Individual and combined effects of cadmium and lead exposure in rats.

The exposure of humans and animals to environmental compounds is rarely restricted to a single chemical. Cadmium (Cd) and lead (Pb) are two heavy metals known to be the most toxic. Deleterious effects of each metal alone are well documented. Unfortunately, very few studies were conducted to determine their combined effect. Four groups of Wistar rats were treated intravenously for 15 days. The control group received physiological saline solution; groups 2 and 3 were treated with Cd chloride and lead acetate, respectively ; and the treatment group 4 received a combined treatment of Cd and Pb . A significant decrease was recorded for hematological parameters , with an increase in white blood cells and an inhibition in δ-ALAD level. Cell injury in the livers and kidneys was clearly shown by the significant elevation of the biochemical markers. Cd and Pb induced oxidative stress and had adverse health effects at lower exposure levels than previously thought.

Ecophysiological responses of Glycine max L. under single and combined cadmium and salinity stresses.

Soil contamination by cadmium (Cd) and degradation by salinity are likely to become one of the most important problems hindering food production and human health. However, their combined effect on crops is still ambiguous. A hydroponic study was made to investigate the separate and combined exposure of 100 µM Cd and 150 µM NaCl on soybeans (Glycine max L.) growth, photosynthetic pigment, and antioxidant systems for 7 days. Both Cd and NaCl, applied separately decreased the seedlings growth, chlorophyll contents and caused oxidative stress. However, the toxic effects of salinity applied alone were more pronounced. Interestingly, combined exposure of Cd and NaCl induced higher decreases in all growth parameters and lipid peroxidation than single exposure suggesting synergistic effects. The results implicate that the phytotoxicity of both stressors can be associated with redox status imbalance. Our finding may provide insight into the physiological mechanisms of heavy metal exposure and salinity stress tolerance in soybeans and suggest that saline stress changes the effects of Cd toxicity on crops in Cd-salt-polluted soils.

Pharmacophore-based virtual screening approaches to identify novel molecular candidates against EGFR through comprehensive computational approaches and in-vitro studies.

Alterations to the EGFR (epidermal growth factor receptor) gene, which primarily occur in the axon 18-21 position, have been linked to a variety of cancers, including ovarian, breast, colon, and lung cancer. The use of TK inhibitors (gefitinib, erlotinib, lapatinib, and afatinib) and monoclonal antibodies (cetuximab, panitumumab, and matuzumab) in the treatment of advanced-stage cancer is very common. These drugs are becoming less effective in EGFR targeted cancer treatment and developing resistance to cancer cell eradication, which sometimes necessitates stopping treatment due to the side effects. One in silico study has been conducted to identify EGFR antagonists using other compounds, databases without providing the toxicity profile, comparative analyses, or morphological cell death pattern. The goal of our study was to identify potential lead compounds, and we identified seven compounds based on the docking score and four compounds that were chosen for our study, utilizing toxicity analysis. Molecular docking, virtual screening, dynamic simulation, and in-vitro screening indicated that these compounds' effects were superior to those of already marketed medication (gefitinib). The four compounds obtained, ZINC96937394, ZINC14611940, ZINC103239230, and ZINC96933670, demonstrated improved binding affinity (-9.9 kcal/mol, -9.6 kcal/mol, -9.5 kcal/mol, and -9.2 kcal/mol, respectively), interaction stability, and a lower toxicity profile. In silico toxicity analysis showed that our compounds have a lower toxicity profile and a higher LD50 value. At the same time, a selected compound, i.e., ZINC103239230, was revealed to attach to a particular active site and bind more tightly to the protein, as well as show better in-vitro results when compared to our selected gefitinib medication. MTT assay, gene expression analysis (BAX, BCL-2, and ß-catenin), apoptosis analysis, TEM, cell cycle assay, ELISA, and cell migration assays were conducted to perform the cell death analysis of lung cancer and breast cancer, compared to the marketed product. The MTT assay exhibited 80% cell death for 75 µM and 100µM; however, flow cytometry analysis with the IC50 value demonstrated that the selected compound induced higher apoptosis in MCF-7 (30.8%) than in A549.

Ameliorative or corrective effects of Fig "Ficus carica" extract on nickel-induced hepatotoxicity in Wistar rats.

