Abstract
BackgroundAlthough the influence of copper ([Cu]) on chronic hepatitis (CH) has been widely studied in dogs, little information is available about the accumulation of other metals.Hypothesis/ObjectivesWe assessed the concentration of lead ([Pb]) in the livers of dogs with CH with or without abnormal hepatic [Cu] to establish if any association existed between [Pb] and either hematologic or biochemical variables, fibrosis, necrosis and inflammation of the liver on histology.AnimalsThirty‐four dogs with CH that had hepatic [Cu] and [Pb] determined.MethodsRetrospective review of medical records of dogs with CH and hepatic [Cu] and [Pb]. Chronic hepatitis was defined using current American College of Veterinary Internal Medicine consensus statement guidelines. Hepatic [Cu] and [Pb] were determined using square wave anodic stripping voltammetry. Dogs were divided into 2 groups based on [Cu]: <400 ppm (LoCu) and ≥400 ppm (HiCu).ResultsThe median [Cu] and [Pb] were 357 ppm (range, 100‐7743 ppm) and 58.7 (range, 6.89‐224.4 ppm), respectively. Nineteen dogs had LoCu and 15 dogs had HiCu. Median [Pb] was significantly higher in HiCu compared to LoCu dogs (P < .001). Hepatic [Pb] and [Cu] were significantly correlated (rho = 0.7; P < .001). Dogs with microcytosis had higher [Pb] than did dogs with normal red cell volume (P = .02). Hepatic [Pb] was not correlated with either necroinflammatory or fibrosis scores.Conclusions and Clinical ImportanceAlthough additional studies are needed to better understand the clinical role of hepatic [Pb], dogs with abnormal hepatic [Cu] may also have higher hepatic [Pb]. In addition, in dogs with high hepatic [Pb], microcytosis may be present.
Highlights
All samples were scored for necroinflammatory activity and fibrosis according to the World Small Animal Veterinary Association (WSAVA) guidelines[20] using the following scoring scheme, with necroinflammatory activity graded as A0 = absent, A1 = slight, A2 = mild, A3 = moderate, A4 = marked, or A5 = very marked.[18,19]
The final cohort consisted of 34 dogs with chronic hepatitis (CH), in which hepatic [Cu] and [Pb] were measured
Regarding the correlation between [Pb] and [Cu] and hematology and serum biochemistry variables, we found a significant association between [Pb] and the presence of microcytosis
Summary
In the last 15 years, the influence of copper (Cu) on liver disease, especially chronic hepatitis (CH), has been widely studied in dogs,[1,2,3,4,5,6,7,8,9] but few clinical studies of other metal accumulations are currently available.[9,10] Both Cu and lead (Pb) may cause hepatic injury, because of defective hepatic metabolism or may be linked to oxidative stress mechanisms associated with their presence within hepatocytes, especially Pb.[3,8,9] At toxic concentrations, free intracellular Cu initiates oxidative damage causing hepatocellular necrosis and inflammation.[3,11] Hepatic Cu accumulation can be associated with substantial hepatic injury resulting in acute hepatitis, CH, and cirrhosis.[11,12] A study on acute and chronic primary hepatitis found that copperassociated hepatitis accounted for one-third of all dogs with liver disease and approximately 35% of CH.[13]. The influence of copper ([Cu]) on chronic hepatitis (CH) has been widely studied in dogs, little information is available about the accumulation of other metals. Hypothesis/Objectives: We assessed the concentration of lead ([Pb]) in the livers of dogs with CH with or without abnormal hepatic [Cu] to establish if any association existed between [Pb] and either hematologic or biochemical variables, fibrosis, necrosis and inflammation of the liver on histology. Hepatic [Pb] and [Cu] were significantly correlated (rho = 0.7; P < .001). Conclusions and Clinical Importance: additional studies are needed to better understand the clinical role of hepatic [Pb], dogs with abnormal hepatic [Cu] may have higher hepatic [Pb]. In dogs with high hepatic [Pb], microcytosis may be present
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