Dataset Information

Hemoadsorption Improves Survival of Rats Exposed to an Acutely Lethal Dose of Aflatoxin B1.

ABSTRACT: Mycotoxins, such as aflatoxin B1 (AFB1), pose a serious threat as biological weapons due to their high toxicity, environmental stability, easy accessibility and lack of effective therapeutics. This study investigated if blood purification therapy with CytoSorb (CS) porous polymer beads could improve survival after a lethal aflatoxin dose (LD90). The effective treatment window and potential therapeutic mechanisms were also investigated. Sprague Dawley rats received a lethal dose of AFB1 (0.5-1.0?mg/kg) intravenously and hemoperfusion with a CS or Control device was initiated immediately, or after 30, 90, or 240-minute delays and conducted for 4?hours. The CS device removes AFB1 from circulation and significantly improves survival when initiated within 90?minutes of toxin administration. Treated subjects exhibited improved liver morphology and health scores. Changes in the levels of cytokines, leukocytes and platelets indicate a moderately-severe inflammatory response to acute toxin exposure. Quantitative proteomic analysis showed significant changes in the level of a broad spectrum of plasma proteins including serine protease/endopeptidase inhibitors, coagulation factors, complement proteins, carbonic anhydrases, and redox enzymes that ostensibly contribute to the therapeutic effect. Together, these results suggest that hemoadsorption with CS could be a viable countermeasure against acute mycotoxin exposure.

SUBMITTER: Ruggeberg KG

PROVIDER: S-EPMC6972926 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Hemoadsorption Improves Survival of Rats Exposed to an Acutely Lethal Dose of Aflatoxin B1.

Ruggeberg Karl-Gustav KG O'Sullivan Pamela P Kovacs Timothy J TJ Dawson Kathryn K Capponi Vincent J VJ Chan Phillip P PP Golobish Thomas D TD Gruda Maryann C MC

Scientific reports 20200121 1

Mycotoxins, such as aflatoxin B1 (AFB1), pose a serious threat as biological weapons due to their high toxicity, environmental stability, easy accessibility and lack of effective therapeutics. This study investigated if blood purification therapy with CytoSorb (CS) porous polymer beads could improve survival after a lethal aflatoxin dose (LD90). The effective treatment window and potential therapeutic mechanisms were also investigated. Sprague Dawley rats receive ...[more]

PMID: 31964964

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Project description:We have previously shown that the antimalarial agent chloroquine can abrogate the lethal cellular effects of low-dose-rate (LDR) radiation in vitro, most likely by activating the ataxia-telangiectasia mutated (ATM) protein. Here, we demonstrate that chloroquine treatment also protects against lethal doses of LDR radiation in vivo.C57BL/6 mice were irradiated with a total of 12.8 Gy delivered at 9.4 cGy/hour. ATM null mice from the same background were used to determine the influence of ATM. Chloroquine was administered by two intraperitoneal injections of 59.4 ?g per 17 g of body weight, 24 hours and 4 hours before irradiation. Bone marrow cells isolated from tibia, fibula, and vertebral bones were transplanted into lethally irradiated CD45 congenic recipient mice by retroorbital injection. Chimerism was assessed by flow cytometry. In vitro methylcellulose colony-forming assay of whole bone marrow cells and fluorescence activated cell sorting analysis of lineage depleted cells were used to assess the effect of chloroquine on progenitor cells.Mice pretreated with chloroquine before radiation exhibited a significantly higher survival rate than did mice treated with radiation alone (80% vs. 31%, p = 0.0026). Chloroquine administration before radiation did not affect the survival of ATM null mice (p = 0.86). Chloroquine also had a significant effect on the early engraftment of bone marrow cells from the irradiated donor mice 6 weeks after transplantation (4.2% vs. 0.4%, p = 0.015).Chloroquine administration before radiation had a significant effect on the survival of normal but not ATM null mice, strongly suggesting that the in vivo effect, like the in vitro effect, is also ATM dependent. Chloroquine improved the early engraftment of bone marrow cells from LDR-irradiated mice, presumably by protecting the progenitor cells from radiation injury. Chloroquine thus could serve as a very useful drug for protection against the harmful effects of LDR radiation.

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Hemoadsorption Improves Survival of Rats Exposed to an Acutely Lethal Dose of Aflatoxin B1.

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Hemoadsorption Improves Survival of Rats Exposed to an Acutely Lethal Dose of Aflatoxin B<sub>1</sub>.

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