Many heavy metals and metalloids (e.g., Pb, Cd, and Ni) can contaminate the environment and cause severe health problems. Through this study, investigated the possible corrective effects of Ficus carica extract (FCE) against nickel (Ni) induced stress response and damage on the liver of rats. Male Wistar rats were divided into four groups (8 rats per group) and co-treated with FCE (350 mg/kg) and exposed to Nickel chloride (10 mg/kg) for 4 weeks. The volatile compounds of FCE were characterized by solid phase micro-extraction (SPME) coupled with GC-MS, and the biochemical parameters of stress were determined. The SPME-GC/MS analysis of FCE indicated the presence of thirty (30) phyto-bioactive compounds including alcohols, aldehydes, organic acids, ketones, furans, terpenes, ester and others. The best capacity for scavenging DPPH free radicals and metal chelating were found with the IC50 values of 0.49 and 2.91 mg/mL, respectively. Ni induced damage to various macromolecules. Malondialdehyde, protein carbonyls, alanine aminotransferase and gamma glutamyl transferarse levels were significantly increased in Ni exposed group compared to control group and co-treatment with FCE reduced the levels of these parameters. In conclusion, current findings showed that Ni-induced oxidative damage and the administration of FCE can improve correct and restore the alteration in the rat liver.

Phytotoxic evaluation of neonicotinoid imidacloprid and cadmium alone and in combination on tomato (Solanum lycopersicum L.).

Neonicotinoids and heavy metals pollution exist simultaneously in agro ecosystem. However, little is known about their combined ecotoxicological effects on non-target crop plants. We have selected imidacloprid (IMI) and cadmium (Cd), applied alone and in combination, to evaluate their effect on growth, physiological and biochemical parameters of tomato. Results showed that the single application of contaminants (IMI and/or Cd) adversely affected both the growth and chlorophyll pigment, and Cd alone application was more phytotoxic than IMI. However, their combined action aggravated the inhibitory effect and indicate a synergistic effect, but it exerted antagonistic effects on chlorophyll pigment inhibition compared with IMI and Cd alone treatments. Both chemicals increased hydrogen peroxide level and generated lipid peroxidation, and the co-contamination exacerbates oxidative stress by their synergistic effect. Those results implicate that disturbance of cellular redox status is the plausible mechanism for IMI and Cd induced toxicity. In conclusion, the single or combined IMI and Cd cause negative effects on tomatoes.

Ethnobotanical and ethnomedicinal analysis of wild medicinal plants traditionally used in Naâma, southwest Algeria.

Algerian people largely rely on traditional medicine practices as part of a community's identity. This first ethnobotanical study aimed to quantify and document the wild medicinal plant taxa from four family and the related traditional knowledge in Naâma province, Algeria. The survey was carried out between 2018 and 2020. The socio-demographic data and the use of medicinal species were recorded and collected randomly from 84 indigenous people using pre-prepared questionnaire. The result was evaluated using quantitative indices. A total of 27 medicinal plant species belonging to 21 genera used in the community were mostly recorded. The most represented families were Lamiaceae and Asteraceae (12 species for each of them). The aerial parts were the most frequently used plant part (73 %), while a decoction (34 %), and infusion (31 %) were the major modes of remedy preparation. The species with high UV were Rosmarinus officinalis L. (0.80), Artemisia herba-alba Asso (0.76), and Juniperus phoenicea L. subsp. phoenicea (0.75). Species with highest FL were: Ephedra alata subsp. alenda (Stapf) Trab (100 %), Teucrium polium L. (60 %), and Ballota hirsuta Benth (57.14.5 %). Atractylis caespitosa Desf and Nepeta nepetella subsp.amethystina (Poir.) Briq were newly cited as medicinal plants and have not been recorded previously in Algeria. Artemisia herba-alba Asso and Thymus algeriensis Boiss. & Reut were reported to treat COVID-19 symptoms. The results obtained indicate the richness of the area with medicinal plants as well as knowledge of alternative medicine. The most cited plants could be contained molecules that can be tested for therapeutic uses.

Antioxidant Activity of Myrtus communis L. and Myrtus nivellei Batt. & Trab. Extracts: A Brief Review.

Myrtus communis L. (myrtle) and Myrtus nivellei Batt. & Trab. (Saharan myrtle) have been used in folk medicine for alleviating some ailments. M. communis is largely distributed in the Mediterranean Basin, whereas M. nivellei is confined in specific zones of the central Saharan mountains. The chemical composition and antioxidant activity of berry and leaf extracts isolated from myrtle are deeply documented, whereas those isolated from Saharan myrtle extracts are less studied. In both species, the major groups of constituents include gallic acid derivatives, flavonols, flavonol derivatives, and hydroxybenzoic acids. In coloured berries, anthocyanins are also present. In M. nivellei extracts are reported for some compounds not described in M. communis so far: 2-hydroxy-1,8-cineole-ß-d-glucopyranoside, 2-hydroxy-1,8-cineole 2-O-α-l-arabinofuranosyl (1→6)-ß-d-glucopyranoside, rugosin A, and rugosin B. Berries and leaves extracts of both species had antioxidant activity. Comparative studies of the antioxidant activity between leaf and berry myrtle extracts revealed that leaf extracts are best antioxidants, which can be assigned to the galloyl derivatives, flavonols, and flavonols derivatives, although the ratio of these groups of compounds might also have an important role in the antioxidant activity. The anthocyanins present in myrtle berries seem to possess weak antioxidant activity. The antioxidant activity of sample extracts depended on various factors: harvesting time, storage, extraction solvent, extraction type, and plant part used, among other factors. Leaf extracts of myrtle revealed to possess anti-inflammatory activity in several models used. This property has been attributed either to the flavonoids and/or hydrolysable tannins, nevertheless nonprenylated acylphloroglucinols (e.g., myrtucommulone and semimyrtucommulone) have also revealed a remarkable role in that activity. The biological activities of myrtle extracts found so far may direct its use towards for stabilizing complex lipid systems, as prebiotic in food formulations, and as novel therapeutic for the management of inflammation.

