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1.
Nat Prod Res ; : 1-17, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38284642

RESUMO

Cancer, a highly deadly disease, necessitates safe, cost-effective, and readily accessible treatments to mitigate its impact. Theabrownin (THBR), a polyphenolic pigment found in Pu-erh tea, has garnered attention for its potential benefits in memory, liver health, and inflammation control. By observing different biological activities of THBR, recently researchers have unveiled THBR's promising anticancer properties across various human cancer types. By examining existing studies, it is evident that THBR demonstrates substantial potential in inhibiting cell proliferation and reducing tumour size with minimal harm to normal cells. These effects are achieved through the modulation of key molecular markers such as Bcl-2, Bax, various Caspases, Poly (ADP-ribose) polymerase cleavage (Cl-PARP), and zinc finger E box binding homeobox 1 (ZEB 1). This review aims to provide in-depth insights into THBR's role in cancer research. This review also elucidates the underlying anticancer mechanisms of THBR, offering promise as a novel anticancer drug to alleviate the global cancer burden.

2.
Curr Pharm Biotechnol ; 24(6): 766-779, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36017829

RESUMO

Currently, nanobiotechnology represents a leading research area that primarily focuses on the safe, eco-friendly synthesis of biocompatible metal oxide nanoparticles. Among these, biosynthesized cerium oxide nanoparticles have particularly received attention in medical science as their unique surface chemistry and dual oxidation state make them excellent antioxidants and freeradical scavengers. Currently, plant extracts are widely explored and employed for the biosynthesis of CeO2NPs. Other biological sources such as marine oyster shell extract, egg-white, biopolymers, e.g., chitosan, agarose, alginate, and others, have also been successfully used for the fabrication of CeO2NPs. This review highlights the recent progress in the biosynthesis of CeO2NPs and the investigation of their medical use as biocompatible anticancer, antibacterial, antifungal, antioxidant, antidiabetic, and wound healing agents. Furthermore, prospects associated with the use of biogenic CeO2NPs in developing novel products in the medical sector are also highlighted.


Assuntos
Cério , Nanopartículas Metálicas , Nanopartículas , Óxidos
3.
Environ Sci Pollut Res Int ; 29(31): 47254-47266, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35182336

RESUMO

Phthalates are multifunctional compounds with extensive applications and emerging environmental pollutants. Due to their ubiquity in the environment and unavoidable exposure to humans, concerns have been voiced about public health dangers. This study was aimed to explore the diethyl phthalate (DEP) toxicity and the potential protective effect of black coffee in female Swiss albino mice. Four-week-old mice, weighing 12 ± 1 g were segregated into five groups (n = 10), designated as G-I (without any treatment), G-II (treated with corn oil), G-III (exposed to 1.5 mg/g body wt. (B.W.) DEP), G-IV (received 2 µg/g B.W coffee), and G-V (co-administrated with 1.5 mg/g DEP and 2 µg/g B.W coffee). Before dose administration, the coffee extract was assessed for its antioxidant potential through FRAP, TPC, and GC-MS analyses. Respective phthalates/coffee doses were administrated orally, once a day for 8 weeks consecutively starting from the prepubescent stage. After 56 days, mice were acclimated for 4 days then dissected. Morphological assessments showed an irregular shape of the ovaries in DEP-treated mice as compared to the control. The average bodyweight of DEP-intoxicated mice (p ≤ 0.05) increased notably against control, while DEP plus coffee group showed a regular gain in the average weight of mice. The gonado-somatic index showed non-significant variations among all groups. Micrometric studies showed that the diameter of secondary follicles (115 µm) in the ovaries of DEP-exposed mice (p ≤ 0.001) decreased significantly as compared to control (204 µm); conversely, follicular diameter in the coffee control group (248) increased significantly. Serum FSH and LH levels were significantly increased in DEP-exposed mice with a noteworthy decrease in estrogen level while hormonal levels of all other groups were comparable to control. Histological sections of DEP-exposed mice ovaries showed anatomical disruptions contrary to other groups, which were comparable with control. Antioxidant potential was checked in ovaries homogenates; FRAP values showed a notable decrease in DEP group in comparison with the control group, in contrast to G-V, when DEP was co-administrated with coffee. This study concluded that black coffee has protective effect, against DEP-instigated reproductive toxicity in Swiss albino female mice.


