Zicam-induced damage to mouse and human nasal tissue.

Intranasal medications are used to treat various nasal disorders. However, their effects on olfaction remain unknown. Zicam (zinc gluconate; Matrixx Initiatives, Inc), a homeopathic substance marketed to alleviate cold symptoms, has been implicated in olfactory dysfunction. Here, we investigated Zicam and several common intranasal agents for their effects on olfactory function. Zicam was the only substance that showed significant cytotoxicity in both mouse and human nasal tissue. Specifically, Zicam-treated mice had disrupted sensitivity of olfactory sensory neurons to odorant stimulation and were unable to detect novel odorants in behavioral testing. These findings were long-term as no recovery of function was observed after two months. Finally, human nasal explants treated with Zicam displayed significantly elevated extracellular lactate dehydrogenase levels compared to saline-treated controls, suggesting severe necrosis that was confirmed on histology. Our results demonstrate that Zicam use could irreversibly damage mouse and human nasal tissue and may lead to significant smell dysfunction.

Adult type 3 adenylyl cyclase-deficient mice are obese.

BACKGROUND: A recent study of obesity in Swedish men found that polymorphisms in the type 3 adenylyl cyclase (AC3) are associated with obesity, suggesting the interesting possibility that AC3 may play a role in weight control. Therefore, we examined the weight of AC3 mice over an extended period of time. METHODOLOGY/PRINCIPAL FINDINGS: We discovered that AC3(-/-) mice become obese as they age. Adult male AC3(-/-) mice are about 40% heavier than wild type male mice while female AC3(-/-) are 70% heavier. The additional weight of AC3(-/-) mice is due to increased fat mass and larger adipocytes. Before the onset of obesity, young AC3(-/-) mice exhibit reduced physical activity, increased food consumption, and leptin insensitivity. Surprisingly, the obesity of AC3(-/-) mice is not due to a loss of AC3 from white adipose and a decrease in lipolysis. CONCLUSIONS/SIGNIFICANCE: We conclude that mice lacking AC3 exhibit obesity that is apparently caused by low locomotor activity, hyperphagia, and leptin insensitivity. The presence of AC3 in primary cilia of neurons of the hypothalamus suggests that cAMP signals generated by AC3 in the hypothalamus may play a critical role in regulation of body weight.