title: The Cardiovascular and Neurotoxic Effects of the  Venoms of Six Bony and Cartilaginous Fish Species.
abstract: Fish venoms are often poorly studied, in part due to the difficulty in obtaining, extracting, and storing them. In this study, we characterize the cardiovascular and neurotoxic effects of the venoms from the following six species of fish: the cartilaginous stingrays Neotrygon kuhlii and Himantura toshi, and the bony fish Platycephalus fucus, Girella tricuspidata, Mugil cephalus, and Dentex tumifrons. All venoms (10-100 μg/kg, i.v.), except G. tricuspidata and P. fuscus, induced a biphasic response on mean arterial pressure (MAP) in the anesthetised rat. P. fucus venom exhibited a hypotensive response, while venom from G. tricuspidata displayed a single depressor response. All venoms induced cardiovascular collapse at 200 μg/kg, i.v. The in vitro neurotoxic effects of venom were examined using the chick biventer cervicis nerve-muscle (CBCNM) preparation. N. kuhlii, H. toshi, and P. fucus venoms caused concentration-dependent inhibition of indirect twitches in the CBCNM preparation. These three venoms also inhibited responses to exogenous acetylcholine (ACh) and carbachol (CCh), but not potassium chloride (KCl), indicating a post-synaptic mode of action. Venom from G. tricuspidata, M. cephalus, and D. tumifrons had no significant effect on indirect twitches or agonist responses in the CBCNM. Our results demonstrate that envenoming by these species of fish may result in moderate cardiovascular and/or neurotoxic effects. Future studies aimed at identifying the molecules responsible for these effects could uncover potentially novel lead compounds for future pharmaceuticals, in addition to generating new knowledge about the evolutionary relationships between venomous animals.
authors.affiliation: Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia. hhan24@student.monash.edu.
authors.forename: Han
authors.initials: H
authors.lastname: Han
authors.affiliation: Venom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, QLD 4072, Australia. kate.baumann@uqconnect.edu.au.
authors.forename: Kate
authors.initials: K
authors.lastname: Baumann
authors.affiliation: Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK. nicholas.casewell@lstmed.ac.uk.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Casewell
authors.affiliation: Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia. dr.syedabidali@gmail.com.|HEJ Research Institute of Chemistry, International Centre for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi 75270, Pakistan. dr.syedabidali@gmail.com.
authors.forename: Syed A
authors.initials: SA
authors.lastname: Ali
authors.affiliation: Venom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, QLD 4072, Australia. jordan.debono@uqconnect.edu.au.
authors.forename: James
authors.initials: J
authors.lastname: Dobson
authors.affiliation: Venom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, QLD 4072, Australia. ivan.koludarov@uq.net.au.
authors.forename: Ivan
authors.initials: I
authors.lastname: Koludarov
authors.affiliation: Venom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, QLD 4072, Australia. jordan.debono@uqconnect.edu.au.
authors.forename: Jordan
authors.initials: J
authors.lastname: Debono
authors.affiliation: Marine Parisitology Group, School of Biological Sciences, University of Queensland, St Lucia, QLD 4072, Australia. scott.cutmore@uqconnect.edu.au.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Cutmore
authors.affiliation: Baker IDI Heart and Diabetes Institute, 75 Commercial Road, Prahran 3181, Australia. niwanthi.rajapakse@bakeridi.edu.au.|Department of Physiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia. niwanthi.rajapakse@bakeridi.edu.au.
authors.forename: Niwanthi W
authors.initials: NW
authors.lastname: Rajapakse
authors.affiliation: Venom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, QLD 4072, Australia. tnwjackson@gmail.com.
authors.forename: Timothy N W
authors.initials: TN
authors.lastname: Jackson
authors.affiliation: The Aquarium Vet, P.O. Box 2327, Moorabbin, VIC 3189, Australia. rob@theaquariumvet.com.au.
authors.forename: Rob
authors.initials: R
authors.lastname: Jones
authors.affiliation: Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia. wayne.hodgson@monash.edu.
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Hodgson
authors.affiliation: Venom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, QLD 4072, Australia. bgfry@uq.edu.au.
authors.forename: Bryan G
authors.initials: BG
authors.lastname: Fry
authors.affiliation: Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia. sanjaya.kuruppu@monash.edu.|Department of Biochemistry & Molecular Biology, Biomedicine Discovery Institute, Monash University, Monash, VIC 3800, Australia. sanjaya.kuruppu@monash.edu.
authors.forename: Sanjaya
authors.initials: S
authors.lastname: Kuruppu
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000503:physiopathology; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D005397:Fish Venoms / Q000378:metabolism / Q000633:toxicity*; D005400:Fishes, Poisonous / Q000145:classification / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000503:physiopathology; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000503:physiopathology; D051381:Rats; D013997:Time Factors
chemical_list: D005397:Fish Venoms
keywords: venom;  cardiovascular;  fish;  neuromuscular;  toxin