Assuntos
Cistos Ovarianos , Neoplasias Ovarianas , Ácidos Ftálicos , Animais , Antioxidantes , Café , Feminino , Gonadotropinas , Humanos , Camundongos , Ácidos Ftálicos/toxicidade
4.
Biotechnol Appl Biochem ; 69(6): 2641-2657, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34993998

RESUMO

Cancer incidences are growing rapidly and causing millions of deaths globally. Cancer treatment is one of the most exigent challenges. Drug resistance is a natural phenomenon and is considered one of the major obstacles in the successful treatment of cancer by chemotherapy. Combination therapy by the amalgamation of various anticancer drugs has suggested modulating tumor response by targeting various signaling pathways in a synergistic or additive manner. Vitamin K is an essential nutrient and has recently been investigated as a potential anticancer agent. The combination of vitamin K analogs, such as vitamins K1, K2, K3, and K5, with other chemotherapeutic drugs have demonstrated a safe, cost-effective, and most efficient way to overcome drug resistance and improved the outcomes of prevailing chemotherapy. Published reports have shown that vitamin K in combination therapy improved the efficacy of clinical drugs by promoting apoptosis and cell cycle arrest and overcoming drug resistance by inhibiting P-glycoprotein. In this review, we discuss the mechanism, cellular targets, and possible ways to develop vitamin K subtypes into effective cancer chemosensitizers. Finally, this review will provide a scientific basis for exploiting vitamin K as a potential agent to improve the efficacy of chemotherapeutic drugs.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Vitamina K/farmacologia , Vitamina K/metabolismo , Vitamina K/uso terapêutico , Vitamina K 3/farmacologia , Vitamina K 3/uso terapêutico , Vitamina K 2/farmacologia , Vitamina K 2/uso terapêutico , Neoplasias/tratamento farmacológico , Vitamina K 1/metabolismo , Vitamina K 1/farmacologia , Vitamina K 1/uso terapêutico , Antineoplásicos/farmacologia
5.
Front Chem ; 10: 1092123, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36618861

RESUMO

Hyaluronan is a biodegradable, biopolymer that represents a major part of the extracellular matrix and has the potential to be fabricated in a fibrous form conjugated with other polymers via electrospinning. Unique physicochemical features such as viscoelasticity, conductivity, and biological activity mainly affected by molecular weight attracted the attention of biomedical researchers to utilize hyaluronan for designing novel HA-based nano-devices. Particularly HA-based nanofibers get focused on a diverse range of applications in medical like tissue implants for regeneration of damaged tissue or organ repair, wound dressings, and drug delivery carriers to treat various disorders. Currently, electrospinning represents an effective available method for designing highly porous, 3D, HA-based nanofibers with features similar to that of the extra-cellular matrix making them a promising candidate for designing advanced regenerative medicines. This review highlights the structural and physicochemical features of HA, recently cited protocols in literature for HA production via microbial fermentation with particular focus on electrospun fabrication of HA-based nanofibers and parameters affecting its synthesis, current progress in medical applications of these electrospun HA-based nanofibers, their limitations and future perspective about the potential of these HA-based nanofibers in medical field.

