Glycogen metabolism and glucose transport in experimental porphyria.
Hexachlorobenzene (HCB) is a fungicide of well-known porphyrinogenic ability, which induces an experimental porphyria that resembles human porphyria cutanea tarda (PCT) in several animal species. It has been demonstrated that high glucose ingestion prevents porphyria development, and high-fat/high-protein diets enhance HCB porphyrinogenic ability. On the contrary, a diet rich in carbohydrates reduces HCB effects. The aim of this work was to study HCB effects on glycogen synthesis and degradation, as well as on glucose synthesis and transport, in order to elucidate whether would justify the beneficial use of carbohydrates in this porphyria. Rats were treated with HCB dissolved in corn oil (five daily doses 100mg/kg body weight). Results showed that: (1) HCB caused an increase in glycogen content; (2) glycogen synthase activity increased three times, and phosphorylase activity decreased about 40% due to fungicide intoxication. The effect of HCB on these two activities accounted for the higher glycogen content observed in treated animals; (3) three gluconeogenic enzymes were reduced 30-50%; (4) glucose uptake in the liver decreased in all weeks studied. The alterations found in glucose synthesis, its uptake in liver and other tissues, and its release from glycogen might contribute to the biochemical porphyria picture and would account for the effect of glucose above mentioned.
Laboratorio de Disturbios Metabólicos por Xenobióticos, Salud Humana y Medio Ambiente (DIMXSA), Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
María Cristina
MC
Taira
Marta Blanca
MB
Mazzetti
Sandra Marcela
SM
Lelli
Leonor Carmen San Martín
LC
de Viale
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005659:Fungicides, Industrial / Q000633:toxicity*; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism*; D006581:Hexachlorobenzene / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D011164:Porphyrias / Q000139:chemically induced* / Q000201:enzymology / Q000378:metabolism; D011166:Porphyrins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D005659:Fungicides, Industrial; D011166:Porphyrins; D006581:Hexachlorobenzene; D006003:Glycogen; D005947:Glucose