are responsible for the attenuation of busulfan-induced adverse References effect in the male reproductive system are speculative. Currently,
there are two representative components in KRGE that might contribute to the attenuation of busulfan-induced adverse effects. The first candidate is ginseng saponins. Ginseng saponins might alleviate busulfan-induced adverse effects, because they are known to have a variety of in vitro and in vivo pharmacological effects [2]. Furthermore, a few reports indicated that ginseng saponin exerts its effects on the male endocrine system and human sperm capacitance. Recent studies have also demonstrated that ginseng contains a G protein-coupled LPA receptor ligand, called gintonin [17]. Gintonin elicits [Ca2þ]i transient through the activation of the LPA receptor and regulates various Ca2þ-dependent ion channels and receptors [18]. Previous reports have indicated that LPA re- ceptors are abundantly expressed in both female and male repro- ductive systems [19] and that LPA receptor-deficient animals showed pregnancy-related problems [20], indicating that LPA re- ceptors in the reproductive systems play an important role in fertility. Thus, gintonin in KRGE might be one of the candidates for alleviation of busulfan-induced adverse effects in the male repro- ductive system. However, further work is required to identify the active ingredients of ginseng that are responsible for attenuating the effects of anticancer agents such as busulfan.
In summary, using an animal model of busulfan-induced adverse effects on the male reproductive system, we herein showed that busulfan elicited various adverse effects in the male reproductive system such as histological changes of the testis, reduction in the concentration of testosterone, and reduction in litter size. We showed that KRGE attenuated various busulfan- induced adverse effects in the male reproductive system. Finally, these novel findings provide new insights that KRGE could be applied as an agent for the attenuation or prevention of various adverse effects induced by anticancer agents.