It leads to Ca 2+ overload within mitochondria.…”

Section: Discussionsupporting

confidence: 93%

“…All in vitro studies indicated a lack of cytotoxicity of silybin (Antonio et al 1991, Oh et al 2004, Varghese et al 2005, Dvorak et al 2006, Pook et al 2006, Angeli et al 2010, Radko et al 2011. Using cytotoxicity tests, we showed that silybin in concentrations above 25 μM led to decrease of viability and growth inhibition of HepG2 cell lines after 24 h incubation.…”

Section: Discussionmentioning

confidence: 99%

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Cytoprotective effect of silybin against lasalocid-induced toxicity in HepG2 cells

Radko¹,

Cybulski²,

Rzeski³

2013

Polish Journal of Veterinary Sciences

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Lasalocid is an ionophore coccidiostatic agent frequently used in poultry. Its extensive use causes the formation of residues in edible tissues and eggs which may pose a risk to consumers. Silybin is the main compound extracted from the herb milk thistle Silybum marianum and its hepatoprotective effect has been reported in literature.The aim of the study was to compare lasalocid and silybin cytotoxic effects followed by their combined use in HepG2 cell line. A cytoprotective effect resulting from the interaction of both pharmacologically active substances was measured.In this study, an MTT test, coomassie brillant blue binding test, and LDH release test determined the effective concentration (EC 50 ) of the compounds. The isobolograms and combination index were used to assess the nature of interaction.The lowest EC 50 -value for lasalocid was established via the MTT test. This study revealed a lack of silybin cytotoxic effect on the cells. Co-actions of the two drugs led to a significant decrease of lasalocid cytotoxicity. The isobolograms and combination index showed a remarkable antagonistic effect in the course of silybin and lasalocid interaction.The results indicate that silybin revealed a cytoprotective effect when incubated with lasalocid since its cytotoxic impact on HepG2 cells has been significantly diminished.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Cytoprotective effect of silybin against lasalocid-induced toxicity in HepG2 cells

Radko¹,

Cybulski²,

Rzeski³

2013

Polish Journal of Veterinary Sciences

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“…Our findings are in accordance with other studies carried out on different cultures. The results both from primary cells and cell lines assays proved that lasalocid causes a chain of cellular damages, which lead to the death of cells [8, 27–29]. The studies on FaO and HepG2 cell lines showed clearly that lasalocid toxicity targeted cell metabolism [29, 30].…”

Section: Discussionmentioning

confidence: 99%

The Protective Effect of Silybin against Lasalocid Cytotoxic Exposure on Chicken and Rat Cell Lines

Radko

Cybulski

Rzeski

2013

BioMed Research International

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Lasalocid, an ionophore coccidiostat, extensive use implies a risk of toxicological impacts. Protective effects of silybin, a herbal compound of Silybum marianum, are reported elsewhere. The aim of this study was to compare effects of the combined use of lasalocid and silybin in chicken hepatoma cells (LMH) and rat myoblasts (L6) cell lines cultures. The cytoprotective effect resulting from an interaction of both pharmaceuticals was measured with the help of MTT reduction and, coomassie brilliant blue binding (CBB) and LDH release assays. Isobolography and the combination index (CI) estimated the nature and scale of interaction. In all performed tests, the lowest lasalocid EC50-values were obtained for chicken hepatocytes. In the rat myoblasts cultures, the lowest lasalocid EC50-values were found with LDH test. Simultaneously, a lack of silybin cytotoxic effect was proven for the studied cell lines. An interaction between both substances led to a considerable decrease of lasalocid cytotoxicity. The isobolograms and combination index showed a significant antagonistic nature of silybin effect in the course of lasalocid cytotoxicity. It is concluded that the mechanism of cytoprotection results from complex reaction at biochemical and biophysical endpoints during chicken hepatocytes and rat myoblasts cell lines exposure to silybin and lasalocid co-action.

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“…Lasalocid is another carboxylic ionophore with a broader ion specificity than monensin including the capacity to bind monovalent and divalent cations [5][6][7]. Produced by Streptomyces lasaliensis, it is widely used as a feed additive in cattle and poultry industries to control coccidiosis, a disease of the intestinal track caused by Eimeria protozoa [8,9].…”

Section: Of 13mentioning

confidence: 99%

Revisiting Old Ionophore Lasalocid as a Novel Inhibitor of Multiple Toxins

Mahtal

Cintrat

et al. 2020

Toxins

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The ionophore lasalocid is widely used as a veterinary drug against coccidiosis. We found recently that lasalocid protects cells from two unrelated bacterial toxins, the cytotoxic necrotizing factor-1 (CNF1) from Escherichia. coli and diphtheria toxin. We evaluated lasalocid’s capacity to protect cells against other toxins of medical interest comprising toxin B from Clostridium difficile, Shiga-like toxin 1 from enterohemorrhagic E. coli and exotoxin A from Pseudomonas aeruginosa. We further characterized the impact of lasalocid on the endolysosomal and the retrograde pathways and organelle integrity, especially the Golgi apparatus. We found that lasalocid protects cells from all toxins tested and impairs the drop of vesicular pH along the trafficking pathways that are required for toxin sorting and translocation to the cytoplasm. Lasalocid also has an impact on the cellular distribution of GOLPH4 and GOLPH2 Golgi markers. Other intracellular trafficking compartments positive for EEA1 and Rab9A display a modified cellular pattern. In conclusion, lasalocid protects cells from multiple deadly bacterial toxins by corrupting vesicular trafficking and Golgi stack homeostasis.

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Alterations in mitochondrial Ca2+ flux by the antibiotic X-537A (lasalocid-A)

Cited by 21 publications

References 28 publications

Cytoprotective effect of silybin against lasalocid-induced toxicity in HepG2 cells

Cytoprotective effect of silybin against lasalocid-induced toxicity in HepG2 cells

The Protective Effect of Silybin against Lasalocid Cytotoxic Exposure on Chicken and Rat Cell Lines

Revisiting Old Ionophore Lasalocid as a Novel Inhibitor of Multiple Toxins

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