RESUMO
BACKGROUND: Hexavalent chromium (CrVI) is known to be a potentially hepatotoxic and nephrotoxic contaminant in humans and other animals, whose toxicity is associated with oxidative stress and inflammation. The aim of this study was to evaluate the potential protective effect of chlorogenic acid (CGA), which has known anti-inflammatory and antioxidant effects, on potassium dichromate (PDC)-induced acute hepatotoxicity and nephrotoxicity in rats. METHODS AND RESULTS: Thirty-six Wistar albino rats were treated with CGA (10, 20, or 40 mg/kg, intraperitoneally) and/or PDC (15 mg/kg/day, intraperitoneally) as a single dose. Serum, liver, and kidney tissues were examined biochemically, histopathologically, and immunohistochemically. Compared to the control group, a significant increase in interleukin-6 (IL-6) levels and a significant decrease in serum and renal reduced glutathione (GSH) levels, liver catalase (CAT), tumour necrosis factor-alpha (TNF-α), and interleukin 1ß (IL-1ß) levels were observed in the PDC group. The administration of PDC led to histopathological and immunohistochemical changes in rat liver and kidney tissues. With the administration of CGA, especially at the 10 mg/kg dosage, the above-mentioned parameters approached normal levels. CONCLUSIONS: CGA had antioxidant and anti-inflammatory effects that alleviated PDC-induced acute hepato- and nephrotoxicity.
Assuntos
Antioxidantes , Ácido Clorogênico , Rim , Fígado , NF-kappa B , Estresse Oxidativo , Dicromato de Potássio , Ratos Wistar , Transdução de Sinais , Animais , Dicromato de Potássio/toxicidade , Ácido Clorogênico/farmacologia , Ratos , Transdução de Sinais/efeitos dos fármacos , NF-kappa B/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Estresse Oxidativo/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Interleucina-6/metabolismo , Glutationa/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-1beta/metabolismo , Catalase/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológicoRESUMO
Lactoferrin (LCF), a potent naturally occurring antioxidant, is a crucial component in preventing potassium dichromate (PDC) toxicity. The goal of the current work was to study the potential efficacy of LCF in preventing PDC(CrVI)-induced testicular toxicity and oxidative injury in rats. Six groups of male rats of Wistar stain were randomly categorized into: group 1, which served as the control; group 2 and 3 received LCF (200 and 300 mg/kg orally, respectively); group 4 received PDC (2 mg/kg i.p.); group 5 and 6 pretreated with LCF, followed by PDC as in group 4 with 90 min apart for 28 days. PDC-intoxicated rats showed a significantly altered spermogram with abnormal sperm morphology. PDC significantly upregulated serum FSH and downregulated testosterone levels. Additionally, PDC decreased the levels of testicular key antioxidant biomarkers (catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH)) with elevated lipid peroxidation marker (TBARS) and testicular chromium content. Moreover, it upregulated testicular proinflammatory cytokines, IL-1, IL-6, IL-10, and TNF-α, induced histopathological changes in testes with significant immunohistochemical expression of FasL and moderate expression of Nrf2. Pretreatment with LCF significantly mitigated PDC-induced testicular toxicity by enhancing spermogram, improving hormonal levels, restoring testicular oxidant/antioxidant balance, and decreasing testicular IL-1, IL6, IL-10, and TNFα levels, and amending both FasL and Nrf2 immunohistochemical-expression. Additionally, LCF improved testicular histopathological picture and spermatogenesis. Our results highlight the importance of LCF as a superior protective modulator of PDC-induced testicular injury.
Assuntos
Antioxidantes , Testículo , Ratos , Masculino , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Lactoferrina/farmacologia , Interleucina-10 , Cromo/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Ratos Wistar , Sêmen/metabolismo , Estresse Oxidativo , Glutationa/metabolismo , Dicromato de Potássio/toxicidade , Interleucina-1RESUMO
Environmental and occupational exposure to chromium compounds, especially hexavalent chromium [Cr(VI)], is widely recognized as a potential nephrotoxic in humans and animals. Its toxicity is associated with the overproduction of free radicals, which induces oxidative damage. Echinacea purpurea (L.) Moench is an herbaceous perennial plant rich in phenolic components and frequently used for its medicinal benefits. The current work evaluated the effectiveness of E. purpurea (EP) against oxidative stress and nephrotoxicity induced by potassium dichromate in male rats. Male Wistar rats were divided into four groups: control, E. purpurea (EP; 50 mg/kg; once daily for 3 weeks), hexavalent chromium (Cr(VI); 15 mg/kg; single intraperitoneal dose), and EP + Cr(VI) where rats were pretreated with EP for 3 weeks before receiving CrVI, respectively. Results revealed that rats exposed to Cr(VI) showed a significant increase in PC, TBARS, and H2 O2 , kidney function biomarkers (Urea, creatinine, and uric acid), lactate dehydrogenase activity (LDH), TNF-α, IL-18, nuclear factor kappa B (NFκB), and IGF-1 (Insulin-like growth factor-1) levels as well as a considerable decline in metallothionein (MT), glutathione (GSH) content, enzymatic antioxidants (SOD, CAT, GPx, GR, and GST), alkaline phosphatase (ALP) activities, and protein content. Cr(VI) induced apoptosis in kidney tissues as revealed by upregulation of Bax and caspase 3 and downregulation of Bcl-2. Furthermore, EP treatment ameliorated the Cr(VI)-induced histopathological and ultrastructure variations of kidney tissue, which was confirmed by the biochemical and molecular data. It is clear from the results of this study that EP exerts nephroprotective effects by improving the redox state, suppressing inflammatory reaction and cell apoptosis as well as ameliorating the performance of kidney tissue architecture, which is eventually reflected by the improvement of kidney function in rats.
