The effect of acetaminophen on methemoglobin and blood glutathione parameters in the cat

Nash, S.; Savides, Michael C.; Oehme, Frederick W.; Johnson, Dallas E.

doi:10.1016/0300-483x(84)90114-8

Cited by 23 publications

(16 citation statements)

References 6 publications

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“…Due to the glucose impermeability of porcine red blood cells (compared with rats and rabbits) there is a diminution in generation of NADPH and hence decreased reduction of methaemoglobin [23]. Levels of methaemoglobinaemia in pigs [24] administered acetaminophen are only one-half those reported in cats [25] and dogs [26]. There are several measures to control methaemoglobin levels in animal models.…”

Section: Discussionmentioning

confidence: 99%

Development of an invasively monitored porcine model of acetaminophen-induced acute liver failure

et al. 2010

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BackgroundThe development of effective therapies for acute liver failure (ALF) is limited by our knowledge of the pathophysiology of this condition, and the lack of suitable large animal models of acetaminophen toxicity. Our aim was to develop a reproducible invasively-monitored porcine model of acetaminophen-induced ALF.Method35kg pigs were maintained under general anaesthesia and invasively monitored. Control pigs received a saline infusion, whereas ALF pigs received acetaminophen intravenously for 12 hours to maintain blood concentrations between 200-300 mg/l. Animals surviving 28 hours were euthanased.ResultsCytochrome p450 levels in phenobarbital pre-treated animals were significantly higher than non pre-treated animals (300 vs 100 pmol/mg protein). Control pigs (n = 4) survived 28-hour anaesthesia without incident. Of nine pigs that received acetaminophen, four survived 20 hours and two survived 28 hours. Injured animals developed hypotension (mean arterial pressure; 40.8 +/- 5.9 vs 59 +/- 2.0 mmHg), increased cardiac output (7.26 +/- 1.86 vs 3.30 +/- 0.40 l/min) and decreased systemic vascular resistance (8.48 +/- 2.75 vs 16.2 +/- 1.76 mPa/s/m3). Dyspnoea developed as liver injury progressed and the increased pulmonary vascular resistance (636 +/- 95 vs 301 +/- 26.9 mPa/s/m3) observed may reflect the development of respiratory distress syndrome.Liver damage was confirmed by deterioration in pH (7.23 +/- 0.05 vs 7.45 +/- 0.02) and prothrombin time (36 +/- 2 vs 8.9 +/- 0.3 seconds) compared with controls. Factor V and VII levels were reduced to 9.3 and 15.5% of starting values in injured animals. A marked increase in serum AST (471.5 +/- 210 vs 42 +/- 8.14) coincided with a marked reduction in serum albumin (11.5 +/- 1.71 vs 25 +/- 1 g/dL) in injured animals. Animals displayed evidence of renal impairment; mean creatinine levels 280.2 +/- 36.5 vs 131.6 +/- 9.33 μmol/l. Liver histology revealed evidence of severe centrilobular necrosis with coagulative necrosis. Marked renal tubular necrosis was also seen. Methaemoglobin levels did not rise >5%. Intracranial hypertension was not seen (ICP monitoring), but there was biochemical evidence of encephalopathy by the reduction of Fischer's ratio from 5.6 +/- 1.1 to 0.45 +/- 0.06.ConclusionWe have developed a reproducible large animal model of acetaminophen-induced liver failure, which allows in-depth investigation of the pathophysiological basis of this condition. Furthermore, this represents an important large animal model for testing artificial liver support systems.

