To clarify the pathophysiological mechanism underlying acute renal injury caused by
acute exposure to arsenic, we subcutaneously injected both BALB/c and C57BL/6 mice
with sodium arsenite (NaAs; 13.5 mg/kg). BALB/c mice exhibited exaggerated elevation
of serum blood urea nitrogen (BUN) and creatinine (CRE) levels, compared with C57BL/6
mice. Moreover, half of BALB/c mice died by 24 h, whereas all C57BL/6 mice survived.
Histopathological examination on kidney revealed severe hemorrhages, acute tubular
necrosis, neutrophil infiltration, cast formation, and disappearance of PAS-positive
brush borders in BALB/c mice, later than 10 h. These pathological changes were remarkably
attenuated in C57BL/6 mice, accompanied with lower intrarenal arsenic concentrations,
compared with BALB/c mice. Among heavy metal inducible proteins including multidrug
resistance-associated protein (MRP)-1, multidrug resistance gene (MDR)-1, metallothionein
(MT)-1, and arsenite inducible, cysteine- and histidine-rich RNA-associated protein
(AIRAP), intrarenal MDR-1, MT-1, and AIRAP gene expression was enhanced to a similar
extent in both strains, whereas NaAs challenge augmented intrarenal MRP-1 mRNA and
protein expression levels in C57BL/6 but not BALB/c mice. Moreover, the administration
of a specific inhibitor of MRP-1, MK-571, significantly exaggerated acute renal injury
in C57BL/6 mice. Thus, MRP-1 is crucially involved in arsenic efflux and eventually
prevention of acute renal injury upon acute exposure to NaAs.