The Association between Cadmium Exposure and Thyroid Function in Animals: A Systematic Review.

BACKGROUND: Several studies have indicated an association between cadmium (Cd) exposure and the induction of thyroid dysfunction in animal models. Objective and Aims: There are inconsistent findings on the effect of Cd on the thyroid gland. Therefore, this systematic study was designed to determine the association between changes in thyroid function markers and Cd exposure in animals. METHOD: The search was performed on Scopus, PubMed, Web of Science and databases, and Google Scholar until May 2023. Studies on the relationship between Cd exposure and fish's thyroid function were conducted on rodents and fish. RESULTS: In total, 171 articles were obtained from the main databases using the search strategy mentioned in this study. Finally, 24 articles were selected according to our inclusion criteria for systematic studies. The findings indicated an increase/decrease or no change in triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) levels in rodents, fish, and animals exposed to Cd. CONCLUSION: Our findings indicated an association between Cd exposure and thyroid dysfunction in rodents, fish, and other animals. However, the association between urinary and blood Cd levels and thyroid function remains unclear in humans because of controversial findings and a lack of strong mechanistic evidence. We perform large cohort human studies to the answer to this question.

Resveratrol in the Treatment of Gynecological Cancer: Mechanisms and Therapeutic Potential.

Gynecological cancers, encompassing endometrial, ovarian, and cervical cancer, pose significant challenges in clinical practice, often marked by high mortality rates and treatment resistance. Despite advances in standard therapies, including chemoradiation and surgery, tumor recurrence and metastasis remain formidable obstacles. In this context, there is a pressing need to explore novel therapeutic strategies that offer improved efficacy and reduced side effects. Herbal medicine, particularly compounds like resveratrol, has garnered attention for its diverse biological properties, including anticancer effects. Resveratrol, a multipotential nutraceutical, holds promise in gynecological cancer therapy through its modulation of key cellular and molecular processes. This review aims to provide an overview of the current status, challenges, and opportunities in utilizing resveratrol for gynecological cancer treatment. We discuss its role in miRNA regulation, clinical trial findings, and the development of effective formulations. By elucidating the underlying mechanisms of resveratrol's anticancer effects and exploring innovative delivery systems, we aim to shed light on the potential avenues for optimizing its therapeutic benefits in gynecological cancers.

Protective Effects of Curcumin and Nanomicelle Curcumin on Chlorpyrifos-induced Oxidative Damage and Inflammation in the Uterus, Ovary and Brain of Rats.

BACKGROUND AND AIMS: Chlorpyrifos (CPF), which is classified as an Organophosphorus Pesticide (OP), has been identified as a toxic agent for the reproductive system due to its capacity to induce oxidative stress and inflammation. Curcumin (CUR) has been reported as a natural antioxidant and anti-inflammatory agent that could combat toxicity in various tissues. This study aims to examine the protective effects of CUR and its nanoformulation against reproductive impairment induced by CPF. METHOD: Forty-eight female Wistar albino rats were randomly allocated to six groups (n=8): control (0.5 mL of corn oil, the solvent for CPF), CPF (10 mg/kg), CPF + CUR 100 mg/kg/day, CPF + CUR 300 mg/kg/day, CPF + nano-micelle curcumin (NMC) 2.5 mg/kg/day, and CPF + NMC 5 mg/kg/day. The experimental treatment was performed for 30 days. Then, brain, ovary and uterus tissues were collected for measuring oxidative stress and inflammatory indices. RESULT: MDA, NO, IL-6, and TNF-α concentrations significantly increased in the brain, ovary and uterus of the CPF group versus the control group (p < 0.001). The levels of GSH and SOD in the uterus, ovaries, and brain exhibited a significant decrease in the CPF group compared to the control group (p < 0.05). However, CUR (300 mg/kg) and NMC (5 mg/kg) significantly decreased MDA, NO, TNF-α, and Il-6 and increased SOD and GSH levels in the uterus, ovaries and brain of the CPF-exposed animals versus the CPF-exposed non-treated animals (p < 0.001). CONCLUSION: Our findings indicated that CUR and NMC could be effective in alleviating CPFinduced reproductive toxicity.

