Hypericin as an inactivator of infectious viruses in blood components

Lavie, Gad; Mazur, Yehuda; Lavie, David; Prince, A. M.; Pascual, Donna; Liebes, Leonard; Levin, Brandi; Meruelo, Daniel

doi:10.1046/j.1537-2995.1995.35595259149.x

Cited by 106 publications

(67 citation statements)

References 27 publications

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“…Importantly, it was reported that hypericin binds to human lipoproteins at high molar ratios (up to 467 and 14 moles per 10 4 Da of low-density lipoproteins (LDL) and high-density lipoproteins (HDL), respectively) (Lavie et al, 1995b). In contrast to human plasma, mouse plasma contains a high HDL/LDL ratio (Kessel and Woodburn, 1993), so that mainly the hypericin -HDL complex is formed in the bloodstream of mice (results not shown).…”

Section: Discussionmentioning

confidence: 95%

Elucidation of the tumoritropic principle of hypericin

Putte¹,

Roskams

Vandenheede

et al. 2005

Br J Cancer

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Hypericin is a potent agent in the photodynamic therapy of cancers. To better understand its tumoritropic behaviour, we evaluated the major determinants of the accumulation and dispersion of hypericin in subcutaneously growing mouse tumours. A rapid exponential decay in tumour accumulation of hypericin as a function of tumour weight was observed for each of the six tumour models investigated, and a similar relationship was found between tumour blood flow and tumour weight. Moreover, there was a close correlation between the higher hypericin uptake in RIF-1 tumours compared to R1 tumours and tumour vessel permeability. To define the role of lipoproteins in the transport of hypericin through the interstitial space, we performed a visual and quantitative analysis of the colocalisation of hypericin and DiOC 18 -labelled lipoproteins in microscopic fluorescent overlay images. A coupled dynamic behaviour was found early after injection (normalised fluorescence intensity differences were on the whole less than 10%), while a shifted pattern in localisation of hypericin and DiOC 18 was seen after 24 h, suggesting that during its migration through the tumour mass, hypericin is released from the lipoprotein complex. In conclusion, we were able to show that the tumour accumulation of hypericin is critically determined by a combination of biological (blood flow, vessel permeability) and physicochemical elements (affinity for interstitial constituents).

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Section: Discussionmentioning

confidence: 95%

Elucidation of the tumoritropic principle of hypericin

Putte¹,

Roskams

Vandenheede

et al. 2005

Br J Cancer

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“…We initially hypothesized a faster blood and liver clearance for the less lipophilic [ (10,12). As is the case for many other photosensitizers, hypericin has been found to associate mainly with lipoproteins and to a lesser extent other proteins in blood (6,13). In contrast to human plasma, mouse plasma has a higher ratio of HDL/LDL (14).…”

Section: Discussionmentioning

confidence: 99%

“…The precise mechanism of tumor accumulation of hypericin is not fully understood. It has been proposed by some authors (7,13) that the mechanism of its delivery to the tumor is by receptormediated endocytosis of lipoprotein bound drug. Van I]MIH as tumor diagnostic agent will involve SPECT imaging during which images will be registered at different time points with the aim of finding the optimal time at which the best target to non-target ratio is reached.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of tumor affinity of mono‐[¹²³I]iodohypericin and mono‐[¹²³I]iodoprotohypericin in a mouse model with a RIF‐1 tumor

Fonge

Putte

Huyghe

et al. 2007

Contrast Media & Molecular

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In this study we have compared the tumour-seeking properties of mono-[(123)I]iodoprotohypericin and mono-[(123)I]iodohypericin in C3H mice with a subcutaneous radiation-induced fibrosarcoma-1 tumor. After intravenous injection, both tracers were rapidly cleared from all organs and were retained by the tumors. There was no significant difference in tumor uptake of the two tracers at all studied time points (p > 0.05). To study the plausible mechanism of hypericin and mono-iodohypericin uptake in tumor, their plasma binding profile was investigated. Both agents show high affinity for low-density lipoproteins and to a lesser extent high-density lipoproteins and other heavy proteins. Mono-[(123)I]iodohypericin appears to be more promising as a tumor diagnostic agent, given its faster clearance from all organs.

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“…The strong interaction between HY and HSA does not prevent HY from exerting its photobiological action, suggesting a reversible interaction of HY with HSA [13,14].…”

Section: Hypericum Perforatum L (H Perforatum)mentioning

confidence: 95%

Determination of hypericin and pseudohypericin in extracts fromHypericum Perforatum L. and pharmaceutical preparations by liquid chromatography-fluorescence detection

Zotou

Loukou

2001

Chromatographia

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SummaryAn isocratic reversed-phase liquid chromatographic method for the simultaneous determination of hypericin and pseudohypericin, l',,vo of the main constituents of Hypericum Perforatum L., has been developed. The compounds were eluted from an Inertsil ODS-3, column by triethylammonium acetate-methanol-acetonirile (5:15:80) eluent and detected fluorimetrically, excitation 478, emission 598 nm. Hypericin and pseudohypericin were extracted from flowering tops by Soxhlet and pseudohypericin was isolated from the extract by collecting its chromatographic peak from the eluent flow. Identification of peaks was by HPLC coupled to a diode array detector and electrospray MS. The method was applied to the determination of hypericin and pseudohypericin in plant extract and in pharmaceutical tablets. For the latter a solidphase extraction procedure was adopted. Riboflavin (0.1 ng.l-tL 1.) was used as internal standard. The linear working range of the method is 0.025-4ng.l-tL 1. and limit of detection 0.2 ng injected on-colu mn. A comparative SPE study for hypericin is presented.

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Hypericin as an inactivator of infectious viruses in blood components

Abstract: The apparent transfusibility of hypericin, taken together with the efficacy of the virucidal activity, the broad range of enveloped viruses affected, and the absence of adverse effects on stored red cells, may render hypericin useful for inactivation of infectious viruses in red cells.

Cited by 106 publications

References 27 publications

Elucidation of the tumoritropic principle of hypericin

Elucidation of the tumoritropic principle of hypericin

Evaluation of tumor affinity of mono‐[¹²³I]iodohypericin and mono‐[¹²³I]iodoprotohypericin in a mouse model with a RIF‐1 tumor

Determination of hypericin and pseudohypericin in extracts fromHypericum Perforatum L. and pharmaceutical preparations by liquid chromatography-fluorescence detection

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Hypericin as an inactivator of infectious viruses in blood components

Abstract: The apparent transfusibility of hypericin, taken together with the efficacy of the virucidal activity, the broad range of enveloped viruses affected, and the absence of adverse effects on stored red cells, may render hypericin useful for inactivation of infectious viruses in red cells.

Cited by 106 publications

References 27 publications

Elucidation of the tumoritropic principle of hypericin

Elucidation of the tumoritropic principle of hypericin

Evaluation of tumor affinity of mono‐[123I]iodohypericin and mono‐[123I]iodoprotohypericin in a mouse model with a RIF‐1 tumor

Determination of hypericin and pseudohypericin in extracts fromHypericum Perforatum L. and pharmaceutical preparations by liquid chromatography-fluorescence detection

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Evaluation of tumor affinity of mono‐[¹²³I]iodohypericin and mono‐[¹²³I]iodoprotohypericin in a mouse model with a RIF‐1 tumor