Protection by &lt;i&gt;L&lt;/i&gt;-Ascorbic Acid against Phototoxicity in Tin-Protoporphyrin-Treated Suckling Rats

Keino, Hiroomi; Mimura, Satoshi; Nagae, Hidetoshi; Banno, Taihei; Kashiwamata, Shigeo

doi:10.1159/000243930

Cited by 5 publications

(4 citation statements)

References 8 publications

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“…Vitamin C also prevents systemic phototoxicity, a common feature observed in some types of porphyria that results from the production of porphyrin-derived free radicals (Bohm et al, 2001). Vitamin C also prevents systemic phototoxicity in tin-protoporphyrin (SnPP)-treated suckling rats (Keino et al, 1993). Although most animals can synthesize vitamin C from glucose, humans must acquire the vitamin from dietary sources because they lack gluconolactone oxidase, the enzyme required for ascorbate biosynthesis.…”

Section: Discussionmentioning

confidence: 99%

Effects of ascorbic acid on UV light-mediated photoreceptor damage in isolated rat retina

Tokuda

Zorumski

Izumi

2007

Experimental Eye Research

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Concerns have been raised about whether operating microscopes and endoillumination used during ophthalmic surgeries contribute to retinal damage. Despite the recognition that ascorbic acid (vitamin C) helps to protect the eye from light and the abundance of vitamin C in the retina, artificial aqueous humors used during surgery only contain the antioxidant glutathione. To test whether inclusion of antioxidants other than glutathione in surgical solutions might help to preserve retinal integrity, we studied the effects of vitamin C on acute toxicity in isolated rat retinas. Male Sprague-Dawley rats (PND 30+/-2) were sacrificed for retinal isolation. In the presence or absence of vitamin C (1 or 3 mM), retinas were exposed to 302 nm ultraviolet B (UVB) light for 1 h and were incubated for a total of 5 h at 30 degrees C. Retinal damage was assessed by morphological examination and biochemical assay measuring the amount of lactate dehydrogenase (LDH) released from injured cells. In control retinas, LDH release was significantly increased after UVB exposure. The presence of 1 mM vitamin C in the incubation media significantly reduced LDH release during the post-incubation period following UV exposure. No difference was found between 1 and 3 mM vitamin C. Microscopic examination revealed that disorganization in the outer nuclear layer after UVB exposure was markedly attenuated by administration of 1 mM vitamin C. Vitamin C (1 mM), a concentration found in the anterior chamber in humans, but not glutathione, prevented phototoxic injury following UV exposure. Although vitamin C itself cannot be used in intraocular irrigating solutions because of adverse interactions with iron released during bleeding, inclusion of antioxidants equivalent to vitamin C should be considered to help protect the retina from intraoperative light toxicity.

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Section: Discussionmentioning

confidence: 99%

Effects of ascorbic acid on UV light-mediated photoreceptor damage in isolated rat retina

Tokuda

Zorumski

Izumi

2007

Experimental Eye Research

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“…We then studied the effects of another antioxidant, ascorbic acid (7). Ascorbate has been reported to protect SnPP-treated rats against phototoxicity (24). Ascorbic acid (1 mM) was given to Caco-2 cells following 24 h treatment with SnPP (10 M basolateral) at the time of mounting the cells in the Ussing chambers.…”

Section: Snpp Induces I Sc In Caco-2 Cellsmentioning

confidence: 99%

Tin protoporphyrin induces intestinal chloride secretion by inducing light oxidation processes

Uç

Reszka²,

Buettner³

et al. 2007

American Journal of Physiology-Cell Physiology

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Heme induces Cl(-) secretion in intestinal epithelial cells, most likely via carbon monoxide (CO) generation. The major source of endogenous CO comes from the degradation of heme via heme oxygenase (HO). We hypothesized that an inhibitor of HO activity, tin protoporphyrin (SnPP), may inhibit the stimulatory effect of heme on Cl(-) secretion. To test this hypothesis, we treated an intestinal epithelial cell line (Caco-2 cells) with SnPP. In contrast to our expectations, Caco-2 cells treated with SnPP had an increase in their short-circuit currents (I(sc)) in Ussing chambers. This effect was observed only when the system was exposed to ambient light. SnPP-induced I(sc) was caused by Cl(-) secretion because it was inhibited in Cl(-)-free medium, with ouabain or 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB). The Cl(-) secretion was not via activation of the CFTR, because a specific inhibitor had no effect. Likewise, inhibitors of adenylate cyclase and guanylate cyclase had no effect on the enhanced I(sc). SnPP-induced I(sc) was inhibited by the antioxidant vitamins, alpha-tocopherol and ascorbic acid. Electron paramagnetic resonance experiments confirmed that oxidative reactions were initiated with light in cells loaded with SnPP. These data suggest that SnPP-induced effects may not be entirely due to the inhibition of HO activity but rather to light-induced oxidative processes. These novel effects of SnPP-photosensitized oxidation may also lead to a new understanding of how intestinal Cl(-) secretion can be regulated by the redox environment of the cell.

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“…This possibility should be further investigated, especially when considering repeated administrations of Sn-PTP-IX to HIV-1infected individuals. Combination of Sn-PTP-IX with I-ascorbic acid may decrease potential phototoxic side effects, and should be considered for chemotherapeutic purposes (Keino et et., 1993). Sn-PTP-IX was shown to have immunostimulatory effects in vitro and to enhance the biological activity of yinterferon (Novogrodsky et al, 1989;Weiss et al, 1993).…”

Section: Sn-protoporphyrin IX As An Anti-hiv-1 Agent 327mentioning

confidence: 99%

Tin Protoporphyrin IX Used in Control of Heme Metabolism in Humans Effectively Inhibits HIV-1 Infection

Neurath

Strick

Kang

et al. 1994

Antivir Chem Chemother

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Recent observations indicated that several porphyrins bound to the V3 loop of the envelope glycoprotein gp120 of the human immunodeficiency virus type 1 (HIV-1) and inhibited infection of cells by HIV-1. The tin derivative of protoporphyrin IX (Sn-PTP-IX) has already been used clinically in humans to suppress hyperbilirubinemia. It was therefore of interest to determine whether Sn-PTP-IX has anti-HIV-1 activity. It is demonstrated here that Sn-PTP-IX effectively inhibited infection by several HIV-1 isolates (HIB, MN, RF, SF-2 and two isolates resistant to azidothymidine). This was surprising, since earlier studies indicated that incorporation of other metals into porphyrins markedly decreased their antiviral activity. Sn-PTP-IX blocked the binding to gp120 of anti-V3-loop-specific antibodies and of monoclonal antibodies specific for the CD4 binding site on gp120. The latter effect appeared to be allosteric and was not observed with a deletion mutant of gp 120 lacking the V3 loop sequence. This suggests that Sn-PTP-IX binds to the V3 loop and distorts the native conformation of the HIV-1 envelope, thereby preventing infection. These results merit the consideration of Sn-PTP-IX as a prophylactic and chemotherapeutic agent against HIV-1.

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Protection by <i>L</i>-Ascorbic Acid against Phototoxicity in Tin-Protoporphyrin-Treated Suckling Rats

Cited by 5 publications

References 8 publications

Effects of ascorbic acid on UV light-mediated photoreceptor damage in isolated rat retina

Effects of ascorbic acid on UV light-mediated photoreceptor damage in isolated rat retina

Tin protoporphyrin induces intestinal chloride secretion by inducing light oxidation processes

Tin Protoporphyrin IX Used in Control of Heme Metabolism in Humans Effectively Inhibits HIV-1 Infection

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