atractyloside and Renal-Insufficiency

In Mediterranean countries, intoxication by Atractylis gummifera L. is frequent and characterized principally by hepatorenal injury, often fatal. Its toxicity after a cutaneous application is unknown. We report a case of poisoning by A. gummifera L. induced by repeated cutaneous application.. A 30-month-old boy was admitted in our pediatric intensive care unit in coma (Glasgow Coma Scale 8). Investigations showed hepatic cellular injury, cholestasis, decreased prothrombin level, and increased creatinine. History from the parents revealed repeated and occlusive cutaneous application of A. gummifera L. on a skin burn. Qualitative analysis of urine confirmed the diagnosis of A. gummifera poisoning. The child was discharged after 16 days of hospitalization with residual renal insufficiency.. Poisoning by A. gummifera L. after cutaneous application has not previously been reported in the literature. The prevention of this poisoning, particularly frequent in Mediterranean countries, is mainly based on the education of the public concerning the dangers of this plant.

Topics: Atractylis; Atractyloside; Child, Preschool; Humans; Liver; Male; Plant Poisoning; Renal Insufficiency

The consumption of plants containing atractyloside, a diterpenoid glycoside, causes selective proximal tubule injury leading to renal failure and death in humans. The underlying mechanisms responsible for its toxicity are still not well understood. The present study was therefore carried out to determine the mechanism and the exact sequence of events that lead to molecular toxic injury. A comparative study using renal cortical slices, suspension of freshly isolated renal proximal tubular fragments and glomeruli of male Wistar rat was made. These in vitro systems were exposed to 100-1000 mM atractyloside for 2-3 h at 37 degrees C. Atractyloside caused a significant alteration in various toxicity parameters in a concentration- and time-dependent manner in renal cortical slices and proximal tubular fragments, but not in glomeruli. The earliest change following exposure to atractyloside (1000 microM) was a significant reduction of intracellular adenosine 5'-triphosphate (ATP) content occurring within 1 h in the tubules and 2 h in slices. The significant depletion of reduced glutathione (GSH) inhibitor of p-aminohippuric (acid) (PAH) uptake and gluconeogenesis occurred simultaneously following loss of cellular energy. These events were only limited to the renal cortical slices and proximal tubular fragments. Increased severity of cellular injury resulted in cytotoxicity with the significant increase in the leakage of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in proximal tubular fragments (occurring at 2 h) and renal cortical slices (occurring at 3 h). There were, however, no alterations in oxidized glutathione (GSSG) levels or in the ratio of GSH/GSSG. Only limited lipid peroxidation in proximal tubular fragments and glomeruli was observed at atractyloside concentrations of 500 microM and above. In all cases of toxicity, the glomeruli were unaffected. Pretreatment of slices or fragments with probenecid (1.0 mM) failed to completely abolish atractyloside toxicity. These data demonstrate dose- and time-dependent toxicity of atractyloside and clearly confirmed the proximal tubular fragments as the target tissue. Atractyloside exhibits a toxicity profile that indicates early alteration in mitochondrial function and consequently loss of cellular energy, followed by reduced metabolic function and transport processes and ultimately cell death. This appears to be the most likely mechanism by which atractyloside exerted its acute cytotoxicity. Renal co

Topics: Adenosine Triphosphate; Animals; Atractyloside; Biological Transport; Cell Death; Dose-Response Relationship, Drug; Gluconeogenesis; Glutathione; In Vitro Techniques; Kidney Cortex; Kidney Glomerulus; Kidney Tubules, Proximal; Lipid Peroxidation; Male; Malondialdehyde; Mitochondria; Oxidative Phosphorylation; Oxidative Stress; p-Aminohippuric Acid; Rats; Rats, Wistar; Renal Insufficiency; Time Factors

Poisoning with impila (Callilepis laureola) is a recurring phenomenon in South Africa. Cases of poisoning with other plants which contain atractyloside also occur in Europe and the Americas. Since poisoning leads to rapid death from renal and/or hepatic failure, it is suspected that many cases are undiagnosed; this is especially so in South Africa, where patients may die without reaching hospital and do not often admit to ingestion of a traditional remedy. We have developed a thin layer chromatographic method for the detection of impila constituents in urine. We describe the clinical symptoms and the application of the screening method to diagnosis in the case of a mother and child, who both showed symptoms of impila poisoning; the mother died but the child survived. This method is rapid and may be used for the definitive diagnosis in cases of poisoning with atractyloside-containing plants.

Topics: Adult; Atractyloside; Chromatography, Thin Layer; Enzyme Inhibitors; Female; Follow-Up Studies; Humans; Infant; Liver Failure, Acute; Liver Function Tests; Plants, Medicinal; Renal Insufficiency