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1.
Toxicol Res (Camb) ; 13(2): tfae050, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38559757

RESUMO

Background: Ehrlich ascites carcinoma (EAC) is a rapidly growing and undifferentiated tumor that can prompt oxidative stress and liver toxicity, whereas chitosan and Grifola Frondosa have widely recognized biological qualities. Therefore, our study designed to assess the potential ameliorative ability of chitosan nanoparticles (CS NPs) and Grifola Frondosa nanoparticles (GF-loaded casein NPs) on EAC-induced hepatic injury in mice. Methods: A total of 60 female albino mice were segregated into 6 groups (10 mice each), G1, control group; G2, CS NPs group; G3, GF-loaded casein NPs group; G4, EAC group; G5, EAC treated with CS NPs; G6, EAC treated with GF-loaded casein NPs. Results: According to the findings, EAC considerably increased serum activities of ALT, AST, ALP as well as LDL, cholesterol, and triglycerides levels coincided with marked decrease in albumin and total protein content in liver tissue. At the same time, it drastically lowered GSH levels and catalase activity while significantly elevating MDA levels. In addition, EAC caused DNA damage and apoptosis by decreasing Bcl-2 while increasing p53 expressions. However, either CS NPs or GF-loaded casein NPs therapy improved liver architecture and functioning, increased antioxidant parameters, and prevented hepatocyte death in EAC mice. Conclusions: Our findings concluded that CS NPs and GF-loaded casein NPs have insulating functions against EAC-induced hepatic damage in mice.

2.
Toxicol Res (Camb) ; 13(2): tfae054, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38617712

RESUMO

Alzheimer's disease (ad) is a neurological condition that worsens over time and is characterized by the buildup of amyloid (Aß) plaques in the brain parenchyma. Neuroprotection and cholinesterase inhibition have been the two primary techniques used in the creation of medications to date. In ad, a novel sort of programmed cell death known as ferroptosis takes place along with iron buildup, lipid peroxidation, and glutathione deficiency. The objective of the current investigation was to examine the neuroprotective and anti-ferroptotic role of nanocurcumin and Donepezil against model of aluminum chloride AlCl3 and D-galactose induced ad. The experiment was performed on 70 rats divided into (G1: control, G2: NCMN, G3: Donepezil, G4: ad-model, G5: Donepezil co-treatment, G6: NCMN co-treatment and G7: NCMN+Donepezil co-treatment). Hematological parameters and biochemical investigations as oxidative stress, liver function, kidney function, iron profile and plasma fibrinogen were evaluated. Treatment with Nanocurcumin alone or in combination with Donepezil improved oxidative stress, liver functions, and kidney functions, improve iron profile and decreased plasma fibrinogen.

3.
Toxicol Res (Camb) ; 13(2): tfae047, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38529200

RESUMO

Trichinellosis is a parasite zoonosis that is spread through ingesting raw or undercooked meat that contains the Trichinella spiralis (T. spiralis) infective larvae. It has three clinical phases: intestinal, migratory, and muscular. Kuth root, also known as Costus (Saussurea lappa) roots, is used in many traditional medical systems all over the world to treat a variety of illnesses, such as dyspepsia, diarrhoea, vomiting, and inflammation. Current study assessed the therapeutic Potential of costus roots extract (CRE) treatment on experimental trichinellosis induce changes in DNA damage, oxidative stress and Proliferating cell nuclear antigen (PCNA) expression in muscle fibers in male rats. A total of 60 male Sprague Dawley rats were divided into 6 groups (Gps) [Gp1, Negative control; Gp2, Costus (CRE); Gp3, Positive control or Infected rats with T. spiralis, Gp4; Pre-treated infection with CRE; Gp5 & Gp6, Post treated infection with CRE for one and two weeks respectively]. Current results revealed that; Trichinella spiralis experimentally infection induced significant elevation in tissue malondialdehyde (MDA), DNA damage, PCNA expression and significant depletion in tissue glutathione (GSH), superoxide dismutase (SOD) and catalase (Cat) activities. Pre or/and post CRE treated infected rats with T. spiralis (Gp4-Gp6) induced improvements and depletion in DNA damage, PCNA expression, MDA and elevation in GSH, SOD, catalase as compared to infected rats with T. spiralis (Gp3) with best results for the pretreatments (Gp4). Trichinella spiralis experimental infection induced DNA damage and oxidative stress in rat skeletal muscles and treatments with costus roots extract modulates these changes.

