Protective Capability of Astragalus (Huangqi) on Auditory Function in a Rat Model of Estrogen Deficiency
The role of estrogen in maintaining auditory integrity has been a subject of significant interest in both clinical and laboratory studies. Estrogen, a key hormone in females, is known to influence various physiological functions, including auditory health. However, the direct impact of estrogen levels on auditory function remains uncertain, as studies have presented conflicting findings. For instance, while some research has shown that ovariectomized rats, which experience estrogen deficiency, exhibit worsened auditory function compared to ovary-intact animals, other studies have reported contradictory results. This inconsistency highlights the complexity of estrogen’s role in auditory health and the need for further investigation.
Estrogen therapy has been explored as a potential intervention to restore auditory function in ovariectomized rats. However, the efficacy of estrogen replacement therapy remains debated, with some studies reporting benefits while others show no significant improvement. Moreover, the impact of estrogen deficiency on auditory function can be exacerbated by additional factors, such as the administration of ototoxic drugs like cisplatin, a commonly used chemotherapy agent. This suggests that individuals with estrogen deficiency, such as those who have undergone ovariectomy or are experiencing menopause, may be at a higher risk of auditory damage when exposed to ototoxic drugs.
Given the potential risks associated with estrogen deficiency and ototoxic drug exposure, there is a growing interest in exploring alternative therapies that can protect auditory function. One such candidate is Astragalus, also known as Huangqi in traditional Chinese medicine. Astragalus has been widely studied for its clinical benefits, including its ability to mitigate the side effects of chemotherapy in cancer patients. This study investigates the protective capability of Astragalus on the auditory function of ovariectomized rats treated with cisplatin, comparing its efficacy to that of estrogen therapy.
Experimental Design and Methodology
The study involved forty-eight female Sprague-Dawley rats, aged two months and weighing between 180 and 200 grams. The rats were randomly assigned to four groups: sham, ovariectomy (OVX), OVX with Huangqi therapy (OVX+H), and OVX with estrogen therapy (OVX+E). Each group consisted of twelve rats. The sham group served as the control and did not undergo ovariectomy or cisplatin treatment. The rats in the other three groups were subjected to ovariectomy, and three weeks later, they were administered cisplatin. Additionally, the OVX+H and OVX+E groups received Huangqi and estrogen therapies, respectively.
The auditory function of all rats was assessed using two primary tests: Distortion Product Otoacoustic Emissions (DPOAE) and Auditory Brainstem Responses (ABR). DPOAE measures the acoustic responses generated by the cochlea when stimulated with two pure tones, providing insights into the peripheral auditory system. ABR, on the other hand, evaluates the electrical responses at the scalp to assess how well sound travels along the auditory nerve to the brainstem, offering information about the central auditory pathway.
Ovariectomy was performed on the rats in the OVX, OVX+H, and OVX+E groups. The procedure 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 their ovarian arteries and ovaries were left intact. Following ovariectomy, the rats in the OVX+H group were injected intraperitoneally with Huangqi extract at a daily dose of 5 mL/kg body weight, while the OVX+E group received Estradiol Valerate via gavage at a daily dose of 0.1 mg/kg body weight. The doses were comparable to those used in human studies, with the aim of providing a realistic comparison to clinical applications.
After three weeks of therapy, all rats in the OVX, OVX+H, and OVX+E groups were administered cisplatin intraperitoneally for four consecutive days at a daily dose of 5 mg/kg body weight. This regimen was chosen to mimic a typical chemotherapy cycle. The auditory function of the rats was tested 24 hours after the completion of cisplatin treatment. The sham group was also tested on the same day to ensure consistency in the experimental timeline.
Results and Analysis
The results of the DPOAE test revealed significant differences in the signal-to-noise ratio (SNR) among the four groups. The SNR is an indicator of cochlear responses, with higher values suggesting better hearing function. The SNRs for the three ovariectomized groups (OVX, OVX+H, OVX+E) were significantly lower than those of the sham group across stimulus frequencies of 2 to 8 kHz. This finding confirms that estrogen deficiency, combined with cisplatin treatment, leads to a notable decline in auditory function.
When comparing the therapeutic effects of Huangqi and Estradiol, the SNRs for the OVX+H group were significantly better than those of the OVX group at 2 and 8 kHz. Similarly, the SNRs for the OVX+E group were significantly better than those of the OVX group at 2, 4, 6, and 8 kHz. These results suggest that both Huangqi and estrogen therapies can mitigate the auditory damage caused by estrogen deficiency and cisplatin exposure, with estrogen therapy showing a slightly broader range of efficacy.
In the ABR test, the hearing thresholds for the three ovariectomized groups were significantly higher than those of the sham group across all stimulus frequencies, indicating a worsened hearing function in the central auditory pathway. However, the hearing thresholds for the OVX+H and OVX+E groups were significantly lower than those of the OVX group across all stimulus frequencies, except at 2 kHz, where the thresholds for the OVX+H and OVX groups were similar. This demonstrates that both Huangqi and estrogen therapies can improve hearing thresholds, with estrogen therapy showing a more consistent effect across frequencies.
Discussion and Implications
The findings of this study highlight the detrimental effects of estrogen deficiency on auditory function, particularly when combined with ototoxic drug exposure. The significant decline in auditory function observed in the OVX group underscores the importance of estrogen in maintaining auditory health. However, the study also demonstrates that both Huangqi and estrogen therapies can protect against this damage, offering potential therapeutic options for individuals with estrogen deficiency.
Astragalus, a traditional Chinese herb, has shown promising results in protecting auditory function in ovariectomized rats treated with cisplatin. The improvement in both DPOAE and ABR measurements suggests that Astragalus can enhance both the peripheral and central auditory systems. The efficacy of Astragalus was found to be comparable to that of estrogen therapy, making it a viable alternative for individuals who may not tolerate or prefer not to undergo estrogen replacement therapy.
It is important to note that Astragalus is often used in combination with other herbal medicines in clinical practice, particularly in China, where it is frequently combined with platinum-based chemotherapy for cancer treatment. However, the current study focused on Astragalus as a single-agent therapy, and the results may not fully represent its efficacy when used in combination with other treatments. Further research is needed to explore the potential synergistic effects of Astragalus in combination with other therapies.
The study also highlights the need for personalized treatment approaches, as the efficacy of Astragalus and estrogen therapies may vary depending on individual health backgrounds. While Astragalus generally has milder side effects compared to estrogen therapy, its use should be carefully considered based on the specific needs and conditions of each patient.
Conclusion
In conclusion, this study provides valuable insights into the protective capabilities of Astragalus on auditory function in a rat model of estrogen deficiency. The findings suggest that Astragalus can mitigate the auditory damage caused by estrogen deficiency and ototoxic drug exposure, offering a potential alternative to estrogen therapy. The comparable efficacy of Astragalus and estrogen therapies, combined with the former’s milder side effects, makes Astragalus a promising candidate for further research and clinical application. As the use of Astragalus continues to be explored in various therapeutic contexts, its role in protecting auditory function may become increasingly significant, particularly for individuals with estrogen deficiency.
doi.org/10.1097/CM9.0000000000000024
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