6.
Biotechnol Appl Biochem ; 69(2): 767-782, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33759222

RESUMO

Cancer is counted as a second leading cause of death among nontransmissible diseases. Identification of novel anticancer drugs is therefore necessary for the effective treatment of cancer. Conventional drug discovery is time consuming and expensive process. Unlike conventional drug discovery, drug repositioning offers a novel strategy for urgent drug discovery since it is a cost-effective and faster process. Bazedoxifene (BZA) is a synthetic selective estrogen receptor modulator, approved by the United States Food and Drug Administration for the treatment of osteoporosis in postmenopausal women. BZA is now being studied for its anticancer activity in various cancers including breast cancer, liver cancer, pancreatic cancer, colon cancer, head and neck cancer, medulloblastoma, brain cancer, and gastrointestinal cancer. Studies have reported that BZA is effective in reducing cancer progression through multiple mechanisms. BZA could effectively inhibit STAT3, PI3K/AKT, and MAPK signaling pathways and induce apoptosis. In addition to its anticancer activity as monotherapy, BZA has been shown to enhance the chemotherapeutic efficacy of clinical drugs such as paclitaxel, cisplatin, palbociclib, and oxaliplatin in multiple neoplasms. This review mainly focused on the anticancer activity, cellular targets, and anticancer mechanism of BZA, which may help the further design and conduct of research and repositioning it for oncological clinic trials.


Assuntos
Indóis , Fosfatidilinositol 3-Quinases , Apoptose , Feminino , Humanos , Indóis/farmacologia , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Estados Unidos
7.
Mol Genet Genomic Med ; 9(12): e1788, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34738740

RESUMO

BACKGROUND: Thalassemia is an inherited hematological disorder categorized by a decrease or absence of one or more of the globin chains synthesis. Beta-thalassemia is caused by one or more mutations in the beta-globin gene. The absence or reduced amount of beta-globin chains causes ineffective erythropoiesis which leads to anemia. METHODS: Beta-thalassemia has been further divided into three main forms: thalassemia major, intermedia, and minor/silent carrier. A more severe form among these is thalassemia major in which individuals depend upon blood transfusion for survival. The high level of iron deposition occurs due to regular blood transfusion therapy. RESULTS: Overloaded iron raises the synthesis of reactive oxygen species (ROS) that are noxious and prompting the injury to the hepatic, endocrine, and vascular system. Thalassemia can be analyzed and diagnosed via prenatal testing (genetic testing of amniotic fluid), blood smear, complete blood count, and DNA analysis (genetic testing). Treatment of thalassemia intermediate is symptomatic; however; it can also be accomplished by folic supplementation and splenectomy. CONCLUSION: Thalassemia major can be cured through regular transfusion of blood, transplantation of bone marrow, iron chelation management, hematopoietic stem cell transplantation, stimulation of fetal hemoglobin production, and gene therapy.


Assuntos
Talassemia beta/diagnóstico , Talassemia beta/terapia , Alelos , Animais , Tomada de Decisão Clínica , Terapia Combinada , Gerenciamento Clínico , Suscetibilidade a Doenças , Testes Genéticos , Genótipo , Humanos , Incidência , Mutação , Fenótipo , Prevalência , Prognóstico , Índice de Gravidade de Doença , Resultado do Tratamento , Globinas beta/genética , Talassemia beta/complicações , Talassemia beta/etiologia
8.
Mol Biol Rep ; 48(12): 8141-8153, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34655018

RESUMO

Aging and age-related disorders have become one of the prominent issue of world. Oxidative stress due to overproduction of reactive oxygen species is the most significant cause of aging. The aim of literature compilation was to elucidate the therapeutic effect of vitamin C against oxidative stress. Various mediators with anti-inflammatory and anti-oxidant properties might be probable competitors of vitamin C for the improvement of innovative anti-aging treatments. More attention has been paid to vitamin C due to its anti-oxidant property and potentially beneficial biological activities for inhibiting aging.Vitamin C acts as an antioxidant agent and free radical scavenger that can protect the cell from oxidative stress, disorganization of chromatin, telomere attrition, and prolong the lifetime. This review emphasizes mechanism of aging and various biomarkers that are directly related to aging and also focuses on the therapeutic aspect of vitamin C against oxidative stress and age-related disorders.


