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Published on: April 1, 2015
Effect of N-acetyl-L-cysteine on Testicular Tissue in Busulfan-Induced Dysfunction in the Male Reproductive System
Kyung Hwan Kim1,2, Min Jung Park3, Nam Cheol Park1,3
1Department of Urology, Pusan National University School of Medicine, Busan, Korea.
Purpose:
This study aimed to evaluate the protective effect of N-acetyl-L-cysteine (NAC) as an antioxidant on busulfan-induced testicular dysfunction in mice and elucidate its possible mechanism of action.
Materials And Methods:
Thirty-two C57BL/6 male mice were randomly divided into four groups (n=8/group) as follows: (1) control group (oral administration of saline [0.1 mL daily] for 35 days); (2) NAC group (oral administration of NAC [10 mg/kg daily] for 35 days); (3) busulfan group (double intraperitoneal injections of 20 mg/kg; total dose of 40 mg/kg); and (4) busulfan+NAC group (after double intraperitoneal injections of 20 mg/kg; total dose of 40 mg/kg, NAC administration [10 mg/kg daily] for 35 days). The testes were removed, weighed, and subjected to sperm parameter analysis and morphology assessment. Reproductive hormone, serum/testicular reactive oxygen species (ROS) level, oxidative stress and antioxidant markers were evaluated. The testicular expression of Nrf2 and HO-1 was examined using RT-qPCR.
Results:
Busulfan treatment significantly decreased testicular weight, sperm count, and serum testosterone levels. Atrophy and degeneration of germinal epithelium were observed in the busulfan group. NAC administration after busulfan treatment partially attenuated the deterioration of testis weight, sperm quality, serum hormones, histomorphometric changes, and oxidative and antioxidative status. NAC treatment resulted in a considerable improvement in Nrf2 and HO-1 mRNA expression levels.
Conclusions:
This study provides compelling evidence that NAC as a potent antioxidant has significant protective effects against busulfan-induced male reproductive impairment possibly through modification of the Nrf2/HO-1 signaling pathway.
Insights
N-acetyl-L-cysteine (NAC) administration protected against busulfan-induced testicular damage in mice. This antioxidant therapy improved sperm parameters and reproductive hormones by modulating the Nrf2/HO-1 pathway.
Area of Science:
- Reproductive Biology
- Toxicology
- Biochemistry
Background:
- Busulfan is a chemotherapeutic agent known to induce male reproductive toxicity.
- Oxidative stress plays a crucial role in busulfan-induced testicular dysfunction.
- N-acetyl-L-cysteine (NAC) is a potent antioxidant with potential therapeutic applications.
Purpose of the Study:
- To evaluate the protective effects of N-acetyl-L-cysteine (NAC) against busulfan-induced testicular dysfunction in a mouse model.
- To investigate the underlying mechanism of NAC's protective action, focusing on oxidative stress and the Nrf2/HO-1 signaling pathway.
Main Methods:
- Male C57BL/6 mice were divided into control, NAC, busulfan, and busulfan+NAC groups.
- Busulfan was administered intraperitoneally, while NAC was given orally.
- Evaluated parameters included testicular weight, sperm analysis, reproductive hormone levels, oxidative stress markers, and testicular expression of Nrf2 and HO-1 via RT-qPCR.
Main Results:
- Busulfan significantly reduced testicular weight, sperm count, and serum testosterone levels, causing germinal epithelium damage.
- NAC treatment partially reversed these negative effects, improving testicular histology, sperm parameters, and hormone levels.
- NAC administration notably increased the mRNA expression of Nrf2 and HO-1 in the testes.
Conclusions:
- N-acetyl-L-cysteine (NAC) demonstrates significant protective effects against busulfan-induced male reproductive toxicity.
- The antioxidant properties of NAC are likely responsible for its protective role.
- NAC may exert its beneficial effects by modulating the Nrf2/HO-1 signaling pathway, offering a potential therapeutic strategy for reproductive impairment.
