Zinc protection against cadmium-induced infertility in female rats. Effect of zinc and cadmium on the progesterone production of cultured granulosa cells

Adult female rats were treated subcutaneously (sc) with zinc chloride (ZnCl, 10 or 20 mg kg body weight, bw) four times during two ovarian cycles. The third injection was accompanied by cadmium chloride (CdCl) administration sc (2.5, 5 and 10 mg kg bw). The fourth zinc (Zn) treatment was followed by mating.ZnCl (20 mg kg) itself impaired fertility by 20%, while CdCl dose-dependently blocked the receptivity of female rats. In combination with 2.5 and 5 mg kg CdCl the metal salts decreased fertility in an additive fashion, whereas at the highest CdCl dose (10 mg kg) a marked ameliorating effect of ZnCl (10 and 20 mg kg) on cadmium (Cd)-caused sterility was observed.In the pregnant animals apart from the higher Cd-induced blood progesterone levels and reduced body weight gain of dams, no significant treatment-related maternal and fetal effects could be observed. ZnCl (10 to 80 m) and CdCl (10 to 80 m) were added to the culture medium of ovarian granulosa cells. CdCl suppressed follicle-stimulating-hormone- (FSH-) and cAMP-stimulated progesterone accumulation. No protective effect of Zn against Cd-induced drop in progesterone production could be seen, while Zn by itself induced a significant increase in FSH-supported progesterone synthesis.In conclusion, while Zn protected against Cd-induced sterility in vivo, it failed to counteract the direct effect of Cd on steroid biosynthesis. The data indicate that Zn protection does not take place at the level of ovary. Moreover, Zn and Cd seem to affect FSH-stimulated progesterone production by different mechanisms.     

Dithiocarbamates and prevention of cadmium teratogenesis in the hamster

Certain dithiocarbamates (DTC) have been reported to protect against cadmium (Cd)-induced lethality and to decrease Cd body burden. The present study evaluated the influence of sodium N-benzyl-D-glucamine dithiocarbamate, sodium N-di(hydroxyethyl)amine dithiocarbamate, sodium 4-carboxyamidopiperidine-N-dithiocarbamate, and sodium N-methyl-D-glucamine dithiocarbamate on Cd-induced teratogenesis in the hamster. When given as a single ip injection at 2.2 mmol/kg 15 min prior to iv CdCl2 (2 mg/kg), all of the DTC afforded significant protection against Cd-induced developmental toxicity and reduced kidney [Cd] in the dam. Maternal liver [Cd] was reduced with the glucamine and dihydroxyethyl amine analogs, but treatment with the piperidine failed to influence hepatic [Cd]. Pretreatment of the dams with DTC 24 hr prior to Cd challenge failed to protect against Cd-induced embryotoxicity, and provided minimal, if any, reduction in renal or hepatic [Cd]. Pretreatment with the N-methyl-D-glucamine congener 24 hr prior to Cd exposure increased embryolethality. The dose-time relationships found here suggest that pharmacologically effective levels of these DTC decline within 24 hr of treatment and that induction of metallothionein does not play a major role in DTC antagonism of Cd poisoning.     

Testicular toxicity induced by dietary cadmium is associated with decreased testicular zinc and increased hepatic and renal metallothionein and zinc in the bank vole <Emphasis Type="Italic">(Clethrionomys glareolus)</Emphasis>

Mechanism of testicular toxicity induced by dietary cadmium (Cd) has been less investigated than that following acute Cd injection. In the present study we characterized testicular injury in a small rodent, the bank vole, exposed subchronically to dietary Cd in a quantity of 0.9 mol/g, and determined the importance of some factors (Cd accumulation, metallothionein (MT), oxidative stress, and zinc (Zn)) in the injury. Dietary Cd induced moderate histopathological changes (hemorrhage in interstitium, necrosis and apoptosis in seminiferous tubule epithelium) in young (1 month old) bank voles fed, for 6 weeks, Fe-adequate (1.1–1.4 mol/g) and Fe-enriched (4.5–4.8 mol/g) diets. In contrast, adult (5 months old) bank voles appeared to be resistant to the toxic effects of dietary Cd, despite the fact that testicular Cd contents were higher and MT levels lower than those in the young animals. The Cd-induced histopathological changes and apoptosis were accompanied by increased testicular lipid peroxidation, decreased testicular Zn concentration and elevated levels of hepatic and renal MT and Zn. Supplemental dietary Zn (1.7–1.8 mol/g) prevented the Cd-induced testicular Zn depletion and injury. The data indicate that dietary Cd produces testicular lesions indirectly, through decreasing testicular Zn, which seems to be due to the sequestration of this element by the Cd-induced hepatic and renal MT.     