Assuntos
Echinacea , Estresse Oxidativo , Preparações de Plantas , Dicromato de Potássio , Animais , Antioxidantes/metabolismo , Apoptose , Cromo/toxicidade , Echinacea/química , Glutationa/metabolismo , Inflamação/metabolismo , Rim , Preparações de Plantas/farmacologia , Dicromato de Potássio/toxicidade , Ratos , Ratos WistarRESUMO
Adenosine monophosphate-activated protein kinase (AMPK) has a crucial role in neuroprotection. It phosphorylates serine/threonine kinase (Akt) Substrate inhibiting the inflammatory responses induced by the nuclear factor-κB (NF-κB). Exposure to chromium VI dust among workers has been reported and induced brain injury, as the absorption of chromium through the nasal membrane has been found to deliver it directly to the brain. The study aimed to investigate the influence of administration of L-carnitine or/and Co Q10 as theraputic agents against potassium dichromate (PD)-induced brain injury via AMPK/AKT/NF-κß signaling pathway. Brain injury was induced by PD intranasally as a single dose of 2 mg/kg, 24 h latter rats received L-carnitine (100 mg/kg; orally), Co Q10 (50 mg/kg; orally) and L-carnitine (50 mg/kg; orally) + Co Q10 (25 mg/kg; orally) respectively for 3 days. Locomotor activity was assessed before and at the end of the experiment, then, biochemical and histopathological investigations were assessed in brain homogenate. The exposure of rats to PD promoted oxidative stress and inflammation via an increase in MDA and a decrease in GSH brain contents with an increase in brain contents of TNF-α, IL-6, and NF-kß and reduced AMPK and AKT brain contents as compared to the control group. Treatment with L-carnitine + Co Q10 ameliorated cognitive impairment and oxidative stress, decreased the brain contents of inflammatory mediators; TNF-α, IL-6, and NF-κß elevated AMPK and AKT, as compared to each drug. Also, L-carnitine + Co Q10 administration restored morphological changes as degenerated neurons and necrosis. L-carnitine + Co Q10 play important role in AMPK/AKT/NF-κß pathway that responsible for their antioxidant and anti-inflammatory effects against PD-induced brain injury in rats.
Assuntos
Lesões Encefálicas/induzido quimicamente , Lesões Encefálicas/tratamento farmacológico , Carnitina/farmacologia , Dicromato de Potássio/toxicidade , Ubiquinona/análogos & derivados , Animais , Biomarcadores/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Distribuição Aleatória , Ratos , Ratos Wistar , Ubiquinona/farmacologia , Vitaminas/farmacologiaRESUMO
BACKGROUND: Chromium hexavalent (CrVI) is known as a toxic contaminant that induced oxidative stress and nephrotoxicity in humans and animals. Rosmarinus officinalis is a perennial herb rich in biologically active constituents that have powerful antioxidant properties. So, the current work evaluated the effectiveness of Rosmarinus officinalis essential oil (REO) against alterations induced by potassium dichromate in the kidney of male rats. METHODS: GC-MS analysis, in vitro total phenol contents, and DPPH scavenging activity of REO were estimated. Thirty-five Wistar male rats were categorized into 5 groups. The first group was the control, the second one was orally administered rosemary essential oil (REO; 0.5 mL/kg BW), the third group was injected intraperitoneally with hexavalent chromium (CrVI; 2 mg/kg BW) for 14 days, the fourth group used as the protective group (REO was administrated 30 min before i.p. injection of CrVI) and the fifth group applied as the therapeutic group (rats injected with CrVI 30 min followed by oral administration of REO), respectively. RESULTS: Twenty-nine components were detected with high total phenolic contents and high DPPH scavenging activity. Results revealed that CrVI- intoxicated rats showed a valuable increase in oxidative stress profile (TBARS and H2O2) and a notable decline in glutathione (GSH), total protein content, and enzymatic antioxidants (SOD, CAT, GPx, and GST). Furthermore, serum kidney functions biomarkers (urea, creatinine, and uric acid) were increased significantly. Also, the administration of CrVI showed histological and immunohistochemical (PCNA-ir) changes in rat kidney tissue. Otherwise, administration of REO pre or post-treatment with CrVI significantly restored most of the biochemical parameters in addition to improvement in kidney tissue architecture. Moreover, individual intake with REO exhibited an amendment in oxidative stress markers. CONCLUSION: Conclusively, REO had a potential antioxidant capacity in ameliorating K2Cr2O7-induced nephrotoxicity, especially in the protection group.
