Toxicology Studies of Antimycin, a Fish Eradicant

Herr, F.; Greselin, E.; Chappel, C.I.

doi:10.1577/1548-8659(1967)96[320:tsoaaf]2.0.co;2

Cited by 10 publications

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“…The recombinant Cba87 strain of WEEV is highly pathogenic in mice [ 56 ], and initial dose-titration experiments indicated that a subcutaneous inoculum of 10 3 pfu routinely produced high mortality in C57BL/6 mice by 14 days after infection with a mean time to death (MTD) of approximately 11 days (data not shown). Antimycin A toxicity is species-dependent and varies widely, from an oral LD 50 of less than 0.2 mg/kg for fish to greater than 50 mg/kg for mice [ 57 ]. The intraperitoneal LD 50 for mice is 1-2 mg/kg [ 57 , 58 ], and therefore we tested three doses: 1 mg/kg, 0.2 mg/kg, and 0.02 mg/kg delivered via intraperitoneal injection twice daily for 7 days starting on the day of infection.…”

Section: Resultsmentioning

confidence: 99%

“…Antimycin A toxicity is species-dependent and varies widely, from an oral LD 50 of less than 0.2 mg/kg for fish to greater than 50 mg/kg for mice [ 57 ]. The intraperitoneal LD 50 for mice is 1-2 mg/kg [ 57 , 58 ], and therefore we tested three doses: 1 mg/kg, 0.2 mg/kg, and 0.02 mg/kg delivered via intraperitoneal injection twice daily for 7 days starting on the day of infection. Initial experiments showed that 1 mg/kg antimycin A accelerated WEEV-induced disease with an MTD of approximately 7 days (data not shown).…”

Section: Resultsmentioning

confidence: 99%

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Discovery of Potent Broad Spectrum Antivirals Derived from Marine Actinobacteria

et al. 2013

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Natural products provide a vast array of chemical structures to explore in the discovery of new medicines. Although secondary metabolites produced by microbes have been developed to treat a variety of diseases, including bacterial and fungal infections, to date there has been limited investigation of natural products with antiviral activity. In this report, we used a phenotypic cell-based replicon assay coupled with an iterative biochemical fractionation process to identify, purify, and characterize antiviral compounds produced by marine microbes. We isolated a compound from Streptomyces kaviengensis, a novel actinomycetes isolated from marine sediments obtained off the coast of New Ireland, Papua New Guinea, which we identified as antimycin A1a. This compound displays potent activity against western equine encephalitis virus in cultured cells with half-maximal inhibitory concentrations of less than 4 nM and a selectivity index of greater than 550. Our efforts also revealed that several antimycin A analogues display antiviral activity, and mechanism of action studies confirmed that these Streptomyces-derived secondary metabolites function by inhibiting the cellular mitochondrial electron transport chain, thereby suppressing de novo pyrimidine synthesis. Furthermore, we found that antimycin A functions as a broad spectrum agent with activity against a wide range of RNA viruses in cultured cells, including members of the Togaviridae, Flaviviridae, Bunyaviridae, Picornaviridae, and Paramyxoviridae families. Finally, we demonstrate that antimycin A reduces central nervous system viral titers, improves clinical disease severity, and enhances survival in mice given a lethal challenge with western equine encephalitis virus. Our results provide conclusive validation for using natural product resources derived from marine microbes as source material for antiviral drug discovery, and they indicate that host mitochondrial electron transport is a viable target for the continued development of broadly active antiviral compounds.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Discovery of Potent Broad Spectrum Antivirals Derived from Marine Actinobacteria

et al. 2013

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“…Antimycin (trade name, Fintrol) was selected as the fish toxicant. Antimycin has several desirable qualities, including specificity (Walker et al 1964;Herr et al 1967;Schnick 1974aSchnick , 1974b, lack of repellency (Binns 1967;Lennon et al 1970), short exposure time (Gilderhus 1972), and rapid biodegradation (Walker et al 1964;Lee et al 1971;Marking and Dawson 1972). This toxin has been widely used since the early 1960s for renovation projects (Lennon et al 1970), and it has been used in several national parks (including Yellowstone National Park) and wilderness areas in conjunction with programs designed to protect or reintroduce native fishes (Varley et al 1976;USFWS 1985;Coman, no date).…”