4.
Toxicol Res (Camb) ; 13(2): tfae042, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38529199

RESUMO

Millions of individuals have used illicit anabolic-androgenic steroids (AAS), but the long-term cardiovascular associations of these drugs remain incompletely understood. Boldjan is AAS medication which is used in veterinary medicine and by young adults aiming to have a better appearance improving their self-esteem. Therefore; the objective of the current investigation was to examine any potential preventative effects of amygdalin extract against anabolic steroid Boldjan induced cardic toxicity, injury and oxidative stress in male rat. Forty adult male Wistar rats were classified into five groups (Gp1, Control Gp; Gp2, Amygdalin Gp in which rats treated with amygdalin (100 mg/kg body weight/day) daily for 2 weeks; Gp3, Boldjan Gp in which rats treated with Boldjan (10 mg/Kg BW/week) for 4 weeks; Gp4, Boldjan + Amygdalin). Boldjan induced a significant rises in serum lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase MB (CK MB), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), and very-low-density lipoprotein-cholesterol (VLDL-C), cardiac injury, and malondialdehyde (MDA) levels and a significant depletion in serum high-density lipoprotein-cholesterol (HDL-C), cardiac reduced glutathione (GSH), Superoxide dismutase (SOD) and catalase (Cat) activities as compared to control Gp. In contrast, Amygdalin significantly reversed the Boldjan induced cardiac toxicity in post treated rats Gp (Boldjan + Amygdalin). Amygdalin could be an efficient preventive supplement for mitigating Boldjan induced cardiac toxicity, possibly via controlling oxidative stress events.

5.
Basic Clin Pharmacol Toxicol ; 134(4): 472-484, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38368905

RESUMO

In this study, the impact of chitosan (CS) and maitake (GF) nanoparticles towards the renal toxicity induced by Ehrlich ascites carcinoma (EAC) in vivo model was conducted. Besides benchmark negative control group, EAC model was constructed by intraperitoneal injection (i.p.) of 2.5 × 106 cells. Alongside positive control, two groups of EAC-bearing mice received 100 mg/kg of CS and GF nanoparticles/body weight daily for 14 days. The kidney function was conducted by measuring urea, creatinine, ions, (anti)/oxidative parameters and DNA damage. Also, measuring immunoreactivity of P53, proliferating cell nuclear antigen (PCNA), and B-cell lymphoma 2 (Bcl-2) and apoptosis protein. The outcomes illustrated notable kidney toxicity, which indicated by elevations in urea, creatinine, oxidative stress, DNA damage and induction of apoptosis. These events were supported by the drastic alteration in kidney structure through histological examination. Administration of CS and GF nanoparticles was able to enhance the antioxidant power, which further reduced oxidative damage, DNA injury, and apoptosis. These results indicated the protective and therapeutic role of biogenic chitosan and maitake nanoparticles against nephrotoxicity.


Assuntos
Carcinoma de Ehrlich , Quitosana , Grifola , Animais , Camundongos , Ascite/metabolismo , Quitosana/uso terapêutico , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/patologia , Creatinina , Dano ao DNA , Ureia , Apoptose
6.
Prostaglandins Other Lipid Mediat ; 170: 106791, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37918555

RESUMO

Alzheimer's disease (AD) hallmarks include amyloid-ßeta (Aß) and tau proteins aggregates, neurite degeneration, microglial activation with cognitive impairment. Phosphatidylinositol-3-kinase/protein kinase B/Glycogen synthase kinase-3-beta (PI3K/AKT/GSK-3) pathway is essential for neuroprotection, cell survival and proliferation by blocking apoptosis. This study aimed to assess protective role of nanocurcumin (NCMN) as strong antioxidant and anti-inflammatory agent with elucidating its synergistic effects with Donepezil as acetylcholinesterase inhibitor on AD in rats via modulating PI3K/AKT/GSK-3ß pathway. The experiment was performed on 70 male Wistar albino rats divided into seven groups (control, NCMN, Donepezil, AD-model, Donepezil co-treatment, NCMN only co-treatment, and NCMN+Donepezil combined treatment). Behavioral and biochemical investigations as cholinesterase activity, oxidative stress (malondialdehyde, reduced glutathione, nitric oxide, superoxidedismutase, and catalase), tumor necrosis factor-alpha, Tau, ß-site amyloid precursor protein cleaving enzyme-1 (BACE-1), Phosphatase and tensin homolog (Pten), mitogen-activated protein kinase-1 (MAPK-1), Glycogen synthase kinase-3-beta (GSK-3ß) and toll-like receptor-4 were evaluated. Treatment with NCMN improved memory, locomotion, neuronal differentiation by activating PI3K/AKT/GSK-3ß pathway. These results were confirmed by histological studies in hippocampus.


