Changes of Rat Embryon Nephrogenesis during Cadmium Salt Intoxication in Pregnant Females

The purpose of the experimental study was to determine morphogenetic disorders of embryonic and fetal kidney development in chronic intragastric exposure to cadmium salts (cadmium chloride, cadmium citrate) in pregnant females. Materials and methods. Low doses of cadmium salts were selected for the study, which can be compared with the actual concentration of cadmium in the daily diets of women, including pregnant women, in industrial regions. In the experiment, female rats with a given gestational age were divided into groups as follows: Group 1 – control (number of females – n = 16, of which 8 left the experiment on the 13th day of pregnancy, and 8 on the 20th; the number of embryos – n13 = 76; n20 = 77); Group 2 – administration of cadmium chloride at a dose of 1.0 mg/kg body weight of the female (number of females – n = 16; number of embryos – n13 = 65; n20 = 62); Group 3 – administration of cadmium citrate at a dose of 1.0 mg/kg body weight of the female (number of females – n = 16; number of embryos – n13 = 69; n20 = 70). Results and discussion. New quantitative data on the effect of cadmium salts were obtained on the thickness of the cortical and cerebral layers of the kidneys, the diameter and area of the cavity of the nephron capsule in the prenatal period of development in chronic female intoxication. On the 13th day, the effect of cadmium salts on the development of embryonic kidneys was multidirectional: the effect of cadmium chloride led to an increase in the thickness of the mesonephros and mesonephric duct, and the effect of cadmium citrate reduced the studied parameters. On the 20th day of rat embryogenesis in the group exposed to cadmium chloride, the renal weights increased, and when exposed to cadmium citrate, the weight of the kidneys decreased significantly (p˂0.05) both in comparison with control values and in the group exposed to cadmium chloride. On the 20th day of development, in order to exclude an error in estimating the dynamics of changes in the weight of embryo mass and kidney mass, the nephrofetal index was calculated, i.e. the ratio of wet kidney mass to wet weight of fixed fetus. Histological parameters of nephron diameters were also compared. Conclusion. Cadmium citrate has been shown for the first time to be less non-photoxic than cadmium chloride. Calculation of the area of the cavity of the nephron capsule by the spline contour method showed a 2.6-fold decrease in the average area of the capsule cavity in the group exposed to cadmium chloride relative to the control mean values, indicating a violation of nephrogenesis. When exposed to cadmium citrate, there was also a decrease in the area of the cavity of the nephron capsule by 1.8 times, which indicates a lower level of nephrotoxic cadmium citrate compared to cadmium chloride, despite the identity of the dose of exposure

Putative protective effect of Cadmium chloride highdiluted solution on LLC-PK1 cell intoxicated by high concentration of this same metal: an isopathic in vitro assay.

Cadmium is an important toxic environmental heavy metal. Several studies have demonstrated that a major site of cadmium toxicity in humans and in other animals is the proximal tubule of the kidney. A well established model for nefrotoxicity is the use of in vitro technique with proximal tubule epithelial cell lines, as LLC-PK1. Herein, we have the intention to study the possible protective effect of highdiluted CdCl2 solutions. In a blinding way, LLC-PK1 cells were pre-treated with highdiluted cadmium chloride in the potencies 10 cH, 15 cH and 20cH. After 4 days, these cells have received CdCl2 in a pre-determined toxic concentration. The cell viability was assessed by MTT assay. We have identified a protective effect of two CdCl2 highdiluted solutions, 10 cH and 20 cH, when cells were intoxicated by sublethal CdCl2 concentration. The results indicate that probably the highdilutions have an expressive action on cells in sublethal intoxication.