Assuntos
Envelhecimento/efeitos dos fármacos , Envelhecimento/fisiologia , Ácido Ascórbico/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Ácido Ascórbico/metabolismo , Sequestradores de Radicais Livres/farmacologia , Humanos , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio
9.
Environ Sci Pollut Res Int ; 28(39): 55265-55276, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34129163

RESUMO

Phthalates, plasticizing chemicals, are top-rated environmental contaminants. Diethyl phthalate (DEP), a chief member of this family, was declared a potent endocrine disruptor and carcinogen in animals and humans. The current study was designed to explore the probable reproductive damage induced by DEP and the therapeutic efficacy of raw honey in male albino mice. Four-week-old 50 male mice were randomized equally in five groups, as control (C) received 0.1 ml distilled water; vehicle control (VC) received corn oil (0.1 ml/mouse); DEP (3mg/g/BW) dissolved in corn oil; honey control (HC) administered with honey (0.2 mg/g/day); and phthalate plus honey (P+H) administered with DEP and honey (3mg and 0.2 mg/g/BW/day respectively). Mice were treated through oral gavage for 54 days routinely, acclimatized for 6 days, and dissected. In the first instance, the antioxidant potential and total phenolic contents (TPC) of honey were analyzed through ferric reducing antioxidant power (FRAP) assay and Folin-Ciocalteu assay to confirm the antioxidant capacity of honey. The morphological, morphometric, histological, micrometric, sperm count, and hormonal analyses, and antioxidant capacity test in tissue homogenates were conducted by using tissues (testis, epididymis) and blood samples of mice. Mice exposed to DEP have a significant increase in body weight, LH level, and seminiferous tubule lumen diameter and decrease in the gonado-somatic index, testosterone level, sperm count, and seminiferous tubule diameter. Additionally, histopathology of testes showed interstitial space dilations, exfoliations, Leydig cell atrophy, germ cell degenerations, and spermatid retention in DEP-exposed testes sections. However, concomitant use of honey and DEP had shown a significant improvement in histopathological lesions, steroid hormone levels, and healthy sperm count. By these results, it is concluded that honey possessed antioxidant potential that can efficiently protect DEP-induced anomalies in male mice.


Assuntos
Mel , Animais , Carcinógenos , Hormônios Esteroides Gonadais , Masculino , Camundongos , Ácidos Ftálicos
10.
Chem Phys Lett ; 767: 138379, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33518774

RESUMO

The interactions of two crucial proteins of COVID-19 have been investigated with potential antiviral compounds from Moringa oliefera using quantum chemical, molecular docking and dynamic methods. The results of the present investigation show that ellagic acid and apigenin possess the highest binding affinities of -7.1 and -6.5 Kcal.mol-1against nsp9 and -6.9 and -7.1 Kcal.mol-1 against nsp10, respectively. The dynamic behavior of individual proteins and their respective best docked ligand-protein complexes are also studied at 30 ns timescale. Both of these compounds also show the highest intestinal absorption and total clearance rate as compared to the other compounds under present investigation without any toxicity.

11.
Mol Biol Rep ; 48(2): 1409-1422, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33608810

RESUMO

Staphylococcus aureus causes a wide range of skin diseases such as bacterial keratitis, follicles, psoriasis, cellulitis and atopic dermatitis. This study aims to investigate the S. aureus mediated molecular modulation, and the effect of HR in reversing the deleterious impact of S. aureus in keratinocytes. Human keratinocyte (HaCaT) cells were cultured in DMEM, supplemented with 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin. Subcultures were divided into three flasks: control with no S. aureus and extract (C), S. aureus infected (SA) and S. aureus infected cells and extract (SE). RNA was isolated and microarray analysis was performed. The data was annotated using GO functional analysis and DAVID functional annotation. For each comparison group, significant probes were filtered out at significant cut off by fold change (P < 0.05 and/or > twofold change). For SA vs control, SE vs control, and SE vs SA, 204, 9369, 9900 probes were filtered respectively. In SA vs control, TNF signaling, NOD-like receptor and chemokine receptor signaling pathways were upregulated with key genes such as CCL2, CCL20 and BIRC3. The SE vs SA, showed significant expression variations of a number of important genes. Molecular pathways associated with ILs, TNFs, TGFs, IFNs, FGFs, MAPKs, MMPs, caspases and Wnts were either up regulated or downregulated. This effect was reversed by the extract, possibly through downregulating various proinflammatory cytokines and apoptotic pathways. Our study reveals that S. aureus inserts a negative impact on the regulation of various key genes which is apparently reversed by the HR extract.


