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

Exp Oncol. 2008 Sep;30(3):212-9.

Abstract

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 ( lambda = 685 nm, D = 50 J/cm(2), 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminolevulinic Acid / therapeutic use*
  • Animals
  • Anticholesteremic Agents / therapeutic use*
  • Carcinosarcoma / metabolism
  • Carcinosarcoma / pathology
  • Carcinosarcoma / therapy*
  • Chitosan / therapeutic use*
  • Combined Modality Therapy
  • Drug Therapy, Combination
  • Light
  • Lipid Peroxidation
  • Male
  • Malondialdehyde / metabolism
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Oxidative Stress
  • Photochemotherapy*
  • Photosensitizing Agents / therapeutic use*
  • Protoporphyrins / metabolism
  • Rats
  • Rats, Wistar

Substances

  • Anticholesteremic Agents
  • Photosensitizing Agents
  • Protoporphyrins
  • Malondialdehyde
  • Aminolevulinic Acid
  • Chitosan
  • protoporphyrin IX
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9