Efects of PDT with 5-aminolevulinic acid and chitosan on Walker carcinosarcoma

Filip A., Clichici S., Muresan A., Daicoviciu D., Tatomir C., Login C., Dreve S., Gherman C.

Porphyrins and new chitosan hydrogels based composites with porphyrins are used as active cytotoxic antitumor agents in photodynamic therapy (PDT). Aim: The present study evaluates the effects of photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) and 5-ALA associated with chitosan (CS) using Walker carcinosarcoma in rats as experimental model. Methods: The animals were irradiated with red light (l = 685 nm, D = 50 J/cm2, 15 min) 3 h after i.p. administration of 5-ALA (250 mg/kg b.w.) or a mixture of 5-ALA (250 mg/kg b.w.) and CS (1.5 mg/kg b.w.). The animals were sacrificed at 1, 3, 6, 24 h and 14 days after the treatment. The effects of PDT were investigated by morphological studies, monitoring the 5-ALA induced protoporphyrin IX (Pp IX) level in tumor tissue and serum, MMP 2 and 9 (gelatinases) activity in tumor and malondialdehyde level (MDA), marker of the lipoperoxidation process, in tumor and serum. Results: Zymography revealed an increased activity of MMP 2 in tumors from animals treated with 5-ALA PDT. PDT with 5-ALA induced a higher lipid peroxidation in tumor tissue compared with 5-ALA-CS. CS associated to 5 ALA PDT enhanced the accumulation of PS in tumors inducing earlier necrotic changes. In the same time CS reduced MMP 2 activity. Conclusion: Our results suggest that MMPs activation and oxygen reactive species are involved in PDT effects.

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