Dietetic treatment is one of the important therapies in veterinary medicine. Especially in cardiovascular and kidney diseases, low-protein diet is suggested to be beneficial in minimizing their clinical signs. It is reported in human that high-protein diet activates cytochrome P450 (CYP) which is an important enzyme for metabolism of xenobiotics. In a preclinical study, hepatic CYP activity was decreased when low-protein diet was given to rats. In dogs, however, there is little information about the relationship between protein intake and CYP activities. In the present study, we clarified whether dietary protein affected activity of CYP2D, one of the responsible isozymes in metabolism of many drugs. Although it has been clarified that propranolol is metabolized by CYP2D in human liver, there is no information about the responsive CYP that metabolizes propranolol in dogs. Thus, we first clarified by chemical inhibition method using hepatic microsome that propranolol is metabolized by CYP2D also in canine liver. Then, one of the 3 diet with different rates of protein (low: 12.3%, middle: 25.3%, high: 40.1%) was given repeatedly to 7 Beagles and propranolol was administered intravenously to analyze CYP2D activity. This study was conducted in a cross over design. The plasma concentrations of propranolol were determined using a high performance liquid chromatography. The pharmacokinetic parameters of propranolol were analyzed by non-compartment model. When dog was given with middle- and high-protein diet, the values of area under the concentration of propranolol were low and the clearance was high when compared to those with low-protein diet. These data suggest that dietary protein may affect CYP2D activity in dogs.

View full abstract

The uncoupling proteins (UCPs) play an important role in energy homeostasis. To date, five UCP homologs, UCP1 to UCP5, have been identified in mammals. Both UCP2 and UCP3 have been found to decrease membrane potential and increase thermogenesis. They are regarded as inducers of obesity and type 2 diabetes in humans. We showed that the dog UCP2 and UCP3 cDNAs consisted of a part of the 5'-UTR sequence and a complete open reading frame in each gene. Comparisons with the gene structure in humans, dog genome sequences, and the transcripts in this study showed that dog UCP2 consists of exons 1 to 8 and dog UCP3 consists of exons 1 to 7. In dog UCP 3, exon 3-skipped transcripts were also observed. A UCP2 and UCP3 gene expression study using reverse transcription-polymerase chain reaction and 27 kinds of total RNA from dog tissues showed that tissue distribution of gene expression was different between dog UCP2 and UCP3. The present data may provide us with information regarding DNA polymorphism and help in further investigations of the influence of UCP2 and UCP3 activity on canine energy balance.

View full abstract

Diabetes mellitus (DM) is one of the risk factors for periodontitis. Periodontal treatment improved glycemic control in diabetic human patients. Furthermore, it had been noticed that oxidant stress was increased in diabetic patients with periodontal diseases. The purpose of this study is to evaluate whether periodontal treatment effect for glycemic control and oxidant stress level in dogs with DM. Four dogs with DM maintained in our laboratory were used in this study. All diabetic dogs had chronic periodontitis, gingivitis and dental calculus. We evaluated glycated albumin (GA) and fasting blood glucose concentration (FBG) as glycemic control markers, and evaluated C-reactive protein (CRP) and tumor necrosis factor alpha (TNF-α) as inflammation markers, and evaluated d-ROMs (reactive oxygen metabolites) and BAP ( biological antioxidant potential) levels as oxidant stress markers before and after the periodontal treatment. Results indicated significant decrease in GA and CRP levels after periodontal treatment. Furthermore, a significant increase was observed in BAP level. However, there was no significant difference in FBG and TNF-α concentration and d-ROM level. These results suggested that periodontal treatment could improve glycemic control in dogs with DM.

View full abstract