Astaxanthin as an Anticancer Agent against Breast Cancer: An In Vivo and In Vitro Investigation.

AIM: This study aimed to investigate the antioxidant properties, cytotoxic activity, and apoptotic effects of astaxanthin (ASX) on genes and pathways involved in breast cancer in Balb/c mice models injected with the 4T1 cell line. BACKGROUND: ASX could inhibit some tumor progression by using in vivo and in vitro models. OBJECTIVE: The effect of ASX on breast cancer was not fully understood till now. METHOD: In an in vivo model, 4T1 cells-injected mice were administered with different concentrations of ASX (100 and 200 mg/kg), and histopathological evaluations were done using an optical microscope and the hematoxylin and eosin (H&E) staining. The real- time PCR investigated the expression levels of B-cell lymphoma 2-associated X (Bax), B-cell lymphoma 2 (Bcl-2), and Caspase 3 genes in mice treated with 100 and 200 mg/kg ASX. Also, the level of superoxide dismutase (SOD) and malondialdehyde (MDA) were examined in ASX-treated cancer mice. RESULTS: ASX (200 mg/kg) caused a significant reduction in the mitotic cell count of tumor tissues compared to ASX (100 mg/kg). The antiproliferative effects of different concentrations of ASX were shown based on the MTT results. The treatment of breast tumor mice with both concentrations of ASX, especially 200 mg/kg, elevated the expression of Caspase 3, Bax, and SOD enzyme levels and decreased Bcl-2 expression and MDA enzyme levels. CONCLUSION: ASX can be considered a promising alternative treatment for breast cancer.

Corrigendum to "Oxidative stress and apoptotic index modifications in the hippocampus of rat pups born to mothers exposed to buprenorphine during lactation" [Toxicol. Rep. 2022 Nov 19; 9: 2050-2054. doi: 10.1016/j.toxrep.2022.11.005. PMID: 36518388; PMCID: PMC9742962].

[This corrects the article DOI: 10.1016/j.toxrep.2022.11.005.].

Curcumin in treatment of hematological cancers: Promises and challenges.

Hematological cancers include leukemia, myeloma and lymphoma and up to 178.000 new cases are diagnosed with these tumors each year. Different kinds of treatment including radiotherapy, chemotherapy, immunotherapy and stem cell transplantation have been employed in the therapy of hematological cancers. However, they are still causing death among patients. On the other hand, curcumin as an anti-cancer agent for the suppression of human cancers has been introduced. The treatment of hematological cancers using curcumin has been followed. Curcumin diminishes viability and survival rate of leukemia, myeloma and lymphoma cells. Curcumin stimulates apoptosis and G2/M arrest to impair progression of tumor. Curcumin decreases levels of matrix metalloproteinases in suppressing cancer metastasis. A number of downstream targets including VEGF, Akt and STAT3 undergo suppression by curcumin in suppressing progression of hematological cancers. Curcumin stimulates DNA damage and reduces resistance of cancer cells to irradiation. Furthermore, curcumin causes drug sensitivity of hematological tumors, especially myeloma. For targeted delivery of curcumin and improving its pharmacokinetic and anti-cancer features, nanostructures containing curcumin and other anti-cancer agents have been developed.

Neuroprotective Effects of Curcumin against Chronic ChlorpyrifosInduced Oxidative Damage in Rat Brain Tissue.

