Assessment of hepatic function and damage in animal species. A review of the current approach of the academic, governmental and industrial institutions represented by the Animal Clinical Chemistry Association

Woodman, David

doi:10.1002/jat.2550080405

Cited by 14 publications

(2 citation statements)

References 44 publications

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“…Til-HCO-SLN caused slight decrease of the albumin (ALB)/globulin (GLB), while blank HCO-SLN leads to minor reduction of ALB and GLB. The hepatocellular damage is often indicated by changes of albumin, globulins and total protein [ 28 ]. However, other liver function related parameters such as alanine aminotransferas (ALT), aspartate aminotransferase (AST), ALT/AST, bilirubin and urea were normal, suggesting that the damage of liver was slight and reversible [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Acute toxicity study of tilmicosin-loaded hydrogenated castor oil-solid lipid nanoparticles

Xie

Wang

et al. 2011

Part Fibre Toxicol

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BackgroundOur previous studies demonstrated that tilmicosin-loaded hydrogenated castor oil solid lipid nanoparticles (Til-HCO-SLN) are a promising formulation for enhanced pharmacological activity and therapeutic efficacy in veterinary use. The purpose of this work was to evaluate the acute toxicity of Til-HCO-SLN.MethodsTwo nanoparticle doses were used for the study in ICR mice. The low dose (766 mg/kg.bw) with tilmicosin 7.5 times of the clinic dosage and below the median lethal dose (LD50) was subcutaneously administered twice on the first and 7th day. The single high dose (5 g/kg.bw) was the practical upper limit in an acute toxicity study and was administered subcutaneously on the first day. Blank HCO-SLN, native tilmicosin, and saline solution were included as controls. After medication, animals were monitored over 14 days, and then necropsied. Signs of toxicity were evaluated via mortality, symptoms of treatment effect, gross and microscopic pathology, and hematologic and biochemical parameters.ResultsAfter administration of native tilmicosin, all mice died within 2 h in the high dose group, in the low dose group 3 died after the first and 2 died after the second injections. The surviving mice in the tilmicosin low dose group showed hypoactivity, accelerated breath, gloomy spirit and lethargy. In contrast, all mice in Til-HCO-SLN and blank HCO-SLN groups survived at both low and high doses. The high nanoparticle dose induced transient clinical symptoms of treatment effect such as transient reversible action retardation, anorexy and gloomy spirit, increased spleen and liver coefficients and decreased heart coefficients, microscopic pathological changes of liver, spleen and heart, and minor changes in hematologic and biochemical parameters, but no adverse effects were observed in the nanoparticle low dose group.ConclusionsThe results revealed that the LD50 of Til-HCO-SLN and blank HCO-SLN exceeded 5 g/kg.bw and thus the nanoparticles are considered low toxic according to the toxicity categories of chemicals. Moreover, HCO-SLN significantly decreased the toxicity of tilmicosin. Normal clinic dosage of Til-HCO-SLN is safe as evaluated by acute toxicity.

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Section: Discussionmentioning

confidence: 99%

Acute toxicity study of tilmicosin-loaded hydrogenated castor oil-solid lipid nanoparticles

Xie

Wang

et al. 2011

Part Fibre Toxicol

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“…The biological effect of cytokines, such as TNF-α, is dependent on the effective concentration: low concentrations are involved in homeostasis, while an increasing local concentration of TNF-α is associated with local inflammatory response and focal hepatic necrosis [Simpson et al, 1997]. ALT was one of the first enzymes to become established as a diagnostic marker in man and animals and is a good indicator of necrotic liver damage [Woodman, 1988]. The elevation sham-operated rats administered with 3-phthalimido-3-(3,4-dimethoxyphenyl)-propanamide (PDP), (F) bile duct-ligated rats administered with PDP.…”

Section: Discussionmentioning

confidence: 99%

Effects of thalidomide and 3‐phthalimido‐3‐(3,4‐dimethoxyphenyl)‐propanamide on bile duct obstruction‐induced cirrhosis in the rat

