Neurobehavioral, neurotransmitter and redox modifications in Nauphoeta cinerea under mixed heavy metal (silver and mercury) exposure.

Heavy metals are encountered in nature, and are used in several human endeavors, including in dental fillings. It is well known that the safety of metals depends on their chemical form, as well as the dose and route through which biological systems are exposed to them. Here, we used the Nauphoeta cinerea model to examine the mechanism by which salts of the heavy metals used in dental fillings - silver and mercury - exert their neurotoxicity. Nymphs exposed to heavy metals presented with reduced motor and exploratory abilities as they spent more time immobile, especially in the periphery of a novel object, and covered less distance compared with control nymphs. Exposure to AgNO3 and HgCl2 also exacerbated levels of oxidative stress markers (MDA & ROS) and the neurotransmitter regulators - AChE and MAO, while reducing antioxidant activity markers, both in biochemical (thiol & GST) and RT-qPCR (TRX, GST, SOD, Catalase) examinations, in neural tissues of the cockroach. The observed disruptions in neurolocomotor control, synaptic transmission and redox balance explain how heavy metal salts may predispose organisms to neurological disorders.

Selenium alleviates pancreatic fibrosis in chickens caused by mercuric chloride: Involvement of the MAPK signaling pathway and selenoproteins.

Mercuric chloride (HgCl2) is a widespread inorganic mercury with digestive toxicity. The pancreas is an important digestive organ in animals, and pancreatic fibrosis (PF) is a major pathological feature of chronic pancreatitis, which can be caused by heavy metals. Selenium (Se) is an essential trace element for the animal organism, performing biological functions in the form of selenoproteins, as well as alleviating the toxicity of heavy metals. In this study, we explored the specific mechanisms underlying the protective effect of Se on HgCl2-induced pancreatic injury in chickens. Morphological observation and serum biochemical analysis showed that Se attenuated HgCl2-caused pancreatic tissue damage and elevated glucose concentration and α-amylase activity. Next, the expression of oxidative stress indicators such as MDA and GSH-Px as well as inflammation-related markers including IL-1ß, IL-6, and TNF-α were detected. Results showed that Se had an inhibitory effect on HgCl2-induced oxidative stress and inflammation. Furthermore, we found that Se alleviated HgCl2-induced PF by detecting the expression of markers related to PF including TGF-ß1, α-SMA, COL1A1, and FN1. Mechanistically, Se attenuated HgCl2-induced PF via the MAPK signaling pathway. Importantly, several selenoproteins, especially those with antioxidant activity, were involved in the protective effect of Se on HgCl2 toxicity. In conclusion, our findings demonstrated that Se inhibited HgCl2-induced oxidative stress and inflammation and alleviated chicken PF through the MAPK signaling pathway, in which some antioxidant selenoproteins were involved.

Selenium represses microRNA-202-5p/MICU1 aixs to attenuate mercuric chloride-induced kidney ferroptosis.

Mercuric chloride (HgCl2) is a nephrotoxic contaminant that is widely present in the environment. Selenium (Se) can effectively antagonize the biological toxicity caused by heavy metals. Here, in vivo and in vitro models of Se antagonism to HgCl2-induced nephrotoxicity in chickens were established, with the aim of exploring the specific mechanism. Morphological observation and kidney function analysis showed that Se alleviated HgCl2-induced kidney tissue injury and cytotoxicity. The results showed that ferroptosis was the primary mechanism for the toxicity of HgCl2, as indicated by iron overload and lipid peroxidation. On the one hand, Se significantly prevented HgCl2-induced iron overload. On the other hand, Se alleviated the intracellular reactive oxygen species (ROS) levels caused by HgCl2. Subsequently, we focused on the sources of ROS during HgCl2-induced ferroptosis. Mechanically, Se reduced ROS overproduction induced by HgCl2 through mitochondrial calcium uniporter (MCU)/mitochondrial calcium uptake 1 (MICU1)-mediated mitochondrial calcium ion (Ca2+) overload. Furthermore, a dual luciferase reporter assay demonstrated that MICU1 was the direct target of miR-202-5p. Overall, Se represses miR-202-5p/MICU1 axis to attenuate HgCl2-induced kidney ferroptosis.

