Cadmium-treated Rats Research Articles

Gender Differences in the Effects of Cadmium Exposure on Hematological Parameters in Wistar Rats

This study aims to investigate the gender dimorphism in cadmium exposure on hematological parameters in male and female Wistar rats. Twenty Wistar rats (120g-150g) were divided into four groups: male control, male cadmium-treated, female control, and female cadmium-treated. Cadmium chloride (50 mg/kg) was administered orally to the experimental groups for 45 days. Hematological parameters were analyzed using an auto hematological analyzer. Data were statistically evaluated using two-way ANOVA with significance set at p < 0.05. Cadmium exposure significantly increased white blood cell (WBC) counts in male rats compared to controls, with notable decrease in neutrophils and an increase in lymphocytes. Female rats showed significant increase in monocyte and basophil levels. Furthermore, red blood cell (RBC) parameters showed significant reductions in hemoglobin concentration, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) in female cadmium-treated rats. No significant effects were observed on platelet count or distribution width in both male and female rats. The study concluded there are gender-specific hematological alterations due to cadmium exposure in Wistar rats. These findings underscore the need for gender-specific approach in the understanding and amelioration of cadmium toxicity.

Differentially expressed long non-coding RNAs and mRNAs of cadmium exposure on learning disability of offspring rats

BackgroundCadmium (Cd) exposure has been found to have detrimental effects on the development of the central nervous system and cognitive ability in children. However, there is ongoing debate regarding the impact of maternal Cd exposure on the cognitive ability of offspring. In this study, we aimed to investigate the mechanisms underlying the influence of maternal Cd exposure on the cognitive ability of offspring rats.MethodsHere, we constructed a model of cadmium poisoning in first-generation rats through gavage. The cognitive and memory abilities of its offspring were evaluated by water maze experiment. Then, we used the gene chip to find out the key genes, and we performed qRT-PCR detection of these genes. Subsequently, enrichment analysis was employed to identify pathways. Finally, we constructed a co-expression network consisting of LncRNAs and mRNAs to elucidate the biological functions and regulatory mechanisms of LncRNAs.ResultsThe results of the water maze trial demonstrated that the offspring of rats exposed to cadmium in the first generation had reduced cognitive and memory abilities. Through an analysis of gene expression in the hippocampus of the cadmium-treated rats' offspring and the control group, we identified a correlation between the islet secretion pathway and the cognitive impairment observed in the offspring. Utilizing various algorithms, we identified Cpa1 and Prss1 as potential key genes associated with the cognitive impairment caused by cadmium. The results of qRT-PCR demonstrated a decrease in the expression levels of these genes in the hippocampus of the cadmium-treated rats’ offspring. In addition, in the co-expression network, we observed that Cpa1 was co-expressed with 11 LncRNAs, while Prss1 was associated with 4 unexplored LncRNAs. Furthermore, we conducted an analysis to examine the relationship between Cpa1, Prss1-related transcription factors, and LncRNAs.ConclusionOverall, this study provides novel insights into the molecular effects of first generation Cd exposure on the cognitive ability of offspring. The target genes and signaling pathways investigated in this study could serve as potential targets for improving neurodevelopment and cognitive ability in children.

Exposure to Cadmium Alters the Population of Glial Cell Types and Disrupts the Regulatory Mechanisms of the HPG Axis in Prepubertal Female Rats.

Despite the fact that the brain is susceptible to neurotoxicity induced by cadmium (Cd), the effects of Cd on the neuroanatomical development in the hypothalamus and regulatory mechanisms of the hypothalamic-pituitary-gonadal (HPG) axis are not fully understood. To clarify this issue, we investigated the effects of 25mg/kg BW/day cadmium chloride (CdCl2) on neuroanatomical alterations in the hypothalamus of prepubertal female rats. Twenty-four Sprague-Dawley rats were randomly assigned to two groups (n = 12), and CdCl2 was administered via gavage from postnatal days (PND) 21 to PND35. The results of the stereological analysis demonstrated that prepubertal exposure to Cd reduced the number of neurons and oligodendrocytes in the arcuate (ARC) and dorsomedial hypothalamus nucleus (DMH) nuclei. In contrast, Cd exposure increased the number of microglial cells in the ARC and DMH nuclei. Cd exposure decreased the mRNA levels of gonadotropin-releasing hormone (GnRH) and increased the mRNA levels of RFamide-related peptide (RFRP-3), but not kisspeptin (Kiss1) in the hypothalamus. Moreover, hormonal assay showed that Cd exposure caused a reduction in the concentration of gonadotropins: luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in serum. Immunohistochemical expression of RFRP-3 in neuronal cell bodies demonstrated that the mean number of RFRP-3 expressing neurons in the DMH nucleus of cadmium-treated rats was dramatically higher than the vehicle group. Overall, exposure to Cd during the prepubertal period alters the population of neurons and glial cell types in the hypothalamus. Additionally, Cd exposure disrupts the regulatory mechanisms of the HPG axis.