Oxidative Signaling Response to Cadmium Exposure.

Changes in the intracellular thiol-disulfide balance are considered major determinants in the redox status/signaling of the cell. Cellular signaling is very sensitive to both exogenous and intracellular redox status and respond to many exogenous pro-oxidative or oxidative stresses. Redox status has dual effects on upstream signaling systems and downstream transcription factors. Redox signaling pathways use reactive oxygen species (ROS) to transfer signals from different sources to the nucleus to regulate such functions as growth, differentiation, proliferation, and apoptosis. Mitogen-activated protein kinases are activated by numerous cellular stresses and ligand-receptor bindings. An imbalance in the oxidant/antioxidant system, either resulting from excessive ROS/reactive nitrogen species production and/or antioxidant system impairment, leads to oxidative stress. Glutathione (GSH) is known to play a critical role in the cellular defense against unregulated oxidative stress in mammalian cells and involvement of large molecular antioxidants include classical antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR). Cadmium (Cd), a potent toxic heavy metal, is a widespread environmental contaminant. It is known to cause renal dysfunction, hepatic toxicity, genotoxicity, and apoptotic effects depending on the dose, route, and duration of exposure. This review examines the signaling pathways and mechanisms of activation of transcription factors by Cd-induced oxidative stress thus representing an important basis for understanding the mechanisms of Cd effect on the cells.

Cadmium-induced oxidative damages in the human BJAB cells correlate with changes in intracellular trace elements levels and zinc transporters expression.

Cadmium (Cd), a potent toxic heavy metal, is a widespread environmental contaminant. Its cellular traffic via pathways dedicated to transition metals contributes to the toxicity mechanisms. Zinc (Zn) homeostasis is complex, involving both zinc importers (Zip) and zinc exporters (ZnT). Cellular signal transduction pathways are influenced by Zn and redox status of the cell. The aim of the present study is to examine if the accumulation of Cd in the human lymphocyte B cell line BJAB and its capacity to promote oxidative stress and adverse effects could result from changes in the mRNA expression pattern of Zn transporters and metallothioneins. Cells were exposed to 5, 10, 20 and 40µM of CdCl2 equivalent to 0.91, 1.83, 3.66 and 7.33µg/ml respectively, for 24h. Cd significantly reduced the viability of BJAB cells and induced a dose-dependent increase in DNA damage. Cd also induced the formation of 8-hydroxy-2'-deoxyguanosine adducts and augmented MTF1 expression in BJAB cells. We observed interesting responses in relative gene expression to Cd exposure among the seven transporters we analyzed. Cd exposure increased the expression of DMT1 and caused an up-regulation of ZnT1. However, the T calcium channel alpha1G subunit could not be detected. A change in expression of ZnTs and Zips in response to Cd exposure emphasizes the involvement of Zn transporters in Cd cellular metabolism and induced oxidative stress.

Protective effect of olive oil and colocynth oil against cadmium-induced oxidative stress in the liver of Wistar rats.

Cadmium (Cd) is one of the most common heavy metal pollutants. It is accumulated particularly in liver and kidney. The present study examined the possible protective effect of olive oil and colocynth oil consumption against Cd-induced damage on plasma lipids and stress biochemical parameters of rats. Male albino Wistar rats were randomly divided into 6 groups of 5 animals each and treated orally with Cd (50 mg/l), olive oil and colocynth oil (4%) alone or in combination with cadmium for 8 weeks. It was shown that Cd exposure induced significant increases in the activities of serum alanine aminotransferase, aspartate aminotransferase, lipid peroxidation levels (MDA) and protein carbonyl contents in exposed groups of rats compared to control group while the antioxidant enzymes, reduced glutathione and vitamins (C, A and E) were significantly decreased. Co-treatment with olive oil or colocynth oil significantly improved the oxidative damage induced by Cd. The antioxidant potential in plasma and liver were markedly restored with a significant decline in MDA levels and activity of transaminases. In conclusion, these results suggest that olive oil or colocynth oil consumption could protect the rat liver against Cd-induced injury by increasing the activities of antioxidant enzymes and reducing oxidative stress.

