Effects of genetics, sex, and age on the toxicity of rubratoxin B in mice

Abstract

To improve an animal model used in toxicological studies, we investigated the effects of genetics, sex, and age on rubratoxin B toxicity in mice. Treatment with rubratoxin B for 24 h increased serum alanine aminotransferase (ALT) activity, a common indicator of hepatic injury, in C3H/He, BALB/c, DBA/2, and C57BL/6 mice. The increase in serum ALT levels was most pronounced in rubratoxin B-treated C3H/He mice, as was the decrease in serum glucose concentration. In addition, these effects were greater in C3H/He male mice than female. Serum ALT activities were more elevated in rubratoxin B-exposed 9- and 12-week-old animals than that of 6-week-olds. The effect of rubratoxin B on the serum glucose concentration was greatest in 9-week-old male C3H/He mice. Therefore, our findings show that the genetics, sex, and age of the mice treated all contributed to the toxicity of rubratoxin B and that 9-week-old male C3H/He mice were the most susceptible of the animals we tested. Moreover, rubratoxin B-exposed mice had fatty livers and increased levels of triglycerides (the typical lipid involved in the development of fatty liver).