Assuntos
Doença de Alzheimer , Proteínas Proto-Oncogênicas c-akt , Ratos , Masculino , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Donepezila/farmacologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Acetilcolinesterase/metabolismo , Peptídeos beta-Amiloides/metabolismo , Ratos Wistar , Fosforilação
7.
J Neuroendocrinol ; 36(1): e13356, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37985011

RESUMO

Besides COVID-19, two of the most critical outbreaks of our day are insulin resistance, type 2 diabetes mellitus (T2DM), and Alzheimer's disease (AD). Each disease's pathophysiology is well established. Furthermore, a substantial overlap between them has coexisted. Uncertainty remains on whether T2DM and AD are parallel illnesses with the same origin or separate illnesses linked through violent pathways. The current study was aimed at testing whether the insulin resistance in the brain results in AD symptoms or not. Insulin resistance was induced in the brains of rats using a single intracerebroventricular streptozotocin (STZ) dose. We then measured glucose, insulin receptor substrate 2 (IRS-2), amyloid ß (Aß) deposition, and tau phosphorylation in the brain to look for signs of insulin resistance and AD. The results of this study indicated that a single dose of STZ was able to induce insulin resistance in the brain and significantly decline IRS-2. This resistance was accompanied by obvious memory loss, Aß deposition, and tau phosphorylation, further visible diminishing in neurotransmitters such as dopamine and acetylcholine. Furthermore, oxidative stress was increased due to the antioxidant system being compromised. Interestingly, the pancreas injury and peripheral insulin resistance coexisted with brain insulin resistance. Indeed, the antidiabetic metformin was able to enhance all these drastic effects. In conclusion, brain insulin resistance could lead to AD and vice versa. These are highly linked syndromes that could influence peripheral organs. Further studies are required to stabilize this putative pathobiology relationship between them.


Assuntos
Doença de Alzheimer , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Metformina , Ratos , Animais , Doença de Alzheimer/metabolismo , Resistência à Insulina/fisiologia , Peptídeos beta-Amiloides/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Metformina/farmacologia , Metformina/metabolismo , Insulina/metabolismo , Encéfalo/metabolismo , Modelos Animais de Doenças
8.
Environ Toxicol ; 39(1): 388-397, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37782692

RESUMO

Although curcumin possesses anti-inflammatory, antioxidant, and cytoprotective qualities, its low absorption limits its medicinal uses. Before examining how curcumin influenced rats' liver fibrosis when thioacetamide (TAA) was produced, the current study employed nanoparticles (NPs) to improve curcumin bioavailability. Sixty mature rats were separated into six groups (Group 1, control; Group 2, curcumin; Group 3, curcumin nanoparticles; Group 4, TAA; Group 5, TAA + curcumin; Group 6, TAA + curcumin NPs). TAA administration caused considerable increases in serum liver enzymes associated with a remarkable depletion in the levels of albumin and total protein relative to the control. In addition, a significant elevation in malonaldehyde (MDA) level with a significant depletion in the antioxidant enzymes activity was detected. Also, TAA had a significant effect on the inflammation markers represented by the elevation in tumor necrosis factor (TNFα) and DNA damage. Administration of curcumin or curcumin NPs in TAA-intoxicated rats significantly (p < .001, p < .0001) alleviates liver injury by correcting antioxidant status, inflammatory markers, and oxidative stress. The results of comparing TAA-intoxicated rats treated with curcumin NPs to TAA-intoxicated rats treated with bulk curcumin revealed that the ameliorative effect of nanocurcumin was stronger. These observations concluded that nanoparticle formulation can increase curcumin bioavailability and solubility, enhancing its antioxidant and anti-inflammatory efficiency, resulting in greater potential against thioacetamide-induced hepatotoxicity in rats.