Assuntos
Óleos Voláteis , Dicromato de Potássio/toxicidade , Rosmarinus , Animais , Antioxidantes/metabolismo , Glutationa/metabolismo , Peróxido de Hidrogênio/metabolismo , Rim/metabolismo , Peroxidação de Lipídeos , Masculino , Óleos Voláteis/metabolismo , Óleos Voláteis/farmacologia , Estresse Oxidativo , Fenóis/metabolismo , Ratos , Ratos Wistar , Rosmarinus/metabolismoRESUMO
We have reported sub-fertility in F1 progeny rats with gestational exposure to hexavalent chromium [Cr(VI)], which had disrupted Sertoli cell (SC) structure and function, and decreased testosterone (T). However, the underlying mechanism for reduced T remains to be understood. We tested the hypothesis "transient prenatal exposure to Cr(VI) affects testicular steroidogenesis by altering hormone receptors and steroidogenic enzyme proteins in Leydig cells (LCs)." Pregnant Wistar rats were given drinking water containing 50, 100, and 200 mg/L potassium dichromate during gestational days 9-14, encompassing fetal differentiation window of the testis from the bipotential gonad. F1 male rats were euthanized on postnatal day 60 (peripubertal rats with adult-type LCs alone). Results showed that prenatal exposure to Cr(VI): (i) increased accumulation of Cr(III) in the testis of F1 rats; (ii) increased serum levels of luteinizing and follicle stimulating hormones (LH and FSH), and 17ß estradiol, and decreased prolactin and T; (iii) decreased steroidogenic acute regulatory protein, cytochrome P450 11A1, cytochrome P450 17A1, 3ß- and 17ß-hydroxysteroid dehydrogenases, cytochrome P450 aromatase and 5α reductase proteins, (iv) decreased specific activities of 3ß and 17ß hydroxysteroid dehydrogenases; (v) decreased receptors of LH, androgen and estrogen in LCs; (vi) decreased 5α reductase and receptor proteins of FSH, androgen, and estrogen in SCs. The current study concludes that prenatal exposure to Cr(VI) disrupts testicular steroidogenesis in F1 progeny by repressing hormone receptors and key proteins of the steroidogenic pathway in LCs and SCs.
Assuntos
Carcinógenos Ambientais/toxicidade , Cromo/toxicidade , Dicromato de Potássio/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Testículo/efeitos dos fármacos , 17-Hidroxiesteroide Desidrogenases/metabolismo , Animais , Colestenona 5 alfa-Redutase/metabolismo , Cromo/sangue , Feminino , Hormônios/sangue , Masculino , Troca Materno-Fetal , Dicromato de Potássio/sangue , Gravidez , Ratos Wistar , Receptores do LH/metabolismo , Receptores da Prolactina/metabolismo , Receptores de Esteroides/metabolismo , Testículo/metabolismo , Testículo/patologiaRESUMO
OBJECTIVES: Exposure to arsenic and hexavalent chromium is a major public health concern especially in the developing part of the world and there is paucity of information on reliable treatment modalilities. It is in this regard that this study evaluates the efficacy of methanol leaf extract of Rauvolfia vomitoria (MRV) when used as pretreatment agent against potassium dichromate (K2Cr2O7) and sodium arsenite (NaAsO2) exposure. METHODS: Swiss albino mice between 7 and 10 weeks old were divided into eight cohorts of five animals each. Treatment groups consisted of a distilled water control, MRV alone (275 mg/kg po daily), K2Cr2O7 (12.0 mg/kg, single ip injection) +/- MRV pretreatment, NaAsO2 (2.5 mg/kg, single ip injection) +/- MRV pretreatment, Na2AsO2 + K2Cr2O7 +/- MRV pretreatment. MRV was given for seven consecutive days, while K2Cr2O7 and NaAsO2 were injected on day seven of the experiment. The frequency of micronucleated polychromatic erythrocytes (mPCEs) was determined in bone marrow cells, while aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were assessed in the plasma. Hepatic glutathione (GSH), malondialdehyde (MDA), catalase (CAT) and glutathione-S-transferase (GST) levels were also determined. RESULTS: The NaAsO2 and K2Cr2O7 significantly (p<0.05) increased mPCE formation, AST, ALT, and CAT when compared with the control. Simultaneous exposure to NaAsO2 and K2Cr2O7 further increased the levels of the markers. Furthermore, GSH and GST were significantly reduced by NaAsO2 or K2Cr2O7 or their combination. Pretreatment with MRV reversed the markers towards that of control. CONCLUSIONS: Methanol extract of Rauvolfia vomitoria may therefore ameliorate NaAsO2 and K2Cr2O7-induced toxicities via reduction of oxidative stress and fortification of anti-oxidant system.
