MODIFICATION OF GRISEOFULVIN-INDUCED PORPHYRIA BY THE DEVELOPMENT OF EXPERIMENTAL DIABETES MELLITUS

Yalouris A1, Grigoriadou M2, Marakomichelakis G2, Diamantopoulos E2, Raptis S1

 

1Second Department of Internal Medicine, 2Fourth Department of Internal Medicine, Athens University, Evangelismos Hospital, Athens, Greece

 

 

Diabetes is known to affect the activity of some haem synthetic enzymes. In clinical practice the coexistence of diabetes and porphyria is not uncommon and as we have previously indicated (BMJ 1987; 295:1237-8) may alter the natural course of porphyria. The aim of our study was to investigate whether the development of diabetes in porphyric animals could change their fecal porphyrin excretion, which can be used as a reliable index of porphyric activity. Four white mice became porphyric by the per os administration of high-dose griseofulvin (210 mg/kg b.w. daily). Fecal porphyrins (FP) increased from 1.63±1.07 to 70.91±43.74 µg/g (p<0.001). When the mice were made diabetic by streptozotocin a significant further increase of FP was observed (105.91±34.34 µg/g, p=0.001). In another 12 mice the administration of a low dose griseofulvin (70 mg/kg b.w. daily) produced a less pronounced but also significant increase in FP (6.84±3.78 µg/g, p<0.001). In 8 of these animals streptozotocin-induced diabetes led to a further increase of FP (8.28±3.40 µg/g, p=0.024). In 4 porphyric (with low-dose griseofulvin) and in 4 porphyric/diabetic mice phenobarbital, a potent inducer of porphyrin synthesis, was also administered (200 mg/kg b.w. daily) to aggravate their mild porphyria. FP significantly increased in both groups, but more in the diabetic than in the non-diabetic porphyric mice (14.6±1.35 versus 8.71±1.35 µg/g, p<0.001). It is concluded that diabetes significantly increased the porphyric activity (as estimated by FP) in mice with severe or mild porphyria and made them more responsive to an aggravating factor.