Sulfite leads to neuron loss in the hippocampus of both normal and SOX-deficient rats

Sulfites are compounds commonly used as preservatives in foods, beverages and pharmaceuticals. Sulfite is also endogenously generated during the metabolism of sulfur-containing amino acids and drugs. It has been shown that sulfite is a highly toxic molecule. Many studies have examined the effects of sulfite toxicity, but the effect of ingested sulfite on the number of neurons in the hippocampus has not yet been reported. The present study was undertaken to investigate the effect of ingested sulfite on pyramidal neurons by counting cells in CA1 and CA3-2 subdivisions of the rat hippocampus. For this purpose, rats were assigned to one of four groups (6 rats per group): control (C), sulfite (S), deficient (D) and deficient+sulfite (DS). Sulfite oxidase deficiency was established by feeding rats a low molybdenum diet and adding 200ppm tungsten (W) to their drinking water. Sulfite (70mg/kg) was also administered to the animals via their drinking water. At the end of the experimental period, the rats were sacrificed by exsanguination under anesthesia, and their brains and livers quickly removed. The livers were used for a SOX activity assay, and the brains were used for neuronal counts in a known fraction of the CA1 and CA3-2 subdivisions of the left hippocampus using the optical fractionator method, which is a stereological method. The results showed that sulfite treatment caused a significant decrease in the total number of pyramidal neurons in three subdivisions of the hippocampus (CA1 and CA3-2) in the S, D and DS groups compared with the control group. It is concluded that exogenous administration of sulfite causes loss of pyramidal neurons in CA1 and CA3-2 subdivisions in both normal and SOX deficient rat hippocampus. This finding provides supporting evidence that sulfite is a neurotoxic molecule.     

Effect of sulfite on antioxidant enzymes and lipid peroxidation in normal and sulfite oxidase-deficient rat erythrocytes

Sulfite and related chemical such as sulfite salts and sulfur dioxide has been used as a preservative in food and drugs. This molecule has also been generated from the catabolism of sulfur-containing amino acids. Sulfite is a very reactive and potentially toxic molecule and has to be detoxified by the enzyme sulfite oxidase (SOX). The aim of this study was to investigate the effects of ingested sulfite on erythrocyte antioxidant status by measuring glucose-6-phosphate dehydrogenase (G-6-PD), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities and oxidant status by measuring thiobarbituric acid reactive substances (TBARS) in normal and SOX-deficient rats. Rats were assigned to four groups (n = 10 rats/group) as follows; control (C), sulfite (CS), deficient (D), and deficient + sulfite (DS). SOX deficiency was established by feeding rats a low molybdenum diet and adding to their drinking water 200 ppm tungsten (W). Sulfite (25 mg/kg) was administered to the animals via their drinking water. At the end of 6 weeks, Erythrocyte G-6-PD, SOD, and GPx but not CAT activities were found to be significantly increased with and without sulfite treatment in SOX-deficient groups. Sulfite treatment alone was also significantly increased erythrocytes’ SOD activity in CS group compared to control. TBARS levels were found to be significantly increased in CS and DS groups and decreased in D group. When SOX-deficient rats treated with sulfite, TBARS level was still higher than other groups. In conclusion, these results suggested that erythrocyte antioxidant capacity, a defense mechanism against the oxidative challenge, increased by endogenous and exogenous sulfite due to its oxidant nature. This increase was also observed in CS and DS groups but it was insufficient to prevent lipid peroxidation.     

Sulfite suppresses the mutagenic property of coffee

The mutagenicity of instant and freshly brewed coffee on Salmonella typhimurium TA100 and TA98 without S9 mix was inactivated by sodium sulfite. Sulfite ion at a dose of 200 ppm almost completely inactivated the mutagenicity of coffee made in the ordinary way (5-15 mg dry weight/ml). Sodium bisulfite and potassium metabisulfite had similar effects. On the contrary, L-ascorbic acid enhanced the mutagenicity of coffee. Sodium sulfite also inactivated the phage-inducing activity of coffee in inductest III. Sodium sulfite completely suppressed the mutagenicities of 1,2-dicarbonyls, namely diacetyl and glyoxal. Diacetyl is present in coffee, beer, butter and other foods and drinks. Because sodium sulfite, sodium bisulfite and potassium metabisulfite are widely used as food additives, they should be useful in reducing the levels of mutagens in foods.     

