Cadmium-induced Alterations Research Articles

Cadmium-induced Alterations in the Expression Profile of MicroRNAs: A Comprehensive Review

Cadmium-induced Alterations in the Expression Profile of MicroRNAs: A Comprehensive Review

Resolution to Expression of Concern: “Refat et al. Antioxidant, Antigenotoxic, and Hepatic Ameliorative Effects of Quercetin/Zinc Complex on Cadmium-Induced Hepatotoxicity and Alterations in Hepatic Tissue Structure. Coatings 2021, 11, 501”

The journal’s editorial office and journal editors are jointly issuing a resolution to the Expression of Concern [...]

Ameliorating potential of Cassia absus seed-powder against cadmium-induced alterations in Zebrafish and identification of flavonoids in different extracts of seed

Ameliorating potential of Cassia absus seed-powder against cadmium-induced alterations in Zebrafish and identification of flavonoids in different extracts of seed

Protective effect of quercetin and curcumin against cadmium-induced alterations in brain cortex and heart of rats

Protective effect of quercetin and curcumin against cadmium-induced alterations in brain cortex and heart of rats

Expression of Concern: Refat et al. Antioxidant, Antigenotoxic, and Hepatic Ameliorative Effects of Quercetin/Zinc Complex on Cadmium-Induced Hepatotoxicity and Alterations in Hepatic Tissue Structure. Coatings 2021, 11, 501

Following acceptance of the Special Issue article by the Guest Editor, El-Sayed Abd El-Aziz, concerns were raised regarding the integrity of the peer review process [...]

Effect of quercetin and curcumin in rats sub-acutely exposed to cadmium chloride: haemato-biochemical changes, oxidative stress parameters and histopathological changes in intestine, liver and kidney of rats

Quercetin is a flavonoid mostly found in fruits and vegetables. Curcumin is the main natural polyphenol found in the rhizome of Curcuma longa and in others Curcuma spp.. Individually, quercetin and curcumin had shown to have various pharmacological properties. The increasing level of cadmium in the environment is alarming as cadmium affects the antioxidant defense system with ability to persist in the body for long time. The bioaccumulation of cadmium is well-known, which is dangerous for the health of human and animals after continuous exposure to it. The present experiment was carried out to evaluate the ameliorating effect of quercetin (50 mg/kg daily orally for 28 days) and curcumin (100 mg/kg daily orally for 28 days) alone and in combination of both against cadmium-induced (100 ppm in water for 28 days) alterations in biochemical markers and histological changes in intestine, liver and kidney of rats. Body weight gain in rats of toxicity group during the 4th week of study period was significantly affected by the cadmium. Cadmium exposure significantly increased the levels of AST, ALT, ALP, bilirubin and glucose in serum along with higher level of MDA in intestine, liver and kidney of rats. The administration of quercetin and curcumin in combination as compared to individual treatment along with cadmium exposure had shown significantly lower levels of above parameters. Various histological changes were noticed in intestine, liver and kidney of rats following exposure to cadmium which were improved in rats treated with individual or combined treatment of quercetin and curcumin. Quercetin alone had shown the ameliorating effect against cadmium-induced alteration in kidney of rats. While, combination of quercetin and curcumin has been found to protect the intestine and liver from cadmium-induced damage following sub-acute exposure in rats. However, further study is needed to explore the mechanism of protective effect of the quercetin and curcumin against cadmiuminduced changes in intestine, liver and kidney.

