Low glutathione S -transferase dogs

Abstract

Liver and kidney glutathione S-transferase (GST) activities to 1,2-dichloro-4-nitrobenzene (DCNB) as a substrate (GST-D activities) were measured in 280 dogs from five different breeders, and significant individual differences in this activity were observed in both organs. Interestingly, 34 out of the 280 dogs (i.e. 12.1%) were those in which liver GST-D activities were less than 10 nmol/min per mg cytosolic protein, "low GST dogs", and the other dogs were classified as "middle" and "high" GST dogs for which the liver GST-D activities were 10-80 and >80 nmol/min per mg protein, respectively, and occurred at similar percentages (41.4% for the middle GST dog and 46.4% for the high GST dog). Furthermore, the existence of the low GST dogs was not limited to one particular breeder. There was a good correlation (r=0.910) between the liver and kidney GST-D activities, showing low activity in not only the liver but also the kidney in the low GST dogs. Although liver GST activity to 1-chloro-2,4-dinitrobenzene as a substrate (GST-C activity), catalyzed by various GST isozymes in dogs, was significantly correlated with liver GST-D activity, GST-C activity showed more than 450 nmol/min per mg protein even in the low GST dogs. There was no significant difference in cytochrome P450 content, 7-ethoxycoumarin O-deethylase activity or UDP-glucuronosyltransferase activity to p-nitrophenol as a substrate between low GST dogs and the other dogs. Finally, remarkably high plasma concentrations of DCNB were observed in the low GST dogs after single doses of DCNB at 5 or 100 mg/kg. The individual differences in GST-D activity are probably attributable to the content and/or activity of the theta class GST isozyme Yd(f)Yd(f) since it has been reported that glutathione conjugation of DCNB is specifically catalyzed by GSTYd(f)Yd(f) in dogs. In conclusion, we identified a number of low GST dogs in which the GST-D activities were not observed either in vivo or in vitro. The feasibility of using a single low dose of DCNB to phenotype dogs based on GST-D activity was confirmed. It was also suggested that low GST dogs have high susceptibility, including unexpected toxicity or abnormal exposure, to chemicals metabolized by GSTYd(f)Yd(f).

Occurrence of mycotoxins in extruded commercial dog food

“…In particular, the dog appears to be one of the domestic species most sensitive to the effects deriving from intoxication by aflatoxins, most likely because of the low activity of glutathione S-transferase, which is involved in the detoxification of these mycotoxins (Watanabe et al, 2004). In acute forms of aflatoxicosis, dogs exposed to doses exceeding 500-1000 g/kg of BW died within a few days, showing signs of hepatic hyperplasia, disseminated intravascular coagulation and hemorrhages.…”

Positive association between a glutathione‐S‐transferase polymorphism and lymphoma in dogs

“…Epidemiologic studies have found significant associations between canine lymphoma and exposure to industrial pollutants, solvents and herbicides, but the role of specific environmental carcinogens in the development of lymphoma in dogs is not clear . GSTT1 activities have been characterized in livers from research beagles, and 12% of these dogs had virtually no GSTT1 protein expression or activity . However, the genetic basis for this variability, and its toxicological consequences, has not been explored.…”

An outbreak of canine aflatoxicosis in Gauteng Province, South Africa

“…9 Dogs appear more susceptible because of their inherently lower hepatocellular concentration of GSH compared with other species, as well as their inter-individual differences in activity of GSH-S-transferase. 13,14 Furthermore, AF are reported to exert an anti-coagulation effect as a result of their coumarin-like structure. 15 Exposure to lower AF concentrations in feed over a prolonged period can induce chronic liver failure, indicating a cumulative effect.…”