Hepatoprotective Potentials of Onion and Garlic Extracts on Cadmium-Induced Oxidative Damage in Rats

The hepatoprotective effect of onion and garlic extracts on cadmium (Cd)-induced oxidative damage in rats is reported. Control group received double-distilled water alone. Cd group was challenged with 3CdSO₄·8H₂O (as Cd; 1.5 mg/kg bw per day per oral) alone, while extract-treated groups were pretreated with varied doses of onion and/or garlic extract (0.5 and 1.0 ml/100 g bw per day per oral) for a week and thereafter co-treated with Cd (1.5 mg/kg bw per day per oral) for 3 weeks. Cd caused a marked (p?<?0.001) increase in the levels of lipid peroxidation and glutathione S-transferase, whereas glutathione, superoxide dismutase, and catalase levels were decreased in the liver. We also observed a decrease in hepatic activities of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase and a concomitant increase in the plasma activities of ALT and AST. Onion and garlic extracts significantly attenuated these adverse effects of Cd. Onion extract proffered a dose-dependent hepatoprotection. Our study showed that Cd-induced oxidative damage in rat liver is amenable to attenuation by high dose of onion and moderate dose of garlic extracts possibly via reduced lipid peroxidation and enhanced antioxidant defense system that is insufficient to prevent and protect Cd-induced hepatotoxicity.     

Cadmium-dependent generation of reactive oxygen species and mitochondrial DNA breaks in photosynthetic and non-photosynthetic strains of Euglena gracilis

The photosynthetic strain Z of Euglena gracilis is more susceptible to cadmium chloride (Cd) than the non-photosynthetic strain SMZ. We investigated the correlation of intracellular reactive oxygen species (ROS) levels with Cd-induced cellular damage. Flow cytometry with dihydrorhodamine 123 showed that strain Z generated higher levels of ROS, probably H(2)O(2) and/or ONOO(-), than strain SMZ, and that this difference between the two strains became more pronounced with increasing Cd dose. The levels of ROS increased at cytotoxic concentrations of Cd, at over 10 microM Cd for Z and 50 microM Cd for SMZ. These results show an association of Cd cytotoxicity with ROS generation. Considering that strain SMZ is non-photosynthetic, the higher levels of ROS in strain Z might be due to blockage of photosynthetic electron flow by Cd. Using terminal deoxyribonucleotidyl transferase-mediated dUTP nick end-labeling analysis in combination with 4',6-diamidino-2-phenylindole, dihydrochloride staining, we observed DNA breaks in the mitochondria of both strains after Cd exposure. The results suggest that the mitochondrion is the primary target organelle of Cd in E. gracilis cells.     

Conversion of Lesquerolic Acid to 14-Oxo-11(<Emphasis Type="Italic">Z</Emphasis>)-Eicosenoic Acid by Genetically Variable <Emphasis Type="Italic">Sphingobacterium multivorum</Emphasis> Strains

This study focuses on the isolation and characterization of a high cadmium (Cd)-resistant bacterial strain, and possible exploitation of its Cd-accumulation and Cd-induced siderophore production property to improve plant growth in cadmium-contaminated soil through root colonization. The bacterial strain could tolerate up to 8 mM of Cd and could accumulate Cd intracellularly. The strain showed Cd-induced siderophore production maximally at 1.75 mM of Cd concentration under culture condition. It stimulated the growth of mustard and pumpkin plants in Cd-added soil through its establishment in rhizosphere. Through biochemical characterization and 16S rDNA sequence analysis, the strain KUCd1, as the name given to it, was identified as a strain of Pseudomonas aeruginosa.     

Cadmium-induced elevation of hepatic isometallothionein concentrations in inbred strains of mice