Effect of dietary copper and zinc levels on tissue copper,zinc, and iron in male rats

The interaction between dietary copper and zinc as determined by tissue concentrations of trace elements was investigated in male Sprague-Dawley rats. Animals were fed diets in a factorial design with two levels of copper (0.5, 5 μg/g) and five levels of zinc (1, 4.5, 10, 100, 1000 μg/g) for 42 d. In rats fed the low copper diet, as dietary zinc concentration increased, the level of copper decreased in brain, testis, spleen, heart, liver, and intestine. There was no significant effect of dietary copper on tissue zinc levels. In the zinc-deficient groups, the level of iron was higher in most tissues than in tissues from controls (5 μg Cu, 100 μg Zn/g diet). In the copper-deficient groups, iron concentration was higher than control values only in the liver. These data show that dietary zinc affected tissue copper levels primarily when dietary copper was deficient, that dietary copper had no effect on tissue zinc, and that both zinc deficiency and copper deficiency affected tissue iron levels.     

A Preliminary and Qualitative Metallomics Study of Mercury in the Muscle of Fish from Amazonas, Brazil

In this study, we report the effect of zinc supplementation on the distribution of elements in kidney tissue of diabetic rats subjected to acute swimming exercise. Diabetes was induced by two subcutaneous injections of 40 mg/kg of streptozotocin within a 24-h period. Zinc was given intraperitoneally at a dose of 6 mg/kg per day for a period of 4 weeks. The rats (n = 80) were equally divided into eight study groups: controls, zinc-supplemented, swimming, diabetic, zinc-supplemented diabetic, zinc-supplemented swimming, diabetic swimming, and zinc-supplemented diabetic swimming. The levels of lead, cobalt, molybdenum, chromium, boron, magnesium, iron, copper, calcium, zinc, and selenium were determined in the kidney tissue samples by ICP-AES. Higher molybdenum, calcium, zinc, and selenium values were found in both swimming and nonswimming diabetic rats. Significantly higher iron values were found in swimming, diabetic, diabetic swimming, and zinc-supplemented diabetic swimming rats (p < 0.001). Diabetic, zinc-supplemented diabetic, diabetic swimming, and zinc-supplemented diabetic swimming rats had the highest copper values. These results show that zinc supplementation normalized the higher levels of molybdenum, calcium, selenium, and iron levels seen in diabetic rats, indicating that zinc may have a regulatory effect on element metabolism in kidney tissue.     

Ceruloplasmin, Copper, Selenium, Iron, Zinc, and Manganese Levels in Normal and Sulfite Oxidase Deficient Rat Plasma: Effects of Sulfite Exposure

A noticeable effect of sulfite treatment was observed on the plasma ceruloplasmin ferroxidase activity of rats with normal sulfite oxidase activity when compared to normal controls. The plasma levels of selenium, iron, and zinc were unaffected by sulfite in normal and sulfite oxidase (SOX)-deficient rats. While plasma level of Mn was decreasing, plasma Cu level increased in SOX-deficient rats. Treating SOX-deficient groups with sulfite did not alter plasma level of Mn but made plasma level of Cu back to its normal level. This is the first evidence that Cu and Mn status were affected in experimental sulfite oxidase deficiency induced by low molybdenum diet with tungsten addition deserving further research to determine the underlying mechanisms of these observations in experimental sulfite oxidase deficiency.     

Effect of 2,3,7,8-Tetrachlorodibenzo-p-dioxin on the Hepatic Distribution of Iron,Copper, Zinc,and Magnesium in Rats

The distribution of iron, copper, zinc, and magnesium in hepatic subcellular fractions of male and female rats treated with 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) was determined. Animals received 40 μg TCDD per kilogram per day for three days by mouth (PO) or the vehicle and were killed seven or nine days posttreatment. Iron, copper, zinc, and magnesium were determined by atomic absorption spectroscopy. The iron content of liver from female animals was twofold higher than male animals. The administration of TCDD increased the iron content of mitochondria in female and male rats and decreased iron content of microsomes of both sexes. Significant increases occurred in the copper content of whole liver, mitochondria, and cytosol of male rats and in whole liver and cytosol of female rats. Decreases in the copper content of the microsomes of male rats were observed following TCDD treatment; however, TCDD produced no changes in the zinc content of hepatic subcellular fractions of either sex. The magnesium content of female TCDD-treated rats increased in whole liver, mitochondria, and cytosol, while the magnesium content of microsomes was not altered. With respect to the subcellular distribution of iron, copper, zinc, and magnesium, TCDD produces differential effects. The altered distribution of some cations may contribute to the broad range of effects of TCDD.     

