Genomics and metabolomics of early-stage thioacetamide-induced liver injury: An interspecies study between guinea pig and rat.

To study the complex processes involved in liver injuries, researchers rely on animal investigations, using chemically or surgically induced liver injuries, to extrapolate findings and infer human health risks. However, this presents obvious challenges in performing a detailed comparison and validation between the highly controlled animal models and development of liver injuries in humans. Furthermore, it is not clear whether there are species-dependent and -independent molecular initiating events or processes that cause liver injury before they eventually lead to end-stage liver disease. Here, we present a side-by-side study of rats and guinea pigs using thioacetamide to examine the similarities between early molecular initiating events during an acute-phase liver injury. We exposed Sprague Dawley rats and Hartley guinea pigs to a single dose of 25 or 100 mg/kg thioacetamide and collected blood plasma for metabolomic analysis and liver tissue for RNA-sequencing. The subsequent toxicogenomic analysis identified consistent liver injury trends in both genomic and metabolomic data within 24 and 33 h after thioacetamide exposure in rats and guinea pigs, respectively. In particular, we found species similarities in the key injury phenotypes of inflammation and fibrogenesis in our gene module analysis for liver injury phenotypes. We identified expression of several common genes (e.g., SPP1, TNSF18, SERPINE1, CLDN4, TIMP1, CD44, and LGALS3), activation of injury-specific KEGG pathways, and alteration of plasma metabolites involved in amino acid and bile acid metabolism as some of the key molecular processes that changed early upon thioacetamide exposure and could play a major role in the initiation of acute liver injury.

Efficacy and safety of topical selamectin to eradicate pinworm (Syphacia spp.) infections in rats (Rattus norvegicus) and mice (Mus musculus).

We evaluated the efficacy and safety of topical selamectin, a novel avermectin, in eliminating naturally acquired Syphacia muris infections in rats and S. obvelata infections in mice. S. muris-positive rats were assigned randomly to 4 groups: selamectin (0.6 mg/kg), selamectin (6.0 mg/kg), fenbendazole-medicated (150 ppm) chow, and untreated. S. obvelata-positive mice were allocated into 4 groups similar to those for rats. Animals not exposed to pinworm-contaminated bedding were designated as negative controls. Treatment success was assessed weekly by anal tape impressions and by necropsy examinations at the end of week 9. Evaluations of intestinal contents at necropsy revealed that, although safe, topical selamectin was 100% ineffective in eliminating Syphacia spp. infections in rats and mice. Treatment with fenbendazole-medicated chow resulted in negative anal tape impressions beginning at week 2 in rats and week 1 in mice. Negative anal tape impressions in fenbendazole-treated animals were confirmed by negative intestinal content evaluations. Of the 2 treatments evaluated, fenbendazole-medicated chow remains an effective and practical method to eliminate pinworm infections in mice and rats.