Mercuric chloride (HgCl2) is extremely toxic to both humans and animals. It could be absorbed via ingestion, inhalation, and skin contact. Exposure to HgCl2 can cause severe health effects, including damages to the gastrointestinal, respiratory, and central nervous systems. The purpose of this work was to explore if carvacrol (CRV) could protect rats lungs from damage caused by HgCl2. Intraperitoneal injections of HgCl2 at a dose of 1.23 mg/kg body weight were given either alone or in conjunction with oral CRV administration at doses of 25 and 50 mg/kg body weight for 7 days. The study included biochemical and histological techniques to examine the lung tissue\'s oxidative stress, apoptosis, inflammation, and autophagy processes. HgCl2-induced reductions in GSH levels and antioxidant enzymes (SOD, CAT, and GPx) activity were enhanced by CRV co-administration. Furthermore, MDA levels were lowered by CRV. The inflammatory mediators NF-κB, IκB, NLRP3, TNF-α, IL-1β, IL6, COX-2, and iNOS were all reduced by CRV. When exposed to HgCl2, the levels of apoptotic Bax, caspase-3, Apaf1, p53, caspase-6, and caspase-9 increased, but the levels of antiapoptotic Bcl-2 reduced after CRV treatment. CRV decreased levels of Beclin-1, LC3A, and LC3B, which in turn decreased HgCl2-induced autophagy damage. After HgCl2 treatment, higher pathological damage was observed in terms of alveolar septal thickening, congestion, edema, and inflammatory cell infiltration compared to the control group while CRV ameliorated these effects. Consequently, by preventing HgCl2-induced increases in oxidative stress and the corresponding inflammation, autophagy, apoptosis, and disturbance of tissue integrity in lung tissues, CRV might be seen as a useful therapeutic alternative.

BACKGROUND: Mercuric chloride (HgCl2) is poisonous to humans and animals and typically damages the nervous system and other organs. Mercuric chloride exposition disclosed to initiation of oxidative stress pathway can result in a defect in male fertility and testis tissue. Synthesized selenium nanoparticles (SeNPs) were characterized with a diameter range minimal than 100 nm, having the effective sets of the biological matter. The present study aimed to evaluate the effect of biosynthesized SeNPs, prepared by leek extract on Wistar rats\' testicles and brain.
METHODS: Thirty-five Wistar male rats (120-150 g) were randomly split into five groups (n = 7), orally ingested with leek aqueous extract loaded on SeNPs, and then the animals were administered with mercury II chloride (HgCl2) to induce testis injury and damage the nervous system.
RESULTS: The used dose of mercuric chloride led to oxidative stress damage in the testis of the rats which was evidenced by a decrease in testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and proliferating cell nuclear antigen (PCNA) levels, and an increase in nuclear factor-kappa B (NF-κB) and caspase-3. Also, HgCl2 decreased the levels of dopamine (DA), serotonin (5-HT), norepinephrine (NE) and brain-derived neurotrophic factor (BDNF) in the brains of rats. In addition, A decrease was observed in the levels of antioxidant markers, B-cell lymphoma-2 (Bcl-2), as well as an increase in malondialdehyde (MDA), nitric oxide (NO), NF-κB, tumor necrosis factor (TNF)-α, interleukin (IL)-1β and Bax in both testes and brains. Pre-treatment with leek extract loaded on SeNPs significantly ameliorated testosterone, LH, FSH, PCNA and caspase-3 levels in the testis and DA, 5-HT, NE and BDNF in brains. Although the contents of MDA, NO, TNF-α, IL-1β, NF-κB and Bax decreased significantly in both. glutathione, glutathione peroxidase, glutathione reductase, catalase, superoxide dismutase and Bcl-2 levels were significantly improved in both organs.
CONCLUSIONS: Our findings suggest that treatment with aqueous leek extract loaded on SeNPs may offer promising prospects for the advancement of anti-inflammation activity against testis injury and also have a very key role in neurobehavioral alterations as a result of mercury toxicity. © 2024 Society of Chemical Industry.

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.

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-1β, 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-β1, 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.

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.

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, TGFβ, and NFϏβ. 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.

Because of their beneficial properties, natural products, especially medicinal plants, are becoming increasingly popular worldwide and play a significant role in research. This study was aimed to evaluate the nephroprotective effect of sinapic acid against mercuric chloride-induced renal toxicity in mice. The mice were allocated to four groups named a normal group (G1), model group (G2; received HgCl2, 1 mg/kg bw), treatments groups (G3 and G4: received 50 and 100 mg/kg bw of sinapic acid together with HgCl2). Mice received HgCl2 remarkably showed alteration in all examined biochemical biomarkers (urea, creatinine, and bilirubin), and induced alteration in blood cell picture and anemia. HgCl2 intoxication decreased both systemic and renal antioxidant activity and induced over all oxidative stress as indicated by alteration in inflammation and oxidative stress associated markers. HgCl2 affected renal histology with leukocytic and inflammatory cell infiltration, fibrosis and tubular necrosis. Administration of sinapic acid (50 and 100 mg/kg bw) markedly restored the HgCl2-induced oxidative stress (serum and renal: MDA, GSH, CAT, SOD, and T-AOC), proinflammatory cytokines (serum and renal: TNF-α, IL-6, IL-1β, and PGE2) and restored the changes on biochemical markers, and hematological parameters (hemoglobin, erythrocytes, platelets, and leukocytes). Taken together, the results of the present study disclose that sinapic acid has the potential to attenuate HgCl2-induced renal toxicity and may be an ideal choice against mercury poisoning.

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-1β, 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.

Protein aggregation is related to numerous pathological conditions like Alzheimer\'s and Parkinson\'s disease. In our study, we have shown that an already existing FDA-approved drug; methotrexate (MTX) can be reprofiled on preformed α-chymotrypsinogen A (α-Cgn A) aggregates. The zymogen showed formation of aggregates upon interaction with mercuric ions, with increasing concentration of Hg2Cl2 (0-150 µM). The hike in ThT and ANS fluorescence concomitant with blue shift, bathochromic shift and the hyperchromic effect in the CR absorbance, RLS and turbidity measurements, substantiate the zymogen β-rich aggregate formation. The secondary structural alterations of α- Cgn A as analyzed by CD measurements, FTIR and Raman spectra showed the transformation of native β-barrel conformation to β-inter-molecular rich aggregates. The native α- Cgn A have about 30% α-helical content which was found to be about 3% in presence of mercuric ions suggesting the formation of aggregates. The amorphous aggregates were visualized by SEM. On incubation of Hg2Cl2 treated α- Cgn A with increasing concentration of the MTX resulted in reversing aggregates to the native-like structure. These results were supported by remarkable decrease in ThT and ANS fluorescence intensities and CR absorbance and also consistent with CD, FTIR, and Raman spectroscopy data. MTX was found to increase the α-helical content of the zymogen from 3 to 15% proposing that drug is efficient in disrupting the β-inter-molecular rich aggregates and reverting it to native like structure. The SEM images are in accordance with CD data showing the disintegration of aggregates. The most effective concentration of the drug was found to be 120 µM. Molecular docking analysis showed that MTX molecule was surrounded by the hydrophobic residues including Phe39, His40, Arg145, Tyr146, Thr151, Gly193, Ser195, and Gly216 and conventional hydrogen bonds, including Gln73 (bond length: 2.67Å), Gly142 (2.59Å), Thr144 (2.81Å), Asn150 (2.73Å), Asp153 (2.71Å), and Cys191 (2.53Å). This investigation will help to find the use of already existing drugs to cure protein misfolding-related abnormalities.

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.