Veterinary Medicine - RBC Oxidants - Spring 2025 Lecture Notes PDF

RBC Oxidants Methemoglobin Producers: Acetaminophen, Nitrates Hemolytic Agents: Onions, Zn Acetaminophen “Blue Cat Syndrome”  Acetaminophen OTC Analgesic, antipyretic Tylenol®; generic (325, 500, 625 mg tab) Combination drugs Prescription meds: L...

RBC Oxidants Methemoglobin Producers: Acetaminophen, Nitrates Hemolytic Agents: Onions, Zn Acetaminophen “Blue Cat Syndrome”  Acetaminophen OTC Analgesic, antipyretic Tylenol®; generic (325, 500, 625 mg tab) Combination drugs Prescription meds: Lortab (500-750 mg) Vicodin Dogs & humans Toxicity: 100-900 mg/kg Cats Lower dose: 40-60 mg/kg (deaths at 10 mg/kg reported) RBC: hemoglobin  Acetaminophen Toxicokinetics Absorption Rapid BIOTRANSFORMATION Phase II conjugation Dogs: 50 -75% glucuronide Cats: < 3% Phase I oxidation Deacetylation Excretion Urine  Acetaminophen (APAP) Liver: 1ry target Dogs, Cats: RBCs Dogs lack NAT 1,2 Cats NAT 1,2 NAT1 slow (PAP) (NAPQI) McConkey et al., 2009  Acetaminophen Mechanism RBC Redox cycling of PAP oxidizes Hb to MetHb Reduced activity of reductase GSH depletion 2009  Acetaminophen Clinical presentation Cats (& dogs) 3-12 h Decreased O2 transport & hemolytic anemia Cyanosis or dark mucous membranes, dyspnea, tachypnea Hypothermia, tachycardia Hematuria, hemaglobinuria Edema and swelling of face and front paws* (cats) Death Labs Chocolate brown blood Methemoglobinemia; Heinz bodies Elevated liver enzymes  Acetaminophen Treatment Transfusion, O2 therapy Emesis, activated charcoal with sorbitol Antidote  N-acetylcysteine (Mucomyst, Acetadote)  8 hrs post-ingestion  Others  Sodium sulfate  Ascorbic acid  (Cimetidine – inhibitor of cytP450)  *SAMe – s-adenosyl-l-methionine  Silymarin  Nitrates Nitrites “Blue baby syndrome”  Nitrate/Nitrite Nitrate: NO3- (nitrite: NO2-) Soil, plants, water Stems, stalks Hay, forage Alfalfa, fescue, sorghum, sudan grass Corn, soybean Many poisonous plants Fertilizers Nitrate-based Phenoxy herbicides : 2,4 D (dichlorophenoxy acetic acid)  Nitrate/Nitrite Target site Mechanism of action Hemoglobin Ruminal microflora Species NO3- [ NO2-] NH3 Nitrate: Cattle, (horses) Nitrite: all species FLORA – overwhelmed Toxicity NO3-, NO2- >10,000 ppm dry wt < 5000 ppm safe 5000-10,000 ppm Not safe for pregnant cows METHEMOGLOBIN < 1,000 ppm water  Nitrate/Nitrite Clinical presentation Acute 1-4 h following rapid ingestion of materials high in nitrate Respiratory distress Exercise intolerance, cyanosis, tachypnea, gasping Ataxia, tachycardia, seizures, DEATH (6-24 h) GI distress Salivation, diarrhea Abortion 3-7 days after sublethal ingestion  Nitrate/Nitrite Diagnostics Treatment Discolored blood, tissues Reduce MetHgb Methemoglobinemia Antidote: methylene blue May not be evident in animals dead more than few hours Nitrate/Nitrite Blood, urine, ocular fluid Hay, water  Nitrate/Nitrite Treatment Prevention Reduce ruminal NO2- Testing Cold water lavage Adaptation Ruminal antibiotics Dilution Penicillin Ensiling Proprionic bacteria Nitrate/Nitrite toxicosis: July 2020 Case Neochim Chemical Plant: Summer of 2020 incident Neochim Plant Summer of 2020 incident: location The cows Plant-to-river canal The plant  Neochim Plant Summer of 2020 incident: the aftermath 28 Pasture-based dairy cows: dead within 5-10 min Went into the river for cooling/drinking No signs of illness Terminal anoxic convulsions right before death River water samples at the site of canal entry into the river (about a day after the incident) Post mortem animal tissue Nitrites: 358 times higher than samples: collected by local environmental water standard university veterinarians (EU/Bulgaria) about 1 day after