BACKGROUND: Chlorpyrifos (CPF) is an organophosphate pesticide that inhibits acetylcholinesterase (AChE) activity. Investigations have also focused on its neurotoxicity, which is independent of AChE inhibition. Here, we evaluated the effect of CPF on oxidative indices in the brain tissue and explored the protective effect of curcumin (Cur) against its toxicity. METHODS: Forty male Wistar rats were divided into five groups, each consisting of eight rats (n = 8) per group. Animals were administrated by oral gavage for 90 days with the following treatments: control (C), CPF, CPF + CUR 25 mg/kg, CPF + CUR50, and CPF + cur 100 received olive oil, CPF, CPF plus 25 mg/kg of CUR, CPF plus 50 mg/kg of CUR, and CPF plus 100 mg/kg of CUR, respectively. After anesthetization, animal brain tissues were obtained for assessment of oxidative stress indices. RESULTS: The concentration of MDA significantly increased in the brains of the CPF group as compared to the control group (p < 0.01). Also, a significant decrease in MDA concentrations was observed in the brains of rats in the CPF + Cur 100 group compared to the CPF group (p < 0.05). A significant decrease was noted in the GSH concentration in the brains of the CPF group compared to the control group (p < 0.05). Treatment with Cur at 100 mg/kg exhibited a significant increase in GSH concentrations in the brains of the CPF-exposed group compared to the CPF group without Cur administration (p < 0.05). The concentration of NO exhibited a significant increase in the brains of the CPF group when compared to the control group (p < 0.05). Also, a significant decrease in NO concentration was observed in the brain tissue of the CPF + Cur 100 group compared to the CPF group (p < 0.05). CONCLUSION: Our data establish that chronic exposure to CPF induced oxidative stress in brain tissue, which was reversed by CUR administration. Additional experimental and clinical investigations are needed to validate the efficacy of CUR as a potential antidote for CPF poisoning.

A Review of the Dual Role of MicroRNA-21 in Cardiovascular Diseases: Risk Factor or a Potential Therapeutic Target.

Cardiovascular diseases [CVD] are the number one reason for morbidity and mortality in the modern world, and their incidence is increasing at an incredible pace. Increasing evidence has shown the significant functions of microRNAs in the cardiovascular system and has highlighted their potential application as a new era of diagnostic and therapeutic targets for CVD that can improve the prognosis and life expectancy of patients. Among more than 2,000 microRNAs, microRNA-21 [miR-21] is highly expressed in human hearts and has earned the interest of researchers as a potential biomarker in a wide range of common heart conditions. Here, we summarized recent research progress regarding the significant role of miR-21 in CVD, focusing on cardiotoxicity, heart arrhythmias, cardiomyopathies, and hypertension. Several signaling pathways [TGF-ß1/Smad2 signaling, FGFR1/FGF21/PPARγ, NF-κB/miR-21/SMAD7, miR-21/SPRY1/ERK/mTOR …] and molecular targets [BTG2, PDCD4, PTEN, STAT3…] were reported to be controlled, at least partially, by miR-21 and are linked to CVD pathogenesis. Most investigations highlighted miR-21 cardioprotective functions in heart injury, while some other studies showed that this miR is elevated in the serum/tissue of patients, promoting fibrosis and cardiac dysfunction. This dual role can be explained by the fact that miR-21 has multiple regulatory functions depending on the microenvironment, downstream signaling, and target genes, which indicates that cell-type-specific investigations should receive more attention. With further investigations, miR-21 can be considered a novel tailored therapy with favorable outcomes.

Nrf2 Mediates Effect of Resveratrol in Ischemia-reperfusion Injury.

Ischemia-Reperfusion Injury (IRI) is a paradoxical phenomenon where removing the source of injury can cause additional damage. Ischemia reduces ATP production and intracellular pH, reducing oxidative reactions, increasing lactic acid release, and activating anaerobic metabolism. Reperfusion restores aerobic respiration and increases ROS production, leading to malfunction of transmembrane transport, activation of proteases, DNA dissolution, and protein denaturation, leading to apoptotic cell death. Nrf2 is a transcription factor that regulates cellular inflammation and oxidative responses. It is activated by oxidants and electrophiles and enhances detoxifying enzyme expression, maintaining redox homeostasis. It also activates ARE, which activates several ARE-regulated genes that favor cell survival by exhibiting resistance to oxidants and electrophiles. Nrf2 regulates the antioxidant defense system by producing phase II and antioxidant defense enzymes, including HO-1, NQO-1, gglutamylcysteine synthetase, and rate-limiting enzymes for glutathione synthesis. Nrf2 protects mitochondria from damage and supports mitochondrial function in stress conditions. Resveratrol is a stilbene-based compound with a wide variety of health benefits for humans, including antioxidant, anticarcinogenic, antitumor, and estrogenic/antiestrogenic. Resveratrol protects against IRI through several signaling pathways, including the Nrf2/ARE pathway. Here, we review the studies that investigated the mechanisms of resveratrol protection against IRI through modulation of the Nrf2 signaling pathway.