Assuntos
Curcumina , Nanopartículas , Ratos , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Curcumina/farmacologia , Curcumina/uso terapêutico , Tioacetamida/toxicidade , Fígado , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Estresse Oxidativo , Anti-Inflamatórios/farmacologia , Nanopartículas/uso terapêutico
9.
Toxicol Res (Camb) ; 12(6): 1152-1158, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38145095

RESUMO

Background: A broad spectrum carbamate fungicide called carbendazim (Carb) is used to combat a number of different fungal diseases. One of the extensively utilized medicinal plants in oriental countries is Coriandrum sativum. Aim: In the current study, the impact of C. sativum seeds extract (CSE) on albino rats' testicular toxicity caused by carbendazim was investigated. Materials and methods: A total of 50 male albino rats were classified into 5 groups [Gp1, Control Gp; Gp2, Coriandrum Gp (CSE); Gp 3, carbendazim Gp (Carb); Gp 4, Co treated CSE with Carb (CSE + Carb); Gp 5, Post treated Carb with CSE (Carb + CSE)]. Results: Carb induced elevation in serum LH. FSH, testicular malondialdehyde (MDA), testicular nitric oxide (NO) markers and testicular injury and it reduced serum testosterone, testicular glutathione (GSH), testicular catalase and PCNA. Treatments of Carb with CSE (CSE + Carb and/or Carb + CSE) improved these parameters and reduced testicular toxicity with best results for Carb + CSE than CSE + Carb. Conclusions: The above findings revealed that; Carb induced testicular toxicity and it supported the hypothesis that the antioxidant characteristics of one or more of CSE constituents can reduce the testicular toxicity of Carb.

10.
Pharmaceutics ; 15(8)2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37631277

RESUMO

Lung cancer is a major public health problem and a leading cause of cancer-related deaths worldwide. Despite advances in treatment options, the five-year survival rate for lung cancer patients remains low, emphasizing the urgent need for innovative diagnostic and therapeutic strategies. MicroRNAs (miRNAs) have emerged as potential biomarkers and therapeutic targets for lung cancer due to their crucial roles in regulating cell proliferation, differentiation, and apoptosis. For example, miR-34a and miR-150, once delivered to lung cancer via liposomes or nanoparticles, can inhibit tumor growth by downregulating critical cancer promoting genes. Conversely, miR-21 and miR-155, frequently overexpressed in lung cancer, are associated with increased cell proliferation, invasion, and chemotherapy resistance. In this review, we summarize the current knowledge of the roles of miRNAs in lung carcinogenesis, especially those induced by exposure to environmental pollutants, namely, arsenic and benzopyrene, which account for up to 1/10 of lung cancer cases. We then discuss the recent advances in miRNA-based cancer therapeutics and diagnostics. Such information will provide new insights into lung cancer pathogenesis and innovative diagnostic and therapeutic modalities based on miRNAs.

11.
Cells ; 12(7)2023 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-37048097

RESUMO

The study evaluated the antitumor efficacy of APAN, "synthesized indoloquinoline analog derived from the parent neocryptolepine isolated from the roots of Cryptolepis sanguinolenta", versus the chemotherapeutic drug etoposide (ETO) in Ehrlich solid tumor (EST)-bearing female mice as well as its protective effect against etoposide-triggered hepatic disorders. APAN showed an ameliorative activity against Ehrlich solid tumor and hepatic toxicity, and the greatest improvement was found in the combined treatment of APAN with ETO. The results indicated that EST altered the levels of tumor markers (AFP, CEA, and anti-dsDNA) and liver biomarker function (ALT, AST, ALP, ALB, and T. protein). Furthermore, EST elevated CD68 and anti-survivin proteins immuno-expressions in the solid tumor and liver tissue. Molecular docking studies were demonstrated to investigate their affinity for both TNF-α and topoisomerase II as target proteins, as etoposide is based on the inhibition of topoisomerase II, and TNF-α is quite highly expressed in the solid tumor and liver tissues of EST-bearing animals, which prompted the authors' interest to explore APAN affinity to its binding site. Treatment of mice bearing EST with APAN and ETO nearly regularized serum levels of the altered parameters and ameliorated the impact of EST on the tissue structure of the liver better than that by treatment with each of them separately.


