Browsing by Author "Rodini, Andreina L."

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Hepatic and intestinal responses to antibiotic-arsenic driven sepsis
(Undergraduate Scholars Program, 2024-04) Rodini, Andreina L.; Wolfe, Trenton M.; Walk, Seth T.
Arsenic is a potent group 1 carcinogen and immunosuppressant. Globally, it is estimated that 200 million people are exposed to unsafe levels in their drinking water. Previous work in the Walk lab has established that in murine models the microbiome is required for full protection against arsenicosis as antibiotic perturbation disrupts this protective mechanism. In epidemiological studies of humans, similarly exposed individuals exhibit high interindividual variability in arsenicosis outcome which is not explained by host genetics alone. We have developed a murine model co-exposed to the third-generation cephalosporin antibiotic cefoperazone and inorganic arsenic which recapitulates this interindividual variability. To the best our of knowledge, this is the only whole-organism arsenicosis model that does so. Currently, the reasons behind the interindividual variability in arsenicosis susceptibility remain unclear. However, recent work in our lab has demonstrated that co-exposed mice that succumb to arsenicosis exhibit altered blood chemistry indicative of liver and kidney dysfunction and decreased white blood cell counts indicative of immune dysfunction. Additionally, these sick mice have ceca with gross anatomical features suggestive of infection. In contrast, co-exposed mice that remain healthy exhibit normal blood chemistry and cecal anatomy. These observations suggest that co-exposed mice are succumbing to sepsis, which is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Current work in our lab is aimed at identifying septic infection through culture-dependent and culture-independent methods, and determining which immune cells are involved.