High dietary protein regimens provide significant protection from mercury nephrotoxicity in rats

The effects of high protein dietary regimens prior to the administration of inorganic mercury were investigated. Male Sprague-Dawley rats were pair-fed on purified test diets containing either normal (20%) or high (60%) concentrations of protein. Mercury was administered as a single intravenous injection of mercuric chloride (1 mg/kg). All rats maintained on normal dietary protein prior to and following mercury injection exhibited severe kidney dysfunction, extensive necrosis of both second (S2) and third (S3) segments of the kidney proximal tubules, and 100% mortality. In contrast, rats maintained on high dietary protein for 48 hr or longer just prior to mercury injection and returned to normal dietary protein immediately following mercury administration all survived and exhibited normal serum creatinine and BUN values within 4 days following mercury administration. The kidneys of this latter group took up significantly less radiolabeled mercury during the first 12 hr following mercury injection, and exhibited relatively little damage to the second segments (S2) of the proximal tubules. The third segments (S3) of the proximal tubules, however, exhibited the same degree of necrosis as that observed in the control group. Maintaining rats on high dietary protein regimens for shorter periods of time prior to mercury infusion (i.e., 12 or 24 hr) also dramatically reduced subsequent acute renal failure and improved survival, although not to the extent noted following 48 hr or longer on these diets. These observations suggested that high dietary protein regimens may protect from mercury nephrotoxicity by reducing mercury uptake to the second segments (S2) of the proximal tubules during the initial period of exposure to intravenously administered mercury.