Assuntos
Hippophae/química , Extratos Vegetais/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Células Cultivadas , Citocinas/genética , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/microbiologia , Dermatite Atópica/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Queratinócitos/efeitos dos fármacos , Extratos Vegetais/química , Transdução de Sinais/efeitos dos fármacos , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Staphylococcus aureus/patogenicidade , Transcriptoma/efeitos dos fármacos , Transcriptoma/genética
12.
Nutr Cancer ; 73(9): 1541-1552, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32762370

RESUMO

Cancer is one of the leading causes of death worldwide. Despite improvement in existing treatment modalities and addition of new anticancer drugs in the cancer clinic, cancer associated mortalities are continuously increasing. It is therefore, necessary to explore alternative treatment options to reduce the burden of cancer. In recent years, there is growing concern toward the use of natural products for treating cancer because of their ability to target multiple signaling molecules. α-solanine is a glycolalkaloid mainly present in potato tuber and Nightshade family plants. It possesses anti-pyretic, anti-diabetic, anti-allergic, anti-inflammatory and antibiotic activities. In recent years, α-solanine has been explored for its anticancer activity and showed promising results. Among all sources, potato peel contains adequate concentration of α-solanine. Every year, a large volume of potato peel is produced as a waste or sold at low cost. So α-solanine can be proved as an effective and cheap source for cancer therapy. The aim of this review is to summarize the recent data on anticancer activity of α-solanine and discuss it as a potential lead for cancer therapy.


Assuntos
Neoplasias , Solanina , Solanum tuberosum , Humanos , Neoplasias/tratamento farmacológico , Transdução de Sinais , Solanina/farmacologia
13.
Environ Sci Pollut Res Int ; 28(5): 6111-6121, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32986191

RESUMO

Mammalian reproduction is a highly regulated process that can be distorted following exposure to synthetic antimicrobial preservatives like butylparaben (BP). Besides, studies have not investigated the potential antioxidant effects of turmeric on BP-provoked reprotoxicity. The present research was planned on prepubertal mice, orally treated with BP (150 µg/g body weight/day) with and without Curcuma longa (turmeric) (400 µg/mice/day) from postnatal day 35 to 65 routinely. Results showed an insignificant reduction in body weight of both sexes but contrary to these, gonadal weight increased significantly in PB-exposed mice. Additionally, elevated levels of follicle-stimulating hormone and luteinizing hormone while decreased estrogen levels were observed in BP-treated females against control. Sperm count and motility were disturbed, coupled with abnormal sperm morphology in BP-intoxicated group. These findings were synchronized with a decreased testosterone levels in the same group as compared with control. The follicular count revealed reduction in the number of antral follicles while an increase in empty follicles. The BP also significantly increased lipid peroxidation and decreased glutathione content, superoxide dismutase, and catalase activities, while the morphometric, biochemical, and histological deviations were less pronounced in the group, which was co-administered with BP and turmeric. Results indicated that turmeric has antioxidant potential to protect BP-induced oxidative stress and reprotoxicity in mice.


Assuntos
Curcuma , Estresse Oxidativo , Animais , Antioxidantes , Feminino , Masculino , Camundongos , Parabenos/toxicidade
14.
Biol Trace Elem Res ; 199(9): 3457-3469, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33125667