Assuntos
Carcinoma de Ehrlich , Doença Hepática Induzida por Substâncias e Drogas , Neoplasias , Camundongos , Feminino , Animais , Etoposídeo/farmacologia , Etoposídeo/uso terapêutico , Cryptolepis , Fator de Necrose Tumoral alfa , Simulação de Acoplamento Molecular , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/metabolismo , Carcinoma de Ehrlich/patologia , DNA Topoisomerases Tipo II/uso terapêutico
12.
Environ Toxicol ; 38(2): 415-421, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36286243

RESUMO

Copper oxide nanoparticles (CuO NPs) have developed as a significant class of nanomaterial with potential dangers to organisms and the environment in a variety of applications. This study aimed to investigate the impact of costus root extract against CuO NPs induced oxidative stress, alterations in heart structure and functions. 40 adult male rats were assigned randomly to four groups: first; control, second; costus (300 mg/kg body weight/day) orally for 2 weeks, third; CuO NPs (100 mg/kg body weight/day) intraperitoneally for 4 weeks and fourth; CuO NPs + costus. Current results revealed, significant increases in serum levels of creatine kinase-MB, creatine kinase enzyme, lactate dehydrogenase, myoglobin, aspartate aminotransferase, alkaline phosphatase, cardiac TBIRS, total thiol, nitric oxide, and cardiac proliferating cell nuclear antigen after CuO NPs administration when compared with control group. Conversely, statistical significant decreases were detected in cardiac reduced glutathione, catalase, and superoxide dismutase in CuO NPs group as compared with control group. Interestingly, treatment of CuO NPs with costus root extract was associated with significant improvements of the studied parameters, heart structure and functions. CuO NPs-induced toxicity, injury and oxidative stress in rat heart and treatment with Costus root extract could scavenge free radicals producing beneficial effects against CuO NPs.


Assuntos
Cardiotoxicidade , Nanopartículas Metálicas , Estresse Oxidativo , Extratos Vegetais , Saussurea , Animais , Masculino , Ratos , Peso Corporal , Cobre/toxicidade , Creatina Quinase , Nanopartículas Metálicas/toxicidade , Nanopartículas Metálicas/química , Nanopartículas , Óxidos/farmacologia , Saussurea/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Cardiotoxicidade/patologia
13.
Environ Sci Pollut Res Int ; 30(7): 17374-17383, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36192590

RESUMO

This study was designed to evaluate the protective potentials of chitosan nanoparticles (ChNPs) against silver nanoparticle (AgNP)-induced reproductive toxicity in male Wister albino rats. AgNPs, ChNPs, and AgNPs particles coated with ChNPs were characterized by using transmission electron microscope. Control rats were injected interperitoneally with 0.5% aqueous carboxymethyl cellulose. Second group was given ChNPs at a dose 300 mg/kg bwt. Third group was given AgNPs at a dose 50 mg/kg bwt. Fourth group was given AgNPs with chitosan nanoparticles simultaneously. Fifth group was given silver nanoparticles coated with chitosan nanoparticles at a dose 300 mg/kg bwt. TEM showed the formation of AgNPs with average size of 42.7 nm, ChNPs with average size of 33.3 nm, and AgNPs coated with ChNPs with average size of 48.1 nm. AgNPs significantly reduced serum levels of FSH, LH, testosterone and prolactin, sperm count, morphology index, vitality, total motility and progressive motility, the activities of catalase and superoxide dismutase, and the concentration of reduced glutathione in testicular tissues. However, it significantly increased malondialdehyde concentration in testicular tissues, sperm abnormalities, testicular tissue damages, non-progressive motility, and immotile sperms. On the contrast, ChNPs ameliorated AgNP-induced alteration in serum levels of sex hormones, spermogram, and testicular tissue's structure and functions. These results indicated that ChNPs had protective potential against AgNP-induced reproductive toxicity and ChNPs coating AgNPs had more potent protective effect than ChNPs administrated together with AgNPs.


