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1.
J Biochem Mol Toxicol ; 36(11): e23179, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35906875

RESUMO

This study investigated the protective effect of quercetin against cyclophosphamide-induced immunosuppressive indoleamine 2,3-dioxygenase (IDO) via the mechanism of oxidative-inflammatory stress and behavioral indices. Cyclophosphamide (CYP) was administered to male Wister rats at a dose of 100 mg/kg with or without quercetin 50 mg/kg every other day for 7 days. Experimental techniques including western blotting, immunohistochemistry analysis, and inflammatory and oxidative stress marker assays were carried out. We also conducted behavioral analyses such as open field, tail suspension, and Y-maze tests for cognitive assessment. The results indicated that quercetin attenuated oxidative-inflammatory stress induced by CYP in the hippocampus and cerebral cortex of male Wister rats by augmenting the activities of antioxidant enzymes and suppressing lipid peroxidation as well as inflammatory mediators such as interleukin-6 and interferon-γ. Concomitantly, quercetin partially prevented the alteration in brain tissue histological architecture and mitigated the activities of IDO/tryptophan 2,3-dioxygenase (TDO) and protein expression of IDO1. This was corroborated by the IDO-quercetin model obtained in silico, revealing a favorable inhibitory interaction between quercetin and the enzyme. Finally, the results of behavioral tests suggested that quercetin significantly prevented the depressive-like posture of the CYP-treated rats. Our study for the first time revealed that quercetin ameliorates the effect of CYP-instigated IDO/TDO activities in the cerebral cortex and hippocampus via restoration of antioxidant enzymes and preventing oxidative-inflammatory stress.


Assuntos
Indolamina-Pirrol 2,3,-Dioxigenase , Quercetina , Animais , Ratos , Masculino , Quercetina/farmacologia , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenase/farmacologia , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Ratos Wistar , Hipocampo/metabolismo , Ciclofosfamida/toxicidade , Córtex Cerebral/metabolismo
2.
Toxicology ; 472: 153191, 2022 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-35489423

RESUMO

The present study investigated the attenuating effects of Zn following Cd-exposure in the activities/expression of indoleamine 2, 3-dioxygenase (IDO), tryptophan 2, 3-dioxygenase (TDO), oxidative-inflammatory response, behavioral indices and histologic architecture in cerebral cortex and hippocampus of male rats. Adult male Wistar rats were exposed to 200 µg/L and 100 µg/L of Cd and/or Zn in drinking water for 42 days. Cd exposure significantly increased IDO and TDO activities, IDO 1 protein expression, inflammatory response, with attendant disruption in antioxidant systems and concomitant elevation in malondialdehyde (MDA) levels in the cerebral cortex and hippocampus. Following Zn co-treatment, Cd-mediated increase in IDO 1 protein expression, IDO, and TDO activities, and decrease in antioxidant enzymes, and an increase in markers of inflammatory response and MDA production were significantly (p < 0.05) reversed compared with control. Moreover, altered behavioral indices and histological architecture of brain sections following Cd exposure was evidently (p < 0.05) prevented by Zn co-treatment relative to control. Overall, Cd-induced alterations in IDO 1 expression, IDO and TDO activities, oxidative-inflammatory response, behavioral indices, and histological architecture in the cerebral cortex and hippocampus of rats within the time course of the investigation were prevented by Zn co-treatment.


Assuntos
Fármacos Neuroprotetores , Triptofano , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Cádmio/toxicidade , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Masculino , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo , Ratos , Ratos Wistar , Triptofano/farmacologia , Zinco/farmacologia
3.
Drug Chem Toxicol ; 45(5): 2202-2211, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34013798