Signaling Proteins That Regulate Spermatogenesis Are the Emerging Target of Toxicant-Induced Male Reproductive Dysfunction

There is emerging evidence that environmental toxicants, in particular endocrine disrupting chemicals (EDCs) such as cadmium and perfluorooctanesulfonate (PFOS), induce Sertoli cell and testis injury, thereby perturbing spermatogenesis in humans, rodents and also widelife. Recent studies have shown that cadmium (e.g., cadmium chloride, CdCl2) and PFOS exert their disruptive effects through putative signaling proteins and signaling cascade similar to other pharmaceuticals, such as the non-hormonal male contraceptive drug adjudin. More important, these signaling proteins were also shown to be involved in modulating testis function based on studies in rodents. Collectively, these findings suggest that toxicants are using similar mechanisms that used to support spermatogenesis under physiological conditions to perturb Sertoli and testis function. These observations are physiologically significant, since a manipulation on the expression of these signaling proteins can possibly be used to manage the toxicant-induced male reproductive dysfunction. In this review, we highlight some of these findings and critically evaluate the possibility of using this approach to manage toxicant-induced defects in spermatrogenesis based on recent studies in animal models.

Role of microRNAs in response to cadmium chloride in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal and aggressive malignancies with a 5-year survival rate less than 9%. Early detection is particularly difficult due to the lack of symptoms even in advanced stages. microRNAs (miRs/miRNAs) are small (~ 18–24 nucleotides), endogenous, non-coding RNAs, which are involved in the pathogenesis of several malignancies including PDAC. Alterations of miR expressions can lead to apoptosis, angiogenesis, and metastasis. The role of environmental pollutants such as cadmium (Cd) in PDAC has been suggested but not fully understood. This study underlines the role of miRs (miR-221, miR-155, miR-126) in response to cadmium chloride (CdCl2) in vitro. Lethal concentration (LC50) values for CdCl2 resulted in a toxicity series of AsPC-1 > HPNE > BxPC-3 > Panc-1 = Panc-10.5. Following the treatment with CdCl2, miR-221 and miR-155 were significantly overexpressed, whereas miR-126 was downregulated. An increase in epithelial–mesenchymal transition (EMT) via the dysregulation of mesenchymal markers such as Wnt-11, E-cadherin, Snail, and Zeb1 was also observed. Hence, this study has provided evidence to suggest that the environmental pollutant Cd can have a significant role in the development of PDAC, suggesting a significant correlation between miRs and Cd exposure during PDAC progression. Further studies are needed to investigate the precise role of miRs in PDAC progression as well as the role of Cd and other environmental pollutants.

The beneficial effect of a phytonutrient-rich product against cadmium chloride-induced hepatorenal toxicity

This study was designed to investigate the hepatorenal protective effects of trévo, on cadmium-induced renal and hepatic injury in male Wistar rats. Methods. Fifteen healthy male Wistar rats were divided into three groups of five rats per group. Group I (control); group II (35mg/kg cadmium chloride (CdCl2); Group III (2 ml/kg trévo+ CdCl2. The rats were treated with trévo (2ml/kg orally) and administered CdCl2 3 hrs later. Twenty-four hours after the last administration rats were sacrificed and blood was collected via cardiac puncture and processed for hematological parameters and assessment of urea, creatinine (CREA), and uric acid (UA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin (ALB). The liver and kidney were excised and processed for markers of oxidative stress. Results intraperitoneal administration of 35 mg/kg of CdCl2 caused a significant increase in serum concentration of urea, CREA, UA, AST, ALT, while the concentration of ALB was significantly lower (P<0.0001). CdCl2 caused a significant reduction in packed cell volume, hemoglobin while the total white blood cell count, neutrophils, lymphocytes, monocytes, eosinophils, and basophils were increased. Oxidative stress was significantly pronounced in the liver and kidney of rats exposed to CdCl2 as observed in the high concentration of malondialdehyde, decreased concentration of glutathione, the activity of catalase, superoxide dismutase, and glutathione-S-transferase. Pretreatment with trévo was able to significantly prevent the anemic, oxidative damage, renal and hepatic injury initiated by CdCl2. Conclusions. The study reveals that trévo is effective in attenuating cadmium-induced hepatorenal toxicity in male Wistar rats.