Prolonged exposure to mercuric chloride induces oxidative stress-mediated nephrotoxicity in freshwater food fish Channa punctatus.

Mercury (Hg) is regarded as a serious hazard to aquatic life and is particularly prevalent in aquatic ecosystems. However, there is little evidence available regarding the toxicity of mercury chloride (HgCl2) in vital organs of fish. This study was conducted to assess the effects of HgCl2 (0.039 mg/L and 0.078 mg/L) on oxidative stress-mediated genotoxicity, poikilocytosis, apoptosis, and renal fibrosis after 15, 30, and 45 days of the exposure period. According to the findings, HgCl2 intoxication in fish resulted in a significantly (P < 0.05) elevated lipid peroxidation (LPO), protein carbonyls (PC), lactate dehydrogenase (LDH) activity levels in kidney tissues and significantly (P < 0.05) increased reactive oxygen species (ROS), poikilocytosis, DNA tail length, and the frequency of apoptotic cells (AC%) in blood cells. Kidney's ultra-structure and histopathology revealed its fibrosis, which was evident by mRNA expression of targeted genes KIM1, NOX4, TGFß, and NFϏß. Different indicators of oxidative stress, apoptosis, and genotoxicity were altered in a dose and time-dependent manner, according to a two-way ANOVA analysis. There was a considerable positive link between oxidative stress and kidney fibrosis in the fish Channa punctatus, and it is evident from regression correlation and PCA data analysis. The kidney's ultra-structure evaluation and histopathology both revealed a noticeable fibrosis state. Additionally, a significant (P < 0.05) downregulation in PPARδ reveals that fish body was unable to combat diseases such as kidney fibrosis induced by HgCl2. This study shed fresh light on the mechanisms underlying nephrotoxicity caused by HgCl2 exposure.

Oxidative stress, inflammation, and steatosis elucidate the complex dynamics of HgCl2 induced liver damage in Channa punctata.

Water bodies are highly pollution-prone areas in which mercury (Hg) is considered as a major menace to aquatic organisms. However, the information about the toxicity of mercuric chloride (HgCl2) in a vital organ such as the liver of fish is still inadequate. This study aimed to assess the impact of mercuric chloride (HgCl2) exposure on the liver of Channa punctata fish over 15, 30, and 45 days, at two different concentrations (0.039 mg/L and 0.078 mg/L). Mercury is known to be a significant threat to aquatic life, and yet, information regarding its effects on fish liver remains limited. The results of this study demonstrate that exposure to HgCl2 significantly increases oxidative stress markers, such as lipid peroxidation (LPO) and protein carbonyls (PC), as well as the levels of serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) in the fish. Additionally, the transcriptional and protein analysis of specific genes and molecules associated with necroptosis and inflammation, such as ABCG2, TNF α, Caspase 3, RIPK 3, IL-1ß, Caspase-1, IL-18, and RIPK1, confirm the occurrence of necroptosis and inflammation in the liver. Histopathological and ultrastructural examinations of the liver tissue further reveal a significant presence of liver steatosis. Interestingly, the upregulation of PPARα suggests that the fish's body is actively responding to counteract the effects of liver steatosis. This study provides a comprehensive analysis of oxidative stress, biochemical changes, gene expression, protein profiles, and histological findings in the liver tissue of fish exposed to mercury pollution in freshwater environments.

Effects of naringenin on oxidative damage and apoptosis in liver and kidney in rats subjected to chronic mercury chloride.