the Nitrates: 10 times higher incident Ammonia: two times higher Nitrites/nitrates: 50 times higher than maximal allowable animal tissue levels Presumptive diagnosis: Acute, nitrite-induced, lethal toxicosis due to massive, sudden release of nitrite and nitrate-based chemicals into the river, leading to the rapid development of ≥80% methemoglobinemia. Hemolytic Agents: Onions…  Onions & Friends Family Amaryllidaceae Genus Allium Onions, garlic, shallots, leeks, chives More than 400 species Toxicity N-propyl disulfides Potent odor Varies with plant type, growing conditions, processing, animal species Greater in areas with higher soil sulfur content Louisiana, Texas, Colorado, Nevada, Wyoming, California  Onions & Friends Reported poisonings Wild or cultivated Raw: fresh or culled Dried or dehydrated: minced, flakes Cooked: onion soufflé, meatloaf Powders: baby foods Species Dogs, cats, cattle, horse Small ruminants are more resistant  Onions & Friends DOG CAT HORSE DAIRY COWS Raw onions 11-15 28 mg/kg 1-4 lbs 0.04 kg/kg mg/kg onion tops (adults) 0.5% BW 8-15 kg/head (calves) Dehydrated 0.17 oz/kg onion Boiled onions 200 g Garlic extract 1.25 ml/kg Baby food 0.3% with onion powder 1 g = 0.035 oz; med-large onion weighs ~ 220 g/8 oz  Onions & Friends Mechanism of action Plants high in sulfur Chewing, processing Redox cycling of Sulfur thiosulfinates disulfides: free radicals N-propyl disulfides are thiosulfinates disulfides oxidants Decrease NADPH, GSH n-propyl disulfides: greatest RBC is most sensitive toxicity Oxidation of Hb  Onions & Friends Clinical presentation Hemolytic anemia Acute to delayed onset Pale mucous membranes, tachypnea, tachycardia, weakness, icterus, hematuria Possible vomiting, diarrhea, and anorexia Labs: anemia, hemoglobinemia, heinz bodies  Onions & Friends Treatment Blood transfusion Fluids GI Decontamination Emesis (if not vomiting) Activated charcoal Monitor hematocrit for several days Hemolytic Agents: Zinc  Zinc Essential nutrient Sources Pennies 1982: >97% zinc 2.4 g/penny Skin ointments Galvanized metals Bolts, nails Paints (55%) Dietary excess Monogastrics Dogs, pigs Birds  Zinc Toxicokinetics Absorption Upper small intestine: Zn2+ Increased by dietary Zn deficiency Acidic pH Distribution Transport proteins Liver – release back to circulation Accumulation: liver, pancreas, muscle, bone Excretion Feces: bile, pancreatic fluids, GI mucosa  Zinc Mechanism Oxidative damage Heinz bodies RBC hemolysis Treatment Fluids, transfusions Acute toxicosis Remove source Initial: gastroenteritis Antacids (metallic Hemolytic anemia: Zn) Icterus, tachycardia, H2 antagonists hemoglobinuria, renal failure Chelation: Ca++Na2EDTA Cardiovascular/CNS Toxicants Methylxanthines  Methylxanthines Origin Plant alkaloids found in: Chocolate, coffee, tea, cola 3 alkaloids: theobromine, caffeine, theophylline Other sources Cocoa bean shell mulch OTC medications/stimulants, herbal Human & veterinary medications  Methylxanthines Chocolate Theobromine (80%) & caffeine (20%) 1 oz. cacao beans = > 600 mg theobromine 1 oz. baking chocolate = 400 mg theobromine 1 oz. dark chocolate = 130 mg “ 1 oz milk chocolate = 58 mg “  Methylxanthines PRODUCT CAFFEINE CONCENTRATION OTC Stimulants (ex Vivarin) 200 mg / tablet Dexatrim diet pill 200 mg / tablet Excedrin 65 mg / tablet Coffee beans 280-570 mg / oz Coffee Per 5 oz cup Drip 80-85 mg Instant 30-90 mg Tea 20-90 mg / 5 oz cup Cola containing soft drinks 40-60 mg / 8 oz Guarana 3%-5% Chocolate products 2-40 mg / oz “Average” piece chocolate cake 70-100 mg  Methylxanthines Dogs (cats) LD50: 80-200 mg/kg Mild signs: 20 mg/kg Severe signs: 40-50 mg/kg Seizures: 60 mg/kg 1 oz milk chocolate/lb BW