Yukmijihwang-tang protects against cyclophosphamide-induced reproductive toxicity.
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.
Oh
Myung Sook
MS
Department of Prescriptionology, College of Oriental Medicine, Kyung Hee University, 1 Hoegi-Dong, Dongdaemun-Gu, Seoul, Republic of Korea.
Chang
Mun Seog
MS
Park
Wansu
W
Kim
Do Rim
DR
Bae
Hyunsu
H
Huh
Youngbuhm
Y
Park
Seong Kyu
SK
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity*; D051786:Cyclic AMP Response Element Modulator / Q000235:genetics / Q000378:metabolism; D003520:Cyclophosphamide / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008518:Medicine, East Asian Traditional; D009929:Organ Size / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013076:Sperm Count; D013081:Sperm Motility; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013739:Testosterone / Q000097:blood
D018906:Antineoplastic Agents, Alkylating; C497412:Crem protein, rat; D010936:Plant Extracts; D020011:Protective Agents; D051786:Cyclic AMP Response Element Modulator; D013739:Testosterone; D003520:Cyclophosphamide