Assuntos
Quitosana , Nanopartículas Metálicas , Nanopartículas , Animais , Ratos , Masculino , Nanopartículas Metálicas/toxicidade , Nanopartículas Metálicas/química , Quitosana/química , Prata/toxicidade , Prata/química , Ratos Wistar , Sêmen , Nanopartículas/química
14.
Environ Toxicol ; 37(10): 2412-2418, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35765203

RESUMO

Silver nanoparticles (Ag NPs or nanosilver) have pulled in expanding interest because of their novel physical, substance, and organic properties contrasted with their full scale scaled partners. The goal of this study was to investigate if Avena sativa (AVS) extract could ameliorate Ag NPs toxicity-induced alterations in liver structure and function, DNA damage, apoptosis, and oxidative stress. Twenty adult male rats were assigned randomly to four groups: control, AVS (intragastrically, 5 g/Kg body weight/day) for 2 weeks, Ag NPs (400 mg/kg body weight/day) for 1 week as acute toxicity and Ag NPs + AVS (same therapy of Ag NPs as acute toxicity with AVS). This study demonstrated a statistical significant increase in serum levels of liver function tests (AST, ALT, ALP and globulin), liver DNA damage, apoptotic P53 and Malondialdehyde after Ag NPs administration when compared to control group. Conversely, statistical significant decreases were detected in serum albumin, total proteins, liver reduced glutathione, catalase, superoxide dismutase, glutathione S-transferase and anti-apoptotic Bcl2 in Ag NPs group as compared to control group. Interestingly, treatment of Ag NPs with AVS (Ag Nps + AVS) was associated with significant improvements of the studied parameters, liver structure and functions. Avena sativa (AVS) extract could scavenge free radicals producing beneficial effects against acute Ag NPs hepatotoxicity in rats induced through activation of oxidative stress and apoptosis.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Nanopartículas Metálicas , Animais , Apoptose , Avena , Peso Corporal , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Dano ao DNA , Fígado , Masculino , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Estresse Oxidativo , Ratos , Prata/química , Prata/toxicidade
15.
Environ Sci Pollut Res Int ; 29(32): 48573-48587, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35194715

RESUMO

Epilepsy is one of the most common serious brain disorders, affecting about 1% of the population all over the world. Ginkgo biloba extract (GbE) and L-carnitine (LC) reportedly possess the antioxidative activity and neuroprotective potential. In this report, we investigated the possible protective and therapeutic effects of GbE and LC against pentylenetetrazol (PTZ)-induced epileptic seizures in rat hippocampus and hypothalamus. Adult male albino rats were equally divided into eight groups: control, GbE (100 mg/kg), LC (300 mg/kg), PTZ (40 mg/kg), protective groups (GbE + PTZ and LC + PTZ), and therapeutic groups (PTZ + GbE and PTZ + LC). The oxidative stress, antioxidant, and neurochemical parameters, viz., malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), acetylcholine esterase (AchE), dopamine (DA), norepinephrine (NE), and serotonin (5-HT), in the hippocampal and hypothalamic regions have been evaluated. PTZ injection leads to an increase in the seizure score, the levels of MDA and NO, and to a decrease in the activity of GSH, SOD, CAT, and GPx. Besides, monoamine neurotransmitters, DA, NE, and 5-HT, were depleted in PTZ-kindled rats. Furthermore, PTZ administration caused a significant elevation in the activity of AchE. Hippocampal and hypothalamic sections from PTZ-treated animals were characterized by severe histopathological alterations and, intensely, increased the ezrin immunolabeled astrocytes. Pre- and post-treatment of PTZ rats with GbE and LC suppressed the kindling acquisition process and remarkably alleviated all the aforementioned PTZ-induced effects. GbE and LC have potent protective and therapeutic effects against PTZ-induced kindling seizures via the amelioration of oxidative/antioxidative imbalance, neuromodulatory, and antiepileptic actions.