Carbamate compounds induced toxic effects by affecting Nrf2 signaling pathways.

Carbamate (CBs) is a class of insecticides which is being known as an important cause of intentional or accidental poisoning. CBs, cause carbamylation of acetylcholinesterase at neuronal synapses and neuromuscular junction. Exposure to CBs through skin contact, inhalation, or ingestion can result in significant cholinergic toxicity. This is due to the elevation of acetylcholine levels at ganglionic synapses found in both the sympathetic and parasympathetic nervous systems, as well as muscarinic receptors located in target organs of the parasympathetic nervous system, nicotinic receptors situated in skeletal muscle tissue, and the central nervous system. The association between human illnesses and environmental exposures to CBs have been extensively studied in several studies. Although CBs-triggered toxicity leads to overproduction of reactive oxygen species (ROS), the detailed association between the toxicity under CBs exposure and NFE2-related factor 2 (Nrf2) signaling pathways has not been completely clarified. In this review we aimed to summarize the latest findings on the functional interrelationship between carbamates compounds and Nrf2 signaling.

Therapeutic Effect of Resveratrol and its Novel Formulations on Lung Cancer: Focus on Biological Aspects and Underlying Pathways.

Lung cancer is a leading cause of mortality and morbidity worldwide. Due to significant advances in therapeutic strategies, patients' survival and life quality have been improved, however there is still an urgent requirement for developing more effective therapeutic methods. Resveratrol, a natural polyphenol with numerous biological potentials, has been widely studied. It has shown therapeutic potetial in various diseases including neurodegenerative diseases, cardiovascular disorders, and cancers through the regulation of key cellular signaling such as apoptosis, as well as molecular pathways such as microRNA modulation. It has been reported that resveratrol acts as an anticancer agent against lung cancer in vivo and in vitro. Resveratrol could combat against lung cancer by modulating various molecular targets and signaling pathways involved in oxidative stress, inflammation, apoptosis and autoghagy and also microRNAs expression. Moreover, novel delivery systems and analogs have recently been introduced to promote the anticancer impacts of resveratrol. In this article, we review current evidence on the anticancer effects of resveratrol and its novel formulations in the treatment of lung cancer with a focus on underlying mechanisms.

Anticancer Properties of Baicalin against Breast Cancer and other Gynecological Cancers: Therapeutic Opportunities based on Underlying Mechanisms.

Gynecological cancers are serious life-threatening diseases responsible for high morbidity and mortality around the world. Chemotherapy, radiotherapy, and surgery are considered standard therapeutic modalities for these cancers. Since the mentioned treatments have undesirable side effects and are not effective enough, further attempts are required to explore potent complementary and/or alternative treatments. This study was designed to review and discuss the anticancer potentials of baicalin against gynecological cancers based on causal mechanisms and underlying pathways. Traditional medicine has been used for thousands of years in the therapy of diverse human diseases. The therapeutic effects of natural compounds like baicalin have been widely investigated in cancer therapy. Baicalin was effective against gynecological cancers by regulating key cellular mechanisms, including apoptosis, autophagy, and angiogenesis. Baicalin exerted its anticancer property by regulating most molecular signaling pathways, including PI3K/Akt/mTOR, NFκB, MAPK/ERK, and Wnt/ß-catenin. However, more numerous experimental and clinical studies should be designed to find the efficacy of baicalin and the related mechanisms of action.

Application of Quercetin and its Novel Formulations in the Treatment of Malignancies of Central Nervous System: An Updated Review of Current Evidence based on Molecular Mechanisms.