RESUMO

Cadmium is a heavy metal and a non-biodegradable environmental contaminant, and its omnipresence ensures its recurrent exposure to humans and animals. Its intake by chicks leads to fatal implications. Cadmium chloride (CdCl2) because of its bio-accumulative nature is an emerging threat to the poultry industry as well as to the humans which consumes these cadmium-intoxicated chickens. In the current study, the target was to elucidate the toxic effects of CdCl2on body weight, hematological, and biochemical parameters as well as its bioaccumulation in different organs of broiler chicks. Various concentrations of CdCl2 (0, 12, 24, 38, and 48 mg/kg body weight) were administered orally to five groups (A, B, C, D, and E) of broiler chicks, respectively. The biometric screening of the exposed birds was carried out by hematological parameters such as packed cell volume (PCV), total erythrocyte count (TEC), mean corpuscular hemoglobin concentration (MCHC), total protein, white blood cells (WBC), and hemoglobin (Hb), as well as biochemical parameters superoxide dismutase (SOD), low-density lipoprotein (LDL), glutathione peroxidase (GPx), and high-density lipoprotein (HDL) with commercially available kits. Metal accumulation in different organs was detected using atomic absorption spectrophotometer. The compound exposure produced a varied impact on broiler birds. Hematological parameters showed a significant decrease except for WBC. Biochemical parameters also decreased significantly in a dose-dependent manner. However, it was revealed that the body weight of chickens was not affected considerably after CdCl2 exposure. A direct relationship was detected between the accumulation of metal within tissues (lungs, heart, and flesh) and exposure frequency. It can be deduced that an increase in Cd deposition in tissues may lead to an alteration in hematological-biochemical markers which may significantly contribute to systemic toxicity in broilers.


Assuntos
Intoxicação por Cádmio , Cádmio , Animais , Cádmio/toxicidade , Cloreto de Cádmio/toxicidade , Galinhas , Cloretos , Humanos
15.
Environ Sci Pollut Res Int ; 27(23): 29266-29279, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32436095

RESUMO

Mercury and cadmium are highly dangerous metals that can lead to disastrous effects in animals and humans. The aim of the current research was to elucidate the poisonous effects of mercuric chloride and cadmium chloride individually and in combination on biochemical profiles of plasma and their accumulation in heart. The therapeutic effect of vitamin C against these metals in rabbits was also studied. Mercuric chloride (1.2 µg/g), cadmium chloride (1.5 µg/g), and vitamin C (150 µg/g of body weight) were orally given to treatment groups of the rabbits (1-control; 2-vitamin; 3-CdCl2; 4-HgCl2; 5-vitamin + CdCl2; 6-vitamin + HgCl2; 7-CdCl2 + HgCl2, and 8-vitamin + CdCl2 + HgCl2. After the biometric determination of all intoxicated rabbits, biochemical parameters, viz low-density lipoproteins (LDL), high-density lipoproteins (HDL), cholesterol, creatine kinase, and troponin T (TnT) were analyzed using available kits. Levels of cholesterol (0.7 ± 0.1 mmol/l), creatine kinase (2985.2 ± 11 IU/L), LDL (20.35 ± 1.31 mg/dl), and troponin T (1.22 ± 0.03 µg/l) were significantly (P < 0.05) increased. HDL (84.78 ± 4.30 mg/dl) was significantly (P < 0.05) decreased, while supplementation of vitamin C decreased the adverse effects of CdCl2 and HgCl2 on biochemical parameters in all metal-exposed groups. A similar trend was also seen in rabbits treated with CdCl2 + vitamin and vitamin + CdCl2 + HgCl2. Accumulation of Cd and Hg was higher in heart tissues. This study, therefore, provides awareness on the cardiac toxicity of mercury and cadmium chlorides in the rabbits and the possible protective role of vitamin C against the perturbations induced by metals.


Assuntos
Cádmio , Mercúrio , Animais , Ácido Ascórbico , Cloreto de Cádmio , Cardiotoxicidade , Humanos , Cloreto de Mercúrio , Coelhos , Vitaminas
16.
J Cancer ; 11(13): 3725-3735, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32328177

