Combined Low-Frequency Ultrasound and Microbubble Contrast Agent for the Treatment of Benign Prostatic Hyperplasia

Abstract

Background and Purpose: Benign prostatic hyperplasia is one of the most common conditions in middle-aged and elderly men. The aim of the study was to investigate the treatment effects of low-frequency ultrasound combined with a microbubbles agent on benign prostatic hyperplasia. Methods: Eighteen 7-year-old male beagles with prostatic hyperplasia were randomly divided into six groups (n = 3): Control group, 21 kHz ultrasound group, 21 kHz ultrasound and microbubble contrast agent group, 1 MHz ultrasound group, 1 MHz ultrasound and microbubble contrast agent group, and microbubble contrast agent group. The histopathologic damage to prostate cells was assessed via transmission electron microscopy and optical microscopy. The protein expressions of prostate-specific antigen (PSA), inducible nitric oxide synthase (iNOS), and super oxidase dimutase (SOD) were detected by enzyme-linked immunosorbent assay. Levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine (Cr) were detected by the Biochemistry Automatic Analyzer. Results: Significant tissue injury, mitochondria injury, and cell apoptosis were observed in 21 kHz ultrasound and the microbubble contrast agent group. Compared with the control and microbubbles contrast agent groups, the decrease in levels of PSA or increase in levels of iNOs and SOD in the other four groups were statistically significant (P < 0.05). The lowest level of PSA and the highest levels of iNOs and SOD were observed in the 21 kHz ultrasound and microbubbles contrast agent group. No significant changes in levels of AST, ALT, BUN, and Cr were observed between the six groups. Conclusions: Our results suggest that lower frequency ultrasound may have a better effect on benign prostatic hyperplasia, and microbubble contrast agent application further strengthens this biological effect.

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“…It has previously been reported that ultrasound combined with microbubbles induces cavitation, resulting in mitochondrial damage and subsequently mitochondria-dependent cell apoptosis (44,45). Cavitation is associated with inducing the opening of the mitochondrial permeability transition pore (44).…”

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“…However, other researches clearly proved that combined low-ultrasound microbubbles without payload can harmed cells and even be used as a treatment approach to cure diseases. S. Yang et al investigated this treatment effects on benign prostatic hyperplasia and observed serious tissues injury and cell apoptosis at only 21 kHz with combined ultrasound microbubbles compared to ultrasound and microbubbles separately [31]. In addition, preventive measures should be taken into consideration when correlating in vitro ultrasound parameters to in vivo conditions.…”