Quercetin, a naturally occurring polyphenolic compound found in abundance in vegetables and fruits, has emerged as a compelling subject of study in cancer treatment. This comprehensive review delves into the significance and originality of quercetin's multifaceted mechanisms of action, with a particular focus on its application in various brain tumors such as glioblastoma, glioma, neuroblastoma, astrocytoma, and medulloblastoma. This review scrutinizes the distinctive facets of quercetin's anti-cancer properties, highlighting its capacity to modulate intricate signaling pathways, trigger apoptosis, impede cell migration, and enhance radiosensitivity in brain tumor cells. Significantly, it synthesizes recent research findings, providing insights into potential structure-activity relationships that hold promise for developing novel quercetin derivatives with heightened effectiveness. By unraveling the unique attributes of quercetin's anti-brain tumor effects and exploring its untapped potential in combination therapies, this review contributes to a deeper comprehension of quercetin's role as a prospective candidate for advancing innovative treatments for brain cancer.

The protective impact of curcumin, vitamin D and E along with manganese oxide and Iron (III) oxide nanoparticles in rats with scrotal hyperthermia: Role of apoptotic genes, miRNA and circRNA.

BACKGROUND: Infertility is one of the major factors affecting most people around the world. Short-term exposure to high temperatures can cause hyperthermia, which is one of the causes of male infertility. The aim of this study was to investigate the protective effect of curcumin, vitamins D and E along with Iron (III) oxide nanoparticles (Fe2O3-NPs) and manganese oxide nanoparticles (MnO2-NPs) on semen parameters and its effect on miRNA21 and circRNA0001518 expression. MATERIAL AND METHODS: In this study, the lower part of the rat was exposed to 43 °C for 5 weeks every other day for 5 weeks. Then the animals were killed. Tissue samples were collected for sperm parameters analysis, and tissue samples were taken for evaluation of apoptosis levels in germ cells, and RNA extraction in order to examine the expression of Bax, Bcl-2, miRNA, and CircRNA genes. RESULTS: The results of this study showed that administration of curcumin, vitamin D, and vitamin E with Fe2O3-NPs and MnO2-NPs can improve the parameters of semen, Bax gene expression, Bcl-2 as well as miRNA and CircRNA in rats with testicular hyperthermia. In addition, curcumin by reducing the toxicity of Fe2O3 nanoparticles was able to reduce its negative effects and also reduce apoptosis in germ cells. This decrease in apoptosis was attributed to decreased Bcl-2 gene expression and increased expression of Bax, miRNA-21, and circRNA0001518. CONCLUSION: All the results of this study confirmed that Fe2O3-NPs and Mno2-NPs containing antioxidants or vitamins are useful in improving fertility in rats due to scrotal hyperthermia. Although Fe2O3-NPs and Mno2-NPs containing both antioxidants and vitamins had a greater effect on improving fertility and reducing the toxic effects of nanoparticles.

The effect of banana leaf package on the shelf life of rainbow trout fillet in comparison with plastic bag s / O efeito da embalagem de folha de bananeira na vida de prateleira do filé de truta arco-íris em comparação com sacos de plástico

The aim of this study was to evaluate the effect of banana leaf extract on the quality and shelf life of rainbow trout compared to plastic bags at freezing temperature for 40 days. For evaluating this propose, the antioxidant activity of banana leaf extract was assessed. In addition, the shelf life of fish filets was determined by measuring thiobarbituric acid (TBA) and pHof fish. The banana leaves extract showed the highest content of vitamin E (5.8 ± 0.61 mg /g) and carotenoids (12.8 ± 0.1 mg /g). The potential of Cu (II) reduction the extract was 1.76 ± 0.09. The magnitude of modification in TBA and pH of the packed fish with banana leaves were less than the control samples. The present study demonstrated that the use of banana leaf extract will retard lipid oxidation in fish. fillet during freezing storage that may due to its strong antioxidant properties.