Assuntos
Arsenitos , Extratos Vegetais , Dicromato de Potássio , Rauwolfia , Animais , Antioxidantes/metabolismo , Arsenitos/toxicidade , Biomarcadores/metabolismo , Glutationa/metabolismo , Fígado/metabolismo , Metanol , Camundongos , Estresse Oxidativo , Extratos Vegetais/farmacologia , Dicromato de Potássio/toxicidade , Ratos , Ratos Wistar , Rauwolfia/química , Compostos de Sódio/toxicidadeRESUMO
Chromium (Cr) threatens health by causing oxidative stress. However, effective therapy for cardiac damage mediated by potassium dichromate (K2Cr2O7) still has not been defined. Melatonin (MT) possesses a number of biological activities. Our study was performed to explore the effect and mechanism of MT on Cr(VI)-induced cardiac damage by conducting both in vitro and in vivo studies. Twenty eight male Wistar rats were randomly assigned to four groups: control, MT (20â¯mg/kg subcutaneously), K2Cr2O7 (4â¯mg/kg intraperitoneally), and K2Cr2O7â¯+â¯MT. We measured biomarkers of oxidative stress and cardiac function, and performed histopathological analysis, assay of terminal deoxynucleotidyl transferase-mediated deoxyuracil nucleoside triphosphate nick end labeling and protein levels, and the viability assay of cultured cardiomyocytes in vitro. Our results showed that MT ameliorated K2Cr2O7-induced oxidative stress, apoptosis, and the release of inflammatory mediators in the rat heart. MT also promoted adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, upregulated expression of proteins that nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1, and nicotinamide adenine dinucleotide phosphatase: quinone-acceptor 1, and inhibited nuclear factor kappa B in the heart of rats exposed to K2Cr2O7. Furthermore, MT increased B-cell lymphoma gene 2 (Bcl-2) and B-cell lymphoma extra large protein levels and decreased cleaved caspase 3, P53, and Bcl-2-associated X protein levels. Furthermore, the experiment in vitro showed that MT increased the cells viability and protein levels of Nrf2 and phosphorylated-AMPK in H9C2 cells treated with K2Cr2O7. Collectively, our results demonstrate that MT protects against Cr-induced cardiac damage via activating the AMPK/Nrf2 pathway.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Cardiotônicos/farmacologia , Cromo/toxicidade , Cardiopatias , Melatonina/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Cardiopatias/induzido quimicamente , Cardiopatias/metabolismo , Cardiopatias/patologia , Cardiopatias/prevenção & controle , Masculino , Dicromato de Potássio/toxicidade , Ratos , Ratos WistarRESUMO
Curcumin exhibits several therapeutic properties. Potassium dichromate (K2Cr2O7)-induced nephropathy is associated with oxidative stress. Reactive oxygen species production affects renal oxygenation that may participate in the progression of renal damage. The aim of the present work was to elucidate whether K2Cr2O7-induced nephropathy is associated to partial O2 pressure (pO2) impairment and if curcumin is able to prevent it. Four groups of rats were studied: control group; K2Cr2O7 group (12.5 mg/kg, s.c.); curcumin + K2Cr2O7 group, in which animals were treated with curcumin (400â¯mg/kg/day, p.o.) for 10 days before K2Cr2O7 injection; and curcumin group. All animals were sacrificed 48â¯h after the end of the treatments. K2Cr2O7 administration increased renal function markers and decreased glomerular filtration rate, pO2 and renal perfusion. Concerning hemodynamic parameters, K2Cr2O7 increased mean arterial pressure and renal vascular resistance and reduced renal blood flow. The hemodynamic changes were attributed to decreased availability of nitric oxide and increased 3-nitrotyrosine levels. Moreover, increased superoxide anion production and vascular endothelial growth factor levels were observed after K2Cr2O7 administration. Curcumin attenuated all the above-described alterations. Our results suggest that the protective effects of curcumin in K2Cr2O7-induced nephropathy are associated with its ability to prevent O2 supply reduction.
Assuntos
Curcumina/farmacologia , Rim/efeitos dos fármacos , Oxigênio/metabolismo , Dicromato de Potássio/toxicidade , Animais , Taxa de Filtração Glomerular/efeitos dos fármacos , Hemodinâmica , Masculino , Nitratos/urina , Óxido Nítrico Sintase/metabolismo , Dióxido de Nitrogênio/urina , Fitoterapia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Fator A de Crescimento do Endotélio VascularRESUMO
The current study examined the ameliorative effects of nano-elemental selenium (Nano-Se) against chromium-VI (K2Cr2O7)-induced apoptosis in chickens. The expression of apoptosis-related genes was evaluated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot. A total of 60, one-day-old broiler chickens allotted to six equal groups, i.e., control group (standard diet), Cr(VI)-exposed group (K2Cr2O7 via drinking water), Nano-Se group (Nano-Se at 0.5 mg/kg via diet), protection group (K2Cr2O7 + Nano-Se), cure group (K2Cr2O7 for initial 2 weeks and then Nano-Se), and prevention group (opposite to the cure group) and were detected by the activities of pro-apoptosis (Bax, Caspase-3) and anti-apoptosis (Bcl-2) genes expression at day 35 of the experiment. Intense apoptosis was observed in liver tissues of chickens exposed to K2Cr2O7. The Nano-Se supplementation caused a significant decrease (P < 0.01) in the mRNA expression levels of Bax and Caspase-3 genes, while significantly elevated (P < 0.05) mRNA expression level of Bcl-2 gene was observed in Nano-Se experimental groups as compare to control and Cr(VI)-exposed group. The results quantified by the RT-qPCR were further confirmed by the western blot analysis. Altogether, these results suggest anti-apoptotic effects of Nano-Se in the chicken liver, which is interesting for further study. The present findings suggested that Nano-Se has protective effects against K2Cr2O7-induced apoptosis in broilers liver and can serve a key role as a protective agent against apoptosis.