Assuntos
Epilepsia , Pentilenotetrazol , Animais , Masculino , Antioxidantes/metabolismo , Carnitina/farmacologia , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Epilepsia/patologia , Ginkgo biloba , Glutationa Peroxidase , Estresse Oxidativo , Pentilenotetrazol/uso terapêutico , Pentilenotetrazol/toxicidade , Extratos Vegetais/uso terapêutico , Serotonina/metabolismo , Superóxido Dismutase/metabolismo , Ratos
16.
Saudi J Biol Sci ; 28(11): 6384-6395, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34764756

RESUMO

The present study aimed, for the first time, to examine the biochemical effects of new phthalimide analog, 2-[2-(2-Bromo-1-ethyl-1H-indol-3-yl) ethyl]-1H-isoindole-1,3(2H)-dione, compared to thalidomide drug against liver injury induced in mice. Carbon tetrachloride was intraperitoneal injected in mice for 6 consecutive weeks at a dose of 0.4 mL/kg twice a week for liver injury induction. Histopathological examination, levels of malondialdehyde, nitric oxide, and antioxidant enzymes were determined. Additionally, the protein levels of vascular endothelial growth factor, proliferating cell nuclear protein, tumor necrosis factor-alfa, nuclear factor kappa B-p65, B-cell lymphoma-2, and cysteine-aspartic acid protease-3 were determined. Results revealed that the treatment with phthalimide analog improved the detected liver damage and presented an obvious antioxidant activity through decreasing malondialdehyde and nitric oxide levels accompanied by increasing the levels of the antioxidant enzymes. Furthermore, the analog exhibited an effective inhibitory activity towards the studied protein expressions in liver tissues. Moreover, the B-cell lymphoma-2 protein level was increased while the cysteine-aspartic acid protease-3 level was suppressed after the treatment with phthalimide analog. Together, these results propose that phthalimide analog can ameliorate carbon tetrachloride-induced liver injury in mice through its potent inhibition mediating effect in oxidative stress, inflammation, and apoptosis mechanisms.

17.
Sci Rep ; 11(1): 15688, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34344946

RESUMO

Hepatitis is one of earlier, but serious, signs of liver damage. High doses of statins for a long time can induce hepatitis. This study aimed to evaluate and compare the therapeutic potential of thymoquinone (TQ) and bee pollen (BP) on fluvastatin (F)-induced hepatitis in rats. Rats were randomly divided into: group 1 (G1, control), G2 (F, hepatitis), G3 (F + TQ), G4 (F + BP), and G5 (F + TQ + BP). Single treatment with TQ or BP relieved fluvastatin-induced hepatitis, with best effect for the combined therapy. TQ and/or BP treatment significantly (1) reduced serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transpeptidase, and total bilirubin, (2) decreased malondialdehyde levels and increased level of reduced glutathione, and activities of glutathione peroxidase and catalase in the liver, (3) improved liver histology with mild deposition of type I collagen, (4) increased mRNA levels of transforming growth factor beta 1, nuclear factor Kappa B, and cyclooxygenase 1 and 2, and (5) decreased tumor necrosis factor alpha and upregulated interleukin 10 protein in the liver. These data clearly highlight the ability of TQ and BP combined therapy to cause better ameliorative effects on fluvastatin-induced hepatitis than individual treatment by each alone.


Assuntos
Abelhas , Benzoquinonas/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Fluvastatina/efeitos adversos , Hepatite Animal/tratamento farmacológico , Pólen , Animais , Antioxidantes/metabolismo , Biomarcadores , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Gerenciamento Clínico , Suscetibilidade a Doenças , Expressão Gênica , Hepatite Animal/diagnóstico , Hepatite Animal/etiologia , Hepatite Animal/metabolismo , Imuno-Histoquímica , Testes de Função Hepática , Estresse Oxidativo/efeitos dos fármacos , Ratos , Resultado do Tratamento
18.
Front Pharmacol ; 12: 708785, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262464

RESUMO

Breast cancer remains the most common cause of cancer deaths among women globally. Ehrlich solid tumor (EST) is a transplantable tumor model for simulating breast cancer. This study aims to describe the protective role of costus (Saussurea lappa) root against EST-induced cardiac toxicity. Forty female mice were randomly and equally divided into four groups (G1, control group; G2, costus group; G3, EST group; G4, EST + costus). The results showed that compared to the control, EST induced a significant increase in lactate dehydrogenase, creatine kinase, creatine kinase myoglobin, aspartate aminotransferase, and alkaline phosphatase activities; in potassium, chloride ion, cholesterol, triglyceride, and low density lipoprotein levels; in DNA damage and cardiac injury; and in p53 and vascular endothelial growth factor expression. Conversely, EST induced a significant decrease in sodium ion and high density lipoprotein levels and Ki67 expression compared to the control. Treatment of EST with costus improved cardiac toxicity, lipid profiles, electrolytes, and apoptosis, and protected against EST. This indicates the potential benefits of costus as an adjuvant in the prevention and treatment of cardiac toxicity.

