Toxicology Flashcards
CO-oximetry measurements and antioxidant effects of ascorbic acid and methylene blue in equine methemoglobinemic blood
• Venous blood samples stored in ice water showed a significant increase in oxyhemoglobin (O₂Hb) and oxygen saturation (SO₂) after 4 hours.
• Arterial blood samples exhibited stable CO-oximetry parameters over the storage period, likely due to the higher baseline SO₂ and O₂Hb levels in arterial blood.
Methemoglobin (MetHb) Concentration:
• In untreated control samples, MetHb concentration increased over time due to autoxidation, particularly when MetHb levels were initially high (>20%).
• Ascorbic acid (AscAc) effectively stabilized MetHb concentrations over the 48-hour period.
• Methylene blue (MetBlue) significantly reduced MetHb concentrations, particularly at 48 hours, suggesting its effectiveness in reducing MetHb levels. (contrary to earlier studies- whole blood (rather than washed red blood cells) was used).
Antioxidant Effects
Ascorbic Acid (AscAc):
• AscAc prevented further oxidation of MetHb but had limited reducing effects.
•The antioxidant effect may depend on timing and the concentration of AscAc added relative to the MetHb induction process.
Methylene Blue (MetBlue):
• MetBlue effectively reduced MetHb over time, suggesting its potential for clinical use in treating methemoglobinemia.
• The effect was less pronounced compared to its use in human cases, possibly due to species-specific differences in red blood cell metabolism.
Plasma l-indospicine and 3-nitropropionic acid in ponies fed creeping indigo: Comparison with results from an episode of presumptive creeping indigo toxicosis
Weight Loss and Plasma Protein Changes:
• Ponies experienced a significant median weight loss of 6% during and after creeping indigo feeding. This weight loss persisted despite a return to normal diet and access to pasture.
• A significant increase in plasma proteins (median 18 g/L) was observed within 24 hours of consuming creeping indigo, likely attributable to the plant.
Plasma l-Indospicine (IND):
• IND accumulated progressively in the blood of ponies fed creeping indigo. Plasma IND levels reached over 3 mg/L after 5 days of feeding.
• Pharmacokinetic modeling revealed:
-An elimination half-life of 25.2 days for IND.
-Significant tissue accumulation, with a predicted steady-state plasma concentration of 22 mg/L after prolonged exposure.
• IND concentrations in affected horses during field investigations were elevated compared to unaffected horses but did not directly correlate with the severity of clinical signs.
Role of 3-Nitropropionic Acid (NPA):
• NPA was detected in trace amounts in the experimental and field samples, making its role in creeping indigo toxicity unclear.
• While NPA is neurotoxic in other species, the minimal levels found in horses suggest either an unusually high sensitivity in horses or the involvement of other toxins.
Comparative Analysis
• IND is a known hepatotoxin in other species but did not cause overt liver damage in horses during the study. Instead, it led to cumulative tissue retention and a prolonged clearance period.
• Prior studies in camels and other ruminants reported similar IND accumulation, but horses exhibited a longer elimination half-life, indicating species-specific differences.
Field Observations:
• Affected horses in the field exhibited symptoms consistent with creeping indigo toxicity (neurological signs, ocular and oral lesions).
• Plasma IND levels in sick horses were about twice as high as in unaffected horses but lower than levels reported in experimental ponies fed creeping indigo, complicating the establishment of a clear plasma IND threshold for clinical toxicity.
Unclear Role of NPA:
• Despite its documented neurotoxic effects in other species, the low levels detected in both experimental and affected horses challenge its significance in creeping indigo toxicity.
• Future studies should evaluate potential synergistic effects between IND, NPA, and other unidentified compounds in creeping indigo.
Bromide intoxication in a 3-year-old Thoroughbred filly
• The filly exhibited multifocal CNS disease with neurological signs such as ataxia, proprioceptive deficits, and behavioral changes.