Effect of low dietary rubidium on plasma biochemical parameters and mineral levels in rats

The effects of low dietary rubidium on plasma biochemical parameters and mineral levels in tissues in rats were studied. Eighteen male Wistar rats, weighing about 40 g, were divided into two groups and fed the diets with or without supplemental rubidium (0.54 vs 8.12 mg/kg diet) for 11 wk. Compared to the rats fed the diet with supplemental rubidium, the animals fed the diet without rubidium supplementation had higher urea nitrogen in plasma; lower rubidium concentration in tissues; lower sodium in muscle; higher potassium in plasma, kidney and tibia, and lower potassium in testis; lower phosphorus in heart and spleen; lower calcium in spleen; higher magnesium in muscle and tibia; higher iron in muscle; lower zinc in plasma and testis; and lower copper in heart, liver, and spleen, and higher copper in kidney. These results suggest that rubidium concentration in tissues reflects rubidium intake, and that rubidium depletion affects mineral (sodium, potassium, phosphorus, calcium, magnesium, iron, zinc, and copper) status.     

Effect of sulfite treatment on total antioxidant capacity, total oxidant status, lipid hydroperoxide, and total free sulfydryl groups contents in normal and sulfite oxidase-deficient rat plasma

Sulfites, which are commonly used as preservatives, are continuously formed in the body during the metabolism of sulfur-containing amino acids. Sulfite oxidase (SOX) is an essential enzyme in the pathway of the oxidative degradation of sulfite to sulfate protecting cells from sulfite toxicity. This article investigated the effect of sulfite on total antioxidant capacity (TAC), total oxidant status, lipid hydroperoxide (LOOH), and total free sulfydryl groups (-SH) levels in normal and SOX-deficient male albino rat plasma. For this purpose, rats were divided into four groups: control, sulfite-treated, SOX-deficient, and sulfite-treated SOX-deficient groups. SOX deficiency was established by feeding rats a low molybdenum diet and adding to their drinking water 200 ppm tungsten. Sulfite (70 mg/kg) was administered to the animals via their drinking water. SOX deficiency together with sulfite treatment caused a significant increase in the plasma LOOH and total oxidant status levels. -SH content of rat plasma significantly decreased by both sulfite treatment and SOX deficiency compared to the control. There was also a significant decrease in plasma TAC level by sulfite treatment. In conclusion, sulfite treatment affects the antioxidant/oxidant balance of the plasma cells of the rats toward oxidants in SOX-deficient groups.     

Iron Excess Disturbs Metabolic Status and Relative Gonad Mass in Rats on High Fat, Fructose, and Salt Diets

The aim of this study was to assess the metabolic and physiological changes in rats fed a diet high in fat, fructose, and salt, and with excess iron level. Mineral status was also estimated. Wistar rats were assigned to groups fed either a standard control diet (C) or a diet high in fat, fructose, and salt. The noncontrol diets contained either normal (M) or high level (MFe) of iron. After 6 weeks, the length and weight of the rats were measured, and the animals were euthanized. The kidneys and gonads were collected, and blood samples were taken. Serum levels of insulin, nitric oxide, and iron were measured. The iron, zinc, copper, and calcium concentrations of tissues were determined. It was found that the M diet led to a significant increase in the relative kidney mass of the rats compared with the control group. Among the rats fed the M diet, markedly higher serum level of iron and lower levels of zinc and copper were observed in tissues, while significantly higher calcium levels were found in the gonads. The MFe diet resulted in decreased obesity index, insulin level, and nitric oxide serum concentration in the rats, when compared with both the M and C diets. The high iron level in the modified diet increased the relative mass of the gonads. The excess iron level in the diet disturbed the zinc, copper, and calcium status of tissues. The decrease in insulin and nitric oxide in rats fed the diet high in iron, fat, fructose, and salt was associated with disorders of zinc, copper, and calcium status, as well as with an increase in the relative mass of the gonads.     

