Laboratory Animal Models Flashcards
First Veterinarian in laboratory medicine.
Dr. Simon Brimhall, VMD
Role of Veterinarians in Biomedical Research
- Provide Veterinary Care
- Oversee Animal husbandry
- Manage Animal Facilities and Breeding Colonies
- Study laboratory animal diseases
- Perform collaborative independent research
Uses of toxicological testing
- Pharmaceutical products
- Agrochemical products
- Veterinary drug
-Safety in food animals
-Safety assessment of residues
3 “R”s
Replacement
Reduction
Refinement
DA Administrative Order 40
Authority of BAI
Species of choice in Reproductive toxicity testing
Rats and Mice
Primarily used to determine hazard regarding the potential effect of prenatal exposure on the developing fetus
Developmental toxicity testing
Species of Choice: Rodents and Rabits
Measurement of reproductive functional and structural defects in both sexes
Reproductive toxicity test
Species of choice in cutaneous toxicity test
Albino rabbit and guinea pigs
Asses potential acute local limitation and to evaluate acute subchronic and chronic systemic toxic effects
Cutaneous toxicity testing
Species of choice in genotoxicity testing
Rodents
Detect gene damage induced by the test compound
Genotoxicity testing
Examine the possibility that a tested agent might cause tumors and other chemically related effects in one or more animal soecie
Carcinogenicity testing
Detect adverse effects of xenobiotics on the immune system including all the relevant cells, organs and immune mechanisms
Immunotoxicity testing
Chemical Injury MOA
Direct contact»_space; Coagulate protein or damage cell membrane lipids
Mercuric chloride poisoning MOA
Increased membrane permeability and inhibition of ion transport
Damage Kidney and GIT cells
Necrosis of epithelial cells MOA
Affect key enzymes and metabolic intermediate of affected cells
Mechanism of Oxalic Acid (Plant toxin)
Inhibit succinic dehydrogenase
Mechanism of Fluoroacetate (Rodenticide)
Aconitase
Toxicant in the inhibition of Oxidative Phosphorylation and its mechanism
Cyanides
Inhibition of enzymes containing iron, predominantly of cytochrome oxidase
Limited oxygen uptake
Low ATP production
- Fatigue
-Weakness
Toxicants of Uncoupling Phosphorylation and its mechanism
Dinitriphenols
Chlorophenol
Arsenates
Increase oxygen utilization
Energy dissipated as heat
No ATP formation
-Fatigue
-Weakness
-Fever
Plants that can cause Cyanide poisoning
Peach
Apricos
Arrowgras
Johnsongrass
Plum
Cherry
Almond
Elderberry
Toxicants of inhibition nucleic acid and protein synthesis and its mechanism
Aflatoxin
Organimecurials
Amantin (Mushroom Toxin)
Combine with large or small ribosomal unit
Alkylation of DNA and inhibit replication/transcription
MOA of Aflatoxin
Produced by Aspergillus flavus and A. parasiiticus
Inhibit transcription and translation
“thiol poisons”
Organimercurials
React with the -SH groups of proteins and they disturb the activity of proteins
Example of organimercurials and its MOA
Methylmercury inhibit choline acetyl transferase
✓Signs and symptoms of motor dysfunction
Carbon tetrachloride toxicity
Failure of the liver to transport triglyceride-rich low density lipoproteins into the plasma
=accumulation of fats in the cells
MOA of Strychnine
Antagonizes the inhibitory neurotransmitter glycine
Strychnos nux-vomica
MOA of DDT
Dichloro-diphenyl-trichloroethane
Delay closing og Na+ channels and slowing opening K+ gates»_space; enhanced initiation of Action potentials»_space; increase seizure tendencies
MOA of organophosphate insecticides
Inhibit acetylcholinesterase by bunding irreversibly to its esteric state
Direct and indirect effect of neuronal necrosis
Direct:
Organomecurials»_space; impairment of protein synthesis
Indirect:
Carbon monoxide or cyanide»_space; anoxia
Toxicants in Demyelination and its MOA
Hexachlorophene
Uncoupling of oxidative phosphorylation»_space; decreased Na+ K+ ATPase activity»_space; retention of water in myelin lamellae»_space; intramyelinic edema»_space; separation of myelin lamellae
Toxicants in impaired axonal transport and its MOA
Vincristine
Bind to tubulin»_space; inhibit microtubule formation»_space; disruption of fast axonal transport which relies on microtubules
Hypoplasia and aplasia of cellular components of blood will lead to?
Direct toxic effect on bone marrow precursor cells
MOA of nitrite and paracetamol poisoning
Fe in heme is oxidized»_space; methemoglobin»_space; incapable of reversible oxygenation»_space; decreased oxygen content of blood
MOA of Carbon monoxide poisoning
CO competes with O2»_space; carboxyhemoglobin» cannot carry oxygen»_space; decreased oxygen content of the blood
Any xenobiotic associated with adverse effects on development of male or female reproductive function.
Reproductive toxicants
Cause of osteodystrophy due to excessive level of nutrients.
Dietary phosphorus stimulate PTH
Effect of any synthetic or naturally occurring xenobiotic which can affect the endocrine system of exposed individuals
Endocrine disruption
Immunotoxicants
✓Heavy Metals
✓Mycotoxins
✓Organophosphates
Substances that induce birth defects
Teratogens
✓ Heavy Metals
✓ Antifungal drugs
✓ Nicotiana spp. - crooked calf disease in cattle
Chemicals or its reactive metabolite causes a permanent change in the DNA of the target cell, such as mutation, a distortion of the DNA
Tumor initiators
Influence the proliferation of initiated cells which results in the proliferation of preneoplastic cells
Tumor promoters
T/F
Initiator exposure followed by repeated promoter exposure will result tumor.
True
T/F
Repeated promoter exposure followed by initiator exposure will result tumor.
False