The Effect of Short-Term Exposure to Cadmium on the Expression of Vascular Endothelial Barrier Antigen in the Developing Rat Forebrain and Cerebellum: A Computerized Quantitative Immunofluorescent Study.

Clinical and laboratory studies have shown that environmental exposure to cadmium produces damage to several organs, including bones, lungs, and kidneys. The involvement of cadmium in central nervous system (CNS) disorders has also been widely reported, but the precise pathophysiological mechanism is not yet fully understood. Children who were exposed to cadmium during pregnancy are known to suffer from developmental delays, learning difficulties, attention deficit hyperactivity disorder (ADHD), and other cognitive and neurobehavioral deficits. Results from numerous studies suggest that dysfunction of the blood-brain barrier (BBB) structures is an important step in the neurotoxicity of cadmium. A rat-specific BBB marker protein, the endothelial barrier antigen (EBA), has been previously isolated and classified by Sternberger and others. The mouse IgG1 clone, anti-endothelial barrier antigen (anti-EBA), detects a protein triplet (23.5kDa, 25 kDa, and 30kDa) localized to the luminal surface of central and peripheral nervous system (CNS and PNS) vascular endothelial cells with selective permeability barrier functions. This marker has been widely used for characterizing BBB alterations under demyelinating, inflammatory, and other CNS pathologies. Many studies have been published using the rat model system for studying the neurotoxic effect of acute and chronic exposure to cadmium.We applied the indirect immunofluorescent techniques using the anti-EBA antibody in conjunction with the Olympus cellSens computerized image analysis to detect and quantify the surface areas of BBB-competent microvessel profiles in paraformaldehyde-fixed, paraffin-embedded brains of term-delivered young rats after intraperitoneal injection of a single dose of cadmium chloride. We detected a statistically significant reduction in EBA-positive microvessel surface areas in the forebrain (t = 5.86, df = 1789, p-value < 0.001) and cerebellum (t=73.40, df=1337, p < 0.001) of cadmium-treated rats compared to the normal controls. Thus, this study supports the hypothesis that the EBA is a sensitive and measurable indicator for quantitative assessment of the impact of cadmium exposure in the developing rat brain.

Study the effect of crocin on the expression of PAX2 and WT1 genes in renal tissues and serum levels of NGAL and cystatin C in cadmium-treated rats

Study the effect of crocin on the expression of PAX2 and WT1 genes in renal tissues and serum levels of NGAL and cystatin C in cadmium-treated rats

Protective impacts of gallic acid against cadmium-induced oxidative toxicity in the ovary of rats

This study evaluates the probable effects of induced reproductive toxicity by cadmium and its amelioration by gallic acid (GA). Adult female rats were daily administered with cadmium (CdCl2) (5 mg/kg) singly or combined with GA (20 mg/kg) for 14 days to evaluate the effect on antioxidant status and ovary function using biochemical and histological analysis. Cadmium-treated rats alone revealed a considerable increment in total body weight and ovaries’ weight due to muscle wasting. However, GA + cadmium reversed considerably the tread and offered protection against cadmium-induced muscle wasting. Cadmium treatment alone decreased reduced glutathione (GSH) level, activities of superoxide dismutase (SOD), and catalase (CAT) and also increased malondialdehyde (MDA) level. Besides, the administration of GA alone or in combination mitigated the cadmium-mediated decrease in GSH, SOD, and CAT, respectively. Serum concentrations of estrogen (E), testosterone (T), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were reduced significantly in cadmium-treated rats. Histopathology of the ovaries showed a considerable reduction in follicle number. GA treatment alone and CdCl2 + GA-treatment group decreased cell death of follicular cells in the ovaries of rats and increased serum reproductive hormones. Taken together, gallic acid prevented the deleterious impacts of CdCl2 on the biomarkers of oxidative stress, antioxidant enzymes, and ovarian histopathological structure.