Effects of Vitamin E and Selenium on Serum Trace and Major Elements in Horses

The combined effects of vitamin E and selenium were studied in native Anatolian horses subject to strenuous exercise. The concentrations of copper, zinc, iron, calcium, potassium, and magnesium were determined in serum by atomic absorption spectrometry in two study groups (n = 25 each), one of which served as untreated controls. After exercising the horses by running 1,500 m in about 7 min, only the copper level and the copper/zinc ratio significantly increased (p < 0.05), but the concentrations of calcium, potassium, iron, and magnesium remained unchanged. In horses treated with vitamin E and selenium, the calcium and potassium levels decreased to levels lower than those of untreated controls before and after exercise. The iron levels were not changed by exercise or treatment alone but increased when the horses had been supplemented and exercised. The copper level and the copper/zinc ration increased as a result of exercise in both treated and untreated horses. These changes suggest that supplementation with vitamin E and selenium had an important effect on the serum concentrations of calcium, potassium, copper, iron, and the copper/zinc ratio.     

Developmental changes of selected minerals in Zucker rats

Effects of obesity and age on copper, iron, zinc, sodium, potassium, and protein were compared in liver, kidney, brain, and muscle of obese (fa/fa) and nonobese (non-fa/fa) male Zucker rats. Blood plasma cerulopasmin, copper, zinc, sodium, and potassium were also determined. Mean brain weight of fa/fa rats was less than that of non-fa/fa rats at 12 weeks of age; mean brain protein concentration was greater in fa/fa than in non-fa/fa at 5 and 12 weeks of age. At 18-19 days of age, mean sodium concentration (mg/g protein) in liver of fa/fa was less than that of non-fa/fa. At 5 weeks of age, mean copper concentration (microgram/g protein) in kidney was greater in fa/fa. Mean total copper, iron, zinc, sodium, and potassium in liver and kidney were greater in fa/fa than in non-fa/fa at 5 weeks because of the larger livers and kidneys of fa/fa. Mean concentrations of copper, zinc, sodium, and potassium per gram of brain protein were slightly (6-10%) less in fa/fa than in non-fa/fa at 5 weeks. By 12 weeks, mean concentrations of copper in liver, kidney, (tibialis) muscle, and blood plasma, ceruloplasmin in blood plasma, zinc in liver and muscle, iron in muscle, and sodium in liver were greater in fa/fa than in non-fa/fa. However, total amount of each mineral in muscle at 12 weeks was less in fa/fa than in non-fa/fa because of the smaller mean muscle weight of fa/fa. Mean concentrations of copper and zinc in brain and of iron in liver and brain were less in fa/fa than in non-fa/fa at 12 weeks. The major age-related changes in fa/fa that were not observed in non-fa/fa were large increases in liver and kidney copper between 5 and 12 weeks of age. It seems that the abnormal mineral metabolism is a consequence of the obesity, but the mechanisms are not identified.     

Copper accumulation in the soluble and particulate fractions of renal cortex in the streptozotocin-diabetic rat

The accumulation and subcellular distribution of copper in the kidney of streptozotocin-diabetic rats were investigated. Male Sprague-Dawley rats received streptozotocin (50 mg/kg body wt on two consecutive days) intraperitoneally and were fed either commercial or purified diet. The concentrations of copper, zinc, iron, and manganese present in intact kidney, renal cortex, and renal medulla were compared at various times. Chow-fed diabetic rats had a renal copper concentration 2.6 times greater than age-matched controls after 2 weeks. The concentration of zinc was only 30% higher in diabetic kidney than in control tissue, whereas the iron and manganese concentrations were similar for both groups. The additional complement of renal copper was localized entirely in the cortex and was significantly reduced by oral treatment with penicillamine, a copper chelating agent. When diabetic rats were fed purified diet (15-20 ppm Cu), the quantity of copper accumulated in the renal cortex increased from 2.3 to 8.7-fold higher than in control tissue from 1 to 4 weeks, respectively, after injection with streptozotocin. Copper levels in. both the soluble and particulate (165, 000g pellet) fractions of diabetic renal cortex were similarly increased at each time. Gel filtration Chromatographic analysis of the cytosol showed that all of the copper accumulated in the soluble fraction was associated with metallothionein. The distribution of excess copper in the particulate fraction was determined by differential centrifugation. The additional quantity of metal was localized in the crude nuclear fraction of renal cortex in the diabetic rat. Further analysis revealed that the lysosomal fraction from 3-weeek diabetic rats had a copper level 16-fold higher than in the controls. The possibility that accumulation of excessive levels of copper in the streptozotocin-diabetic kidney may contribute to the development of diabetic nephropathy is discussed.     

