LAUSR

With great interest, we read the article by Gunyeli et al. [1], which investigated the detrimental effects of methotrexate and the potential protective effects of astaxanthin on urogenital tissues (ovary, fallopian tube, uterus, cervix, vagina, urethra). It is an indisputable fact that methotrexate causes oxidative stress and increases the production of pro-inflammatory mediators. On the other hand, as we have seen in our laboratory, astaxanthin shows excellent anti-inflammatory, immunomodulatory and antioxidant effects. We would like to commend the authors for investigating the effect of this powerful antioxidant on the detrimental effects of methotrexate through a multimodal approach (biochemical, histopathological, immunohistochemical). Whether astaxanthin, in the future, will find its place in terms of protecting the reproductive health of women undergoing cancer treatment remains to be seen. It will certainly require more comprehensive human studies in the future, but there are still many issues that need to be explored in animal models. The researchers gave group 3 20 mg/kg of methotrexate intraperitoneally in a single dose on the first day and administered astaxanthin orally at a dose of 100 mg/kg for 7 days. On the 8th day, the animals were killed. There is no doubt that the oral administration is the most suitable for possible human use in the future, but we must not neglect possible other routes of administration such as intraperitoneal and intravenous. The route of administration of the potential drugs is of great importance as some studies have shown limitations after oral administration such as low stability, bioavailability and bioefficiency with astaxanthin, revealing the need for new biomaterials acting as carriers in vivo [2]. A dose of 100 mg/kg has been used, but we believe that in future studies the dose may be reduced to keep the dose within the range currently recommended for use in humans, despite the fact that no adverse effects have been found in recent toxicological studies and at much higher doses. Natural astaxanthin is sold in the European Union in a range of products in daily doses up to 12 mg and are approved by national authorities worldwide in daily doses up to 24 mg. Structural features such as size, shape, and polarity are key determinants of astaxanthin ability to fit properly into its molecular environment to increase its own activity [3]. Studies, involving more than 2000 participants, found no significant toxicity at any dose for natural astaxanthin. Natural astaxanthin has shown an excellent clinical safety pro-file at short-term daily doses up to 100 mg and longterm daily doses averaging between 8 and 12 mg, which is particularly encouraging [4]. The safety of astaxanthin has been assessed in rats after receiving daily oral administration of astaxanthin-rich H. pluvialis biomass at concentrations up 500 mg/kg/day for 90 days, or synthetic astaxanthin in a range between 880 and 1240 mg/kg/day for 13 weeks [5, 6]. Katsumata et al. performed a sub-chronic toxicity evaluation of a natural astaxanthin-rich carotenoid extract produced from the natural bacteria Paracoccus carotinifaciens suspended in olive oil and administered daily to rats by oral gavage at doses of up to 1000 mg/kg/day for 13 weeks. The only result highlighted was the excretion of dark-red colour feces without reporting any considerable adverse effect [7]. Given these results and current knowledge, it is unlikely that there will be an obstacle to recommending higher than current doses for human use in the future. For optimal administration, the pharmacokinetics and pharmacodynamics of astaxanthin must be investigated in detail. Research on this topic has not been completed [8, 9]. It would also be interesting to see what the results would be if the time of oral * Marko Bašković [email protected]