The Effect of Crocin on the Expression of MMP-2 and MMP-9 Genes in the Liver Tissue of Cadmium-Treated Rats: A Short Report

The Effect of Crocin on the Expression of MMP-2 and MMP-9 Genes in the Liver Tissue of Cadmium-Treated Rats: A Short Report

Neuroprotective potentials of Lycopersicon esculentum fruit extract on cadmium-induced toxicity in postnatal developing cerebellum of rats

The neuroprotective potemtials of Lycopersicon esculentum fruit extract on cadmium-induced oxidative stress in postnatal developing cerebellum of rats. Twenty-five pregnant Wistar rats (110-200g) were divided into five groups (n=5) and used for the experiment. Group I served as control and received water, Group II received 0.5mg/kg of Cadmium only, Group III received 50mg/kg aqueous extract of Lycopersicon esculentum only, Group IV received 0.5mg/kg body weight of cadmium+50mg/kg aqueous extract of Lycopersicon esculentum and Group V received 0.5mg/kg of cadmium +200mg/kg of vitamin C, orally from the first day of gestation to postnatal day 21. Lycopersicon esculentum was administered one hour before the administration of cadmium. Neurobehavioural tests was done on the pups of day 21. Then, pups of day 1, 7, 14, 21, and 28 were weighed, sacrificed and their brains dissected out, weighed with the cerebellum preserved for biochemical and histomorphological evaluations. Data were analysed using ANOVA at p &lt; 0.05. Cadmium-treated rats showed significant decreased in body and brain weight, decreased time spent on the forelimb grip, increased negative geotaxis, increased lipid peroxidation (LPO), and decreased glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the developing cerebellum. Histologically, there was persistent external granular layer (EGL), reduced molecular layer (ML) thickness and increased astrocytes population in the cerebellar cortex of cadmium-treated day 21pups. Lycopersicon esculentum extract and vitamin C reversed the behavioural and morphological alterations induced by cadmium toxicity. Cadmium-induced oxidative stress, behavioural deficit and morphological alterations in the postnatal developing cerebellum of rat was ameliorated by Lycopersicon esculentum fruit extracts as such may be a potential neuroprotective agent.&#x0D; Key words: Cadmium - oxidative stress - Lycopersicon esculentum – Neurobehaviour - Developing cerebellar cortex

Effect of crocin on PKHD1 and KLLN genes expression in kidney tissue of female rats treated with cadmium

According to data from studies, antioxidant herbal compounds are, likely to have a useful role in reducing the harmful effects of environmental pollutants and toxic chemicals that most people are exposed to. Cadmium is one of the toxic elements that accumulate in many organs, especially in kidneys. The aim of this study was to investigate the effect of crocin on the expression of PKHD1 and KLLN genes in cadmium-treated rats. In this experimental study, 40 adults male Wistar rats (200-250 g) were randomly divided into the following groups: control group received normal saline, cadmium group (15mg/kg), crocin group (20mg/kg) and cadmium group daily fed with crocin at a dose of 20 mg/kg. After eight weeks of treatment, rats were dissected, and kidney tissues were removed for evaluation of PKHD1 and KLLN gene expression by real time method. The data were analyzed using oneway ANOVA and significant difference between groups was P&lt;0.05. Our results showed an increase in PKHD1 gene expression and a decrease in KLLN gene expression in kidney tissue in the cadmium group compared to the control group (P &lt;0.001). Also, a significant decrease in PKHD1 gene expression (P &lt;0.001) and an increase in KLLN gene expression P &lt;0.05) were observed in the tissues of all cadmium-treated rats compared to cadmium. Crocin consumption can have a protective effect against the impaired expression of PKHD1 and KLLN cadmium-induced apoptotic pathway.

