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Glutathione isopropyl ester reduces UVB-induced skin damage in hairless mice
S Kobayashi1, M Takehana, C Tohyama
1Kyoritsu College of Pharmacy, Tokyo, Japan.
Abstract:
The protective effect of administration of glutathione (GSH) isopropyl ester on photodamage, such as lipid peroxidation, inflammation and tumorigenesis induced by UV exposure (290-400 nm, max. 312 nm), was investigated using hairless mice. Pretreatment with 20 mg/kg GSH isopropyl ester prevented the increases of thiobarbituric acid-reactive substance (TBARS) formation in skin and serum sialic acid, indices of lipid peroxidation and inflammatory reaction, respectively, which were caused by a single dose (15 kJ/m2) of UV irradiation. The level of epidermal GSH in skins of the GSH ester-treated mice was maintained within normal limits. When mice were exposed to UV at a dose of 2 kJ/m2, three times weekly, skin tumors developed in all of them after 25 weeks. The formation of skin tumors was significantly inhibited by administration of 10 mg/kg GSH ester prior to each UV irradiation for 25 weeks. Moreover, the increases of cutaneous TBARS and serum sialic acid in the tumor-bearing mice were also prevented by continuous pretreatment with GSH ester. Even after 24 weeks, the epidermal GSH content of the pretreated mice was mostly retained compared to nonirradiated mice. However, administration of GSH prior to acute or chronic UV irradiation had no effect on the UV-induced damage. The present results suggest that the protection from photodamage afforded by pretreatment with GSH ester is due to maintenance of a normal GSH level.
Insights
Glutathione (GSH) isopropyl ester pretreatment protects against UV-induced photodamage and skin tumors in mice by maintaining normal GSH levels. Oral GSH administration showed no protective effects.
Area of Science:
- Dermatology
- Biochemistry
- Photobiology
Background:
- UV radiation causes significant photodamage, including lipid peroxidation and inflammation.
- UV-induced skin damage can lead to tumorigenesis.
- Glutathione (GSH) is a key antioxidant, but its direct administration may not be effective against UV damage.
Purpose of the Study:
- To investigate the protective effects of glutathione (GSH) isopropyl ester against UV-induced photodamage and skin tumors.
- To determine if GSH ester pretreatment can prevent lipid peroxidation, inflammation, and tumorigenesis.
- To compare the efficacy of GSH ester with oral GSH administration.
Main Methods:
- Hairless mice were used to investigate the effects of UV exposure (290-400 nm).
- Mice were pretreated with GSH isopropyl ester (20 mg/kg or 10 mg/kg) or oral GSH before UV irradiation.
- Skin and serum markers of lipid peroxidation (TBARS) and inflammation (sialic acid) were measured.
- Tumor formation was monitored over 25 weeks.
Main Results:
- GSH isopropyl ester pretreatment prevented UV-induced increases in TBARS and serum sialic acid.
- Epidermal GSH levels were maintained in mice treated with GSH ester.
- Skin tumor formation was significantly inhibited by GSH ester pretreatment.
- Oral GSH administration did not protect against UV-induced damage.
Conclusions:
- GSH isopropyl ester effectively protects against UV-induced photodamage and skin tumorigenesis in mice.
- The protective mechanism involves maintaining normal epidermal GSH levels.
- GSH ester is a promising agent for mitigating UV-related skin damage, unlike oral GSH.