Mercury chloride is a type of heavy metal that causes the formation of free radicals, causing hepatotoxicity, nephrotoxicity and apoptosis. In this study, the effects of naringenin on oxidative stress and apoptosis in the liver and kidney of rats exposed to mercury chloride were investigated. In the study, 41 2-month-old male Wistar-Albino rats were divided into five groups. Accordingly, group 1 was set as control group, group 2 as naringenin-100, group 3 as mercury chloride, group 4 as mercury chloride + naringenin-50, and group 5 as mercury chloride + naringenin-100. For the interventions, 1 mL/kg saline was administered to the control, 0.4 mg/kg/day mercury (II) chloride to the mercury chloride groups by i.p., and 50 and 100 mg/kg/day naringenin prepared in corn oil to the naringenin groups by gavage. All the interventions lasted for 20 days. Mercury chloride administration was initiated 1 h following the administration of naringenin. When mercury chloride and the control group were compared, a significant increase in plasma urea, liver and kidney malondialdehyde (MDA) levels, in kidney superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST) activities (p < .001), and a significant decrease in liver and kidney glutathione (GSH) levels (p < .001), in liver catalase (CAT) activity (p < .01) were observed. In addition, histopathological changes and a significant increase in caspase-3 levels were detected (p < .05). When mercury chloride and treatment groups were compared, the administration of naringenin caused a decrease aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH) (p < .01), urea, creatinine levels (p < .001) in plasma, MDA levels in liver and kidney, SOD, GSH-Px, GST activities in kidney (p < .001), and increased GSH levels in liver and kidney. The addition of naringenin-100 increased GSH levels above the control (p < .001). The administration of naringenin was also decreased histopathological changes and caspase-3 levels (p < .05). Accordingly, it was determined that naringenin is protective and therapeutic against mercury chloride-induced oxidative damage and apoptosis in the liver and kidney, and 100 mg/kg naringenin is more effective in preventing histopathological changes and apoptosis.

Mitigation effect of alpha-tocopherol and thermo-priming in Brassica napus L. under induced mercuric chloride stress.

Soil pollution with heavy metals has grown to be a big hassle, leading to the loss in farming production particularly in developing countries like Pakistan, where no proper channel is present for irrigation and extraction of these toxic heavy metals. The present study aims to ameliorate the damages caused by heavy metal ions (Hg-Mercury) on rapeseed (Brassica napus L.) via a growth regulator (α-tocopherol 150 mg/L) and thermopriming technique at 4 °C and 50 °C to maintain plant agronomical and physiological characteristics. In pot experiments, we designed total of 11 treatments viz.( T0 (control), T1 (Hg4ppm), T2 (Hg8ppm), T3 (Hg4ppm + 4 °C), T4 (Hg4ppm + 4 °C + tocopherol (150 m/L)), T5 (Hg4ppm + 50 °C), T6 (Hg4ppm + 50 °C + tocopherol (150 mg/L)), T7 (Hg8ppm + 4 °C), T8 (Hg8ppm + 4 °C + tocopherol (150 mg/L)), T9 (Hg8ppm + 50 °C), T10 (Hg8ppm + 50 °C + tocopherol (150 mg/L) the results revealed that chlorophyll content at p < 0.05 with growth regulator and antioxidant enzymes such as catalase, peroxidase, and malondialdehyde enhanced up to the maximum level at T5 = Hg4ppm + 50 °C (50 °C thermopriming under 4 ppm mercuric chloride stress), suggesting that high temperature initiate the antioxidant system to reduce photosystem damage. However, protein, proline, superoxide dismutase at p < 0.05, and carotenoid, soluble sugar, and ascorbate peroxidase were increased non-significantly (p > 0.05) 50 °C thermopriming under 8 ppm high mercuric chloride stress (T9 = Hg8ppm + 50 °C) representing the tolerance of selected specie by synthesizing osmolytes to resist oxidation mechanism. Furthermore, reduction in % MC (moisture content) is easily improved with foliar application of α-tocopherol and 50 °C thermopriming and 4 ppm heavy metal stress at T6 = Hg4ppm + 50 °C + α-tocopherol (150 mg/L), with a remarkable increase in plant vigor and germination energy. It has resulted that the inhibitory effect of only lower concentration (4 ppm) of heavy metal stress was ameliorated by exogenous application of α-tocopherol and thermopriming technique by synthesizing high levels of proline and antioxidant activities in maintaining seedling growth and development on heavy metal contaminated soil.

