The current studies were conducted to investigate the degree and type of protein binding of hydroquinone (HQ) in the rat following single oral or intraperitoneal (ip) or repeated oral administrations. Male or female F-344 rats or male SD rats received a single dose of HQ at 0, 25, 50, or 100 mg/kg by either gavage or ip injection (SD rats only). In addition, male or female F-344 or male SD rats received HQ by gavage for 6 weeks (5 days/week) at 0, 25, or 50 mg/kg/day. Sulfhydryl-bound HQ was quantitated in protein from blood, kidneys, livers, or spleens 24 h after treatment using an alkaline permethylation procedure. The amount of total protein-S adducts increased with increasing dose in all the tissues that were assayed. Female rats had higher levels of adducts in blood, livers, and kidneys than did male rats when they were treated orally. Male F-344 rats treated orally had elevated levels of adducts in these same tissues compared to SD rats treated orally. For all genders and strains of rats and for all treatment regimens, mono-adducts predominated in livers (>72% of total). In the kidneys, tri- and tetrasubstituted adducts predominated with the summation accounting for >60% of the total. Ip administration of HQ resulted in significantly elevated levels of adducts in all the tissues that were examined, with the greatest increases seen for protein from blood and spleens. Levels of protein-S adducts of HQ in rat kidney following a single gavage administration correlated well with previously published differences in acute HQ nephrotoxicity in rats (female F-344 rat > male F-344 rat > male SD rat). Elevated levels of HQ protein-S adducts following repeated gavage administration did not correlate to measurable clinical signs of nephrotoxicity. Evidence is presented suggesting a possible role for the prostaglandin H synthase complex in the metabolic activation of HQ. In addition, protein arylation alone cannot account for the greater sensitivity of male F-344 rats toward chronic administration of HQ. The sensitivity of male F-344 rats to HQ is likely due to other factors, including the incidence and severity of chronic progressive nephropathy.
Riparian ecosystems in the western USA have been invaded by non-native woody species deliberately introduced for stream bank stabilization, agricultural windbreaks, and urban shade. Recent work suggests that the non-native tree Ulmus pumila (Siberian elm) is capable of significant spread in western riparian ecosystems, that range infilling is still incomplete, and that the invasion is dispersal-limited. We analyzed the interacting roles of propagule pressure from upland U. pumila, human influence based on road and farmstead density, and river geomorphology in promoting U. pumila invasion into riparian corridors along the South Platte River, Colorado, USA. U. pumila stem density increased with increasing channel and floodplain restriction and increasing human influence from both urban and rural development. Model selection indicated that local upland U. pumila seed sources were relatively unimportant to riparian U. pumila stem density, suggesting that upland propagule pressure is currently contributing less than human influences to U. pumila spread along the South Platte River. In particular, higher road density was the most important predictor for the proportional abundance of smaller U. pumila individuals (DBH < 5-cm and 5-15-cm), suggesting that human influence in densely populated areas has been the primary driver of recent U. pumila population expansion. U. pumila stem density was only weakly associated with abundance of other common riparian tree species. Land managers and other entities concerned with non-native tree invasion into important riparian habitat may be able to reduce U. pumila spread most effectively by focusing U. pumila control efforts where human influences are greatest.
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