Distribution patterns of trace metals and of lipid peroxidation in plasma and erythrocytes of rat exposed to aluminum

Significant decreases of the hematocrit, hemoglobin, and plasma iron levels were observed in rats receiving daily intraperitoneal injections of aluminum at a dose of 27 mg Al/kg body wt for 3 wk, as compared to untreated controls. The activity of alkaline phosphatase was also significantly lower in the treated animals as a result of the accumulation of aluminum in the liver (p<0.05). Following aluminum administration, the plasma concentrations of aluminum and copper were also significantly increased, whereas the plasma zinc levels and oxidative stress measured through thiobarbituric acid reaction products showed nonsignificant differences between the two groups (p>0.05). The erythrocyte concentrations of aluminum, copper, zinc, and iron and of superoxide dismutase activity were found to be significantly higher in the study group as compared to controls. The treated animals also showed evidence of higher oxidative stress in comparison to controls. These results suggest that erythrocyte aluminum accumulation could result in abnormal trace element homeostasis and increasing oxidative stress, which might be a mechanism of aluminum-induced anemia.     

The influence of dietary iron on zinc in rat

The purpose of this study was to clarify the influence of iron on zinc status. The animals were divided into four groups, consisting of five rats in each group. The control group was fed on basal diet with adequate levels of zinc and iron, whereas the experimental group was fed diets containing different levels of iron ad libitum for 15 d. Low levels of iron (LFe) significantly increased the zinc absorption percentage but there was a decrease in high (HFe) and very high iron (VHFe) level groups (p<0.001). The retention percentage changes were found to be parallel to the changes in the absorption percentage curve. It was found that zinc (per total dry tissue) and Zn-65 (per total tissue) increased in the rats fed the LFe, whereas in general they decreased in the rats fed the HFe and VHFe diets. Significant changes were found in the duodenum and liver. Zn-65 (per g wet tissue) significantly increased in the brain and liver in the LFe group, but there was a decrease in the duodenum, ileum, kidney, liver, and brain in the HFe and VHFe groups. Changes in the level of zinc (per g dried tissue) were found to be parallel to the changes in Zn-65 in all the groups. The dietary proportions of iron appear to influence zinc metabolism at the intestinal and cellular transport levels over a given period of time.     

Silicon metabolism

The influence of silicon treatment on the levels of trace elements zinc (Zn), copper (Cu), and iron (Fe) in serum and tissues was studied in rats. The concentrations of silicon, iron, and zinc were estimated in samples of sera and tissues of rats receivingper os a soluble, inorganic silicon compound—sodium metasilicate nonahydrate (Na₂SiO₃·9H₂O), dissolved in the drinking water. An increase of copper concentrations in liver and aortic walls in the experimental group was observed, with simultaneous reduction of zinc amounts in serum and all the tissue samples in the course of the experiment. The iron concentrations in the analyzed samples did not show any significant changes between both groups. The silicon levels in serum and in all the examined tissues were significantly higher in the tested group. The results provide evidence for the silicon interaction with copper and zinc, which could result in a number of metabolic process modifications, antiatheromatous activity among them.     

Lipid Peroxidation and Changes of Trace Elements in Mice Treated with Paradichlorobenzene

Paradichlorobenzene (pDCB) has been used as a space deodorant and moth repellant, as well as an intermediate in the chemical industry. Given its broad applications and high volatility, considerable concern exists regarding the adverse health effects of pDCB in the home and the workplace. In this study, changes in lipid peroxidation, antioxidants, and trace element levels in the liver and kidney of pDCB-treated mice were investigated to determine their roles in toxicity. Mice were orally gavaged once daily for seven consecutive days with pDCB (0 (corn oil control), 450, and 900 mg/kg). The level of malondialdehyde (MDA), an end product of lipid peroxidation, markedly increased in the high-dose pDCB group in both the liver and kidney compared with the control group. Changes in hepatic levels of reduced glutathione (GSH) in the pDCB groups were indistinguishable from the control group, while renal levels of reduced GSH in the high-dose pDCB group were significantly lowered in comparison to the control and the low-dose groups. Superoxide dismutase (SOD) activity in the liver of mice treated with pDCB showed a downward trend, whereas there was no consistent trend associated with changes in SOD activity in the kidney. Additionally, renal iron levels in the high-dose pDCB group were significantly decreased compared with the low-dose group and the controls, whereas hepatic iron content in the low-dose pDCB group was significantly lower compared with the controls. Selenium and zinc levels in the kidney were both significantly decreased in the high-dose pDCB group vs. the control and low-dose groups. There were no treatment-induced changes in copper levels in either the kidney or liver. However, a significant increase was found in the liver zinc/copper ratio in the high-dose pDCB group vs. the controls. In addition, blood zinc levels showed a downward trend with increased pDCB dosage. These results suggest that pDCB toxicity is mediated by oxidative damage and tissue-specific alterations in trace element levels both in the liver and the kidney of mice.     