19.
Pak J Pharm Sci ; 34(1(Supplementary)): 337-343, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34275859

RESUMO

Most clinical investigations about the impact of nanoparticles on cells and tissues show that nanoparticles may enter the human body by means of respiratory tracts. Humans, animals, plants and environments are continually presented to a wide scope of business items containing silver nanoparticles (Ag NPs) in their piece. Ag NPs, utilized in various consumer products as room showers, surface cleaners, wound dressings, food storage containers and many textiles. The current examination planned to explore the defensive role of Avenanthramide-C (Avns) contrary to the lung toxicity initiated by Ag NPs injection in rats. 40 male Wistar rats were separated into 4 groups (Gp1, control; Gp2, Avns; Gp3, Ag NPs; Gp4, Ag NPs+Avns). Current results revealed that; Ag NPs induced a significant depletion in RBCs count, hemoglobin, platelets counts and a significant increase in total WBCs, lung injury, cyclooxygenase-2 (COX2) and TNFα expressions as compared to control. Treatments of Ag NPs with Avenanthramide-C extract (Ag NPs+Avns) improved the lung structure and blood complete pictures as compared to Ag NPs group.


Assuntos
Células Sanguíneas/efeitos dos fármacos , Lesão Pulmonar/patologia , Pulmão/efeitos dos fármacos , Nanopartículas Metálicas/efeitos adversos , Prata/efeitos adversos , ortoaminobenzoatos/farmacologia , Animais , Ciclo-Oxigenase 2/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Contagem de Eritrócitos , Hematócrito , Hemoglobinas/efeitos dos fármacos , Hemoglobinas/metabolismo , Contagem de Leucócitos , Pulmão/patologia , Lesão Pulmonar/induzido quimicamente , Contagem de Plaquetas , Ratos , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
20.
Environ Sci Pollut Res Int ; 28(32): 44226-44238, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33851294

RESUMO

This study evaluated the ameliorative potential of grape seed extract (GSE) against Ehrlich solid tumor (EST)-induced hepatic tissue alterations in mice. The control group was infused with physiological saline. The second group received GSE (50 mg/kg day by day orally) for 2 weeks. The third group was subcutaneously injected with 2.5 million of EST cells. The fourth group was injected with EST cells and treated with GSE extract simultaneously. The fifth group was injected with EST cells and kept for 2 weeks until the appearance of a solid tumor, then treated with GSE for 2 weeks. The phytochemical analysis of GSE revealed the presence of total phenols (17.442 mg GAE/g) and total flavonoid (6.687 mg CE/g) with antioxidant activity of 81.506 mg TE/g DPPH. The Ehrlich solid tumor significantly raised the activities of ALT, AST, and ALP; the level of alpha fetoprotein (AFP) in serum; and the protein expressions of hepatic proliferating cell nuclear antigen (PCNA) and tumor suppressor protein (P53), as well as induced DNA damage and pathological alterations in liver tissue. However, it significantly reduced serum albumin and total protein levels. In contrast, the co- or post-treatment of EST-bearing mice with GSE reduced the activities of ALT, AST, and ALP; the level AFP in serum; and hepatic P53 and PCNA protein expressions. In addition, it reduced EST-induced hepatic DNA damage and pathological alterations, while it increased serum albumin and total protein levels. This study suggested that GSE is a potent hepatoprotective agent and both co- and post-treatment of EST-bearing mice with GSE almost had the same effects.


Assuntos
Dano ao DNA , Extrato de Sementes de Uva , Fígado/efeitos dos fármacos , Animais , Antioxidantes , Carcinoma de Ehrlich , Extrato de Sementes de Uva/farmacologia , Camundongos , Antígeno Nuclear de Célula em Proliferação , Proteína Supressora de Tumor p53
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