Efecto del zumo del fruto Solanum quitoense (lulo) sobre el daño cerebral y cognitivo inducido por cloruro de mercurio en ratones / Effect of Solanum quitoense (lulo) fruit juice on brain and cognitive damageinduced by mercury chloride in mice

Introducción: Las enfermedades neurodegenerativas han ido en aumento durante las últimas décadas, siendo la demencia la principal patología con mayor repercusión a nivel global. Objetivo: Evaluar el efecto neuroprotector del zumo del fruto Solanum quitoense (lulo) frente a la toxicidad del cloruro de mercurio (II) en los ratones. Materiales y métodos: Diseño experimental, con grupo control y posprueba. Se empleó 42 ratones machos. Para inducir a la toxicidad se empleó una solución de HgCl2 (10 mg/kg), vía orogástrica, por un periodo de siete días. Durante ese periodo recibieron los siguientes tratamientos: grupos I y II suero fisiológico; grupos III vitamina E (40UI/kg); grupo IV-V-VI zumo de lulo, 0,5; 2,0 y 8,0 mL/kg, respectivamente. Terminado el tratamiento los animales fueron sacrificados por decapitación, el cerebro y cerebelo fueron extraído de la cavidad craneana. El hemisferio izquierdo fue homogenizado para la determinación de la lipoperoxidación, glutatión (reducido y total), actividad de superóxido dismutasa y catalasa. El hemisferio derecho y cerebelo fueron conservados, para la evaluación histológica. Se evaluó la función cognitiva (aprendizaje y memoria), según protocolo de Deacon y Rawlis. Resultados: La administración del zumo de lulo disminuyeron los índices de cerebro en los grupos V-VI. La lipoperoxidación disminuyó (grupos IV-VI), la relación GSH/GSSG aumentaron (grupos V-VI). La actividad de la catalasa aumentó (grupos IV-VI). La relación SOD/CAT disminuyeron (grupos IV-VI). El tiempo de latencia y número de intentos fueron menores en los grupos IV-VI. Conclusiones: La administración del zumo del fruto Solanum quitoense presenta efecto neuroprotector para el modelo estudiado. Palabras clave: Neuroprotección, Solanum quitoense, cloruro de mercurio, función cognitiva, alimento funcional (Fuente: DeCS BIREME).(AU)

Introduction: Neurodegenerative diseases have beenincreasing in recent decades, with dementia being the mainpathology with the greatest impact globally. Objective: To evaluate the neuroprotective effect ofSolanum quitoense (lulo) fruit juice against the toxicity ofmercury (II) chloride in mice. Materials and methods: Experimental design, withcontrol group and post-test. 42 male mice were used. Toinduce toxicity, a solution of HgCl2 (10 mg/kg) was used viathe orogastric route for a period of seven days. During thisperiod, they received the following treatments: groups I and II physiological saline; groups III vitamin E (40IU/kg); groupIV-V-VI lulo juice, 0.5; 2.0 and 8.0 mL/kg, respectively. Oncethe treatment was completed, the animals were sacrificed bydecapitation, the brain and cerebellum were removed fromthe cranial cavity. The left hemisphere was homogenized forthe determination of lipoperoxidation, glutathione (reducedand total), superoxide dismutase and catalase activity. Theright hemisphere and cerebellum were preserved forhistological evaluation. Cognitive function (learning andmemory) was evaluated according to the Deacon and Rawlisprotocol. Results: The administration of lulo juice decreased brainindices in groups V-VI. Lipoperoxidation decreased (groupsIV-VI), the GSH/GSSG ratio increased (groups V-VI). Catalaseactivity increased (groups IV-VI). The SOD/CAT ratiodecreased (groups IV-VI). The latency time and number ofattempts were lower in groups IV-VI. Conclusions: The administration of Solanum quitoensefruit juice has a neuroprotective effect for the model studied.(AU)

Mercury chloride causes cognitive impairment, oxidative stress and neuroinflammation in male Wistar rats: The potential protective effect of 6-gingerol-rich fraction of Zingiber officinale via regulation of antioxidant defence system and reversal of pro-inflammatory markers increase.