RESUMO

The various mediums of exposure to nickel (Ni) compounds have raised enormous public health concerns, as it has been illustrated to exert toxic effects in biological organs, including the brain. We have previously implicated the involvement of elevated nitric oxide (NO) in Ni-induced oxidative stress in the brain. Hence, the present study investigated the ameliorative potential of Nω-nitro-L-arginine (L-NA), a NO synthase inhibitor, following Ni-induced neurotoxicity. Adult male rats were divided into four groups; control (normal saline), 10 mg/kg Ni chloride (NiCl2) only, 1 mg/kg L-NA, or 2 mg/kg L-NA co-administered with NiCl2. The administration was via daily intraperitoneal injections for three weeks. Neurobehavioural assessments performed thereafter ascertained short-term spatial memory and anxiety. Furthermore, histological evaluations of the cortex, hippocampus, and striatum were carried out using routine hematoxylin and eosin technique, while the phosphotungstic acid hematoxylin method was used to express the degree of astrogliosis. Biochemical analysis of NO levels was examined along with other oxidative stress markers (superoxide dismutase, catalase, glutathione, glutathione S transferase, glutathione peroxidase, myeloperoxidase, and lipid peroxidation). The results illustrated altered behavioral responses, a higher population of degenerating neurons, and astrocytes in the NiCl2 group. There was also an elevation in the NO level and a corresponding reduction in antioxidant activities. However, these debilitating changes were ameliorated in the L-NA treated groups. These results demonstrate an association between alterations in NO synthesis pathway and Ni neurotoxicity, which may render neuronal cells susceptible to damage by oxidative stress. This may yet be another mechanism and useful therapeutic marker in deciphering Ni-induced neurotoxicity.


Assuntos
Arginina , Síndromes Neurotóxicas , Animais , Arginina/farmacologia , Inibidores Enzimáticos/farmacologia , Glutationa/metabolismo , Hematoxilina/farmacologia , Masculino , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/prevenção & controle , Níquel/toxicidade , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase/farmacologia , Estresse Oxidativo , Ratos
4.
Naunyn Schmiedebergs Arch Pharmacol ; 394(4): 591-602, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33064168

RESUMO

Selenium nanoparticles (SeNPs) are well reported to exhibit pharmacological activities both in vitro and in vivo. However, literature is devoid of studies on the impact of SeNPs and/or metformin (M) against streptozotocin (STZ)-mediated oxidative brain injury and behavioral impairment. Consequently, to fill this gap, diabetes was induced in male Wistar rats by feeding with 10% fructose solution for 2 weeks, followed by a single dose intraperitoneal injection of STZ (40 mg/kg body weight [bwt]). After rats were confirmed diabetic, they were treated orally with 0.1 mg/kg bwt of SeNPs ± M (50 mg/kg bwt), and normal control (NC) received citrate buffer (2 mg/mL) for 5 weeks. In comparison with the diabetic control (DC), SeNPs, and/or M significantly (p < 0.05) lowered blood glucose levels, but increased insulin secretion and pancreatic ß-cell function. An increase in locomotor and motor activities evidenced by improved spontaneous alternation, locomotor frequency, hinding, and increased mobility time were observed in treated groups. In addition, there was enhanced brain antioxidant status with a lower acetylcholinesterase (AChE) activity and oxidative-inflammatory stress biomarkers. A significant downregulation of caspase 3 and upregulation of parvalbumin and Nrf2 protein expressions was observed in treated groups. In some of the studied parameters, treated groups were statistically (p < 0.05) insignificant compared with the normal control (NC) group. Overall, co-treatment elicited more efficacy than that of the individual regimen.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Nanopartículas/administração & dosagem , Selênio/administração & dosagem , Acetilcolinesterase/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Caspase 3/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Quimioterapia Combinada , Glutationa/metabolismo , Glutationa Transferase/metabolismo , Insulina/sangue , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Oxirredutases/metabolismo , Parvalbuminas/metabolismo , Ratos Wistar
5.
Biol Trace Elem Res ; 198(2): 544-556, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32103411

