Biodistribution and Acute Toxicity Evaluation in vivo of the Natural Anthraquinones

COMINI, L.; FERNANDEZ, I.; NUÑEZ MONTOYA, S.; CABRERA, J.; RIVAROLA, V.

Córdoba.

Jornada; XVII JORNADAS CIENTÍFICAS DE LA SOCIEDAD DE BIOLOGÍA DE CÓRDOBA; 2009

Sociedad de Biología de Córdoba

Photodinamic therapy (PDT) is based on the toxicity induced in tumor tissue for combined action of a photozensitizer and light. Rubiadin (1), anthraquinone isolated from Heterophyllaea pustulata, exhibit photosensitizing properties, which suggested it could be considered a drug for PDT. Therefore, we evaluated the photodynamic activity of 1 in vitro on a human carcinoma cell line, obtaining promising results, which motivate to achieved studies in vivo (mice). This work intends to determine the biodistribution of 1 and evaluate their acute toxicity in possible target tissue, with the aim to determine the non-toxic dose that will be used in phototherapeutic studies. The biobistribution was studied by means of a quali-quantitative HPLC analysis from liver, kidney, spleen, lung, muscle, intestines and skin tissue, extracted from BALB/c mice at 24-48 hs and 7 days after intraperitoneal (i.p.) administration of 1 (80 mg/kg). Acute toxicity was established by a histopathological analysis of the same tissue, after i.p. injection of 1 (20, 40, 80 mg/kg) at the times above mentioned. Results showed that levels of 1 are important at 24 hs in liver, kidney, skin, muscle and spleen, declining to 48 hs and 7 days. However, no alterations are observed in the analyzed tissues at doses and times tested. Therefore, 1 would fulfill with the primary requirements for future phototherapeutic studies.