Susceptibility to Cd toxicity differs among inbred strains of mice. For example, C3H/He mice are sensitive to Cd-induced hepatotoxicity while DBA/2 mice are resistant. Metallothionein (MT), which in rodents exists predominantly as two isoproteins (MT-I and MT-II), is an important endogenous protein in the detoxication of Cd. The present investigation examines the possibility that strain-dependent susceptibility to Cd-induced liver injury is mediated by an inherited inability to accumulate a specific isoform of MT in response to Cd exposure. Hepatic concentrations of MT-I and MT-II were measured in C3H/He (Cd-sensitive) and DBA/2 (Cd-resistant) mice at various times after the administration of non-toxic (2.5 mumol Cd/kg) to hepatototoxic (80 mumol Cd/kg) dosages of Cd. The concentration of MT-I and MT-II in these strains was similar 24 h after injection of non-hepatotoxic dosages of Cd (10 mumol Cd/kg or less) as well as 6-12 h after a mildly hepatotoxic dose of Cd (20 mumol Cd/kg). The concentration of total MT in liver of Cd-sensitive mice was greater than that present in resistant mice 24-72 h after 20 mumol Cd/kg injection. The data indicates that susceptibility to Cd-induced hepatotoxicity observed in C3H/He mice is not due to a deficit in the induction of a particular isoform of MT.     

Morin mitigates cadmium-induced testicular impairment by stimulating testosterone secretion and germ cell proliferation in mice

Cadmium (Cd) is one of the heavy metal pollutants present in the environment due to human intervention. It is well known that Cd causes toxicological effects on various organs, including the testes. Morin hydrate is a plant-derived bioflavonoid with antioxidant, anti-inflammatory, and anti-stress properties. Thus, the question can be raised as to whether Morin has an effect on Cd-intoxication-induced testicular impairment. Therefore, the aim of this study was to investigate the role of Morin on Cd-mediated disruption of testicular activity. Mice were divided into three groups: group 1 served as the control group, group 2 was given Cd (10 mg/kg) orally for 35 days, and group 3 was given Cd and Morin hydrate (100 mg/kg) for 35 days. To validate the in vivo findings, an in vitro study on testicular explants was also performed. The results of the in vivo study showed that Cd-intoxicated mice had testicular disorganization, reduced circulating testosterone levels, decreased sperm density, and elevated oxidative stress and sperm abnormality. The expression of the germ cell proliferation marker, germ cell nuclear acidic protein (GCNA), and adipocytokine visfatin were also downregulated. It was observed that Morin hydrate upregulated testicular visfatin and GCNA expression in Cd-intoxicated mice, along with improvement in circulating testosterone, testicular histology, and sperm parameters. Furthermore, the in vitro study showed that Cd-mediated downregulation of testicular visfatin and GCNA expression, along with the suppressed secretion of testosterone from testicular explants, was normalized by Morin treatment, whereas visfatin expression was not. Overall, these data indicate that environmental cadmium exposure impairs testicular activity through downregulation of visfatin and GCNA expression, and Morin might play a protective role against Cd-induced testicular toxicity.     

Role of beta-carotene in ameliorating the cadmium-induced oxidative stress in rat brain and testis

The role of oxidative stress in chronic cadmium (Cd) toxicity and its prevention by cotreatment with beta-carotene was investigated. Adult male rats were intragastrically administered 2 mg CdCl2/kg body weight three times a week intragastrically for 3 and 6 weeks. Brain and testicular thiobarbituric acid reactive substances (TBARS) was elevated after 3 and 6 weeks of Cd administration, indicating increased lipid peroxidation (LPO) and oxidative stress. Cellular damage was indicated by inhibition of adenosine triphosphatase (ATPase) activity and increased lactate dehydrogenase (LDH) activity in brain and testicular tissues. Chronic Cd administration resulted in a decline in glutathione (GSH) content and a decrease of superoxide dismutase (SOD) and glutathione S-transferase (GST) activity in both organs. Administration of beta-carotene (250 IU/kg i.g.) concurrent with Cd ameliorated Cd-induced LPO. The brain and testicular antioxidants, SOD, GST, and GSH, decreased by Cd alone, were restored by beta-carotene cotreatment. Concurrent treatment with beta-carotene also ameliorated the decrease in ATPase activity and the increase in LDH activity in brain and testis of Cd-treated rats, indicating a prophylactic action of beta-carotene on Cd toxicity. Therefore, the results indicate that the nutritional antioxidant beta-carotene ameliorated oxidative stress and the loss of cellular antioxidants and suggest that beta-carotene may control Cd-induced brain and testicular toxicity.     

