Chronic Lead Exposure Results in Auditory Deficits and Disruption of Hair Cells in Postweaning Rats

Objective. The effects of lead exposure on cognitive function have been studied intensively over the past decade, but less attention has focused on its impact on auditory function. This study is aimed at investigating the effect of lead on the cochlea and the molecular mechanisms responsible for its actions. Methods. 0.2% lead acetate was administered to rats in drinking water for 30, 60, and 90 days. Brainstem auditory evoked responses (ABR) were recorded, and morphological changes in the hair cells were observed. We also measured glutathione (GSH) and malondialdehyde (MDA) concentrations and antioxidant enzyme activities such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione reductase (GR) activities in the cochlea. Results. Lead exposure increased the ABR threshold and slightly prolonged the latencies of wave II and wave IV in rats. Abnormally shaped hair cells and loss of hair cells were found in the cochlea basilar membrane, together with degenerative changes in spiral ganglion neurons following lead exposure. The activities of some antioxidant enzymes were also reduced in association with upregulation of MDA expression. These effects may be caused by impaired catalytic function of the enzymes as a result of lead interaction. Conclusion. The antioxidant system of the cochlea in the immature rat brain is highly vulnerable to developmental lead exposure. Oxidative stress may therefore represent a possible mechanism for lead-induced auditory deficits

Peniciketals A–C, New Spiroketals from Saline Soil Derived <i>Penicillium raistrichii</i>

Peniciketals A–C (<b>1</b>–<b>3</b>), three new spiroketals with a benzo-fused 2,8-dioxabicyclo[3.3.1]­nonane moiety, were isolated from the saline soil derived fungus <i>Penicillium raistrichii</i>. Their structures including absolute configurations were established by NMR, X-ray diffraction, and ECD calculations. Their cytotoxicities were tested against A549, HL-60, and K562 cell lines, and <b>1</b>–<b>3</b> showed the selective effects on HL-60 cells with IC₅₀ values of 3.2, 6.7, and 4.5 μM, respectively