Cytoprotective and antioxidant potential of Aegle marmelos on cadmium-induced hepato-renal toxicity: an in vivo study

The current study investigated the protective and antioxidant potential of Aegle marmelos leaf extract against Cadmium-induced alterations in hepatic and renal tissues of BALB/c mice. Cadmium (Cd) is known for its toxicity and induction of oxidative stress even at a low level of exposure with prolonged persistence in the environment. Its metabolism and excretion depend on the endogenous antioxidant defense system, which gets compromised. For the present study thirty BALB/c mice were equally divided into six groups, namely Control (normal saline via gavage for 10 days), Cadmium (intraperitoneal dose of 5 mg/kg b.wt. for 5 days), Aegle alone (500 mg/kg b.wt. for 10 days via gavage), Pre-treatment of Aegle (500 mg/kg b.wt. for 10 days+5 mg/kg b.wt. of Cd for 5 days), Post-treatment of Aegle (5 mg/kg b.wt. of Cd for 5 days+500 mg/kg b.wt. for 10 days) and Vehicle group (0.5 mL oil/kg b.wt. through gavage for 10 days). The liver and kidney tissues of different groups were screened for oxidative stress indices, antioxidant enzyme systems, hepatic-renal biomarkers, histopathological alterations, chromosomal aberrations, and micronucleus formation. Sub-acute Cadmium exposure caused marked oxidative damage and tissue dysfunction evident from increased lipid peroxidation, liver-kidney serum function markers, and a subsequent decrease in reduced glutathione, catalase, superoxide dismutase, glutathione-S-transferase, glutathione reductase (p < 0.001). Histopathological analysis exhibited both reversible and non-reversible alterations.Additionally, a marked increase in chromosomal aberrations and micronucleation was observed. Both pre-and post-treatments with Aegle significantly restored altered antioxidant enzyme status, serum function markers, histomorphological alterations and reduced the percentage of chromosomal aberrations and micronucleation in the treated groups. Aegle exerts its protective efficacy due to its rich bio-active phytoconstituents, which regulated Cadmium evoked reactive oxygen species (ROS) and enhanced endogenous defense system to combat the cyto-genotoxic alterations. Moreover, all the parameters profoundly indicate higher efficacy of the pre-treatment dose.

Multifactorial Screening Reveals New Insight into Early Cadmium Exposure and Garlic Interactions in Dicentrarchus labrax.

Environmental pollutants and especially metal trace elements remain an unmitigated threat to the overall life support system. Their chemical stability and accumulation pattern in the ecosystem make them a persistent hazard. This study aims to characterize the early cadmium (Cd) histological and hematological alterations and their corresponding plasma indicators in the Mediterranean sea bass (Dicentrarchus labrax). We also assessed garlic potential to prevent cadmium toxicity. For this purpose, 200 fish of 55g mean weight were separated into 3 cylindroconical fiberglass tanks of 500-L capacity, each with a stocking density of 4kgm-3. The fish were regularly hand-fed 0% (control group), 2%, and 6% garlic-supplemented diets to apparent satiation twice a day for 1month. At the end of the experiment, we injected 22.2mM cadmium (CdCl2) intraperitoneally to the experimental groups and a placebo solution (9% NaCl) to the control groups; liver, kidney, heart, and blood tissue alterations were monitored with a full screening of their plasmatic indicators, 24h before and 48h after Cd injection. Subsequently, whole blood count and blood smears were performed to follow up on Cd-induced vascular damages. Our data showed that Cd induced thrombotic thrombocytopenic purpura, leading to widespread bleeding and cellular alterations in the targeted tissues. These alterations were associated with an obvious normochromic normocytic anemia in favor of microangiopathic hemolytic anemia. Cd injection has also seriously inhibited the overall enzymatic activities triggering a metabolic shift. Although garlic supplementation had little effect on cadmium-induced alterations, it significantly reduced biomass dispersion. Our data is the first evidence of the cadmium versatile toxicity involving vascular alterations as a central and a leading cause of the overall parenchymal lesions. Cd toxicity was associated with a specific enzymatic signature, which must be considered during the interpretation.