Involvement of testicular DAAM1 expression in zinc protection against cadmium‐induced male rat reproductive toxicity

In order to verify the effects of exposure to Cd and Zn on testicular DAAM1 gene and protein expression and also to ascertain their involvement in the protective role of Zn in prevent the testicular toxicity Cd‐induced in male offspring rats at adult age after gestational and lactational exposure, male offspring rats, from mothers receiving either tap water, Cd, Zn, or Cd + Zn during gestation and lactation periods, were scarified on postnatal days (PND) 70. The reproductive organ (testis, epididymis, and vesicle seminal) were collected, weighed, and analyzed. The results showed that exposure to Cd in utero and through lactation decreased the relative reproductive organ weight, altered the testicular histology at the interstitial and tubular levels, and causing a significant reduction in the daily sperm production (DSP) per testis and per gram of testis, and other then altering the epididymal sperm quality. Furthermore, both mRNA and protein expression of rat testicular DAAM1 were also inhibited in Cd‐treated group. Zn supply has completely corrected the most of these toxic effects. Our results imply that Zn could prevent Cd‐induced testicular toxicity and sperm quality alteration in adult male rat after gestational and lactational exposure, probably via the restoration of the testicular DAAM1 expression inhibited by Cd.     

镉中毒大鼠睾丸与肝脏金属硫蛋白表达的时相研究

啮齿目动物睾丸对镉毒性较肝脏更敏感.为阐明睾丸的镉毒性分子机制,比较了肝脏与睾丸金属硫蛋白（MT）表达的时相变化.mRNA采用RT-PCR技术分析并用光密度扫描定量;蛋白质定量用ELISA方法.结果显示,睾丸中存在MT,镉中毒后MT1与MT2 mRNA明显升高,但MT没有相应增加;肝脏镉中毒后MTmRNA与MT均明显升高.结果提示：镉虽然能诱导睾丸MTmRNA的转录,但没有促进其MT的合成,这可能是睾丸对镉毒性与致癌作用较肝脏更敏感的重要原因.     

Reversal of Cadmium-Induced Thyroid Dysfunction by Selenium, Zinc, or Their Combination in Rat

The aim of this study was to evaluate the potential benefit of combined treatment with zinc (Zn) and selenium (Se) in reversing cadmium (Cd)-induced thyroid dysfunction compared to Se or Zn treatment alone in rats exposed to Cd. For this purpose, 30 adult male Wistar albino rats were equally divided into control and four treated groups receiving either 200 ppm Cd (as CdCl2), 200 ppm Cd + 500 ppm Zn (as ZnCl2), 200 ppm Cd + 0.1 ppm Se (as Na2SeO3), or 200 ppm Cd + 500 ppm Zn + 0.1 ppm Se in their drinking water for 35 days. The results showed that Cd exposure increased significantly the relative thyroid weight (RTW), the thyroid Cd concentration, and the serum thyroid stimulating hormone (TSH) level, whereas the serum thyroxine (T4) level was decreased compared to control rats. The treatment of Cd-exposed rats with Se alone only partially protected from the Cd-induced decrease in serum T4 level. The treatment of Cd-exposed animals with Zn alone partially protected against Cd-induced thyroid dysfunction by maintaining normal RTW and by decreasing Cd concentration in the thyroid. It also partially prevents Cd-induced decrease in serum T4 level. The combined treatment of Cd-exposed animals with Se and Zn induced a more significant decrease in the thyroid Cd concentration than the Zn supplement and a total correction of the RTW. This treatment was also more effective than that with Se or Zn alone in reversing Cd-induced decrease in serum T4 level and Cd-induced increase in serum TSH level. Se and Zn can have a synergistic role against Cd-induced thyroid dysfunction.     

Onion and garlic extracts lessen cadmium-induced nephrotoxicity in rats

Cadmium (Cd) is a well-known nephrotoxicant inducing kidney damage via oxidative stress. Since kidney is the critical target organ of Cd toxicity, this study was designed to evaluate the protective effects of onion (Allium cepa L.) and garlic (Allium sativum L.) aqueous extracts on Cd-induced renal oxidative stress in male Wistar rats. The control group received double distilled water alone and Cd group was challenged with 3CdSO₄ · 8H₂O (as Cd) (1.5 mg/100 g bw/day per oral) alone. Extract-treated groups were pre-treated with varied doses (0.5 ml and 1.0 ml/100 g bw/day per oral) of onion and/or garlic extract for 1 week after which they were co-treated with Cd (1.5 mg/100 g bw/day per oral) for 3 weeks. The results showed that the levels of renal lipid peroxidation (LPO) and glutathione-S transferase (GST) were significantly (P < 0.001) increased in rats that received Cd alone relative to the control group. More so, the levels of renal glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and Na⁺/K⁺-ATPase were significantly (P < 0.001) decreased in rats that received Cd alone. Treatment of Cd-intoxicated rats with varied doses of onion and/or garlic extract significantly (P < 0.05) restored the alterations in these parameters relative to the group that received Cd alone. While treatment with high dose of onion extract exerted a significant dose-dependent restoration of these parameters, treatment with high dose of garlic elicited a pro-oxidant effect, relative to their respective low dose. Our study suggests that onion and garlic extracts may exert their protective effects via reduction in LPO and enhanced antioxidant defense. These extracts may, therefore, be useful nutritional option in alleviating Cd-induced renal damage.     

