Bombyx mori used as a fast detection model of liver melanization after a clinical drug - Acetaminophen exposure

Acetaminophen (APAP) is an effective and widely used analgesic. However, APAP overdose is the principal cause of acute liver failure (ALF) in many countries. Here, we report the phenomenon of liver melanization which occurred before APAP-induced ALF in mice. A melanic surface induced by APAP which was time- and dose-dependent in the silkworm invertebrate model was observed. In addition, an APAP-induced acute tissue failure model (ATF) was established using a metabolic detoxification tissue fat body which simulated mouse liver. An investigation of the anabolic mechanism of melanin in experimental animals showed that dopaquinone and dopamine which were synthesized from tyrosine via dopa in silkworms were further metabolized to melanin, while in mice, epinephrine was synthesized via the dopamine branch and melanin was only synthesized via the dopaquinone branch. On this basis, it is proposed that melanin-metabolic levels in plasma could be used as an early diagnostic marker of APAP overdose and the black spots on insect epidermis could be used as a fast detection model of toxicity.