Nano-encapsulation using macrocyclic carbohydrate polymers (β-cyclodextrins) of Periploca angustifolia extract: Physical stability and protective effect against cadmium-induced alterations in HepG2 cells

The nano-encapsulation of Periploca angustifolia phenolic extract using the macrocyclic carbohydrate polymers (β‑cyclodextrins) is a most approach compared with other encapsulation methods. In this work, the β‑Cyclodextrins-PAE complex stability has been evaluated by advanced analytical methods and techniques including HPLC, FTIR and XRD. The results showed that CdCl2 treatment caused a significant decrease in cell viability. The CdCl2-induced damage in the HepG2 cells were significantly ameliorated (p < 0.001) by treatment of the PAE and β‑Cyclodextrins-PAE complex. Thus, pretreatment with 100 μg mL−1 of β‑Cyclodextrins-PAE complex significantly protect HepG2 cells against cytotoxicity induced by cadmium exposure more effectively than PAE only. However, Cd-intoxication significantly (p < 0.001) increased these enzymes activity. Additionally, reactive oxygen species generation was significantly decreased when cells were treated with nano-encapsulation PAE. The levels of supernatant antioxidant parameters including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and GSH were significantly (p < 0.001) decreased in Cd-treated cells with concomitant enhancement of lipid peroxidation. In addition, β‑Cyclodextrins-PAE pretreatment significantly (p < 0.01) inhibited Cd-exposure activated the apoptotic pathway caspace-3 and caspace-9. This effect may be due to the ability of β‑Cyclodextrins molecules to enhance stability and permeability properties.

Cadmium-induced alterations in bio-chemical constituents of Labeo rohita and Cyprinus carpio fry: A comparative study

Cadmium is a well known heavy metal toxicant which can interfere with metabolism of carbohydrates, proteins and lipids by inhibiting the enzymes involved in the processes. In the present investigation, the effect of cadmium was evaluated on these biochemical constituents in two fresh water fish fry Labeo rohita and Cyprinus carpio. Fish fry of Labeo rohita and Cyprinus carpio were exposed to their respective sub-lethal concentrations (1/5th of LC50), 0.1998 ppm and 4.938 ppm of cadmium for a period of 20days. Total carbohydrates, proteins and lipids were estimated by standard biochemical procedures in control and exposed fish fry. Results showed significant fall in all the biochemical constituents and energy levels of exposed fish fry, indicating that the organism is under toxicant stress.

Can zinc supplementation ameliorate cadmium-induced alterations in the bioelement content in rabbits?

The study was designed to investigate the influence of zinc (Zn) supplementation on cadmium-induced alterations in zinc, copper (Cu), and magnesium (Mg) status in rabbits. For this purpose, the concentrations of cadmium (Cd), Zn, Cu, and Mg were estimated in the blood, liver, kidney, and bone. The rabbits were divided in a control group, a Cd group-animals intoxicated orally with Cd (10 mg kg-1 bw, as aqueous solution of Cd-chloride), and a Cd+Zn group-animals intoxicated with the same dose of Cd and co-treated with Zn (20 mg kg-1 bw, as aqueous solution of Zn-sulphate). Solutions were administered orally, every day for 28 days. Sample mineralisation was performed with concentrated nitric acid (HNO3) and perchloric acid (HClO4) (4:1) and metal concentrations were determined by atomic absorption spectrophotometry (AAS). Zinc supplementation improved some of Cd-induced disturbances in bioelement levels in the investigated tissues. Beneficial effects of Zn on Zn and Cu levels were observed in blood, as well as on the Cu kidney level. The calculated values for Cu/Zn, Mg/Zn, and Mg/Cu ratios in blood suggest that Zn co-treatment reduces Cd-induced changes in bioelement ratios in blood.

Protective Role of Quercetin in Cadmium-Induced Cholinergic Dysfunctions in Rat Brain by Modulating Mitochondrial Integrity and MAP Kinase Signaling.