Assuntos
Apoptose/efeitos dos fármacos , Galinhas/metabolismo , Cromo/toxicidade , Fígado/efeitos dos fármacos , Dicromato de Potássio/toxicidade , Substâncias Protetoras/farmacologia , Selênio/farmacologia , Ração Animal/análise , Animais , Proteínas Aviárias/genética , Proteínas Aviárias/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Galinhas/genética , Dieta/veterinária , Suplementos Nutricionais/análise , Expressão Gênica , Genes bcl-2/genética , Genes bcl-2/fisiologia , Fígado/fisiopatologia , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
Our study designed to study the potential of potassium dichromate (K2Cr2O7) oral exposure to induce damage in male rat brain and to compare the possible protective role of vitamin C (VC) either pre and/or concurrent supply against (K2Cr2O7) induced changes. Thirty male rats were divided into five groups. First control group received distilled water (C), second received 120 mg/kg b.wt (VC), third received 25 mg/kg b.wt K2Cr2O7 (Cr), fourth group received VC together with K2Cr2O7 by the same former doses (VC + Cr), and the fifth group received the same oral doses of VC 2 weeks prior to and along with K2Cr2O7 for 6 weeks (VC + Cr pro/co treated). The obtained results revealed that K2Cr2O7 induced a significant decrease in cholinergic activity, glutathione reductase GR activity, reduced glutathione content GSH and ATP levels. Furthermore, K2Cr2O7 induced a significant increase in oxidative DNA damage indicated by 8-hydroxy 2'-deoxyguanosine (8OH2'dG) and formation of apoptotic DNA ladders, significant increase in malondialdehyde (MDA), protein carbonyl, and lactate dehydrogenase enzyme. Increased mRNA expression of pro-apoptotic genes, including caspase-3, p53, and Bax, unlike Bcl-2 expression, was decreased. K2Cr2O7 increased caspase-3 and decreased Bcl-2 immuno-labeling. VC supply noticeably ameliorates K2Cr2O7-induced changes which were more significantly in VC pro and concurrent supplement rather than VC concurrent supply only. Finally, it is concluded that K2Cr2O7 oral administration induced oxidative apoptotic changes in rat brain and confirms the usefulness of VC pre and concurrent supply for the amelioration of K2Cr2O7-induced events more significantly than VC concurrent supply only.
Assuntos
Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Ácido Ascórbico/farmacologia , Encéfalo/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Administração Oral , Animais , Apoptose/genética , Encéfalo/metabolismo , Encéfalo/patologia , Caspase 3/genética , Masculino , Estresse Oxidativo/genética , Dicromato de Potássio/toxicidade , Proteínas Proto-Oncogênicas c-bcl-2/genética , Ratos Sprague-Dawley , Proteína Supressora de Tumor p53/genética , Proteína X Associada a bcl-2/genéticaRESUMO
The toxicity of hexavalent chromium [Cr(VI)] in biological systems is thought to be closely associated with the generation of free radicals and reactive oxygen species. These species are produced when Cr(VI) is reduced to its trivalent form in the cell. This process results in oxidative stress due to an imbalance between the detoxifying ability of the cell and the production of free radicals. We have studied the effect of potassium dichromate (K2Cr2O7), a [Cr(VI)] compound, on the antioxidant power of human erythrocytes and lymphocytes under in vitro conditions. Incubation of erythrocytes and lymphocytes with different concentrations of K2Cr2O7 resulted in a marked dose-dependent decrease in reduced glutathione and an increase in oxidized glutathione and reactive oxygen species levels. The antioxidant power of the cells was decreased, as determined by metal reducing and free radical quenching assays. These results show that [Cr(VI)] upregulates the generation of reactive oxygen species and, as a consequence, the cellular antioxidant defences are compromised. The resulting oxidative stress may contribute to Cr(VI)-induced cellular damage.
Assuntos
Cromo/toxicidade , Eritrócitos/efeitos dos fármacos , Radicais Livres/metabolismo , Linfócitos/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Adulto , Células Cultivadas , Eritrócitos/metabolismo , Glutationa/metabolismo , Humanos , Linfócitos/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Dicromato de Potássio/toxicidade , Adulto JovemRESUMO
The biological reactivity of metal and metal oxide nanomaterials is attributed to their redox properties, which would explain their pro- or anti-cancer properties depending on exposure circumstances. In this sense, copper oxide nanoparticles (CuONP) have been proposed as a potential anti-tumoral agent. The aim of this study was to assess if CuONP can exert antigenotoxic effects using Drosophila melanogaster as an in vivo model. Genotoxicity was induced by two well-known genotoxic compounds, namely potassium dichromate (PD) and ethyl methanesulfonate (EMS). The wing-spot assay and the comet assay were used as biomarkers of genotoxic effects. In addition, changes in the expression of Ogg1 and Sod genes were determined. The effects of CuONP cotreatment were compared with those induced by copper sulfate (CS), an agent releasing copper ions. Using the wing-spot assay, CuONP and CS were not able to reduce the genotoxic effects of EMS exposure, but had the ability to decrease the effects induced by PD, reducing the frequency of mutant twin-spots that arise from mitotic recombination. In addition, CuONP and CS were able to reduce the DNA damage induced by PD as determined by the comet assay. In general, similar qualitative antigenotoxic effects were obtained with both copper compounds. The antigenotoxic effects of environmentally relevant and non-toxic doses of CuONP and CS may be explained by their ability to partially restore the expression levels of the repair gene Ogg1 and the antioxidant gene Cu,ZnSod, both of which are inhibited by PD treatment. Environ. Mol. Mutagen. 58:46-55, 2017. © 2016 Wiley Periodicals, Inc.
