A side effect of cyclophosphamide (CP), an alkylating agent widely used to treat tumors and autoimmune disorders, is the alteration of male reproductive function. Yukmijihwang-tang (YJT) is a multi-herbal medicinal formula that has been used in traditional Asian medicine to treat male reproductive problems. In this study, we investigated the effects of YJT on CP-induced reproductive toxicities in rat testes. Eight-week-old male Wistar rats were divided into three groups: vehicle-treated (control), CP-treated and CP + YJT-treated groups. CP was administered for the first 7 days (20 mg/kg/day, p.o.), and YJT was administered for 56 days consecutively (1.0 g/kg/day, p.o.). The CP-treated group showed significant decreases in the weight of the testes, epididymal sperm count and sperm motility compared to the control group, while the CP + YJT-treated group had significant increases for these variables compared to the CP-treated group. The enhancement of lipid peroxidation by CP in the rat testes was reduced by YJT treatment. CP diminished the expression of cAMP-responsive element modulator (CREM), a transcription factor that is highly expressed in male germ cells and is crucial to post-meiotic germ cell differentiation. YJT restored CREM at both the mRNA and protein levels. These results suggest that YJT has a protective effect against CP-induced reproductive toxicities by inhibiting the increases in lipid peroxidation and enhancing CREM expression. © 2007 Elsevier Inc. All rights reserved.
cAMP-responsive element modulator; Cyclophosphamide; Lipid peroxidation; Reproductive toxicity; Sperm count; Sperm motility; Testosterone; Yukmijihwang-tang
EMTREE drug terms: cyclic AMP responsive element modulator; cyclophosphamide; herbaceous agent; testosterone; transcription factor; unclassified drug; yukmijihwang tang
EMTREE medical terms: animal experiment; animal model; animal tissue; article; cell differentiation; controlled study; germ cell; herbal medicine; lipid peroxidation; male; nonhuman; rat; reproductive toxicity; semen analysis; spermatozoon count; spermatozoon motility; testis weight; testosterone synthesis
MeSH: Animals; Antineoplastic Agents, Alkylating; Cyclic AMP Response Element Modulator; Cyclophosphamide; Gene Expression; Lipid Peroxidation; Male; Medicine, Oriental Traditional; Organ Size; Plant Extracts; Plants, Medicinal; Protective Agents; Rats; Rats, Wistar; Sperm Count; Sperm Motility; Testis; Testosterone
Medline is the source for the MeSH terms of this document.
Species Index: Rattus; Rattus norvegicus
Chemicals and CAS Registry Numbers: cyclophosphamide, 50-18-0; testosterone, 58-22-0;Antineoplastic Agents, Alkylating; Crem protein, rat; Cyclic AMP Response Element Modulator, 135844-64-3; Cyclophosphamide, 50-18-0; Plant Extracts; Protective Agents; Testosterone, 58-22-0
Manufacturers:Drug manufacturer: Sigma, United States;wonkwang, South Korea.