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Kidney disease is a frequent consequence of heavy metal exposure and renal anemia occurs secondarily to the progression of kidney deterioration into chronic disease. In contrast, little is known about effects on kidney of chronic exposure to low levels of depleted uranium (DU). Study was performed with rats exposed to DU at 40 mg/l by chronic ingestion during 9 months. In the present work, a approximately 20% reduction in red blood cell (RBC) count was observed after DU exposure. Hence, three hypotheses were tested to determinate origin of RBC loss: (1) reduced erythropoiesis, (2) increased RBC degradation, and/or (3) kidney dysfunction. Erythropoiesis was not reduced after exposure to DU as revealed by erythroid progenitors, blood Flt3 ligand and erythropoietin (EPO) blood and kidney levels. Concerning messenger RNA (mRNA) and protein levels of spleen iron recycling markers from RBC degradation (DMT1 [divalent metal transporter 1], iron regulated protein 1, HO1, HO2 [heme oxygenase 1 and 2], cluster of differentiation 36), increase in HO2 and DMT1 mRNA level was induced after chronic exposure to DU. Kidneys of DU-contaminated rats had more frequently high grade tubulo-interstitial and glomerular lesions, accumulated iron more frequently and presented more apoptotic cells. In addition, chronic exposure to DU induced increased gene expression of ceruloplasmin (x12), of DMT1 (x2.5), and decreased mRNA levels of erythropoietin receptor (x0.2). Increased mRNA level of DMT1 was associated to decreased protein level (x0.25). To conclude, a chronic ingestion of DU leads mainly to kidney deterioration that is probably responsible for RBC count decrease in rats. Spleen erythropoiesis and molecules involved in erythrocyte degradation were also modified by chronic DU exposure.

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The Mule duck develops a fatty liver in response to overfeeding, which results from a dramatic increase in de novo liver lipogenesis, and thus raises questions regarding the role of glucokinase (GK), a key enzyme regulating carbohydrate metabolism in mammals. However, the presence of GK in avian species is still a matter of debate. The aim of the present study was to characterize a GK-like protein (using an immunological technique) and a GK-like activity (using an enzymatic assay) in duck liver and to measure their respective variations during various stages of overfeeding. Duck liver protein cross-reacted with antibodies directed against mammalian GK yielding a band at 50 kDa, i.e., the same molecular weight as mammalian GK. The intensity of the signal varied significantly between overfed and control ducks but in opposing ways according to the GK antibodies used, which suggests the presence of 2 isoforms of GK in the duck liver as in mammals. Enzymatic analysis demonstrated the presence of glucose phosphorylation activity sensitive to high and low glucose concentrations (high/low ratio between 1.7 and 3.7) in the soluble and particulate fractions of liver homogenates. Glucokinase-like activity per milligram protein was strongly induced by overfeeding, and plasma insulin levels increased concomitantly. More than 80% of total GK-like activity was concentrated in the soluble component from 1 to 13 d of overfeeding. These results suggest that a GK-like enzyme may actively contribute to glucose disposal throughout the overfeeding period in Mule ducks fed a carbohydrate-rich diet.

The presence of glucokinase (GK), a critical enzyme controlling glucose homeostasis, particularly liver glucose utilization in mammals, has long been a matter of debate in avian species because a number of investigators have failed to detect GK activity in the livers of chickens and several other avian species. In this study, we cloned a partial GK cDNA from mule duck livers and measured GK-like activity in the livers of mule ducks and broiler chickens under 2 nutritional states. Liver samples from 5-wk-old meal-fed male broiler chickens (Ross) were obtained from overnight-fasted chickens (BC) and 5 h after an oral saccharose load (6 mL/kg of BW of a 50% saccharose solution) given just before the meal (BS). Liver samples from 15-wk-old mule ducks were collected after an overnight fast (DC) and 12 h after the last overfeeding meal (DO). A partial cDNA ( approximately 600 bp) was obtained from duck livers. It presented 99% identity with chicken partial GK cDNA (gi 44888789) and 82% identity with human GK (gi 15967158). Chicken liver weights represented 1.8 and 3.3% of BW, respectively, for BC and BS (n = 8, P < 0.05). Glucokinase and low-Michaelis constant hexokinase (HK) activity levels were similar in BC (respectively, 0.88 and 1.00 mU/mg of protein). In response to the meal load, GK activity increased significantly (+57%), whereas HK decreased (-46%) in BS. Duck liver weights represented 1.4 and 7.6% of BW, respectively, for DC and DO (n = 8, P < 0.05). In DC livers, GK activity was significantly higher than HK activity (respectively, 1.76 and 0.63 mU/mg of protein). Both activities were significantly increased in DO (2 times, n = 8, P < 0.05). In conclusion, GK is present in ducks as well as chickens, and it is nutritionally regulated in avian species as well as in mammals. Further work will determine whether the higher liver GK activity and GK:HK ratio in DC compared with BC is related to age or BW or linked to the high lipogenic capacity of the duck liver.

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