Aflatoxin B 1 reduces Na +-P i co-transport in proximal renal epithelium: studies in opossum kidney (OK) cells

Abstract

In vivo studies indicate that aflatoxin B 1 (AFB 1) may affect the renal regulation of inorganic phosphate (P i), possibly by altering the renal response to parathyroid hormone (PTH). Therefore, the present study utilized opossum kidney (OK) cells, a mammalian renal epithelial cell line, to determine whether AFB 1 exposure alters sodium-phosphate (Na +-P i) co-transport and the hormonal modulation thereof. OK cells are an established renal cell line with many properties analagous to the proximal renal epithelium, including receptors for PTH, insulin, and high levels of Na +-P i co-transport. PTH and insulin have been shown to decrease and increase Na +-P i co-transport, respectively, in OK cells. In the present study, AFB 1-treated cells responded to PTH; however, AFB 1 exposure decreased Na +-P i uptake such that additional decreases in Na +-P i uptake in response to PTH were minimal. In the presence of insulin, AFB 1-treated cells were only able to increase Na +-P i uptake to levels 30% below that of control cells. The net result was that the range of the proximal renal epithelium to adjust Na +-P i co-transport in response to hormonal modulation was reduced by AFB 1 exposure. Sodium-dependent L-alanine uptake was measured and was found not to be affected by the highest concentration of AFB 1; thus, indicating that AFB 1 exposure may have specific effects on Na +-P i uptake and does not generally inhibit Na +-dependent transport. These observations are evidence that AFB 1 exposure may alter key elements of renal function. Such effects raise concern that AFB 1 exposure may have broad physiological impact in addition to its known carcinogenic properties.