Protective Effects of Selenium on Cadmium-Induced Brain Damage in Chickens

Selenium (Se) is an important dietary micronutrient with antioxidative roles. Cadmium (Cd), a ubiquitous environmental pollutant, is known to cause brain lesion in rats and humans. However, little is reported about the deleterious effects of subchronic Cd exposure on the brain of poultry and the protective roles on the brain by Se against Cd. The aim of this study was to investigate the protective effects of Se on Cd-induced brain damage in chickens. One hundred twenty 100-day-old chickens were randomly assigned to four groups and were fed a basal diet, or Se (as 10 mg Na₂SeO₃/kg dry weight of feed), Cd (as 150 mg CdCl₂/kg dry weight of feed), or Cd?+?Se in their basic diets for 60 days. Then, concentrations of Cd and Se, production of nitric oxide (NO), messenger RNA (mRNA) level and activity of inducible NO synthase (iNOS), level of oxidative stress, and histological and ultrastructural changes of the cerebrum and cerebellum were examined. The results showed that Cd exposure significantly increased Cd accumulation, NO production, iNOS activities, iNOS mRNA level, and MDA content in the cerebrum and cerebellum. Cd treatment obviously decreased Se content and antioxidase activities and caused histopathological changes in the cerebrum and cerebellum. Se supplementation during dietary Cd obviously reduced Cd accumulation, NO production, mRNA level and activity of iNOS, oxidative stress, and histopathological damage in the cerebrum and cerebellum of chickens. It indicated that Se ameliorates Cd-induced brain damage in chickens by regulating iNOS-NO system changes, and oxidative stress induced by Cd and Se can serve as a potential therapeutic for Cd-induced brain lesion of chickens.     

Cadmium,iron and zinc interaction and hematological parameters in rat dams and their offspring

The effects of cadmium (Cd) were evaluated in offspring exposed from birth until weaning (neonatal day 0–21) and 4 weeks after exposure cessation focusing on iron (Fe) and zinc (Zn) levels in organs and hematological parameters. Wistar female rats were administered 50 mg Cd/L in drinking water (Cd-exposed) for 4 weeks before mating and during 3 weeks of gestation plus 3 weeks of lactation. Controls were supplied drinking water. At birth, part of Cd-exposed dams’ litters was cross-fostered to control dams (CCd group) and their control litters were cross-fostered to Cd-exposed dams (CdC group). This procedure enabled to discern the effects of gestational, lactational and gestational plus lactational Cd exposure until weaning in F₁ offspring. Elements were analyzed by atomic absorption spectrometry; hematological parameters manually; and histopathological changes by light microscopy. Gestational plus lactational exposure in Cd-exposed dams and their offspring increased Cd and decreased Fe levels, increased Zn in dams and decreased Zn and body weights in 11- and 21-day pups. In 21-day weanling pups, decreased red blood cell (RBC) count, hemoglobin and hematocrit values and increased reticulocytes in peripheral blood were also found with concomitant histopathological finding of extramedullary hematopoiesis in the liver. In cross-fostered pups with gestational exposure (CCd pups), Fe in the liver decreased on day 11 and Zn increased in the kidney on day 21 whereas in pups with lactational exposure (CdC pups) Zn in the brain decreased on day 11 and Fe decreased in the liver and brain on day 21. Regardless of exposure cessation at weaning, in offspring with gestational plus lactational exposure (Cd-exposed) body weights, kidney and brain Fe levels and RBC and hemoglobin remained decreased in blood until puberty. Furthermore Zn levels increased in the liver, kidney and brain. It was concluded that gestational plus lactational Cd exposure caused decreases in Fe and Zn levels and hematotoxic effects in F₁ offspring more pronouncedly than exposure during either gestational or lactational period alone and the adverse effects of maternally mediated Cd exposure continued after exposure cessation into adulthood.     