Tangeritin attenuates oxidative stress, apoptosis and inflammation in cadmium-induced cardiotoxicity in rats by activating Nrf2 signaling pathway

Purpose: To determine the effect of tangeritin on cadmium-induced cardiotoxicity in rats.Methods: Cardiotoxicity was induced by intra-gastric administration of 5 mg/kg cadmium chloride to rats, once daily for 4 weeks. The animals were treated with tangeritin at 10 and 20 mg/kg p.o. 60 min before the administration of cadmium, for 4 weeks. Thereafter, the concentrations of cadmium in serum and cardiac tissue were determined, and markers of cardiac function, antioxidant enzyme activities and levels of pro-inflammatory mediators were evaluated in cardiac tissues. Histopathological examination and western blot assay were also performed.Results: Treatment with tangeritin significantly decreased the cadmium levels in the heart tissue and serum of the cadmium-exposed rats, when compared to the negative control group (p < 0.01). There was significant decrease in cardiac function markers in the tangeritin-treated rats, relative to negative control group (p < 0.01). However, antioxidant enzyme activity and levels of pro-inflammatory mediators were attenuated in the cardiac tissues of cadmium-treated rats by tangeritin treatment. Expressions of HO-1 and Nrf-2 were significantly enhanced in the cardiac tissues of tangeritin-treated group, relative to negative control group (p < 0.01). Histopathology revealed that tangeritin attenuated cadmium-induced cardiac injury in cadmium-exposed rats.Conclusion: These results demonstrate the protective effect of tangeritin against cadmium-induced cardiotoxicity via attenuation of oxidative stress and pro-inflammatory mediators.Keywords: Tangeritin, Cadmium, Cardiotoxicity, Oxidative stress, Anti-inflammation

Combined effect of cadmium and noise on rat’s kidney

Introduction: Recently, the consequence of chemical industries and noise on human health is the update subject for researchers. There are many reports published about nephrotoxicity of noise and cadmium alone. Objectives: The main aim of this study was to detect the combined consequence of noise and cadmium on renal function. Materials and Methods: Forty adult male rats were put into eight groups in random order (n=5). Groups 1 control, group 2 exposed to 90 dB (decibels) noise, groups 3- 5 received (intraperitoneal; ip) cadmium chloride (CdCl2) at doses of 1,2,3 mg/kg and group 6-8 pretreated with CdCl2 at doses of 1, 2, and 3 mg/kg 30 minutes before exposing to 90 dB noise. The exercise was repeated for seven consecutive days. Animals were killed 24 hours afterwards. Blood urea nitrogen (BUN) and creatinine (Cr) levels were analyzed. Kidney tissues were excised for measuring malondialdehyde (MDA) and glutathione (GSH) concentrations. Results: There was significant rise on the levels of BUN, Cr and MDA. Additionally, a decrease on the level of GSH in rats that were exposed to noise or cadmium alone or combined to noise and cadmium was detected. Significant elevation of BUN, Cr, MDA and depletion of GSH were also noted in cadmium-treated rats compared to those in the animals co-exposed to cadmium and noise. Conclusion: This study shows that exposed rats to cadmium and/or noise caused renal function impairment. Production of oxidative stress is responsible for cadmium or noise induced nephrotoxicity. However, co-exposure of cadmium and noise reduced nephrotoxicity of cadmium. The possible explanation for noises suppressing cadmium nephrotoxicity is that noise may enhance excretion and/or induced redistribution and depleted accumulation of cadmium in the kidney.

Prevention of cadmium-induced neurotoxicity in rats by essential nutrients present in nuts

Cadmium, a heavy metal with no physiological function in the human body, is considered a bio-hazard. It is also considered to be a potent neurotoxin. The primary sources of cadmium exposure are diet and cigarette smoke. It has been postulated that nutritional deficiencies can increase the risk of cadmium toxicity. Nuts provide essential nutrients which are necessary for the maintenance of brain health in humans. The present study was designed to investigate the possible protective effects of almond and walnut supplementation on cadmium-induced neurotoxicity. Cadmium was orally administered at a dose of 50 mg/kg weekly with or without the supplementation of almond and walnut in rats. Intensities of depression‑ and anxiety-related behaviors were assessed by the forced swim test and light/dark transition test, respectively. Memory function was also evaluated by the elevated plus maze, Morris water maze and novel object recognition task. After four weeks of treatment it was observed that cadmium administration significantly induced depressogenic and anxiogenic behaviors. Memory function was also impaired by cadmium administration. Cadmium-treated rats exhibited reduced noradrenalin, dopamine and serotonin levels in the brain, whereas the levels of their respective metabolites were significantly increased. The dietary supplementation of almond and walnut at a dose of 400 mg/kg/day significantly attenuated cadmium-induced depression, anxiety and memory impairments. Neurochemical aberrations also normalized following supplementation with these nuts in rats. The present study demonstrates that long-term supplementation with almond and walnut provides essential nutrients which may overcome nutritional deficiencies and thereby reduce heavy-metal intoxication.