Assuntos
Antimutagênicos/farmacologia , Sulfato de Cobre/farmacologia , Cobre/farmacologia , Dano ao DNA/efeitos dos fármacos , Drosophila melanogaster/efeitos dos fármacos , Nanopartículas/química , Animais , Antimutagênicos/química , Ensaio Cometa , Cobre/química , Sulfato de Cobre/química , DNA Glicosilases/genética , Reparo do DNA/efeitos dos fármacos , Reparo do DNA/genética , Relação Dose-Resposta a Droga , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Metanossulfonato de Etila/toxicidade , Mutagênicos/toxicidade , Dicromato de Potássio/toxicidade , Reação em Cadeia da Polimerase em Tempo Real , Superóxido Dismutase/genética , Propriedades de Superfície , Asas de Animais/efeitos dos fármacosRESUMO
Exposure to hexavalent chromate compounds such as other human carcinogens is unavoidable in the developing countries of the world. Research efforts are being directed toward minimizing exposure to them, intercepting their activity in vivo, and/or prophylaxis. The present study therefore evaluates the effect of methanol extract of the leafy vegetable, Corchorus olitorius (MECO), against potassium dichromate (K2Cr2O7)-induced toxicities. Negative control animals were fed distilled water, while the positive control rats received 12 mg/kg body weight K2Cr2O7 once a week for 6 weeks. Test rats were exposed daily to 25, 50, and 100 mg/kg body weight MECO alone for 6 weeks and 12 mg/kg body weight of K2Cr2O7 once a week for 6 weeks before sacrifice. The frequency of micronucleated polychromatic erythrocytes (mPCEs) was monitored in bone marrow cells, while induction of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine levels, and hematological parameters were assessed in the plasma. The phytochemical analysis of MECO was also carried out. K2Cr2O7 significantly (P < .05) increased the levels of mPCEs, AST, ALT, creatinine, total white blood cells, and lymphocytes compared with the control. The percentage pack cell volume and neutrophils were, however, reduced. In contrast, MECO at different doses restored the markers toward the levels of the negative control. MECO is rich in flavonoids, saponins, anthraquinones, terpenoids, and phenols, and they might be responsible for the protective effect observed in this study. Our results suggest that MECO has a promising potential in the treatment/management of chromate-induced toxicities.
Assuntos
Corchorus/química , Intoxicação por Metais Pesados , Extratos Vegetais/administração & dosagem , Intoxicação/tratamento farmacológico , Dicromato de Potássio/toxicidade , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Creatinina/sangue , Flavonoides/administração & dosagem , Flavonoides/análise , Humanos , Masculino , Metais Pesados/sangue , Estresse Oxidativo , Extratos Vegetais/química , Folhas de Planta/química , Intoxicação/sangue , Ratos , Ratos WistarRESUMO
Hexavalent chromium (CrVI) is a heavy metal widely used in more than 50 industries. Nephrotoxicity is a major adverse effect of chromium poisoning. The present study investigated the potential renoprotective effect of lactoferrin (Lf) against potassium dichromate (PDC)-induced acute kidney injury (AKI) in rats. Beside, because previous studies suggest that interlukin-18 (IL-18) and insulin-like growth factor-1 (IGF-1) play important roles in promoting kidney damage, the present work aimed to evaluate the involvement of these two cytokines in PDC model of AKI and in the potential renoprotective effect of lactoferrin. Adult male albino Wistar rats were pretreated with Lf (200 mg/kg/day, p.o.) or (300 mg/kg/day, p.o.); the doses that are usually used in the experiment studies, for 14 days followed by a single dose of PDC (15 mg/kg, s.c.). PDC caused significant increase in serum urea, creatinine, and total protein levels. This was accompanied with decreased renal glutathione content, and increased renal malondialdehyde, IL-18, IL-4, nuclear factor kappa B (NFκB), IGF-1, and the phosphorylated form of forkhead box protein O1 (FoxO1) levels. Moreover, normal expression IFN-γ mRNA and enhanced expression of TNF-α mRNA was demonstrated in renal tissues. Histopathological investigations provoked deleterious changes in the renal tissues. Tubular epithelial hyperplasia and apoptosis were demonstrated immunohistochemically by positive proliferating cell nuclear antigen (PCNA), Bax, and Caspase-3 expression, respectively. Pretreatment of rats with Lf in both doses significantly corrected all previously mentioned PDC-induced changes with no significant difference between both doses. In conclusion, the findings of the present study demonstrated the involvement of oxidative stress, inflammatory reactions, tubular hyperplasia and apoptosis in PDC-induced AKI. It suggested a role of IL-18 through stimulation of IL-4-induced inflammatory pathway, and IGF-1 through triggering FoxO1-induced cell proliferation. Moreover, the study revealed that Lf protected the kidney against Cr-induced AKI in rats and significantly showed antioxidant, anti-inflammatory, and anti-proliferative properties with down-regulation of IL-18 and IGF-1.
