Effects of silica on mitochondrial functions of the proximal tubule cells in rats.
OBJECTIVE
Despite the belief that silica (Si) is an inert and non-toxic ingredient, latest studies indicated that it is a potent mitochondria activator and Si-induced ROS generation is involved in the inflammatory reactions of silicotic lungs. Si cytotoxicity has been well studied in phagocytic cells, but its effects on the mitochondria of proximal tubule cells which are continuously exposed to filtered blood-borne soluble Si were not known.


METHODS
Using renal cortical slices and isolated mitochondria, the effect of high dietary Si on the mitochondrial functions of proximal tubule cells was studied in rats exposed to 50 mg/kg sodium metasilicate-containing water for 8 days.


RESULTS
Digested Si did not accumulate in kidney cortex, it was totally eliminated in the urine. Glomerular filtration rate as well as urine output were normal. Despite unaltered blood and cortex Si levels, ammonia production of cortical slices and isolated mitochondria was increased significantly and this was further increased by L-NAME pre-treatment. Elevated mitochondrial oxygen utilization was associated with increased ammonia production. Cyclosporin-A-sensitive mtPTP increase was associated with unchanged K(ATP) channels in the mitochondria of Si-exposed rats.


CONCLUSIONS
These results suggested that dietary Si increases both extracellular and intracellular ammoniagenesis by elevating mitochondrial oxygen utilisation.
Oner
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G
Akdeniz University, Medical Faculty, Department of Physiology, Kampus-Antalya, Antalya,Turkey. onerg@akdeniz.edu.tr
Cirrik
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S
Bakan
O
O
D000641:Ammonia / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005973:Glutamine / Q000378:metabolism; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D012822:Silicon Dioxide / Q000494:pharmacology*; D012966:Sodium Cyanide / Q000494:pharmacology; D014556:Urine
D004791:Enzyme Inhibitors; D005973:Glutamine; D012822:Silicon Dioxide; D000641:Ammonia; D012966:Sodium Cyanide; D002118:Calcium