benzofurans and Hearing-Loss

Cisplatin (CDDP) is an extensively used chemotherapeutic agent but has a high incidence of severe ototoxicity. Although a few molecules have entered clinical trials, none have been approved to prevent or treat CDDP-induced hearing loss by the Food and Drug Administration. In this study, an amphiphilic drug-drug conjugate was synthesized by covalently linking dexamethasone (DEX) and salvianolic acid B (SAL) through an ester or amide bond. The conjugates could self-assemble into nanoparticles (NPs) with ultrahigh drug loading capacity and favorable stability. Compared with DEX, SAL, or their physical mixture at the same concentrations, both conjugates and NPs showed enhanced otoprotection in vitro and in vivo. More importantly, the conjugates and NPs almost completely restored hearing in a guinea pig model with good biocompatibility. Immunohistochemical analyses suggested that conjugates and NPs activated the glucocorticoid receptor, which may work as one of the major mechanisms for their protective effects.

Topics: Animals; Antineoplastic Agents; Benzofurans; Cisplatin; Dexamethasone; Drug Design; Guinea Pigs; Hearing Loss; Humans; Protective Agents

In 1979, approximately 2000 people in central Taiwan were exposed to polychlorinated biphenyls and dibenzofurans (PCBs/PCDFs) due to ingestion of contaminated rice oil. The children born to mothers exposed to PCBs/PCDFs were called Yucheng children. We conducted a follow-up study to examine the association between gestational PCBs/PCDFS exposure and auditory function in Yucheng children's early adulthood.. In 1985 and early 1992, Yucheng children and their age, gender, socio-economic matched unexposed referent children were recruited for physical examination and long-term follow-ups. In 2007, Yucheng children and referent children were invited to participate in a health examination, including assessment of pure-tone air-conduction thresholds and distortion product otoacoustic emissions (DPOAEs) test. Gestational exposure to PCBs/PCDFs in Yucheng children were estimated by back-extrapolation of their mother's serum concentration to the time of childbirth.. A total of 86 Yucheng children (51.2% males) and 97 referent children (50.5% males) were included for analysis. No difference was found in demographic characteristics between two groups. Among the Yucheng children, 53 had estimated PCBs/PCDFs concentrations. We found that Yucheng children were at higher risk of having elevated hearing threshold at low frequencies in the right ear. Estimated maternal concentrations of 2,3,4,7,8-pnCDF at the time of birth were associated with increased hearing thresholds and decreased DPOAEs amplitudes at low frequencies in the right ear.. Gestational exposure to PCBs/PCDFs caused adverse asymmetrical hearing effects detectable even in early adulthood.

Topics: Adolescent; Adult; Benzofurans; Case-Control Studies; Dibenzofurans, Polychlorinated; Environmental Monitoring; Environmental Pollutants; Female; Follow-Up Studies; Hearing Loss; Humans; Male; Maternal Exposure; Polychlorinated Biphenyls; Pregnancy; Prenatal Exposure Delayed Effects; Taiwan; Young Adult