Hepatic lead and copper concentrations in dogs with chronic hepatitis

Copper (Cu) influence on chronic hepatitis (CH) have been thoroughly studied in dogs, while a few information on other metals accumulation is currently available. Both Cu and lead (Pb) may cause hepatic injury if their hepatic metabolization is defective or due to oxidative stress mechanisms linked to their presence within hepatocytes, especially for Pb. The aim of the study was to evaluate liver Pb and Cu concentration in dogs with CH. Retrospective evaluation of the Teaching Hospital clinical database was performed searching for dogs with CH and hepatic copper ([Cu]) concentrations, on which lead concentrations ([Pb]) were measured. CH was defined using current ACVIM consensus. [Cu] and [Pb] were evaluated using square wave anodic stripping voltammetry (SWASV; limit of detection (LOD) 10ppm and 6 ppm, respectively). Dogs were divided into two groups based on hepatic [Cu]: Group A <400ppm and Group B 400ppm. [Pb] and [Cu] were correlated using a Spearman correlation test. [Pb] and alanine aminotransferase (ALT) were compared between Group A and Group B using Welch’s t-test and Mann-Whitney U-test, respectively. Thirty-six dogs were screened for eligibility and the final population was composed by 29 dogs, since 7 dogs had [Pb] < LOD and they were censored (6 dogs of Group A and 1 dog of Group B, respectively). The median age was 9 years (range 1-15 years), equally divided between males and females, mainly Labrador Retrievers and Cocker Spaniels (n=3 each), followed by mixed-breed (n=9). Twenty-one dogs (58%) were assigned to Group A, while the remaining 15 dogs were in Group B. [Pb] and [Cu] were strongly positively correlated (p=0.0002; r=0.65). Group A had a mean [Cu] and [Pb] of 236.698 and 4422.3ppm respectively, whereas Group B had a [Cu] and [Pb] of 12891944 and 103.159.8ppm, respectively. Group B showed a significantly higher [Pb] than Group A (p=0.003). ALT was not significantly different between groups (159 vs. 94ppm groups A and B, respectively). Although further studies are needed to better understand the clinical role of hepatic [Pb], dogs with hepatic abnormal [Cu] may also have higher [Pb] than dogs with normal [Cu], which may be a concomitant storage defect or a direct consequence of Cu hepatic accumulation. However, since few data are available a concomitant oxidative damage caused by increased [Pb] cannot be excluded.