Acute
hepatic porphyrias are human
metabolic diseases characterized by the accumulation of
heme precursors, such as 5-aminolevulinic
acid (ALA). The administration of
glucose can prevent the symptomatology of these diseases. The aim of this work was to study the relationship between
glucose metabolism disturbances and the development of experimental
acute hepatic porphyria, as well as the role of
reactive oxygen species (ROS) through assays on hepatic key gluconeogenic and glycogenolytic
enzymes;
phosphoenolpyruvate carboxykinase (PEPCK) and
glycogen phosphorylase (GP), respectively. Female Wistar rats were treated with three different doses of the porphyrinogenic
drug 2-allyl-2-isopropylacetamide (AIA) and with a single dose of
3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). Thus, rats were divided into the following groups: group L (100 mg AIA + 50 mg DDC/kg body wt.); group M (250 mg AIA + 50 mg DDC/kg body wt.) and group H (500 mg AIA + 50 mg DDC/kg body wt.). The control group (group C) only received vehicles (
saline solution and
corn oil).
Acute hepatic porphyria markers ALA-synthase (ALA-S) and
ferrochelatase,
heme precursors ALA and
porphobilinogen (PBG), and oxidative stress markers
superoxide dismutase (SOD) and
catalase (CAT) were also measured in hepatic tissue. On the other hand, hepatic cytosolic
protein carbonyl content, lipid peroxidation and urinary chemiluminescence were determined as in vivo oxidative damage markers. All these parameters were studied in relation to the different doses of AIA/DDC. Results showed that
enzymes were affected in a
drug-dose-dependent way. PEPCK activity decreased about 30% in group H with respect to groups C and L, whereas GP activity decreased 53 and 38% in group H when compared to groups C and L, respectively. On the other hand, cytosolic
protein carbonyl content increased three-fold in group H with respect to group C. A marked increase in urinary chemiluminescence and a definite increase in lipid peroxidation were also detected. The activity of liver
antioxidant enzyme SOD showed an induction of about 235% in group H when compared to group C, whereas CAT activity diminished due to
heme depletion caused by both drugs. Based on these results, we can speculate that the alterations observed in
glucose metabolism
enzymes could be partly related to the damage caused by ROS on their enzymatic
protein structures, suggesting that they could be also linked to the beneficial role of
glucose administration in
acute hepatic porphyria cases.