• Laboratory findings of persistent hyperchloremia and a negative anion gap prompted the diagnosis of bromide intoxication, confirmed by elevated serum bromide concentrations.
• The filly had been administered potassium bromide (KBr) for behavioral modification over several months.
• Discontinuation of KBr led to a complete resolution of neurological signs within 20 days without specific medical intervention.
• The spurious hyperchloremia and negative anion gap caused by bromide interference with chloride assays can obscure the diagnosis. Bromide replaces chloride in body fluids, leading to pseudohyperchloremia on laboratory tests.
• Bromide intoxication should be considered in horses presenting with multifocal neurological signs, especially when laboratory findings suggest hyperchloremia and a negative anion gap.
• Bromide interferes with chloride ion channels, altering neural excitability and activity in the CNS. This mechanism, while enhancing sedative effects, can result in toxic side effects at high concentrations
Survival of formalin intoxication in a 13-year-old Thoroughbred gelding
• The horse survived despite receiving a high dose (0.12 g/kg body weight) of formaldehyde through accidental nasogastric intubation.
• Clinical findings included gastrointestinal toxicity, systemic inflammatory response syndrome (SIRS), and concerns for nephrotoxicity, cardiotoxicity, and laminitis.
• Management included fluid therapy, gastroprotectants, analgesia, continuous digital cryotherapy, and nutritional support.
• The absence of long-term complications (e.g., stricture formation, renal or cardiac damage) was confirmed 12 months post-discharge.
Acute, subacute, and chronic sequelae of horses accidentally exposed to monensin-contaminated feed
• Monensin ingestion resulted in cardiac abnormalities in 70% of horses during the acute and subacute periods.
• Persistent cardiac abnormalities were observed in 44% of horses examined during the chronic phase.
• Approximately 22% of horses died or were euthanized, often due to severe exercise intolerance or cardiac failure.
• Despite persistent cardiac abnormalities, 53% of horses returned to their previous level of exercise, demonstrating a variable prognosis.
Clinical Signs:
• Acute-phase signs included anorexia, weakness, tachyarrhythmias, sweating, and sudden death.
• Chronic-phase signs predominantly involved exercise intolerance and, in some cases, delayed neurological symptoms such as ataxia and hyperesthesia.
Associated with a negative outcome:
• Thinning of the myocardium observed at any point
• Heterogeneity of the myocardium observed in the acute/subacute period w
• Chronic period:
-subjective contractile intraventricular dyssynchrony,
-cardiac chamber dilation,
-decreased fractional shortening <28%
- multiple premature ventricular complexes
- anorexia at time of exposure
• Several horses with significant cardiac anomalies (e.g., thinning or heterogeneity of the myocardium) resumed work successfully, indicating some degree of functional compensation.
Management Recommendations:
• Prolonged rest (≥4 months) is recommended for all exposed horses, followed by cardiac evaluation before exercise resumption.
• A two-step approach involving both lunge tests and ridden exercise tests may improve prognosis predictions for performance horses.
Detection of maple toxins in mare’s milk
• The study confirmed the presence of Hypoglycin A (HGA) and associated metabolites in mare’s milk, including methylenecyclopropylacetyl glycine and carnitine, indicating ingestion of toxins from maple seeds or seedlings.
• This supports the hypothesis that toxins can be secreted into milk, raising concerns about vertical transmission from mare to foal.
Clinical Implications:
• The foal in the reported case developed atypical myopathy (AM), with symptoms such as myoglobinuria, elevated creatine kinase, and lactate dehydrogenase activities, likely linked to milk-borne toxins.
• The mare’s clinical recovery did not preclude the presence of residual metabolites in the milk, suggesting potential risks for prolonged exposure.
• Elevated acylcarnitine levels, detected even after the mare was moved to a maple-free diet, demonstrate lasting metabolic effects of the toxins despite the absence of direct clinical signs in the mare.