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Section: Discussionmentioning

confidence: 99%

Development of an invasively monitored porcine model of acetaminophen-induced acute liver failure

et al. 2010

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“…Because of the impermeability of porcine red blood cells to glucose compared with rats and rabbits, there is a diminution in reduced nicotinamide-adenine dinucleotide phosphate (NADPH) generation and hence decreased reduction of methemoglobin. 63 Levels of methemoglobinemia in pigs 39 administered acetaminophen have been shown to be only half those reported in cats 64 and dogs, 65 however. Even so, models of acetaminopheninduced liver failure have been successfully developed in dogs.…”

Section: Acetaminophen Modelsmentioning

confidence: 98%

Animal models of fulminant hepatic failure: A critical evaluation

et al. 2000

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Few conditions in medicine are more dramatic or more devastating than acute liver failure. Our understanding and treatment of this condition have been limited by the lack of satisfactory animal models. The most widely used models consist of surgical anhepatic and devascularization procedures and hepatotoxins, such as galactosamine and acetaminophen. Potential disadvantages with surgical models are their inability to recreate the inflammatory milieu that exists in acute liver failure and their reliance on surgical expertise. Models using hepatotoxins are free of such constraints. Galactosamine-induced hepatotoxicity is more predictable than acetaminophen, but its cost and lack of a human equivalent clinical syndrome has restricted its use. Acetaminophen-based models offer the greatest potential but have proven the most difficult to develop because of difficulties with reproducibility and refractory anemia. Although progress has been made, research must continue in this area to establish an animal model with minimal disadvantages that would accurately reflect the clinical syndrome seen in humans.

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“…Oxidative stress has been found in association with various diseases in cats, including liver disease, FIV infection, steatitis, and acetaminophen toxicity . In a survey of cats with heart disease, a small group of 11 cats with concurrent hyperthyroidism showed trends toward decreases in plasma vitamin E and increases in vitamin A concentrations, but this did not reach statistical significance .…”

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confidence: 99%

Antioxidant Status in Hyperthyroid Cats before and after Radioiodine Treatment

Branter

Drescher

Padilla

et al. 2012

Veterinary Internal Medicne

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Background: Reversible antioxidant depletion is found in hyperthyroid humans, and antioxidant depletion increases the risk of methimazole toxicosis in rats.Objectives: To determine whether abnormalities in concentrations of blood antioxidants or urinary isoprostanes were present in hyperthyroid cats, and were reversible after radioiodine treatment. To determine whether or not antioxidant abnormalities were associated with idiosyncratic methimazole toxicosis.Animals: Hyperthyroid cats presented for radioiodine treatment (n = 44) and healthy mature adult control cats (n = 37).Methods: Prospective, controlled, observational study. Red blood cell glutathione (GSH), plasma ascorbate (AA), plasma free retinol (vitamin A), a-tocopherol (vitamin E), and urinary free 8-isoprostanes in hyperthyroid cats were compared to healthy cats and to hyperthyroid cats 2 months after treatment.Results: Blood antioxidants were not significantly different in hyperthyroid cats (mean GSH 1.6 ± 0.3 mM; AA 12.8 ± 4.9 lM, and vitamin E, 25 ± 14 lg/mL) compared to controls (GSH 1.4 ± 0.4 mM; AA 15.0 ± 6.6 lM, and vitamin E, 25 ± 17 lg/mL). Urinary isoprostanes were increased in hyperthyroid cats (292 ± 211 pg/mg creatinine) compared to controls (169 ± 82 pg/mg; P = .006), particularly in hyperthyroid cats with a USG < 1.035. Plasma free vitamin A was higher in hyperthyroid cats (0.54 ± 0.28 lg/mL versus 0.38 ± 0.21 in controls; P = .007). Both abnormalities normalized after radioiodine treatment. No association was found between oxidative status and prior idiosyncratic methimazole toxicosis.Conclusion and Clinical Importance: Increased urinary isoprostane could reflect reversible renal oxidative stress induced by hyperthyroidism, and this requires additional evaluation.

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The effect of acetaminophen on methemoglobin and blood glutathione parameters in the cat

Cited by 23 publications

References 6 publications

Development of an invasively monitored porcine model of acetaminophen-induced acute liver failure

Development of an invasively monitored porcine model of acetaminophen-induced acute liver failure

Animal models of fulminant hepatic failure: A critical evaluation

Antioxidant Status in Hyperthyroid Cats before and after Radioiodine Treatment

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