World J Mens Health.  2024 Oct;42(4):810-820. 10.5534/wjmh.230254.

Effects of Perilla frutescens Var. Acuta in Busulfan-Induced Spermatogenesis Dysfunction Mouse Model

Affiliations
  • 1Department of Urology, Pusan National University School of Medicine, Busan, Korea
  • 2Medical Research Institute of Pusan National University Hospital, Busan, Korea
  • 3Department of Technical Research, Genoheal, Seoul, Korea
  • 4Department of R&D Center, The Korea Institute for Public Sperm Bank, Busan, Korea
  • 5Infertility Institute, Pohang Women’s Hospital, Pohang, Korea
  • 6Department of R&I Center, COSMAXBIO, Seongnam, Korea
  • 7Department of Urology, Pusan National University Yangsan Hospital, Yangsan, Korea
  • 8Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea

Abstract

Purpose
The leaves of Perilla frutescens var. acuta (PFA) are generally reported to have antioxidant, anti-allergic, anti-inflammatory, and antitumor effects and commonly used as a traditional medicine in East Asia. This study aimed to investigate the protective effect and antioxidant activity of PFA on busulfan-induced testicular dysfunction, histological damage, oxidative stress (OS), sperm quality, and hormone levels using a mouse model.
Materials and Methods
C57BL/6 male mice were divided into four groups: control, busulfan-only treated, and varying concentrations of PFA (100 and 200 mg/kg) with busulfan. In the busulfan group, 40 mg/kg of busulfan was intraperitoneally injected to induce azoospermia. Mice were orally administered PFA for 35 consecutive days after busulfan administration. Samples were collected and assessed for testis/body weight, testicular histopathology, sperm quality, serum hormone levels, and OS to evaluate the effects of PFA treatment on spermatogenesis dysfunction induced by busulfan.
Results
The busulfan-induced testicular dysfunction model showed reduced testis weight, adverse histological changes, significantly decreased sex hormones and sperm quality, and attenuated OS. These results indicate that PFA treatment significantly increased testis weight, testis/body weight, epididymal sperm count, motility, and testosterone level compared with busulfan alone. PFA treatment also attenuated the busulfan-induced histological changes. Furthermore, compared with mice treated with busulfan alone, PFA supplementation upregulated the testicular mRNA expression of the antioxidant enzymes superoxide dismutase 1 (Sod1) and glutathione peroxidase 1 (Gpx1), with a decrease in malondialdehyde (MDA) production and an increase in SOD and GPx activities.
Conclusions
This study shows that PFA exerts a protective effect against testicular damage by attenuating OS induced by busulfan. Our results suggest that PFA is a potentially relevant drug used to decrease the side effects induced by busulfan on testicular function and sperm during cancer chemotherapy.

Keyword

Antioxidants; Busulfan; Drug therapy; Perilla frutescens; Spermatogenesis
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