Assuntos
Injúria Renal Aguda/prevenção & controle , Fator de Crescimento Insulin-Like I/metabolismo , Interleucina-18/metabolismo , Lactoferrina/farmacologia , Dicromato de Potássio/toxicidade , Substâncias Protetoras/farmacologia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/metabolismo , Animais , Modelos Animais de Doenças , Fatores de Transcrição Forkhead/metabolismo , Fator de Crescimento Insulin-Like I/antagonistas & inibidores , Interferon gama/genética , Interleucina-18/antagonistas & inibidores , Interleucina-4/metabolismo , Rim/metabolismo , Rim/patologia , Masculino , NF-kappa B/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Fator de Necrose Tumoral alfa/genéticaRESUMO
Hexavalent chromium [Cr (VI)] is prevalent in ground water in some areas, but evidence on the toxic effects of Cr (VI) via ingestion through drinking water remains insufficient. The aims of our study were to investigate the toxic effects of Cr (VI) through oral water ingestion on oxidative stress and DNA methylation. Thirty-two Sprague-Dawley rats were randomly divided into four groups, and exposed to porassium dichromate (K2 Cr2 O7 ; 0, 30, 100, and 300 mg/L) in drinking water for 4 weeks. Mean body weight gain, mean water consumption, clinical chemistry determinations, and oxidative stress levels in plasma were measured. Global DNA methylation changes and DNA methylation status at the promoter of p16 gene were also detected. After 4 weeks, mild anemic effects and increased plasma malondialdehyde (MDA) levels occurred in rats exposed to 100 mg/L or 300 mg/L of Cr (VI). Plasma glutathione peroxidase (GSH-Px) activity decreased in all exposed groups. Global DNA methylation levels were reduced in 100 mg/L and 300 mg/L exposure groups. However, DNA methylation status at the promoter of P16 gene remained unchanged in all K2 Cr2 O7- treated groups. The correlation analysis indicated that increased MDA levels were closely correlated to global DNA hypomethylation. Our results indicated that oral ingestion of Cr (VI) through drinking water caused not only oxidative stress in plasma, but also global DNA hypomethylation in blood cells from male rats, and a good correlation was found between increased MDA levels and reduced global DNA methylation. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1080-1090, 2016.
Assuntos
Metilação de DNA/efeitos dos fármacos , Água Potável/química , Dicromato de Potássio/toxicidade , 8-Hidroxi-2'-Desoxiguanosina , Administração Oral , Animais , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , DNA/sangue , Desoxiguanosina/análogos & derivados , Desoxiguanosina/análise , Feminino , Glutationa Peroxidase/sangue , Rim/química , Rim/patologia , Fígado/química , Fígado/patologia , Masculino , Malondialdeído/sangue , Estresse Oxidativo/efeitos dos fármacos , Regiões Promotoras Genéticas , Ratos , Ratos Endogâmicos F344 , Ratos Sprague-DawleyRESUMO
Hexavalent chromium (Cr(VI)) is an environmental contaminant that is associated with reproductive abnormalities in both humans and animals. In the present study, we evaluated the cytotoxic effect of Cr(VI) on sperm function and subsequent embryo development after in vitro fertilization (IVF). Sperm obtained from BDF1 male mice were treated with potassium dichromate (0, 3.125, 6.25, 12.5, 25, or 50 µM) for 3 h. Cr(VI) significantly decreased sperm viability and acrosome reaction with increasing dose. These Cr(VI)-treated sperms were further used for IVF of oocytes obtained from BDF1 female mice. Results showed that Cr(VI)-treated sperm caused a significant reduction in IVF success, higher developmental arrest at the two-cell stage of embryos, and delayed blastocyst formation with increasing dose. In particular, most blastocysts from the Cr(VI)-treated sperm resulted in hatching failure as well as decreased inner cell mass and trophectoderm (TE). Furthermore, blastocysts obtained from Cr(VI)-treated sperm showed lower expression of not only TE-associated genes (eomes, cdx2, and krt8) but also pluripotent marker genes (sox2, pou5f1, and klf4) that are responsible for further embryo development of blastocyst embryos. The results of our current study showed that Cr(VI)-treated sperm had negative effects on oocyte fertilization and subsequent embryo development.