This study investigated the effects of 6-gingerol-rich fraction of Zingiber officinale (6-GIRIFZO) on mercury chloride (HgCl2)-induced neurotoxicity in Wistar rats. Thirty -five male Wistar rats weighing between (150-200 g) were divided randomly into five groups (n = 7): group 1: control, received 0.5 mL of normal saline, group 2: received HgCl2 (5 mg/kg), group 3: received N-acetylcysteine (NAC) (50 mg/kg) as well as HgCl2 (5 mg/kg), group 4: received 6-GIRIFZO (100 mg/kg) and HgCl2 (5 mg/kg), group 5: had 6-GIRIFZO (200 mg/kg) and HgCl2 (5 mg/kg), consecutively for 14 days. On the day14, the rats were subjected to behavioural tests using a Morris water maze and novel object recognition tests. The rats were then euthanized to obtain brain samples for the determination of biochemical parameters (acetylcholinesterase (AchE), nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione (GSH), tumor necrosis factor- alpha (TNF-α), nuclear factor kappa-B (NF-κB), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6)) using standard methods. The result revealed a significant increase in escape latency and a significant decrease in recognition ratio in the rats that were exposed to HgCl2 only. However, 6-GIRIFZO produced a significant reduction in the escape latency and (p < 0.05) increase in the recognition ratio. Similarly, HgCl2 exposure caused a significant (p < 0.05) decrease in the brain SOD, GPx, CAT, GSH with increased brain levels of MDA, NO, AchE, TNF-α, NF-κB, IL-1ß and IL-6. Similarly to the standard drug, NAC, 6-GIRIFZO (100 and 200 mg/kg) significantly (p < 0.05) increased brain SOD, GPx, CAT, and GSH levels with decreased concentrations of MDA, NO, AchE, TNF-α, NF-κB, IL-1ß and IL-6. Also, pre-treatment with 6-GIRIFZO prevented the HgCl2-induced morphological aberrations in the rats. This study concludes that 6-GIRIFZO prevents HgCl2-induced cognitive deficit via reduction of brain inflammation as well as oxidative stress in rats.

Carvacrol Reduces Mercuric Chloride-Induced Testicular Toxicity by Regulating Oxidative Stress, Inflammation, Apoptosis, Autophagy, and Histopathological Changes.

Mercuric chloride (HgCl2) is a heavy metal that is toxic to the human body. Carvacrol (CAR) is a flavonoid found naturally in plants and has many biological and pharmacological activities including anti-inflammatory, antioxidant, and anticancer activities. This study aimed to investigate the efficacy of CAR in HgCl2-induced testicular tissue damage. HgCl2 was administered intraperitoneally at a dose of 1.23 mg/kg body weight alone or in combination with orally administered CAR (25 mg/kg and 50 mg/kg body weight) for 7 days. Biochemical and histological methods were used to investigate oxidative stress, inflammation, apoptosis, and autophagy pathways in testicular tissue. CAR treatment increased HgCl2-induced decreased antioxidant enzyme (SOD, CAT, and GPx) activities and GSH levels. In addition, CAR reduced MDA levels, a marker of lipid peroxidation. CAR decreased the levels of inflammatory mediators NF-κB, TNF-α, IL-1ß, COX-2, iNOS, MAPK14, MAPK15, and JNK. The increases in apoptotic Bax and Caspase-3 with HgCl2 exposure decreased with CAR, while the decreased antiapoptotic Bcl-2 level increased. CAR reduced HgCl2-induced autophagy damage by increasing Beclin-1, LC3A, and LC3B levels. Overall, the data from this study suggested that testicular tissue damage associated with HgCl2 toxicity can be mitigated by CAR administration.

Metalloproteomic Investigation of Hg-Binding Proteins in Renal Tissue of Rats Exposed to Mercury Chloride.

