Protection against chronic cadmium toxicity by caloric restriction

Exposure to cadmium (Cd) can result in nephrotoxicity and osteotoxicity. Be cause Cd-induced nephrotoxicity involves oxidative stress and caloric restr iction decreases oxidative stress, we examined whether reduced caloric inta ke will protect against Cd-induced nephrotoxicity. In addition, the protect ion against the osteotoxicity was also examined. Male and female Sprague-Da wley rats were provided drinking water containing 100 mg Cd/l. Since fluid intake relative to the body weight was higher in females as compared to the males, the Cd concentration in their water was reduced to 80 mg/l after 3 months and 65 mg/l after 6.5 months. During the 27 month exposure period th e males and females consumed a total of about 5 g Cd/kg body weight. Food w as restricted to 20 g/day after the first 3 months. During the unrestricted food intake period Cd exposure reduced the bone density in females by 23%, with a partial recovery and stabilization during the caloric restriction p hase. Hepatic and renal Cd accumulation and corresponding metallothionein ( MT) levels were very similar in both sexes. The reported critical Cd concen tration for nephrotoxicity was reached by 9 months. Renal MT levels were ma ximum at this time. Despite a 1.5-fold increase in renal Cd concentration o ver the next 18 months, there was no significant increase in renal MT level s. In spite of high renal Cd levels and lack of availability of sufficient MT, there was no sign of nephrotoxicity, as measured by urinary protein and glucose excretion. It is concluded that caloric restriction prevents Cd-in duced nephrotoxicity and also appears to control the osteotoxicity of Cd. ( C) 1999 Elsevier Science Ireland Ltd. All rights reserved.