Section: Methodsmentioning

confidence: 99%

“…Although information concerning the toxin concentration required for removal of particular species has increased in the last two decades (Herr et al 1967;Gilderhus 1972), streamside bioassays are still important. Toxicity trials before initial application provide valuable information concerning the effects of water temperature and pH on toxin effectiveness, and pretreatment bioassays are recommended for future eradication projects.…”

Section: Arnica Creekmentioning

confidence: 99%

Use of Antimycin for Removal of Brook Trout from a Tributary of Yellowstone Lake

Gresswell

1991

North American Journal of Fisheries Management

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A major spawning migration of native Yellowstone cutthroat trout Oncorhynchus clarki bouvieri occurs in Arnica Creek, a tributary of Yellowstone Lake. An introduced population of brook trout Salvelinus fontinalis was detected in Arnica Creek in May 1985. Subsequent electrofishing surveys of 40 additional tributaries of Yellowstone Lake revealed that brook trout were restricted to Arnica Creek. Because of undesirable ecological consequences to Yellowstone Lake, the U.S. National Park Service decided to eradicate the brook trout population. The Arnica Creek drainage, including a 23.6‐hectare lagoon, was treated with antimycin in August 1985. A second application in August 1986 was limited to the stream. Posttreatment surveys in 1987, 1988, and 1989 indicated that brook trout were eliminated, and spawning migrations of cutthroat from Yellowstone Lake have remained viable. Application techniques and accurate estimates of toxin dispersal within the stream appeared to be the most critical variables affecting treatment success.

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“…Environmental persistence is reduced by factors that accelerate decomposition of the relatively large antimycin molecule; such factors include increased water temperature, turbidity, high pH, and sunlight exposure (Lee et al 1971;Marking and Dawson 1972). Degraded byproducts have an insignificant level of toxicity to fish and mammals (Herr et al 1967).…”

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confidence: 99%

Effects of Antimycin and its Neutralizing Agent, Potassium Permanganate, on Aquatic Macroinvertebrates in a Great Smoky Mountains National Park Watershed

Gibbs

Kulp²,

Moore³

et al. 2015

N American J Fish Manag

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We assessed the effects of antimycin (Fintrol) on benthic macroinvertebrates during a large Brook Trout Salvelinus fontinalis restoration project in the southeastern United States. Control and treatment sites were established in first‐ through fourth‐order streams throughout the watershed and below the fish passage barrier where a neutralizing agent (potassium permanganate [KMnO4]) was administered. Hess samples were collected before and after chemical application (short term: 1 and 2 months after; long term: 9 and 12 months after). Analysis of similarity, nonmetric multidimensional scaling, and repeated‐measures ANOVA were used to determine differences in assemblage metrics among control, treatment, and neutralization sites over time. Macroinvertebrate communities and their responses to antimycin were different at downstream (third‐ and fourth‐order) sites relative to headwater (first‐ and second‐order) sites. Overall, abundances (especially stonefly and caddisfly abundances) increased after antimycin application, reflecting a positive response within the macroinvertebrate assemblage. Several variables, including mayfly and stonefly abundances, were significantly different among control, concentrated‐KMnO4, and dilute‐KMnO4 sites; however, differences were undetectable after 9 months. Many taxa were substantially more abundant several months after treatment, indicating a thriving macroinvertebrate assemblage throughout the watershed. Future studies yielding similar results would suggest that native fish stocking efforts can commence shortly after chemical degradation. Received May 2, 2014; accepted September 10, 2015

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Toxicology Studies of Antimycin, a Fish Eradicant

Cited by 10 publications

References 0 publications

Discovery of Potent Broad Spectrum Antivirals Derived from Marine Actinobacteria

Discovery of Potent Broad Spectrum Antivirals Derived from Marine Actinobacteria

Use of Antimycin for Removal of Brook Trout from a Tributary of Yellowstone Lake

Effects of Antimycin and its Neutralizing Agent, Potassium Permanganate, on Aquatic Macroinvertebrates in a Great Smoky Mountains National Park Watershed

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