Effects of Vitamin E pretreatment on subacute toxicity of mixture of Co, Pb, and Hg nitrate-induced nephrotoxicity in rats.

The aim of the study was to prove that Vitamin E has some beneficial effects on the kidneys of rats by protecting them from the toxicity of certain heavy metals. The protective effect of Vitamin E on Co, Pb, or Hg nitrate and a mixture of them induced nephrotoxicity was tested in a 3-months-old Norway strain (inberd) rat (Raltus norvigus) weighing 100-120g. A study was carried out, which comprised one control group and five experimental groups. In this experiment, nitrate salts of Co, Pb, or Hg were administered subcutaneously (s.c.) either alone (0.5mg/100g body weight) for 4 weeks or as a mixture (0.25mg/100g body weight); Vitamin E internal control (250IU/100g body weight) was administered by oral gavage for 4 weeks, Vitamin E pretreatment for 7 days was followed by concomitant administration of Co, Pb, and Hg, respectively and Vitamin E pretreatment for 7 days, followed by concomitant administration of mixture of three heavy metals for 4 weeks. Blood and kidney tissue samples were taken from the control and all the experimental groups for biochemical and histological study. Nephrotoxicity was characterized by histopathological as well as renal function data. The main pathological changes in the kidney after Co administration were shrunken and degeneration of renal tubule cells, disturbance in their position, size, shape, and staining affinity. Treatment with Hg caused desquamation, necrosis, atrophy, and loss of renal tubule cells and glomeruli. Lead intoxication had a profound effect on the structure and consequently on the function of the rat kidney. Most renal tubule cells were very dense, dehydrated with obscure cytoplasmic details. Most nuclei were shrunken and pyknotic. Also, most glomeruli revealed shrinkage and widening of capsular space. On the other hand, subacute exposure with the mixture of the three heavy metals showed marked destruction and distortion of the renal tubule cells. Marked fibrosis between the damaged tubules was also seen. On the other hand in the recovery groups, i.e., in groups II and III, the previously observed histopathological changes were still present with regression of their intensity. Four-week oral administration with Vitamin E (250IU/100g body weight) revealed no abnormal histological findings as compared with the normal kidney of the control animal, except for some Malpighian corpuscles which demonstrated wide capsular space, and spherical masses were seen within the glomeruli. After pretreatment with Vitamin E for 7 days, followed by treatment with (0.5mg/100g body weight ) Co, Pb, or Hg nitrate alone or with their mixture (0.25mg/100g body weight) for 4 weeks, an improvement in the histological changes were observed compared to those previously seen in groups II and III. The glomeruli showed minimal degenerated changes, the tubular arrangement and cytoplasmic basophilia more or less similar to the normal control. It was also found that the heavy metals were investigated both alone and in combination; the serum creatinine and blood urea level were significantly increased, and this elevation was diminished by Vitamin E pretreatment. According to the present results, it is concluded that combined exposure to a mixture of Vitamin E and examined heavy metals can minimize the histological alteration and diminish the serum creatinine and blood urea level. Also, it was found that the rank order of metal cytotoxicities was Hg > Co > Pb.