The pathogenesis of itai-itai disease continues to be controversial,
although cadmium (Cd) poisoning which arises via polluted water and rice in
Japan is likely involved. Until recently, however, a well-defined animal
model for Cd intoxication was not available. An animal model for itai-itai
disease was produced in rats by low-dose Cd treatment, intraperitoneally for
a period of 70-80 weeks. Osteomalacia followed the renal damage.
gene deletion in the mitochondrial DNA was found in the mitochondria of the
proximal tubule cells of rats with chronic Cd intoxication, as was shown by
the increased smaller PCR product seen by gel electrophoresis in one DNA
region, where ATPase and cytochrome oxidase genes are located. However, the
PCR product was different from that seen with a gene deletion associated
with aging: del4834bp. Renal damage from Cd intoxication initially caused
mitochondrial dysfunction indicated by the disturbance in reabsorption in
the proximal tubules and decreased amounts of ATP, ATPase, and cytochrome
oxidase with gradually progressing tubular proteinuria, and, finally,
chronic renal failure with tubulointerstitial damage throughout the renal
cortex. These gave rise to osteomalacia, subsequently.
concluded that in Cd poisoning, a mitochondrial gene deletion in the
mitochondria of the proximal tubule cells was the primary event for the
pathogenesis of osteomalacia in itai-itai disease.