MAPK and mTOR pathways are involved in cadmium-induced neuronal apoptosis

Cadmium (Cd) may be accumulated in human body through long-term exposure to Cd-polluted environment, resulting in neurodegeneration and other diseases. To study the mechanism of Cd-induced neurodegeneration, PC12 and SH-SY5Y cells were exposed to Cd. We observed that Cd-induced apoptosis in the cells in a time- and concentration-dependent manner. Cd rapidly activated the mitogen-activated protein kinases (MAPK) including extracellular signal-regulated kinase 1/2 (Erk1/2), c -Jun N-terminal kinase (JNK) and p38. Inhibition of Erk1/2 and JNK, but not p38, partially protected the cells from Cd-induced apoptosis. Consistently, over-expression of dominant negative c- Jun or down-regulation of Erk1/2, but not p38 MAPK, partially prevented Cd-induced apoptosis. To our surprise, Cd also activated mammalian target of rapamycin (mTOR)-mediated signaling pathways. Treatment with rapamycin, an mTOR inhibitor, blocked Cd-induced phosphorylation of S6K1 and eukaryotic initiation factor 4E binding protein 1, and markedly inhibited Cd-induced apoptosis. Down-regulation of mTOR by RNA interference also in part, rescued cells from Cd-induced death. These findings indicate that activation of the signaling network of MAPK and mTOR is associated with Cd-induced neuronal apoptosis. Our results strongly suggest that inhibitors of MAPK and mTOR may have a potential for prevention of Cd-induced neurodegeneration.     

Protective effects of vitexin on cadmium-induced renal toxicity in rats

Cadmium (Cd) is an industrial contaminant that poses severe threats to human and animal health. Vitexin (VIT) is a polyphenolic flavonoid of characteristic pharmacological properties. We explored the curative role of vitexin on Cd-induced mitochondrial-dysfunction in rat renal tissues. Twenty-four rats were equally divided into four groups and designated as control, Cd, Cd + vitexin and vitexin treated groups. The results showed that Cd exposure increased urea and creatinine levels while decreased creatinine clearance. Cd reduced the activities of antioxidant enzymes, i.e., catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione content in the Cd exposed group. Cd exposure significantly (p < 0.05) elevated the reactive oxygen species (ROS) and Thiobarbituric acid reactive substances (TBARS) levels in rat kidney. Cd also caused a significant (p < 0.05) reduction in the mitochondrial TCA-cycle enzymes, including isocitrate dehydrogenase, succinate dehydrogenase, alpha-ketoglutarate dehydrogenase, and malate-dehydrogenase activities. Besides, mitochondrial respiratory chain enzymes, including NADH-dehydrogenase, coenzyme Q-cytochrome reductase, succinic-coenzyme Q, and cytochrome c-oxidase activities were also decreased under Cd exposure. Cd exposure also damaged the mitochondrial membrane potential (MMP). However, VIT treatment potentially reduced the detrimental effects of Cd in the kidney of rats. In conclusion, our study indicated that the VIT could attenuate the Cd-induced renal toxicity in rats.     

Histomorphological and ultrastructural cadmium-induced kidney injuries and precancerous lesions in rats and screening for biomarkers

Long-term exposure to cadmium (Cd) can severely damage the kidney, where orally absorbed Cd accumulates. However, the molecular mechanisms of Cd-induced kidney damage, especially the early biomarkers of Cd-induced renal carcinogenesis, are unclear. In the present study, we established a rat kidney injury model by intragastric administration of Cd to evaluate the morphological and biochemical aspects of kidney injury. We randomly divided Sprague-Dawley rats into control, low Cd (3 mg/kg), and high Cd (6 mg/kg) groups and measured biochemical indices associated with renal toxicity after 2, 4, and 8 weeks of treatment. The Cd-exposed mice had significantly higher Cd concentrations in blood and renal tissues as well as blood urea nitrogen (BUN), β2-microglobulin (β2-MG), urinary protein excretion, and tumor necrosis factor-α (TNF-α) levels. Furthermore, histopathological and transmission electron microscopy (TEM) observations revealed structural disruption of renal tubules and glomeruli after 8 weeks of exposure to the high Cd regimen. Besides, microarray technology experiments showed that Cd increased the expression of genes related to the chemical carcinogenesis pathway in kidney tissue. Finally, combining the protein–protein interaction (PPI) network of the Cd carcinogenesis pathway genes with the microarray and Comparative Toxicogenomics Database (CTD) results revealed two overlapping genes, CYP1B1 and UGT2B. Therefore, the combined molecular and bioinformatics experiments’ results suggest that CYP1B1 and UGT2B are biomarkers of Cd-induced kidney injury with precancerous lesions.