Trauma as a Cause for Hepatopathy in Newborn Göttingen Minipigs

Abstract

Routine husbandry procedures during animal toxicity studies can result in incidental pathological changes. We report on trauma-induced hepatopathy in newborn Göttingen minipigs. Sixty-four neonatal minipigs were allocated to 13- and 26-week treatment arms. There was a 4-week recovery period for both arms. The animals were divided into 2 treatment groups and a vehicle group and were dosed 3 times daily by direct oral administration using a syringe. During the feeding procedure in the first weeks, the animals had to be handled firmly. After 13 weeks, randomly distributed foci of degeneration/necrosis and focal congestion and/or hemorrhage were found in the livers of several animals from all groups. Reduced incidence and severity were evident in the recovery phase, and the lesions were absent after 26 weeks. These changes were considered as related to the manual handling of the animals. Knowledge of these findings is crucial for interpretation of studies utilizing newborn minipigs.

Ten-day and four-week toxicity and toxicokinetics studies of alpha-glycosyl isoquercitrin in juvenile Göttingen minipigs

“…33 Such findings are not considered adverse and emphasize the importance of proper knowledge of the normal histopathological findings that can be expected in newborn minipigs. 34 Indeed, the amount of iron that was detected in the histological sections decreased between the 10-day study and the 4-week study, showing that its presence was transient and without any adverse effect on the animals.…”

Nasal Inflammation and Ulceration Secondary to Repeated Use of an Intranasal Delivery Device in Rabbits

“…9 Such anatomical differences can also lead to trauma-induced pathological changes related to the handling of the animal, and it is important that the toxicologic pathologist will not wrongly attribute such changes to the test drug or combination product. [10][11][12] Here, we report on nasal inflammation and ulceration in rabbits, secondary to the mechanical damage induced by the repeated insertion and removal of the intranasal device, which were not related to the tested drug.…”

“…9 Such anatomical differences can also lead to trauma-induced pathological changes related to the handling of the animal, and it is important that the toxicologic pathologist will not wrongly attribute such changes to the test drug or combination product. 10 –12…”

The Neonatal and Juvenile Pig in Pediatric Drug Discovery and Development

“…Continuous efforts are being made to better characterize the (juvenile) pig in the fields of ophthalmology [251,252], neurodevelopment [28], immunology [28], and drug absorption, metabolism and toxicity [35,43,45,[253][254][255][256], although there is still evidence supporting the need for more background information in pigs [253]. Moreover, differences in between breeds exist [257] and, since fully characterizing all the pig breeds available is a long-term task, most efforts concentrate in studying the most used pig breed in pharmacological studies in Europe, the Göttingen Minipig [35,[43][44][45][258][259][260][261][262][263][264][265][266][267][268][269][270][271][272][273][274]. Inter-breed differences are magnified due to the lack of standardization regarding food and feeding patterns, age and sex of pigs used in research [275].…”