With the increasing evidences of cadmium-induced cognitive deficits associated with brain cholinergic dysfunctions, the present study aimed to decipher molecular mechanisms involved in the neuroprotective efficacy of quercetin in rats. A decrease in the binding of cholinergic-muscarinic receptors and mRNA expression of cholinergic receptor genes (M1, M2, and M4) was observed in the frontal cortex and hippocampus on exposure of rats to cadmium (5.0mg/kg body weight, p.o.) for 28days compared to controls. Cadmium exposure resulted to decrease mRNA and protein expressions of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) andenhance reactive oxygen species (ROS) generation associated with mitochondrial dysfunctions, ultrastructural changes, and learning deficits. Enhanced apoptosis, as evidenced by alterations in key proteins involved in the pro- and anti-apoptotic pathway and mitogen-activated protein (MAP) kinase signaling, was evident on cadmium exposure. Simultaneous treatment with quercetin (25mg/kg body weight, p.o.) resulted toprotect cadmium-induced alterations in cholinergic-muscarinic receptors, mRNA expression of genes (M1, M2, and M4), and expression of ChAT and AChE. The protective effect on brain cholinergic targets was attributed to the antioxidant potential of quercetin, which reduced ROS generation and protected mitochondrial integrity by modulating proteins involved in apoptosis and MAP kinase signaling. The results exhibit that quercetin may modulate molecular targets involved in brain cholinergic signaling and attenuate cadmium neurotoxicity.

Polyphenol-rich extract of Vernonia amygdalina (Del.) leaves ameliorated cadmium-induced alterations in feeding pattern and urine volume of male Wistar rats.

Aim:To determine the effects of a polyphenol-rich extract of the leaves of Vernonia amygdalina (PEVA) on the feeding pattern of rats that are exposed to cadmium (Cd) toxicity.Materials and Methods:Thirty male Wistar rats, weighing 160-180 g, were divided into 6 groups of 5 rats each as follows; Group 1 received distilled water orally (0.2 ml a 100 g rats), daily, throughout the period of study. Group 2 received Cd alone (in the form of CdSO4) at 5 mg/kg/day via intraperitoneal route for 5 consecutive days. Group 3 were pre-treated with Cd as Group 2 and thereafter left untreated for a period of 4-week. After the oral lethal dose of PEVA was determined, Groups 4, 5, and 6 received graded doses of PEVA at 100, 200 and 400 mg/kg/day (0.2 ml per 100 g rats), respectively via oral route for 4 weeks after they were pre-treated with Cd as Group 2. Blood samples were collected for some plasma biochemical assays while urine samples were collected using metabolic cages.Results:PEVA administration significantly increased (P < 0.05) the body weight and feeding patterns that were significantly reduced (P < 0.05) by Cd toxicity. PEVA also significantly reinstated the plasma antioxidant status, as well as glucose and urine volume of the rats toward control values (P < 0.05).Conclusion:PEVA can be an herbal alternative in the treatment or management of subjects manifesting alterations in feeding pattern and urine volume that is Cd-induced.

Cadmium‐induced cell death in BY‐2 cell culture starts with vacuolization of cytoplasm and terminates with necrosis

Cadmium is a potent inducer of programmed cell death (PCD) in plants but the morphological changes in cells exposed to cadmium are poorly characterized. Using light and transmission electron microscopy (TEM) we have investigated the changes in ultrastructure of tobacco BY-2 cells treated with 50 µM CdSO4. The cadmium-induced alterations in cell morphology occurred gradually over a period of 3-4 days and the first stages of the response resembled vacuolar type of cell death. The initial formation of numerous small cytoplasmic vacuoles and dilation of endoplasmic reticulum was followed first by fusion of smaller vacuoles with each other and with big vacuoles, and then by the appearance of autophagic vacuoles containing autophagic bodies. The final stages of cell death were accompanied by necrotic features including loss of plasmalemma integrity, shrinkage of the protoplast and unprocessed cellular components. In addition, we observed a gradual degradation of nuclear material. Our results demonstrate that cadmium-induced plant cell death is a slow process featuring elements of vacuolar cell death and terminating with necrosis.

