Melatonin, melanogenesis, and hypoxic stress in the newt, Triturus carnifex

Groups of 6 specimens each of the newt Triturus carnifex were treated with melatonin to see if the hormone inhibited melanogenesis in the Kupffer cells of the liver (melanomacrophages), a process markedly stimulated by hypoxia. A dose of 500 microg/g in 27% ethanol, injected intraperitoneally, induced loss of consciousness and tetany of all the skeletal muscles, which on the contrary appeared relaxed in animals pre-anesthetised by immersion in chlorbutol at 0.2%. Anesthetised specimens injected with melatonin showed a significantly lower increase in hepatic pigmentation after acute hypoxia, a condition attained by sealing each specimen in a 620 mL respiratory chamber with water containing 1.1 ppm of oxygen for the time needed to consume it all (about two hours). If hypoxia is reached gradually, beginning with 8 ppm of oxygen (normoxic condition), the increase in hepatic pigmentation after melatonin injection does not differ significantly from that of non-hormone treated specimens: thus melatonin does not seem to play a direct part in controlling hepatic melanogenesis. Instead, the hormone induces significant increase in oxygen consumption, marked general steatosis of the liver and the almost total disappearance of glycogen. Intraperitoneal injection of 500 microg/g of melatonin in anesthetised animals exposed to the air (normoxic) also causes severe steatosis and an unexpected increase in the hepatic deposits of melanin, as after hypoxic treatment. A dose of 100 ng/g in 1% ethanol, ineffective when injected intraperitoneally, also induces these effects if injected directly into the arterial blood-stream through the conus arteriosus, thus avoiding the hepatic filter. The phenomena observed appear to be induced by a powerful endocrine mechanism that provokes metabolic hypoxia by consuming all the available ATP for synthesizing fat. A less intense form of steatosis can also be observed in animals subjected to hypoxia but without prior hormone treatment, indicating that a natural process triggered by hypoxic stress is pushed to the extreme by exogenous melatonin: the hormone changes the entire energy metabolism of the organism so that it can survive for a long time under adverse environmental conditions.