Induction of oxidative cell damage by photo-treatment with zinc metaN-methylpyridylporphyrin

Abstract

We have previously reported that isomeric Zn(II) N-methylpyridylporphyrins (ZnTM-2(3,4)-PyP^{4 +} ) can act as photosensitizers with efficacy comparable to that of hematoporphyrin derivative (HpD) in preventing cell proliferation and causing cell death in vitro. To better understand the biochemical basis of this activity, the effects of photo-activated ZnTM-3-PyP^{4 +} on GSH/GSSG ratio, lipid peroxidation, membrane permeability, oxidative DNA damage, and the activities of SOD, catalase, glutathione reductase, and glutathione peroxidase were evaluated. Light exposure of ZnTM-3-PyP^{4 +} -treated colon adenocarcinoma cells caused a wide spectrum of oxidative damage including depletion of GSH, inactivation of glutathione reductase and glutathione peroxidase, oxidative DNA damage and peroxidation of membrane lipids. Cell staining with Hoechst-33342 showed morphological changes consistent with both necrotic and apoptotic death sequences, depending upon the presence of oxygen.

• Photodynamic therapy
• Zn meta N-methylpyridylporphyrin
• oxidative stress
• lipid peroxidation
• cell death

Abbreviations
ZnTM-3-PyP4 +	=	meta isomer, Zn(II) tetrakis(N-methylpyridinium-3-yl)porphyrin
PDT	=	photodynamic therapy
HpD	=	hematoporphyrin derivative
SOD	=	superoxide dismutase
MDA	=	malondialdehyde
8-OHdG	=	8-hydroxy-2′-deoxyguanosine
ROS	=	reactive oxygen species
RNS	=	reactive nitrogen species
ANOVA	=	analysis of variance

Abbreviations
ZnTM-3-PyP4 +	=	meta isomer, Zn(II) tetrakis(N-methylpyridinium-3-yl)porphyrin
PDT	=	photodynamic therapy
HpD	=	hematoporphyrin derivative
SOD	=	superoxide dismutase
MDA	=	malondialdehyde
8-OHdG	=	8-hydroxy-2′-deoxyguanosine
ROS	=	reactive oxygen species
RNS	=	reactive nitrogen species
ANOVA	=	analysis of variance

Notes

^‡ M. Alkhalaf, Department of Biochemistry, Faculty of Medicine, Kuwait University—personal communication.