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Phototoxicity: Its Mechanism and Animal Alternative Test Methods.

Kim K, Park H, Lim KM - Toxicol Res (2015)

Bottom Line: Absorption of photons and absorbed energy (hv) by photoactive chemicals results in molecular changes or generates reactive oxygen species and depending on the way how endogenous molecules are affected by phototoxicants, mechanisms of phototoxcity is categorized into two modes of action: Direct when unstable species from excited state directly react with the endogenous molecules, and indirect when endogeneous molecules react with secondary photoproducts.In order to identify phototoxic potential of a chemical, various test methods have been introduced.In chemico methods evaluate the generation of reactive oxygen species or DNA strand break activity employing plasmid for chemicals, or drugs with phototoxic potential.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Ewha Womans University, Seoul, Korea.

ABSTRACT
The skin exposure to solar irradiation and photoreactive xenobiotics may produce abnormal skin reaction, phototoxicity. Phototoxicity is an acute light-induced response, which occurs when photoreacive chemicals are activated by solar lights and transformed into products cytotoxic against the skin cells. Multifarious symptoms of phototoxicity are identified, skin irritation, erythema, pruritis, and edema that are similar to those of the exaggerated sunburn. Diverse organic chemicals, especially drugs, are known to induce phototoxicity, which is probably from the common possession of UV-absorbing benzene or heterocyclic rings in their molecular structures. Both UVB (290~320 nm) and UVA (320~400 nm) are responsible for the manifestation of phototoxicity. Absorption of photons and absorbed energy (hv) by photoactive chemicals results in molecular changes or generates reactive oxygen species and depending on the way how endogenous molecules are affected by phototoxicants, mechanisms of phototoxcity is categorized into two modes of action: Direct when unstable species from excited state directly react with the endogenous molecules, and indirect when endogeneous molecules react with secondary photoproducts. In order to identify phototoxic potential of a chemical, various test methods have been introduced. Focus is given to animal alternative test methods, i.e., in vitro, and in chemico assays as well as in vivo. 3T3 neutral red uptake assay, erythrocyte photohemolysis test, and phototoxicity test using human 3-dimensional (3D) epidermis model are examples of in vitro assays. In chemico methods evaluate the generation of reactive oxygen species or DNA strand break activity employing plasmid for chemicals, or drugs with phototoxic potential.

No MeSH data available.


Related in: MedlinePlus

Photo effect calculation: The photo effect (PEC) at an arbitrary concentration C is defined as the product of the response effect (REC) and the dose effect (DEC), i.e. PEC = REC × DEC. The definition is illustrated as adopted from (31). Calculation of the photo effect at the concentration 0.4 follows the equations given in the text gives: response effect RE0.4 = (66% − 11%)/100% = 0.55, dose effect DE0.4 = (0.4/0.16 − 1)/(0.4/0.16 + 1) = 0.43, and photo effect PE0.4 = 0.24. The mean photo effect is obtained by averaging over the values for the photo effect at various concentrations (31).
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Figure 008: Photo effect calculation: The photo effect (PEC) at an arbitrary concentration C is defined as the product of the response effect (REC) and the dose effect (DEC), i.e. PEC = REC × DEC. The definition is illustrated as adopted from (31). Calculation of the photo effect at the concentration 0.4 follows the equations given in the text gives: response effect RE0.4 = (66% − 11%)/100% = 0.55, dose effect DE0.4 = (0.4/0.16 − 1)/(0.4/0.16 + 1) = 0.43, and photo effect PE0.4 = 0.24. The mean photo effect is obtained by averaging over the values for the photo effect at various concentrations (31).

Mentions: PIF < 2 or an MPE < 0.1 predicts: “no phototoxicity”. A PIF > 2 and < 5 or an MPE > 0.1 and < 0.15 predicts: “probable phototoxicity” and PIF > 5 or an MPE > 0.15 predicts: “phototoxicity” (Fig. 8).