Cadmium-induced apoptosis in the BJAB human B cell line: involvement of PKC/ERK1/2/JNK signaling pathways in HO-1 expression.

Heme oxygenase-1 (HO-1, EC 1.14.99.3) is a key enzyme in the cellular response to tissue injury and oxidative stress. It oxidizes heme, a pro-oxidant and toxic species, to biliverdin, CO, and free iron. Cytoprotection during the heat shock response is a complex phenomenon involving multiple inducible mechanisms. Several important pathways involving serine/threonine kinases mediate the induction of HO-1 in response to external stimuli. The objective of the present study was to investigate the mechanism of HO-1 induction during cadmium (Cd)-induced oxidative stress and apoptosis in the lymphocyte B cell line BJAB. To examine the signal pathways involved in HO-1 expression, cells were pre-treated with various inhibitors of key signaling molecules. Increased DNA fragmentation and caspase-3 activity were observed in BJAB cells exposed to 5-40 µM CdCl(2) revealing that Cd induced apoptosis in these cells. Our results indicate that Cd also induces HO-1 expression which is modulated by the thiol redox status, tyrosine kinase and PI3-kinase. The inhibitory effect of calphostin C suggests that Cd induction of HO-1 expression could be mediated by the PKC pathway in the BJAB cells together with the involvement of ERK ½ and JNK in a dose-dependent manner. The molecular and cellular pathways should not be considered separately. They should be viewed as an array of interconnecting signals, all contributing to the final outcome, thereby allowing fine control of the duration and extent of HO-1 induction.

Cadmium chloride-induced oxidative stress and DNA damage in the human Jurkat T cell line is not linked to intracellular trace elements depletion.

Cadmium (Cd) is a widespread environmental contaminant. Cd affects the cellular homeostasis and generates damage via complex mechanisms involving interactions with other metals, induction of oxidative stress and apoptotic or necrotic cell death, depending on the cell type and the concentration. The goal of the present study was to investigate the effect of exposure to CdCl(2) on the intracellular trace elements levels, the antioxidant enzyme activities and on DNA damage in the Jurkat T cell line. Cells were exposed to 5, 25 and 50 µM of CdCl(2) for 24 h. Cd significantly reduced the viability of Jurkat T cells and induced a dose-dependent increase in DNA damage with statistically significant differences relative to controls (p<0.001); the superoxide dismutase and glutathione peroxidase activities were significantly decreased. Lipid peroxidation and protein carbonyl levels were significantly increased while glutathione and the total intracellular sulfhydryl groups were decreased showing clearly that an oxidative stress was generated by Cd. Surprisingly the treatment with Cd induced a significant increase in the intracellular levels of all the trace elements measured. The results indicate that cellular pro-oxidative stress induced by Cd is most likely mediated by disruption of redox homeostasis associated to a mishandling of redox-active transition metals and causes lipid and protein oxidation and oxidative DNA damage in Jurkat T cells.

Role of alpha-tocopherol in cadmium-induced oxidative stress in Wistar rat's blood, liver and brain.

Cadmium (Cd) a highly toxic metal is considered to be a multitarget toxicant, and it accumulates principally in the liver and kidney after absorption. In vivo studies of mouse and rat liver have shown that apoptosis plays a primary role in Cd-induced hepatotoxicity. However, the detailed mechanisms by which toxic metals such as Cd produce their effects are still largely unknown. The present study aimed at investigating the consequences of exposure to Cd, alpha-tocopherol and their combination on stress biochemical parameters (lipoperoxidation and protein carbonyls levels). Male albino Wistar rats (1 month old) were treated intravenously with cadmium (2 mg CdCl(2)/kg body weight/day), and alpha-tocopherol (100 mg/kg body weight/day), or with alpha-tocopherol+Cd (100 mg Vit E/kg body weight, 2 mg CdCl(2)/kg). The lipoperoxidation was measured by the thiobarbituric acid reactive substances (TBARS) method and oxidatively generated damage to proteins by determining carbonyl (DNPH) levels. Among the hematological parameters measured the haematocrit value and haemoglobin concentration were significantly decreased in the blood of Cd-treated rats. A significant increase was observed in the level of malondialdehyde (MDA) and protein carbonyls in the cadmium exposed group compared to control group (p<0.001), and these values were decreased after administration of alpha-tocopherol (group 4). The activity of lactate dehydrogenase in rat liver and brain showed a significant increase as compared to that found in the control group and significant decrease of catalase and superoxide dismutase activities. In the liver of the Cd-treated group the contents of reduced glutathione were decreased. Our results suggest that cadmium induces an oxidation of cellular lipids and proteins and that administration of alpha-tocopherol can reduce Cd-induced oxidative stress and improve the glutathione level together with other biochemical parameters.