5-aminolevulinic acid-induced alterations of oxidative metabolism in sedentary and exercise-trained rats.
5-Aminolevulinic acid (ALA), a heme precursor that accumulates in acute intermittent porphyria patients and lead-exposed individuals, has previously been shown to autoxidize with generation of reactive oxygen species and to cause in vitro oxidative damage to rat liver mitochondria. We now demonstrate that chronically ALA-treated rats (40 mg/kg body wt every 2 days for 15 days) exhibit decreased mitochondrial enzymatic activities (superoxide dismutase, citrate synthase) in liver and soleus (type I, red) and gastrocnemius (type IIb, white) muscle fibers. Previous adaptation of rats to endurance exercise, indicated by augmented (cytosolic) CuZn-superoxide dismutase (SOD) and (mitochondrial) Mn-SOD activities in several organs, does not protect the animals against liver and soleus mitochondrial damage promoted by intraperitoneal injections of ALA. This is suggested by loss of citrate synthase and Mn-SOD activities and elevation of serum lactate levels, concomitant to decreased glycogen content in soleus and the red portion of gastrocnemius (type IIa) fibers of both sedentary and swimming-trained ALA-treated rats. In parallel, the type IIb gastrocnemius fibers, which are known to obtain energy mainly by glycolysis, do not undergo these biochemical changes. Consistently, ALA-treated rats under swimming training reach fatigue significantly earlier than the control group. These results indicate that ALA may be an important prooxidant in vivo.
Pereira
B
B
Department of Biochemistry, Universidade de São Paulo, Brazil.
Curi
R
R
Kokubun
E
E
Bechara
E J
EJ
D000622:Aminolevulinic Acid / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002950:Citrate (si)-Synthase / Q000378:metabolism; D005260:Female; D007855:Lead Poisoning / Q000378:metabolism; D008660:Metabolism / Q000187:drug effects*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D010805:Physical Conditioning, Animal; D005082:Physical Exertion / Q000502:physiology; D011164:Porphyrias / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000378:metabolism
D000622:Aminolevulinic Acid; D013482:Superoxide Dismutase; D002950:Citrate (si)-Synthase