Ionophore Toxin Maduramicin Produces Haff Disease-Like Rhabdomyolysis in a Mouse Model

Abstract

Maduramicin is a toxic ionophore antibiotic that is isolated from Streptomyces, frequently occurring in an aquatic environment. To understand the potential role of maduramicin in crayfish consumption related Haff disease, a mouse model was established in this study. Two exposure routes of maduramicin in the abdominal muscle and the hepatopancreas tissue homogenates of crayfish were given intragastrically to mice in different doses for seven days. Action changes, clinical symptoms, feed consumption, body weight, blood biochemistry, and histopathology examination of mice were observed and analyzed. In the natural exposure group, relatively low concentration of maduramicin in crayfish muscle and hepatopancreas had no obvious effects on mental state, body weight, blood biochemical indexes, or histologic appearance. However, in the artificial exposure group, with increasing concentrations, maduramicin in crayfish muscle and hepatopancreas homogenates both induced mental sluggishness and weight loss of mice. Blood biochemical examination showed that 3.5 mg·kg−1 and 7 mg·kg−1 maduramicin in crayfish tissue homogenates significantly increased levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), lactate dehydrogenase (LDH), and creatine kinase (CK). Additionally, histopathological examination showed that multiple organs were damaged by maduramicin, including degeneration of liver cells, shedding of renal epithelial cells, and disturbance and partial lysis of myocardial and skeletal muscle filaments in the mice. In summary, maduramicin may not cause Haff disease through contamination of the aquatic environment under normal conditions. Maduramicin can be used as a potential toxin tool to establish a rhabdomyolysis disease animal model for drug development.

Determination of toxicological characteristics of a complex antiemeric drug based on maduramycin and nicarbazine

“…Nicarbazine is a synthetic agent that is a complex of 4,4'-dinitrodiphenylurea (DNC) and 2-hydro-4,6dimethylpyrimidine (HDP), which inhibits energy metabolism in the body of the parasite. Nicarbazine acts mainly at the stage of second-generation schizonts and their merozoites, preventing tissue damage by this stage of coccidian [8,9].…”

“…Significant overdose causes a violation of sodium-potassium metabolism, which in turn leads to problems with the cardiovascular system and skeletal muscle. In animals and birds, muscle weakness, incoordination, drowsiness, depression, diarrhea can be observed [7,8].…”

Haff disease – are we threatened with another epidemic?

“…W badaniach przeprowadzonych na modelach zwierzęcych wykazano, że maduramycyna w wysokich stężeniach może wywołać objawy przypominające chorobę Zalewu Wiślanego. Udowodniono jednak, że zawartość maduramycyny w skorupiakach występujących w środowisku naturalnym jest niewystarczająca do wywołania podobnych dolegliwości [20].…”