Cadmium-induced alterations in morpho-physiology of two peanut cultivars differing in cadmium accumulation

This study examines differences in the morpho-physiological responses of low- and high-cadmium (Cd) accumulating peanut (Arachis hypogaea L.) cultivars to Cd stress. The biomass, Cd accumulation, leaf gas exchange, root morphology, root respiration, and hydraulic conductivity of Qishan 208 (low-Cd accumulator) and Haihua 1 (high-Cd accumulator) were determined via a hydroponic experiment. Exposure of peanut plants to 2 and 20 μM Cd considerably decreased their shoot biomass, net photosynthetic rate, transpiration rate, stomatal conductance, total root length, number of root tips, root respiration, and hydraulic conductivity. The root biomass, root surface area, and average diameter were unaffected by Cd exposure. The two cultivars differed in Cd accumulation and morpho-physiological responses to Cd stress. Qishan 208 accumulated less Cd in plant tissues but was more sensitive to Cd stress than Haihua 1. The total root length, surface area, average diameter, number of root tips, and root respiration rate of Haihua 1 were significantly higher than those of Qishan 208. The well-developed root system and higher root respiration of Haihua 1 may be responsible for its high Cd accumulation capacity.

Some bioactive potentials of two biflavanols isolated from Garcinia kola on cadmium-induced alterations of raw U937 cells and U937-derived macrophages

ObjectiveTo investigate the abilities of two flavonoids - Garcinia biflavanol-1 (GB-1) and Garcinia biflavanol-2 (GB-2) from Garcinia kola (G. kola) in reducing cadmium-induced effects on raw U937 cells and U937-derived macrophages. MethodsMacrophage U937 cells were incubated with cadmium followed by treatment with the flavonoids and cell viability assessed via trypan blue staining. In the other experiment, the U937 cells were transformed to the macrophage form and treated with cadmium in order to activate them. The cells were later incubated with the flavonoids and finally the supernatant of each cell culture was analysed for the secretion of nitric oxide, catalyse activity, and the release of tumour necrosis factor-alpha, interleukin-1 and interleukin-2 as indices of macrophage activation. Quercetin (a flavonol) was used as the reference flavonoid in all experiments. ResultsIt revealed that the flavonoids significantly increased the viability of the cells and also reduced the cadmium-induced activation of the macrophage cells in a concentration-dependent manner. The flavanols GB-1 and GB-2 possessed higher activities than quercetin in all cases (P<0.05). Garcinia biflavanol-2 possessed a higher bioactivity than GB-1 significantly (P<0.05). ConclusionsIn addition to corroborating the several reported importance of G. kola as a potential neutraceutical and pharmacological condiment, the study also clearly indicates the role hydroxylation especially at the 3′- position of polyphenols could play in enhancing bioactivities of flavonoids.

Effect of zinc supplementation on glutathione peroxidase activity and selenium concentration in the serum, liver and kidney of rats chronically exposed to cadmium

It was investigated whether the ability of zinc (Zn) to prevent cadmium (Cd)-induced lipid peroxidation may be connected with its impact on glutathione peroxidase (GPx) activity and selenium (Se) concentration. GPx and Se were determined in the serum, liver and kidney of the rats that received Cd (5 or 50mg/L) or/and Zn (30mg/L) in drinking water for 6 months in whose the protective Zn impact was noted (Rogalska J, Brzóska MM, Roszczenko A, Moniuszko-Jakoniuk J. Enhanced zinc consumption prevents cadmium-induced alterations in lipid metabolism in male rats. Chem Biol Interact 2009;177:142–52). Moreover, dependences between these parameters, and indices of lipid peroxidation (F2-isoprostane, lipid peroxides, oxidized low density lipoprotein cholesterol) as well as concentrations of Cd and Zn were estimated. The supplementation with Zn during the exposure to 5mg Cd/L entirely antagonized the Cd-induced increase in GPx activity and Se concentration in the liver and kidney, but not in the serum. Zn administration during the treatment with 50mg Cd/L totally or partially prevented from the Cd-caused decrease in GPx activity and Se concentration in the serum, liver and kidney. At the higher level of Cd exposure, GPx activity in the serum and tissues positively correlated with Se concentration. Moreover, numerous correlations were noted between GPx and/or Se and the indices of lipid peroxidation. The results indicate that the protective impact of Zn against the Cd-induced lipid peroxidation during the relatively high exposure might be connected with its beneficial influence on Se concentration and GPx activity in the serum and tissues, whereas this bioelement influence at the moderate exposure seems to be independent of GPx and Se.