Fernández-Martínez

Morales‐Ríos

Pérez-Álvarez

et al. 2001

Drug Development Research

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Tumor necrosis factor-alpha (TNF-α) plays a central role in cellular necrosis, apoptosis, organ failure, tissue damage, inflammation, and fibrosis. These processes, occurring in liver injury, may lead to cirrhosis. Thalidomide and its analogs have shown to be effective TNF-α inhibitors. The aim of this work was to synthesize a thalidomide analog, the 3-phthalimido-3-(3,4-dimethoxyphenyl)-propanamide (PDP) and to evaluate its hepatoprotective properties on bile duct obstruction-induced cirrhosis. Synthesis, purification, and spectroscopic characterization of PDP were carried out. Thalidomide (200 mg/kg) or PDP (15 mg/kg) were administered to sham (Sh) or bile duct ligated (BDL) rats. The animals were sacrificed 28 days after treatments. Alkaline phosphatase (Alk. Phosph.), γ-glutamyl transpeptidase (γ-GTP) and alanine aminotransferase (ALT) enzyme activities, bilirubins, and TNF-α concentrations were evaluated in plasma. Collagen was estimated by the liver hydroxyproline content and histopathology was performed. Both drugs showed partial amelioration of cirrhosis. However, the hepatoprotective effects of thalidomide were poor when compared to those afforded by PDP. While PDP improved the majority of the biochemical markers of liver injury and prevented partial but significantly collagen accumulation, thalidomide showed only modest beneficial effects on bilirubins and ALT. PDP was effective in preventing the increase in plasma TNF-α levels, while thalidomide not only failed to inhibit TNF-α, but increased it. Differences between thalidomide and PDP effectiveness may be due to their stability and different mechanism of action, as reported by others. Inhibition of proinflamatory cytokines is an interesting pharmacological aim to treat cirrhosis. Drug Dev.

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Comparison of Quantitative Methods to Assess Hepatic Function: Pugh's Classification, Indocyanine Green, Antipyrine, and Dextromethorphan

Figg,

Dukes,

Lesesne

et al. 1995

Pharmacotherapy

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Study Objectives. To compare three quantitative metabolic markers used to assess hepatic function, indocyanine green (ICG), a high‐extraction marker; antipyrine, a low‐extraction marker; and dextromethorphan, a P‐450IID6 marker, with the clinically used Pugh's classification.Design. Comparison of 12 healthy controls with 12 age‐ and sex‐matched patients with different degrees of liver disease.Setting. Research center in a university‐affiliated teaching hospital.Patients. The 12 patients had different degrees of liver disease: 4 mild (Pugh's score 6 or 7); 4 moderate (Pugh's score 8 or 9); and 4 severe (Pugh's score ≥ 10). Each level had an equal number of men and women subjects.Measurements and Main Results. Clearance of ICG detected mild alterations in hepatic function as efficiently as it did for moderate and severe impairment, but it lacked the specificity to distinguish among the classification groups. In contrast, antipyrine was effective in identifying moderate and severe hepatic impairment; however, its clearance was not reduced in mild liver disease. Pugh's classification appears to be a clinically useful method of assessing the global degree of hepatic impairment in patients with chronic disease, and there was a significant correlation between it and antipyrine clearance (r=0.67, p=0.0003) and ICG clearance (r=0.86, p=0.0001). Four of eight patients with a Pugh's score greater than 8 had a dextromethorphan metabolic ratio expression reflective of a poor metabolizer phenotype based on 0‐ to 4‐hour urine collection, but only two of those eight patients were classified as poor metabolizers based on 4‐ to 12‐hour urine collection. These percentages of poor metabolizers are substantially higher than for historical controls (8.5–10.4%) and most likely reflect a decrease in the P‐450IID6 functional ability with progression of liver disease. However, due to small sample size and lack of knowledge of the patients' genotypes, these data are only suggestive.Conclusion. Pugh's classification appears to be a reliable indicator of the degree of chronic liver disease and could be employed as a drug development research classification tool; however, it does not replace quantitative metabolic markers, especially isozyme‐specific markers.

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Assessment of hepatic function and damage in animal species. A review of the current approach of the academic, governmental and industrial institutions represented by the Animal Clinical Chemistry Association

Cited by 14 publications

References 44 publications

Acute toxicity study of tilmicosin-loaded hydrogenated castor oil-solid lipid nanoparticles

Acute toxicity study of tilmicosin-loaded hydrogenated castor oil-solid lipid nanoparticles

Effects of thalidomide and 3‐phthalimido‐3‐(3,4‐dimethoxyphenyl)‐propanamide on bile duct obstruction‐induced cirrhosis in the rat

Comparison of Quantitative Methods to Assess Hepatic Function: Pugh's Classification, Indocyanine Green, Antipyrine, and Dextromethorphan

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