Photodynamic therapy (PDT) is a treatment modality for various cancers and other diseases associated with selective accumulation or production of photosensitizers in diseased tissue [1]. PDT is undergoing rapid development both with respect to efficacy and extent of application. Recently, so-called 5-aminolevulinic acid based PDT (ALA-PDT) has been introduced, notably, for the treatment of tumours and precancerous lesions of the skin [2].

Exogenously administered ALA enters a pathway of haem biosynthesis and bypasses the haem feedback control upon synthesis of endogenous ALA. Thus exogenous ALA induces the enhanced accumulation of intracellular porphyrins. Protoporphyrin IX (PpIX) is the last intermediate step before its conversion into haem. After exogenous administration of ALA, PpIX is found, in many cases, to be the main photoactive porphyrin (PAP). Tumours appear to have enhanced accumulation of ALA-induced porphyrins than normal tissues [3]. This may result from a combination of higher porphobilinogen deaminase activity [4], lower ferrochelatase activity and lower intracellular iron concentration in cancer cells [5].

ALA can be administered systemically or in an ointment applied topically on the lesion [3]. In the case of topical application the penetration of ALA molecules through the skin can be enhanced using penetration enhancers that facilitate the treatment of deeper lesions [6]. Earlier we have found that an increase of skin temperature might also promote the PpIX-production from ALA in cells and in tissues [7,8]. The efficacy of topical ALA-PDT is limited by the depth of ALA penetration through the skin [9]. ALA-esters, which are more lipophilic than ALA, are currently being investigated as new drugs for PDT [10,11].

When applying an ointment topically on an experimental animal it is hard to ensure its proper application due to activity of animals. Thus, in many cases, the administration of anaesthesia is needed during cream application. The action of anaesthesia depends on the type and amount of anaesthetic. Most of the anaesthetics used for anaesthesia of experimental animals act via vascular vessels that lowers metabolic activity. It is important that anaesthesia would not significantly interfere with the experimental results [12]. We usually observe that action of intraperitoneally injected anaesthetics results in decreased skin temperature, lasting until animals wake up and become normally active. The present work was carried out to study the influence of temperature and anaesthesia on application of ALA and ALA-Me.

TITLE AND ABSTRACT

INTRODUCTION

MATERIALS AND METHODS

RESULTS AND DISCUSSION

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