Cadmium-induced hepatocellular injury: Modulatory effects of γ-glutamyl cysteine on the biomarkers of inflammation, DNA damage, and apoptotic cell death

Cadmium is an extremely toxic pollutant that reaches human body through intake of the industrially polluted food and water as well as through cigarette smoking and exposure to polluted air. Cadmium accumulates in different body organs especially the liver. It induces tissue injury largely through inflammation and oxidative stress-based mechanisms. The aim of the current study was to investigate the ability of γ glutamyl cysteine (γGC) to protect against cadmium-induced hepatocellular injury employing Wistar rats as a mammalian model. The results of the current work indicated that γGC upregulated the level of the anti-inflammatory cytokine IL-10 and downregulated the levels of the pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in the cadmium-exposed rats. In addition, γGC reduced the liver tissues cadmium content in the cadmium-treated rats, suppressed the cadmium-induced hepatocellular apoptosis and oxidative modifications of cellular DNA, lipids, and proteins. Additionally, γGC enhanced the antioxidant potential of the liver tissues in the cadmium-treated rats as evidenced by a remarkable increase in the activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase and significant increase in the levels of the total antioxidant capacity and reduced glutathione as well as a significant reduction in oxidized to reduced glutathione (GSSG/GSH) ratio. Moreover, it effectively improved liver cell integrity in the cadmium-treated rats as demonstrated by a significant reduction in the serum activity of the liver enzymes (ALT and AST) and amelioration of the cadmium-evoked histopathological alterations. Together, these findings underscore, for the first time, the alleviating effects of γGC against cadmium-induced hepatocellular injury that is potentially mediated through reduction of liver tissue cadmium content along with modulation of both hepatocellular redox status and inflammatory cytokines.

Cadmium-induced neurodegeneration and activation of noncanonical sonic hedgehog pathway in rat cerebellum.

Cadmium is a nonessential toxic heavy metal, which enters the body easily and damages the cellular system. The sonic hedgehog (Shh) signaling pathway is one of the key regulatory pathways, which define neural growth and development. This study aimed to explore how cadmium exposure affects neural activities, Shh signaling cascade, and its downstream target genes. Total 18 male Wistar rats were randomly divided into two groups, control and test groups. Test rats were administered with 3 mg cadmium/kg body weight, while the control rats were treated with vehicle continuously for 28 days. Thereafter, rats were killed and the isolated brain samples were examined using oxidative stress assessment, histological and immunohistological behavioral assessment, polymerase chain reaction (PCR), and the comet assay. A disturbed oxidative balance, DNA damage, and an upregulated Shh signaling pathway were observed in cadmium-treated samples. Loss of structural integrity in cerebellum and loss of motor activity were observed in cadmium-treated rats.

Oleic Acid Alleviates Cadmium-Induced Oxidative Damage in Rat by Its Radicals Scavenging Activity

Toxic heavy metal cadmium wildly pollutes the environment and threats the human health. Effective treatment of cadmium-induced toxicity and organ damage is an important issue. Cadmium causes organ damage through inducing oxidative stress. Our previous study also found oleic acid (OA) synthesis-related gene can confer resistance to cadmium and alleviate cadmium-induced stress in yeast. However, its alleviation mechanism on cadmium stress especially in animals is still unclear. In this study, the alleviative effects of OA on cadmium and cadmium-induced oxidative stress in rats were investigated. Oral administration of 10, 20, and 30mg/kg/day OA can significantly increase the survival rate of rats intraperitoneally injected with 30mg/kg/day cadmium continuously for 7days. Similar to ascorbic acid (AA), OA can significantly reduce the cadmium-induced lipid peroxidation in multiple organs of rats. The investigation of OA on superoxide dismutase (SOD) activity showed that OA increased the SOD activity of cadmium-treated rat organs. More important, OA reduced the level of superoxide radical O2- of cadmium-treated rat organs. And OA exhibited a strong DPPH radicals scavenging activity at dose of 10, 20 and 30mg/mL, which may contributed to alleviating cadmium-induced oxidative stress. This study revealed that OA could significantly alleviate cadmium stress via reducing cadmium-induced lipid peroxidation and SOD activity inhibition through its radicals scavenging activity.

