Desiree Gunning

Retinoyl β-glucuronide: A nontoxic retinoid for the topical treatment of acne

The purpose of this study was to evaluate the efficacy towards acne and the skin surface toxicity of all-trans-retinoyl β-glucuronide (RBG), a naturally occurring retinoid possessing low cytotoxicity and teratogenicity in animal and cell culture studies. In a double-blind study, 15 acne patients treated with 1.2% RBG cream for 16 weeks showed median reductions of 56%, 25% and 67% in total, inflammatory, and noninflammatory lesions, respectively, whereas the placebo group (14 patients) showed median reductions of 31%, 4% and 62%, respectively. The median reduction in total lesions was highly significant in the RBG group (P = 0.002) but not in the placebo group (P = 0.06). In a second initially double-blind study, ten acne patients treated topically for 26 weeks with 0.16–0.32% RBG cream and five patients with 0.1% all-trans-retinoic acid (Retin-A) showed similar responses, i.e. median reductions in total facial lesions of 70% (P = 0.001) and 75% (P = 0.01), respectively. Whereas all subjects treated topica...

Comparative Histologic Effects of Daily Topical Application of Creams Containing All-trans-Retinoic Acid or All-trans-Retinoyl β-Glucuronide on Pig Skin

The efficacy of all-trans-retinoic acid (tRA) and all-trans-retinoyl β-glucuronide (RAG), a water-soluble metabolite of vitamin A, in the topical treatment of acne is comparable. However, whereas 3.3 mM tRA shows side effects, 3.3 mM RAG does not. To assess the relative toxic and histologic effects (dermal and epidermal changes) of long-term (24-week) daily applications of tRA and RAG on the skin, separate skin patches were measured and marked dorsally on the skin of six 21-day-old, castrated male pigs. Each skin patch area was treated daily with a cream formulation containing either 3.3 mM RAG, 16.5 mM RAG, 33 mM RAG, 3.3 mM tRA, 16.5 mM tRA or blank cream. To serve as controls, one patch received no treatment, one patch received blank cream only and for 5.3 weeks one ‘washed’ patch was given daily application of 33 mM RAG with routine cleansing using a mild soap typical of skin care. The amount of cream used per square centimeter remained the same during the course of the study. Biopsy tissue was collected at –1, 0, 2, 4, 8, 12 and 24 weeks from 7 test patches. The ‘washed’ patch was biopsied once at the 5.3-week mark. Topically applied RAG cream (3.3 mM) resulted in significantly lower histologic scores when compared with scores from tissue treated with an equimolar concentration of tRA. The highest concentration of RAG tested (33.3 mM) resulted in a response comparable to that observed in the lowest tRA (3.3 mM) treated patch area. Daily cleansing of the test area receiving 33.3 mM RAG completely eliminated any clinical signs or negative histologic changes. In conclusion, long-term topical tRA treatment in young pigs, as in humans, showed dose-dependent adverse effects on the skin, whereas RAG treatment had significantly lower histologic changes and less irritation and/or inflammation.

Effects of subcutaneously injected graded doses of all-trans retinoic acid and all-trans retinoyl beta-glucuronide on the outcome of pregnancy in Sprague-Dawley rats.

The effects of single subcutaneous injections (s.c.) of graded doses (20, 40, 80, 160, 320, and 480 mumol/kg body weight (BW) of all-trans retinoic acid (RA) and all-trans retinoyl beta-glucuronide (RAG) on day 8.5 of gestation on the outcome of pregnancy in Sprague-Dawley rats was studied. At dose levels of 20, 40, and 80 mumol/kg BW, neither RA nor RAG showed any adverse maternal or fetal effects. However, at dose levels of 160, 320, and 480 mumol/kg, RA was found to be much more toxic than RAG to both mother and fetus. Fetuses of animals receiving a 160 mumol/kg BW dose of RA were significantly reduced in weight and length, while animals receiving the same dose of RAG had fetuses of normal size. RA doses of 320 and 480 mumol/kg BW resulted in symptoms of maternal toxicity and even death. In contrast, RAG at these high levels produced no signs of maternal toxicity. RAG doses of 320 and 480 mumol/kg BW were also less toxic to fetuses. RA doses of 320 mumol/kg BW resulted in only 8% live births, while animals treated with an equivalent amount of RAG experienced 95% live births. Animals receiving a dose of 480 mumol/kg BW of RA had no live births, but similar doses of RAG resulted in 28% live births and pups of normal size.