Cisplatin (CSP) is a first-line chemotherapeutic for laryngeal squamous cell carcinoma (LSCC), but its clinical effectiveness is limited by resistance and toxicity. Hesperidin (HESP), a citrus flavonoid, may enhance chemotherapeutic efficacy through pro-apoptotic properties. This study investigated the involvement of the transient receptor potential melastatin-2 (TRPM2) channel in the HESP-mediated potentiation of CSP-induced cytotoxicity in human laryngeal carcinoma (Hep-2) cells. Hep-2 cells were treated with CSP (25 µM), HESP (25 µM), or their combination for 24 h. The findings showed that the combined application of HESP and CSP reduced cell viability by approximately 50% (p < 0.001), which was the lowest compared to CSP alone. Western blot analysis revealed that TRPM2 protein expression was higher in the CSP+HESP group compared to the control group (p < 0.001). This synergistic treatment resulted in an increase in ROS production and a decrease in MDA levels, accompanied by a reduction in cellular GSH levels (p < 0.001). Furthermore, the combination therapy increased pro-inflammatory cytokines such as IL-1β and TNF-α (p < 0.001). Functional analyses showed that HESP treatment enhanced CSP-induced Ca2+ influx and altered mitochondrial membrane potential (p < 0.001). The pharmacological inhibition of TRPM2 with ACA and 2-APB reversed these effects, restoring redox balance and reducing cellular damage. In conclusion, HESP amplifies CSP-induced apoptosis in Hep-2 cells through TRPM2-dependent oxidative stress, Ca2+ dysregulation, and mitochondrial dysfunction. These findings identify TRPM2 as a mechanistic mediator of HESP-enhanced chemosensitivity in LSCC.
Background: Nasal steroids are commonly prescribed in ear, nose, and throat clinics. It is observed that the use of nasal steroids is increasing due to the prevalence of allergic rhinitis. Because beclomethasone (BCM) toxicity is low, it is highly preferred in allergic rhinitis. The rate of toxicity increases with the increase in the duration and dose of BCM use. However, the protective mechanism of Anatolian propolis (AP) and curcumin (Cur) against BCM toxicity has not been fully explained. Aim: The study evaluates the potential BCM-induced toxicity effect on VEGF, MMP-2, IL-25, and IL-10 parameters after Cur and AP treatment. Materials and Methods: Cell viability, oxidative stress, and gene expression were used for toxicity evaluation. Results: AP 2.5 mg/mL and Cur 16 µg/mL show high viability and antioxidant capacity. BCM increased the levels of IL-25, IL-10, and MMP-2, and a decrease was detected in the expression levels of FGF-2 and VEGF. Conclusions: AP and Cur show effective healing, and AP has been shown to improve inflammation more effectively than Cur. However, the combination of AP and Cur significantly improved the induced toxicity effects.
Objective: Obstructive Sleep Apnea Syndrome (OSAS) is a common sleep disorder characterized by respiratory arrests and is thought to affect vestibular system functions. In recent years, the Masseter VEMP test has become an alternative method for evaluating vestibular functions. This study aimed to assess the vestibular system through an mVEMP test in OSAS patients and determine the effects of the disease on vestibular functions. Methods: This prospective study included 36 patients (72 ears) and 36 healthy controls (72 ears) diagnosed with OSAS. All participants underwent the mVEMP test to evaluate the functions of the vestibular system. N1 latency, P1 latency, P1-N1 difference, mean EMG activity, and amplitude values were assessed. Results: N1 latency was significantly longer in the OSAS group compared with the control group (P=0.013). P1 latency and the P1-N1 difference did not differ significantly between the groups (P=0.273 and 0.098, respectively). The mean EMG activity was significantly lower in the OSAS group compared with the control group (P=0.010). Amplitude was significantly higher in the OSAS group compared with the control group (P=0.024). Significant differences were observed in N1 and EMG values between the groups based on the severity of OSAS. Conclusion: In this study, significant changes were observed in N1 latency, EMG activity, and amplitude during vestibular evaluation with mVEMP in patients with severe OSAS. It was noted that vestibular responses (N1 and EMG values) were more impacted in the severe OSAS group.