Effects of cadmium-metallothionein complex exposure on bone tissue through kidney injury

Abstract

Cadmium (Cd) is accumulated in rice and other crops. Chronic exposure to Cd causes itai-itai disease and is characterized by kidney damage and osteomalacia. However, the detailed pathogenic mechanisms are not well understood. It is known that proximal renal tubular damage is induced in mice treated with Cd-metallothionein complex (Cd-MT) intravenously. Therefore, we thought that bone disorders could also be triggered by this model. In this study, we investigated the effects of Cd-MT administration on the bone in a postmenopausal model of ovariectomized (OVX) mice. 8-weeks-old female mice were performed OVX and treated with 0.3 mg Cd/kg Cd-MT intravenously at one week after OVX. The kidney and femur were harvested for histological analysis at 12 or 24 weeks after Cd-MT administration. The bone density and bone mass of the femur was measured by X-ray μCT. We observed kidney damage in mice by Cd-MT administration, as enlarged Bowman's capsules. The femur bone mineral density and bone mass showed no significant change at 12 weeks after Cd-MT administration, but at 24 weeks after administration, bone mass in the Cd-MT group was significantly lower than that in the control group. No additive effects of OVX and Cd-MT administration were observed on bone tissue in this experiment. These results suggested that Cd-MT administration may reproduce pathology similar to chronic Cd toxicity in humans.