Results obtained from rat studies indicate that, even at low concentrations, mercurial species cause harmful effects on the kidneys, by inducing the nephrotic oxidative stress response. In the present work, Hg-associated proteins were identified as possible mercury-exposure biomarkers in rat kidneys exposed to low mercury chloride concentrations for 30 days (Hg-30) and 60 days (Hg-60), using metalloproteomic strategies. The renal proteomic profile was fractioned by two-dimensional electrophoresis and the mercury determinations in kidney samples, protein pellets and protein spots were performed using graphite furnace atomic absorption spectrometry. The characterization of Hg-associated protein spots and the analysis of differentially expressed proteins were performed by liquid chromatography, coupled with tandem mass spectrometry. Eleven Hg-associated protein spots with a concentration range of 79 ± 1 to 750 ± 9 mg kg-1 in the Hg-60 group were identified. The characterization and expression analyses allowed the identification of 53 proteins that were expressed only in the Hg-60 group, 13 "upregulated" proteins (p > 0.95) and 47 "downregulated" proteins (p < 0.05). Actin isoforms and hemoglobin subunits were identified in protein spots of the Hg-60 group, with mercury concentrations in the range of 138 to 750 mg kg-1, which qualifies these proteins as potential mercury-exposure biomarkers.

Protective efficacy of Allium jesdianum on liver parameters, inflammatory cytokines, oxidative injury and apoptotic changes in mercuric chloride-induced hepatotoxicity in rats

Mercuric chloride (MC) is a chemical compound made from a combination of mercury and chlorine causing intracellular oxidative stress generation. Allium jesdianum (AJ), as a member of the Liliaceae family, has various pharmacological and strong antioxidant properties. This study aimed to evaluate the probable therapeutic effects of AJ against hepatocytes degeneration, inflammation, apoptotic changes and oxidative injuries induced by MC ad-ministration. Sixty-four rats were randomly divided in eight groups (n = 8) including groups of control, MC (50 mg/kg), AJ (500, 1000, 2000 Mug/ml), and MC+AJ. They were intraperitoneally and orally administrated for one week. Nitrite oxide, lipid peroxidation (LP) levels, and Ferric Reducing Ability of Plasma (FRAP) assays were conducted to evaluate the intracellular antioxidant index

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Effects of mercury on the mechanical and electrical activity of the Langendorff-perfused rat heart

The effects of increasing concentrations of mercury (Hg2+) chloride (0.5, 1, 2 and 10 uM) on the myocardial electromechanical activity were studied on 10 Langendorff-perfused rat hearts. Hg2+ decreased the development of isovolumic systolic pressure from 20.3 ñ 2.13 mmHg under control conditions to 6.25 ñ 1.32 mmHg at 10 uM HgCl2 (P<0.01) (diastolic pressure = 0 mm Hg). The atrial and ventricular rates also decreased at uM, 1 uM and 2 uM HgCl2 when compared to the Hg2+ - free solution (from 201 ñ 4 to 126 ñ 15 bpm). However, at 10 uM Hg2+ the atrial rate increased (155 ñ 19 bpm) whereas the ventricular rate did not change significantly (119 ñ 13 bpm). A delay in atrioventricular conduction occured at 0.5 uM Hg2+ (64 ñ 4 ms in the Hg2+ free solution to 91 ñ 14 ms in the presence of 0.5 uM Hg2+, P<0.05) with no further changes at higher Hg2+ concentrations. The QRS-T duration also increased as a function of increasing Hf2+ concentrations (58 ñ 5.5 ms in the Hg2+ -free solution to 123 ñ 15 ms in the presence of 10 uM Hg2+ , P<0.01). Qualitative changes of ECG such as extrasystoles , atrial or ventricular arrhythmias and A-V blocks were also observed. The inhibitory action of Hg2+ on ATP hydrolysis and on Ca2+ and Na+-K+ ATPases suggested to occur in other tissues could be the mechanism responsible for the observations reported here

Intoxicación por mercurio / Mercury poisoning

Se presenta el caso de un adolescente intoxicado por mercurio por intento autodestructivo. Se analizan las diversas formas de intoxicación por este metal así como su sintomatología, haciendo énfasis en la terapéutica utilizada y al mismo tiempo se mencionan las causas que pueden motivar esta autodestrucción.