Protective Capability of Astragalus (Huangqi) on Auditory Function of Rats with Estrogen Deficiency
Estrogen plays a crucial role in maintaining auditory integrity in females. Laboratory studies have shown that ovariectomized rats exhibit worsened auditory function compared to ovary-intact animals. However, conflicting findings have also been reported, leaving the direct impact of estrogen levels on auditory function uncertain. Estrogen therapy has been used to restore auditory function in ovariectomized rats, but the benefits of estrogen replacement remain debated. Additionally, the impact of estrogen deficiency on auditory function can be exacerbated by factors such as the administration of Cisplatin, an ototoxic anti-cancer drug. This suggests that females with estrogen deficiency (e.g., due to ovariectomy, menopause, or ovarian failure) may experience significant changes in auditory function when treated with ototoxic drugs like Cisplatin. Given the documented clinical benefits of Astragalus (Huangqi) in traditional Chinese medicine, including reducing chemotherapy side effects in cancer patients, this study investigates the protective capability of Astragalus on the auditory function of ovariectomized rats treated with Cisplatin. The study also compares the performance of Astragalus therapy with estrogen therapy (Estradiol alone) in protecting auditory function.
The study utilized 48 female Sprague-Dawley rats, aged 2 months and weighing 180-200 grams. The rats were randomly assigned to four groups: Sham, Ovariectomy (OVX), OVX+H (OVX + Huangqi), and OVX+E (OVX + Estradiol), with 12 rats in each group. The Sham group served as a control and did not undergo ovariectomy or Cisplatin treatment. The other three groups underwent ovariectomy and were administered Cisplatin three weeks later. The OVX+H and OVX+E groups received Huangqi and estrogen therapies, respectively. All procedures were approved by a university animal ethics committee in China.
The auditory function of the rats was measured using Distortion Product Otoacoustic Emissions (DPOAE) and Auditory Brainstem Responses (ABR). DPOAE records acoustic responses from the cochlea when stimulated with two pure tones, while ABR measures electrical responses at the scalp to assess how well sound travels along the auditory nerve to the brainstem. For ovariectomy and auditory testing, the rats were sedated with 10% chloral hydrate ketamine (3 ml/kg body weight) via intra-peritoneal injection. The animals were monitored daily to ensure hydration and warmth during anesthesia.
Ovariectomy involved cutting open the abdominal skin and peritoneum, ligating the ovarian arteries, and excising the ovaries bilaterally before suturing the muscle wall and skin. The Sham group underwent the same surgical procedures but retained their ovarian arteries and ovaries. Astragalus or estrogen therapy began after ovariectomy and lasted for three weeks. The OVX+H group received intra-peritoneal injections of Huangqi extract (Chiatai Qingchunbao, China) at a daily dose of 5 ml/kg body weight, while the OVX+E group received Estradiol Valerate (Bayer, China) via gavage at a daily dose of 0.1 mg/kg body weight. The Sham and OVX groups received intra-peritoneal injections of saline water (5 mg/kg body weight) daily. After three weeks, the OVX, OVX+H, and OVX+E groups were administered Cisplatin intra-peritoneally for four days at a daily dose of 5 mg/kg body weight. Auditory function was tested 24 hours after the final Cisplatin dose, and the Sham group was tested on the same day.
Figure 1a presents the average Signal-to-Noise Ratios (SNRs) obtained in the DPOAE test for the four groups. A higher SNR indicates better hearing function in the peripheral auditory system. The SNRs for the ovariectomized groups (OVX, OVX+H, OVX+E) were significantly lower than those for the Sham group across stimulus frequencies of 2-8 kHz (p<0.05). Comparing the therapeutic effects of Huangqi and Estradiol, the SNRs for the OVX+H group were significantly better than those for the OVX group at 2 kHz and 8 kHz, while the SNRs for the OVX+E group were significantly better than those for the OVX group at 2, 4, 6, and 8 kHz (p<0.05, marked with an asterisk in Figure 1a).
Figure 1b shows the average hearing thresholds obtained in the ABR test. An elevated hearing threshold indicates worsened hearing function in the central auditory pathway. The hearing thresholds for the ovariectomized groups (OVX, OVX+H, OVX+E) were significantly higher than those for the Sham group across all stimulus frequencies (p<0.05). Additionally, the hearing thresholds for the OVX+H and OVX+E groups were significantly lower than those for the OVX group across all stimulus frequencies (p<0.05, marked with an asterisk in Figure 1b), except at 2 kHz, where the hearing thresholds for the OVX+H and OVX groups were similar.
The study demonstrates significant auditory damage in the OVX group compared to the Sham group when ovariectomized rats are challenged with Cisplatin. However, Huangqi therapy (OVX+H) significantly improved the SNR in the DPOAE test and reduced the hearing threshold in the ABR measurement compared to the OVX group. This suggests that Astragalus, composed primarily of polysaccharides, astragalosides, and flavonoids, can protect the auditory function of ovariectomized rats (estrogen deficiency) under Cisplatin treatment. The benefits of Astragalus therapy were observed in both the peripheral (cochlear) and central auditory systems. The study also found that the protective capability of Astragalus was similar to that of estrogen therapy (Figure 1). Given that Astragalus typically has milder side effects, it may serve as an alternative therapy for protecting auditory function in patients with estrogen deficiency. In China, Astragalus is often combined with platinum-based chemotherapy in cancer treatment. However, it is rarely used alone as an agent therapy in clinical practice, and further investigation is needed to explore its benefits when combined with other herbal medicines.
The study was supported by a grant from the Natural Science Foundation of Zhejiang Province, China (No. LY14H270006). The author reports no conflicts of interest and is responsible for the content and writing of the paper. Acknowledgments are extended to Prof. Ye Su and Dr. Summy Lau for their support in preparing the work.
doi.org/10.1097/CM9.0000000000000028
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