RESUMO

Sesquiterpene lactones have been shown to be promising leads for anticancer drug development. Brevilin A (BLN-A), a sesquiterpene lactone compound of Centipeda minima has been shown to exhibit anticancer effects against various cancer cells. However, the anticancer mechanism and cellular targets of BLN-A remain elusive. Here in this study, BLN-A inhibits proliferation and induces cell morphological changes in A549 and NCI-H1650 non-small cell lung cancer cells in a dose-dependent manner. Moreover, BLN-A increased ROS generation and bax/bcl-2 ratio while decreased intracellular glutathione (GSH), and mitochondrial membrane potential which resulted in induction of apoptosis as evident by annexin-V/FITC staining, caspase-3 activation and PARP cleavage. Supplementation of cells with NAC (ROS Scavenger) effectively protected the cells from BLN-A-induced apoptosis. Finally, BLN-A inhibited constitutive as well as IL-6- and EGF-induced STAT3 activation at Tyr705. Using molecular docking and SPR analyses, we found that BLN-A directly binds with STAT3 and thereby inhibits its activation. Knocking down of STAT3 by stable transfection with shRNA suppressed growth and augmented cytotoxicity of BLN-A, indicating the key role of STAT3 in BLN-A-mediated apoptosis. Cumulative findings suggest that BLN-A is a promising lead structure for developing it into a potent STAT3 inhibitor and therapeutic agent against NSCLC as well.

17.
Environ Sci Pollut Res Int ; 27(13): 15149-15164, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32072413

RESUMO

Lead is one of the utmost contaminated and dangerous heavy metals. This toxicant ultimately enters into the human body through the food chain and accumulated in the body because the animal/human body has not an appropriate mechanism to excrete it from the body. The main objective of the present research was to assess the toxicological effects of lead on body weights, biochemical, and hematological parameters of chickens and also to measure its bioaccumulation in the brain. Lead acetate was administrated orally at doses of 0, 71, 142, 213, and 284 mg/kg of body weight of chicken for groups A, B, C, D, and E, respectively. Along with determination of biometry of all experimental chicks, hematological [hemoglobin (Hb), packed cell volume (PCV), mean corpuscular hemoglobin concentration (MCHC), total erythrocyte count (TEC), white blood cells (WBCs), leukocyte differential count (LDC)] and biochemical [low density lipoprotein (LDL), total protein, high-density lipoprotein (HDL), and alanine aminotransferase (ALT)] parameters were measured. The present study showed that the bodyweight of chickens was not affected significantly by lead acetate exposure. The levels of MCHC, PCV, TEC, Hb, LDL, HDL, and total protein were found to be significantly decreased while WBC, LDC, and ALT profile were enhanced due to administration of lead acetate. Bioaccumulation of lead acetate was found to be higher in the brain. We conclude that the chronic administration of lead acetate affected the blood and biochemical profile of exposed chicken. These effects might be due to the accumulation of the chemical in certain vital organ(s). However, further studies in the future are suggested to refine such findings.


Assuntos
Galinhas , Chumbo , Acetatos , Animais , Índices de Eritrócitos , Hematócrito
18.
Environ Sci Pollut Res Int ; 27(9): 8953-8964, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32036533

RESUMO

Due to industrial and urban sewage, the metal contaminations in aquatic and terrestrial environments are increasing day by day, especially in developing countries. Despite the study of several years, we are inert far away from an actual medication for prolonged toxicity of heavy metals such as mercury, lead, cadmium etc. Lead is one of the most common heavy metals that possess toxicological effects on numerous tissues of animals as well as humans. Several toxic effects of lead on reproductive organs, renal system, central nervous system, liver, lungs, blood parameters, and bones have been reported. On the other hand, several reports depicted that garlic is operative in declining the absorption of lead in bones as well as soft tissues. A combination of vitamin C and vitamin E enhances the biological recovery induced by lead and mobilize the heavy metal such as lead from intra-cellular positions. This review provides therapeutic approaches such as vitamin C, vitamin E, and extract of garlic to treat the detrimental effects caused after the exposure of lead. These therapeutic strategies are beneficial for both the prevention and alleviation of lead noxiousness.


Assuntos
Alho , Animais , Antioxidantes , Ácido Ascórbico , Humanos , Chumbo , Vitaminas
19.
Environ Sci Pollut Res Int ; 26(16): 16727-16741, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30989610