O objetivo deste estudo foi avaliar o efeito do extrato de folhas de bananeira sobre a qualidade e vida de prateleira da truta arco-íris comparada a sacolas plásticas na temperatura de congelamento por 40 dias. Para avaliar essa proposta, foi determinada a atividade antioxidante do extrato de folhas de bananeira. Além disso, a vida de prateleira dos filés de peixe foi determinada medindo o ácido tiobarbitúrico (TBA) e o pH do peixe. O extrato de folhas de bananeira apresentou o maior teor de vitamina E (5,8 ± 0,61 mg/g) e carotenóides (12,8 ± 0,1 mg/g). O potencial de redução de Cu (II) no extrato foi de 1,76 ± 0,09. A magnitude da modificação no TBA e pH do peixe embalado com folhas de bananeira foi menor que as amostras controle. O presente estudo demonstrou que o uso de extrato de folhas de bananeira é capaz de retardar a oxidação lipídica no filé de peixe durante o armazenamento de congelamento, devido às suas fortes propriedades antioxidantes.

The therapeutic effects of Portulaca oleracea L. in hepatogastric disorders / Efectos terapéuticos de Portulaca oleracea L. en trastornos hepatogástricos

Aim: This research was conducted to obtain accurate information on the protective effects of Portulaca oleracea L. against hepatogastric diseases. Results: P. oleracea L. (Purslane) has traditionally been used for the treatment of hepatogastric diseases. However, the low number of research studies has shown that P. oleracea L. possesses protective effects against hepatotoxic agents. The safety of P. oleracea L. has been demonstrated in several clinical trials. Conclusion: Modern pharmacological studies have indicated the gastroprotective and hepatoprotective effects of P. oleracea L. by using in vivo and in vitro models. However, due to lack of information of its effects in humans, more studies should be conducted to confirm the efficacy of P. oleracea L. in humans

Objetivo: Se realizó esta investigación para disponer de información precisa sobre los efectos protectores de Portulaca oleracea L. frente a enfermedades hepatogástricas. Resultados: Portulaca oleracea L. (Purslane) se ha utilizado tradicionalmente para el tratamiento de enfermedades hepatogástricas. Sin embargo, las investigaciones limitadas han demostrado que Portulaca oleracea L. posee efectos protectores frente a sustancias hepatotóxicas. Varios ensayos clínicos han demostrado la seguridad de Portulaca oleracea L. Conclusión: Estudios farmacológicos modernos han revelado los efectos gastroprotectores y hepatoprotectores de Portulaca oleracea L. mediante el uso de modelos in vivo e in vitro. Sin embargo, debido a la falta de información sobre sus efectos en el ser humano, se deben realizar más estudios para confirmar la eficacia de Portulaca oleracea L. en el ser humano

Chrysin reduces proliferation and induces apoptosis in the human prostate cancer cell line pc-3

INTRODUCTION: Honey is a common household product with many medicinal uses described in traditional medicine. Only recently has its antioxidant properties and preventive effects against disease been highlighted. Chrysin is a natural flavone commonly found in honey that has been shown to be an antioxidant agent. In this study, we investigated the antiproliferative and apoptotic effects of honey and chrysin on cultured human prostate cancer cells. METHODS: Cells were cultured in RPMI medium and treated with different concentrations of honey and chrysin for three consecutive days. Cell viability was quantitated by the 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The percentage of apoptotic cells was determined by flow cytometry using Annexin V-fluorescein isothiocyanate. RESULTS: The MTT assay revealed that both compounds had an antiproliferative effect on PC-3 cells in a dose- and time-dependent manner. The IC50 values for honey and chrysin against PC-3 cells were 2.5 percent and 24.5 percent after 48 h and 1.8 percent and 8.5 percent after 72 h, respectively. Chrysin induced apoptosis in PC-3 cells, as determined by flow cytometry. CONCLUSION: Our results suggest that honey has anti-proliferative effects on prostate cancer cells and the effects are mainly due to chrysin. Therefore, chrysin may be a potential compound for both cancer prevention and treatment. Further in vivo investigation is needed to support the use of chrysin in cancer therapy.