Mimosa pudica Protects the Testes Against Cadmium-Induced Inflammation and Oligospermia: Potential Benefits in Treatment of Heavy Metal Toxicity

Cadmium is a known environmental and industrial pollutant with an enormous tissue disrupting potential. Mimosa pudica (M. pudica) is a creeping annual or perennial herb known to possess anti asthmatic, anti-epileptic, anti-tumour, anti-fertility, aphrodisiac, analgesic, anti-depressant, sedative, emetic properties and a strong radical scavenging activity. This research was aimed at investigating the ameliorative effects of M. pudica on cadmium-induced testicular damage in adult male Sprague Dawley rats. Twenty adult Sprague Dawley rats were employed in the study. They were divided into 4 groups (A–D) of 5 rats each, and toxicity was induced by administering 0.4 mg/ml cadmium chloride through drinking water to groups B–D for 21days. M. pudica extract was administered orally at 250 and 500 mg/kg to groups C and D. Animals in Groups C and D showed remarkable histological improvements in testicular tissue and markedly reduced damages when compared with group B.The active sperm motility of group B (6.00 ± 1.00%) was significantly (p = 0.0001) decreased compared to that of the groups A (15.00 ± 0.00%)) and C (13.00 ± 1.22%). Sperm count analysis of group B (1.36 ± 0.28 × 106/cc), C (4.18 ± 0.81 × 106/cc) and D (2.54 ± 1.13 × 106/cc) were significantly lower (p = <0.05) when compared with group A (12.78 ± 0.92 × 106/cc), respectively. Sperm morphology of group A (70.00 ± 3.16%), B (66.00 ± 2.50), C (74.00 ± 2.45%) and D (64.00 ± 2.45%) recorded no significant difference. This study demonstrates that M. pudica has potential protective and restorative properties on the histoarchitecture of the testes of cadmium-treated rats.

Nephroprotective Effect of Essential Oils from Ginger (Zingiber officinale) and Turmeric (Curcuma longa) Rhizomes against Cadmium-induced Nephrotoxicity in Rats.

Several studies have shown that cadmium (Cd) induces nephrotoxicity and many plant foods phytochemicals have been found useful but their possible mechanism of action still remains unexplored. Hence, this study aimed to investigate the nephroprotective effect of essential oils from Nigeria ginger and turmeric rhizomes in cadmium-treated rats by examining their effect on renal function biomarkers (creatinine, urea and BUN), inflammatory cytokines (IL-6, IL-10 and TNF-Alpha) and renal adenosine deaminase (ADA) activity. The result revealed that essential oils from ginger and turmeric rhizomes exert anti-inflammatory effect by preventing alterations of renal function markers and cytokines (IL-6, IL-10 and TNF-Alpha) levels in Cd-treated rats. In addition, the essential oils inhibited renal ADA activity in Cdtreated rats. In conclusion, inhibition of ADA activity and modulation of inflammatory cytokines could be suggested as the possible mechanism of action by which essential oils from ginger and turmeric rhizomes exert their nephroprotective activities.

Protective Effects of Fragaria ananassa Extract Against Cadmium Chloride-Induced Acute Renal Toxicity in Rats.