RESUMO

Cadmium and mercury are non-biodegradable toxic metals that may cause many detrimental effects to the thyroid gland and blood. Vitamin C has been found to be a significant chain-breaking antioxidant and enzyme co-factor against metal toxicity and thus make them less available for animals. The current study was performed to find the effect of individual metals (cadmium and mercury), their co-administration, and the ameliorative effects of vitamin C on some of the parameters that indicate oxidative stress and thyroid dysfunction. Cadmium chloride (1.5 mg/kg), mercuric chloride (1.2 mg/kg), and vitamin C (150 mg/kg of body weight) were orally administered to eight treatment groups of the rabbits (1. control; 2. Vit C; 3. CdCl2; 4. HgCl2; 5. Vit C + CdCl2; 6. Vit C + HgCl2; 7. CdCl2 + HgCl2, and 8. Vit C + CdCl2 + HgCl2). After the biometric measurements of all experimental rabbits, biochemical parameters viz. triidothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), and triglycerides were measured using commercially available kits. The results exhibited significant decline (p < 0.05) in mean hemoglobin, corpuscular hemoglobin, packed cell volume, T3 (0.4 ± 0.0 ng/ml), and T4 (26.3 ± 1.6 ng/ml) concentration. While, TSH (0.23 ± 0.01 nmol/l) and triglyceride (4.42 ± 0.18 nmol/l) were significantly (p < 0.05) increased but chemo-treatment with Vit C reduces the effects of Cd, Hg, and their co-administration but not regained the values similar to those of controls. This indicates that Vit C had a shielding effect on the possible metal toxicity. The Cd and Hg also found to accumulate in vital organs when measured by atomic absorption spectrophotometer. The metal concentration trend was observed as follows: kidney > liver > heart > lungs. It was concluded that Cd and Hg are toxic and tended to bioaccumulate in different organs and their toxic action can be subdued by vitamin C in biological systems.


Assuntos
Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Cádmio/toxicidade , Mercúrio/toxicidade , Glândula Tireoide/efeitos dos fármacos , Hormônios Tireóideos/sangue , Tireotropina/sangue , Animais , Peso Corporal/efeitos dos fármacos , Cádmio/metabolismo , Intoxicação por Metais Pesados , Hemoglobinas/análise , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Mercúrio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Coelhos , Glândula Tireoide/metabolismo
20.
Environ Sci Pollut Res Int ; 26(14): 14087-14096, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30852747

RESUMO

The liver is one of the vital and sensitive organs which are usually exposed against the toxicity of mercury (Hg) and cadmium (Cd). The main objective of the current study was to evaluate the potential toxicological effects of both Cd and Hg as individual and combined. Hepatotoxicity was evaluated by monitoring the biochemical parameters of the liver and their accumulation in the liver as well as therapeutic role of vitamin C in said toxicity in rabbits (Oryctolagus cuniculus). In this research, cadmium chloride (1.5 mg/kg), mercuric chloride (1.2 mg/kg), and vitamin C (150 mg/kg of body weight) were orally administered to treatment groups of the rabbits for 28 alternative days. Various biochemical parameters of the liver such as lactate dehydrogenase (LDH), aspartate aminotransferase (ASAT), bilirubin, alanine aminotransferase (ALAT), total protein, and gamma glutamyl transferase (GGT) were estimated using blood samples. Some biochemical parameters like ASAT, ALAT, LDH, GGT, and bilirubin were significantly elevated (P ≤ 0.001) in individual Cd and Hg treatment groups, while the level of total protein was found to be significantly declined. The effects of Cd and Hg in the presence of vitamin C on these biochemical parameters were low as compared to metals-treated groups. Similar results were found when rabbits were treated with co-administration of both metals and vitamin C. Accumulation of Cd and Hg found to be higher in the liver. However, chemoprevention and chemotreatment with vitamin C significantly (P ≤ 0.01) minimized the toxicological effects of both metals but not regained the accumulation similar to that of the control group. The findings of this study provide awareness on accumulation of metals in the liver in rabbits and their toxicity tested through biochemical parameters as well as the therapeutic role of vitamin C in such alterations.


Assuntos
Ácido Ascórbico/farmacologia , Cádmio/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Mercúrio/toxicidade , Substâncias Protetoras/farmacologia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Cloreto de Cádmio/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Feminino , L-Lactato Desidrogenase/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Cloreto de Mercúrio/toxicidade , Coelhos , gama-Glutamiltransferase/metabolismo
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