Effects of α-tocopherol on serum trace and major elements in rats with bleomycin-induced pulmonary fibrosis

The study was undertaken to investigate the influence of α-tocopherol on zinc, copper, iron, calcium, magnesium, and potassium concentrations in serum of rats with bleomycin-induced pulmonary fibrosis. Fourteen Wistar albino rats were randomly divided into two groups of seven animals each. The first group was treated intratracheally with bleomycin hydrochloride (BM group); the second group was also instilled with BM but received injections of α-tocopherol twice a week (BM+E group). The third group was treated in the same manner with saline solution only, acting as controls (C). The zinc concentrations of the BM and BM+E groups were significantly decreased compared to the controls (p<0.05). The iron concentration of the controls was significantly higher than the other two groups. The magnesium concentration in the controls and the BM+E group was significantly higher than that of the BM group. The serum copper, calcium, and potassium concentrations were not found to be statistically different among the three groups. Distinct histopathologic changes were found in the BM group compared to the untreated rats. Less severe fibrotic lesions were also observed in the BM+E group. The results of this study show that lungs of rats treated with bleomycin were seriously damaged and that vitamin E seemed to counteract some of the damage, as indicated by differences in the serum concentrations of major elements.     

Teratogenesis and low copper status resulting from triethylenetetramine in rats

The teratogenicity of triethylenetetramine (TETA) was studied using the Sprague-Dawley rat. TETA was fed during pregnancy at levels of 0 (control), 0.17, 0.83, or 1.66% in a complete purified diet. The frequency of resorptions and the frequency of abnormal fetuses at term increased with increasing levels of the drug. Maternal and fetal tissue copper levels were significantly lower in the TETA groups than in controls, with levels decreasing in a dose-related manner. Maternal kidney and fetal liver zinc levels increased within the TETA groups in a dose-related manner. Maternal liver iron was increased in the high-dose group compared to controls. Fetal iron concentration and maternal and fetal manganese level were not significantly affected by the drug. These results show that TETA can be a teratogenic agent. Furthermore, the results suggest that the teratogenicity of the drug may be due in part to induction of copper deficiency, and perhaps through induction of zinc toxicity.     

Zinc Supplementation Attenuates Metallothionein and Oxidative Stress Changes in Kidney of Streptozotocin-Induced Diabetic Rats

Zinc is an element that under physiological conditions preferentially binds to and is a potent inducer of metallothionein under physiological conditions. The present study was conducted to explore whether zinc supplementation morphologically and biochemically protects against diabetic nephropathy through modulation of kidney metallothionein induction and oxidative stress in streptozotocin-induced diabetic rats. Thirty-two Wistar albino male rats were equally divided into four groups. The first group was used as untreated controls and the second group was supplemented with 30?mg/kg/day zinc as zinc sulfate. The third group was treated with streptozotocin to induce diabetes and the fourth group was treated with streptozotocin and supplemented with zinc as described for group 2. The blood glucose and micro-albuminuria levels, body and kidney weights were measured during the 42-day experimental period. At the end of the experiment, the kidneys were removed from all animals from the four groups. Diabetes resulted in degenerative kidney morphological changes. The metallothionein immunoreactivity level was lower and the kidney lipid peroxidation levels were higher in the diabetes group than in the controls. The metallothionein immunoreactivity levels were higher in the tubules of the zinc-supplemented diabetic rats as compared to the non-supplemented diabetic group. The zinc and metallothionein concentrations in kidney tissue were higher in the supplemented diabetic group compared to the non-supplemented diabetes group. The activity of glutathione peroxidase did not change in any of the four groups. In conclusion, the present study shows that zinc has a protective effect against diabetic damage of kidney tissue through stimulation of metallothionein synthesis and regulation of the oxidative stress.