For experiments of cadmium toxicity in animal models, cadmium (II) chloride is often used due to its solubility in water and its ability to produce high concentrations of cadmium at the target site. The present study was designed to investigate the potential inhibitory effect of the Fragaria ananassa fruit extract on cadmium (II) chloride-induced renal toxicity in rats. Tested animals were pretreated with the extract of F. ananassa and injected with cadmium (II) chloride (6.5-mg/kg body weight) for 5days. Cadmium (II) chloride significantly increased kidney cadmium concentration, kidney weight, lipid peroxidation, and nitric oxide production. Plasma uric acid, urea, and creatinine levels also increased significantly, indicative of kidney dysfunction. These effects were accompanied by significantly decreased levels of nonenzymatic and enzymatic antioxidant molecules (i.e., glutathione content and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase). Moreover, messenger RNA (mRNA) expression of the antiapoptotic protein, Bcl-2, and the antioxidant proteins, superoxide dismutase 2 and glutathione reductase, were downregulated markedly, whereas mRNA expression of tumor necrosis factor-α was upregulated significantly in kidney tissues of cadmium-treated rats. Histology of kidney tissue demonstrated severe, adverse changes that reflected cadmium-induced tissue damage. Pretreatment of rats with the extract of F. ananassa ameliorated all aforementioned cadmium (II) chloride-induced changes. In conclusion, the present study showed acute renal toxicity in rats treated with cadmium (II) chloride. The study also revealed that pretreatment with the extract of F. ananassa could protect the kidney against cadmium (II) chloride-induced acute renal toxicity.

Role of autophagy in cadmium-induced testicular injury

The testis is sensitive to cadmium, but studies investigating cadmium-induced testicular injury have not yet clearly revealed the underlying mechanisms. This study aimed to investigate the injurious effects of cadmium on rat testes and the role that autophagy plays in this process. Wistar rats were randomly divided into four groups and intraperitoneally injected with 0.2 (low), 0.4 (middle), and 0.8 mg/kg·body weight (high) cadmium chloride for 5 weeks, while the control rats were injected with equal volume of saline. Rats exposed to cadmium appeared inactive and had reduced body weights and increased testicular organ coefficients at the end of treatment compared with control rats. Atomic absorption results showed that cadmium levels increased with increased cadmium exposure. Hematoxylin and eosin staining of testicular sections showed seminiferous tubular atrophy, decreased pipe diameter, spermatogonial stem cells falling off the inner lining, and reduced germ cell layers of disorderly arrangements in cadmium-treated rats. Immunohistochemical and western blot results both showed that levels of the autophagy-related proteins Beclin1 and microtubule-associated protein 1 light chain 3B (LC3B) increased with increased cadmium exposure. We also found that LC3B-II and calcium-sensing receptor (CSR) levels in cadmium-exposed rats significantly increased. By immunofluorescence, we found that the percentage of cells that expressed the CSR was significantly higher in LC3B-positive than LC3B-negative cells. Together, our results showed that cadmium accumulates in the testes causing testicular injury, which may be related to increased autophagy levels. Furthermore, calcium disorders associated with the CSR may reveal a potential way to activate autophagy.

Dendropanax morbifera Léveille extract ameliorates cadmium-induced impairment in memory and hippocampal neurogenesis in rats

BackgroundCadmium leads to learning and memory impairment. Dendropanax morbifera Léveille stem extract (DMS) reduces cadmium-induced oxidative stress in the hippocampus. We investigated the effects of DMS on cadmium-induced impairments in memory in rats.MethodsCadmium (2 mg/kg), with or without DMS (100 mg/kg), was orally administered to 7-week-old Sprague-Dawley rats for 28 days. Galantamine (5 mg/kg), an acetylcholinesterase inhibitor, was intraperitoneally administered as a positive control. A novel-object recognition test was conducted 2 h after the final administration. Cell proliferation and neuroblast differentiation were assessed by immunohistochemistry for Ki67 and doublecortin, respectively. Acetylcholinesterase activity in the synaptosomes of the hippocampus was also measured based on the formation of 5,5′-dithio-bis-acid nitrobenzoic acid.ResultsAn increase in the preferential exploration time of new objects was observed in both vehicle-treated and cadmium-treated rats. In addition, DMS administration increased cell proliferation and neuroblast differentiation in the dentate gyrus of vehicle-treated and cadmium-treated rats. Acetylcholinesterase activity in the hippocampal synaptosomes was also significantly higher in the DMS-treated group than in the vehicle-treated group. The effect of DMS on cadmium-induced memory impairment and cell proliferation in the hippocampus was comparable to that of galantamine.ConclusionsThese results suggest that DMS ameliorates cadmium-induced memory impairment via increase in cell proliferation, neuroblast differentiation, and acetylcholinesterase activity in the hippocampus. The consumption of DMS may reduce cadmium-induced neurotoxicity in animals or humans.