Phototoxicity: Its Mechanism and Animal Alternative Test Methods.

Kim K, Park H, Lim KM - Toxicol Res (2015)

Photo effect calculation: The photo effect (PEC) at an arbitrary concentration C is defined as the product of the response effect (REC) and the dose effect (DEC), i.e. PEC = REC × DEC. The definition is illustrated as adopted from (31). Calculation of the photo effect at the concentration 0.4 follows the equations given in the text gives: response effect RE0.4 = (66% − 11%)/100% = 0.55, dose effect DE0.4 = (0.4/0.16 − 1)/(0.4/0.16 + 1) = 0.43, and photo effect PE0.4 = 0.24. The mean photo effect is obtained by averaging over the values for the photo effect at various concentrations (31).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4505355&req=5

Figure 008: Photo effect calculation: The photo effect (PEC) at an arbitrary concentration C is defined as the product of the response effect (REC) and the dose effect (DEC), i.e. PEC = REC × DEC. The definition is illustrated as adopted from (31). Calculation of the photo effect at the concentration 0.4 follows the equations given in the text gives: response effect RE0.4 = (66% − 11%)/100% = 0.55, dose effect DE0.4 = (0.4/0.16 − 1)/(0.4/0.16 + 1) = 0.43, and photo effect PE0.4 = 0.24. The mean photo effect is obtained by averaging over the values for the photo effect at various concentrations (31).
Mentions: PIF < 2 or an MPE < 0.1 predicts: “no phototoxicity”. A PIF > 2 and < 5 or an MPE > 0.1 and < 0.15 predicts: “probable phototoxicity” and PIF > 5 or an MPE > 0.15 predicts: “phototoxicity” (Fig. 8).

Bottom Line: Absorption of photons and absorbed energy (hv) by photoactive chemicals results in molecular changes or generates reactive oxygen species and depending on the way how endogenous molecules are affected by phototoxicants, mechanisms of phototoxcity is categorized into two modes of action: Direct when unstable species from excited state directly react with the endogenous molecules, and indirect when endogeneous molecules react with secondary photoproducts.In order to identify phototoxic potential of a chemical, various test methods have been introduced.In chemico methods evaluate the generation of reactive oxygen species or DNA strand break activity employing plasmid for chemicals, or drugs with phototoxic potential.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Ewha Womans University, Seoul, Korea.

ABSTRACT
The skin exposure to solar irradiation and photoreactive xenobiotics may produce abnormal skin reaction, phototoxicity. Phototoxicity is an acute light-induced response, which occurs when photoreacive chemicals are activated by solar lights and transformed into products cytotoxic against the skin cells. Multifarious symptoms of phototoxicity are identified, skin irritation, erythema, pruritis, and edema that are similar to those of the exaggerated sunburn. Diverse organic chemicals, especially drugs, are known to induce phototoxicity, which is probably from the common possession of UV-absorbing benzene or heterocyclic rings in their molecular structures. Both UVB (290~320 nm) and UVA (320~400 nm) are responsible for the manifestation of phototoxicity. Absorption of photons and absorbed energy (hv) by photoactive chemicals results in molecular changes or generates reactive oxygen species and depending on the way how endogenous molecules are affected by phototoxicants, mechanisms of phototoxcity is categorized into two modes of action: Direct when unstable species from excited state directly react with the endogenous molecules, and indirect when endogeneous molecules react with secondary photoproducts. In order to identify phototoxic potential of a chemical, various test methods have been introduced. Focus is given to animal alternative test methods, i.e., in vitro, and in chemico assays as well as in vivo. 3T3 neutral red uptake assay, erythrocyte photohemolysis test, and phototoxicity test using human 3-dimensional (3D) epidermis model are examples of in vitro assays. In chemico methods evaluate the generation of reactive oxygen species or DNA strand break activity employing plasmid for chemicals, or drugs with phototoxic potential.

No MeSH data available.


Related in: MedlinePlus