Modulatory Effects of Melatonin on Cadmium-Induced Changes in Biogenic Amines in Rat Hypothalamus

This study was undertaken to examine whether cadmium oral exposure modifies biogenic amine concentration at hypothalamic level in adult male rats, and to investigate the possible modulatory effects of melatonin against cadmium-induced changes on these neurotransmitters. For this purpose, rats were exposed to cadmium (25mg/l of CdCl(2) in the drinking water) with or without melatonin (30μg/rat/day intraperitoneally) for 30days. Norepinephrine (NE), dopamine (DA), serotonin (5-HT), 3,4-dihydroxyphenyl acetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) were quantified by high performance liquid chromatography (HPLC). Oral cadmium administration led to decrease of NE, DA, and 5-HT content and DA turnover within the three hypothalamic regions examined, and therefore an inhibition of 5-HT turnover at posterior hypothalamus. Sensitivity to melatonin was specific to the hypothalamic region evaluated. Thus, the anterior hypothalamus was not nearly sensitive to exogenously administered melatonin, whereas the neurohormone decreased the content of these amines in the mediobasal hypothalamus, and melatonin increased it in the posterior hypothalamic region. Melatonin effectively prevented some cadmium-induced alterations on hypothalamic amine concentration. This is the case of DA in the anterior and posterior hypothalamus, and 5-HT metabolism in the posterior hypothalamic region. In conclusion, the obtained results indicate that melatonin treatment may be effective modulating some neurotoxic effects induced by cadmium exposure, and, more to the point, a possible role of this indolamine as a preventive agent for environmental or occupational cadmium contamination.

Glycine reduces cadmium-induced alterations in the viability and activation of macrophage U937 cells

This study investigates the effect of glycine on cadmium-induced alterations on the viability and activation of the cell line U-937. In this experiment, U-937 cells were pre-treated with 16 μM cadmium (as cadmium chloride). These cadmium-treated cells were later incubated with or without glycine (1–16 μM). After 72 h, it was revealed that glycine significantly ( P < 0.05) reduced the tendency of cadmium to reduce the viability of the cells. U-937 cells were also treated with phorbol, 12-myristate, 13-acetate to enhance their transition to the macrophage form. Thereafter, the cells were treated with cadmium with or without glycine (1–16 μM). Twenty-four hours later, the supernatants of each cell culture were assessed for the production of tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 1 (IL-1), nitric oxide (NO), and catalase activity as indices of the activation of macrophages. The results show that glycine significantly ( P < 0.05) reduced the cadmium-induced production of all the markers of the activation of macrophages in a concentration-dependent manner. The findings support the immense antioxidant role of glycine.

The testes in cadmium intoxication: morphological and vascular aspects.

Cadmium toxicity was tested on young male Wistar rats by injecting 1 mg/ml of cadmium chloride (CdCl2) intra-peritoneally. Post-mortem examination was done 4 hours, 24 hours and 14 days after cadmium administration to observe time-sequence cadmium-induced alterations in vascular permeability of the mesothelium in the pleura, peritoneum and tunica vaginals. This paper mainly reports the alterations observed in the testes. Vascular permeability was assessed by the colloidal carbon technique. Vascular labelling was evidenced as early as 4 hours after CdCl2, injection; 24 hours later severe oedema with leakage of particles to the interstitium and also into the tubules was patent. Fourteen days after CdCl2 administration atrophy of the testes with necrosis of the tubules, fibrosis of the interstitium and vascular thrombosis was found, compatible with chemical castration.