Assuntos
Carcinógenos Ambientais/toxicidade , Cromo/toxicidade , Ectogênese/efeitos dos fármacos , Fertilização in vitro/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Teratogênicos/toxicidade , Reação Acrossômica/efeitos dos fármacos , Animais , Biomarcadores/metabolismo , Blastocisto/efeitos dos fármacos , Blastocisto/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Cultura Embrionária , Feminino , Fator 4 Semelhante a Kruppel , Masculino , Camundongos , Concentração Osmolar , Dicromato de Potássio/toxicidade , Espermatozoides/citologiaRESUMO
Environmental and occupational exposure to chromium compounds, especially hexavalent chromium (Cr(VI)), is widely recognized as potentially hepatotoxic in humans and animals. Its toxicity is associated with overproduction of free radicals, which induces oxidative damage. This study focused on the possible protective effect of propylthiouracil (PTU) against potassium dichromate (K2Cr2O7). Female mice were divided into four groups (groups I-IV) with seven animals in each group. Group I served as a control, which received tap water; group II received K2Cr2O7 alone (75 mg kg(-1) body weight (b.w.)) via drinking water; group III received both K2Cr2O7 via drinking water and PTU by intramuscular injection at a dose 2.5 mg/100 g(-1) b.w. twice a week, and group IV received PTU alone twice a week for 30 days. Exposure of mice to Cr promoted oxidative stress with an increase in malondialdehyde, protein carbonyl, and advanced oxidation protein product levels. Nonenzymatic antioxidants such as glutathione, nonprotein thiol, vitamin C levels and enzymatic antioxidant activities such as glutathione peroxidase and superoxide dismutase were decreased, while catalase activity was increased. Biomarkers of liver injury such as aspartate and alanine transaminases, lactate dehydrogenase activities, bilirubin, albumin, and glucose levels were increased, while triglyceride and cholesterol levels decreased. Coadministration of PTU restored the above-mentioned parameters to near-normal values. The histological findings confirmed the biochemical results.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Cromo/toxicidade , Fígado/efeitos dos fármacos , Propiltiouracila/farmacologia , Alanina Transaminase/sangue , Animais , Antioxidantes/farmacologia , Ácido Ascórbico/metabolismo , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Biomarcadores/sangue , Glicemia/metabolismo , Catalase/metabolismo , Colesterol/sangue , Relação Dose-Resposta a Droga , Água Potável , Feminino , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Injeções Intramusculares , L-Lactato Desidrogenase/sangue , Fígado/enzimologia , Malondialdeído/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Dicromato de Potássio/toxicidade , Albumina Sérica/metabolismo , Superóxido Dismutase/metabolismo , Triglicerídeos/sangueRESUMO
OBJECTIVE: To investigate the changes in lung injury and oxidative stress of sprague-Dawleyy (SD) rats at different times after single intratracheal instillation of potassium dichromate. METHODS: A total of 50 healthy male SD rats were randomly divided into control group and potassium dichromate group. The potassium dichromate group and the control group received 3 ml/kg intratracheal instillation of K2Cr2O7 (1.5 mg/kg) and normal saline, respectively. Rats in these two groups were sacrificed in batches at 1, 3, 7, 14, and 28 days after exposure. The changes in the following indices were observed and analyzed: body weight, lung coefficient, alkaline phosphatase (AKP) in bronchoalveolar lavage fluid, glutathione peroxidase (GSH-Px) in lung homogenate, and reduced glutathione (GSH) in serum. RESULTS: The rats in the potassium dichromate group had significantly decreased body weight on day 1 and day 3 after exposure than the control group (P<0.05). Lung coefficient increased significantly on day 7 (P<0.05) and kept increasing until the end of the experiment. The potassium dichromate group had a significantly higher activity of AKP than the control group on day 1 and day 7 after exposure (P<0.05). However, the potassium dichromate group had a significantly lower activity of GSH-Px than the control group on day 1 and day 3 after exposure (P<0.05). And the potassium dichromate group had a lower activity of reduced GSH than the control group on day 3 and day 7 after exposure. CONCLUSION: Single intratracheal instillation of 1.5 mg/kg potassium dichromate could result in lung inflammatory injury. of SD rats, and the injury is more severe on day 7 after exposure. Body injury is related to antioxidant activity, and the antioxidant.activity cannot recover completely on day 28 after exposure.
Assuntos
Lesão Pulmonar/fisiopatologia , Estresse Oxidativo , Dicromato de Potássio/toxicidade , Fosfatase Alcalina/metabolismo , Animais , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças , Glutationa/sangue , Glutationa Peroxidase/metabolismo , Pulmão/fisiopatologia , Lesão Pulmonar/induzido quimicamente , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Chromium typically occurs in two oxidation states in the natural environment, Cr(3+) [Cr(III)] and Cr(6+) [Cr(VI)]. Out of the two chromium species, Cr(VI) is the most mobile, labile and toxic. Hexavalent chromium [Cr(VI)] compounds are classified by the International Agency for Research on Cancer (IARC) as carcinogenic agents to humans. The main source of release of chromium in aquatic ecosystems is related to the industrial application of this metal in metallurgies, tanneries, and in the manufacturing of paints and dyes. The ecotoxicology of Cr(VI) is linked to its environmental persistence and the ability to induce adverse effects in biological systems. In the present study, we evaluated mutagenic effects of Cr(VI) in animal and plant bioindicators. MATERIALS AND METHODS: We evaluated primary DNA damage and frequencies of micronuclei (MN) and morphological nuclear abnormalities (NA) in erythrocytes in peripheral blood of the fish Oreochromis niloticus exposed to potassium dichromate at 12 mg l(-1). The genotoxicity and cytotoxicity of Cr(VI) in the onion (Allium cepa) test were also assessed. RESULTS: The comet assay showed a significant increase of tailed nucleoids in the erythrocytes of fish treated with K2Cr2O7; MN frequency was also increased in the treatments; cytotoxicity of a low concentration of potassium dichromate, however, was not confirmed. CONCLUSION: The combination of both systems - animal and plant - is adequate and advantageous for mutagenicity evaluation. The findings indicate that at the concentration tested, the chromium compound is a clastogenic as well as an aneugenic.