RESUMO

Selenium nanoparticles (SeNPs) and metformin (Met) elicit individually protective effects against testicular oxidative injury in diabetic rats. However, the combined effects of both compounds have not been investigated. We investigated the effects of SeNPs and Met individual/co-treatment on testicular oxidative injury in diabetic rats. Diabetes was induced by a single intraperitoneal administration of streptozotocin (STZ-40 mg/kg bwt). The rats were equally divided into 6 groups: Group one-non-diabetic; group two-diabetic untreated; and group six-non-diabetic received citrate buffer (2 mL/kg bwt), while group three, four, and five received SeNPs (0.1 mg/kg bwt), Met (50 mg/kg bwt), and SeNPs/Met combined respectively, for 42 days. Results revealed that SeNPs, as well as Met treatment significantly (p < 0.001), lowered blood glucose levels and improved relative organ weights in treated rats than those of the untreated group. Moreover, a synergistic effect was observed in the co-administration group. Additionally, combined treatment elicited better effect, in augmenting the pituitary and testicular hormone (LH, FSH, prolactin, and testosterone) levels, marker enzymes/protein associated with steroidogenesis (3-ßHSD, 17-ßHSD, and StAR protein), and sperm functional parameters than those of individual treatment groups, when compared with control. Furthermore, the combinatorial effects of SeNPs and Met surpassed their influence in attenuating testicular oxidative stress/inflammation and upregulation of Nrf2 protein expression in diabetic rats when compared with control. Overall, normal rats, co-treated with SeNPs and Met, did not reveal any deleterious effect. Therefore, SeNPs and Met combined treatment may better improve testes function in diabetic conditions than an individual regimen.


Assuntos
Diabetes Mellitus Experimental , Metformina , Nanopartículas , Selênio , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Masculino , Metformina/metabolismo , Metformina/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Oxirredução , Estresse Oxidativo , Ratos , Selênio/metabolismo , Selênio/farmacologia , Espermatozoides/metabolismo , Estreptozocina , Testículo/metabolismo
6.
Redox Rep ; 23(1): 194-205, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30376784

RESUMO

OBJECTIVES: Loranthus micranthus is widely used in Nigerian folklore treatment of male infertility and diabetes complications. We investigated this claim in rats rendered diabetic by streptozotocin (STZ). METHODS: Induction of diabetes mellitus in adult male Wistar rats was by intraperitoneal injection of STZ (60  mg/kg). The diabetic rats were thereafter treated orally once/day with 5 mg/kg Gilbenclamide or L. micranthus (100 mg/kg or 200 mg/kg) and monitored for 14 days. Clinical observations, hormonal profile, oxidative stress parameters, glucose metabolism enzymes, histopathological examination, apoptotic marker immunoreactivity and western blotting in testes and sperm parameters were evaluated to examine effects of L. micranthus on STZ-diabetic rats. RESULTS: L. micranthus treatment significantly reduced the blood glucose level (45.9% and 84.7% on the 7th and 14th post-treatment days, respectively); increased antioxidant status, improved microarchitecture of testes, reduced lipid peroxidation and increased BCl-2 protein expression in diabetic rats relative to control. Furthermore, treatment with L. micranthus increased steroidogenic enzymes activities, levels of steroid hormones and improved sperm quality, relative to control. CONCLUSION: The anti-diabetic and aphrodisiac properties exhibited by L. micranthus could be contingent on its ability to restore a balance to the compromised redox status that characterizes male reproductive dysfunction in diabetes.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Loranthaceae/química , Extratos Vegetais/uso terapêutico , Espermatozoides/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Testículo/efeitos dos fármacos , Testículo/metabolismo
8.
Antioxidants (Basel) ; 7(4)2018 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-29677095

RESUMO

Nanosizing represents a straight forward technique to unlock the biological activity of complex plant materials. The aim of this study was to develop herbal nanoparticles with medicinal value from dried leaves and stems of Loranthus micranthus with the aid of ball-milling, high speed stirring, and high-pressure homogenization techniques. The milled nanoparticles were characterized using laser diffraction analysis, photon correlation spectroscopy analysis, and light microscopy. The average size of leaf nanoparticles was around 245 nm and that of stem nanoparticles was around 180 nm. The nanoparticles were tested for their antimicrobial and nematicidal properties against a Gram-negative bacterium Escherichia coli, a Gram-positive bacterium Staphylococcus carnosus, fungi Candida albicans and Saccharomyces cerevisiae, and a nematode Steinernemafeltiae. The results show significant activities for both leaf and (particularly) stem nanoparticles of Loranthus micranthus on all organisms tested, even at a particle concentration as low as 0.01% (w/w). The results observed indicate that nanoparticles (especially of the stem) of Loranthus micranthus could serve as novel antimicrobial agents with wide-ranging biomedical applications.

9.
J Environ Manage ; 210: 114-121, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29331852

RESUMO

Modern food processing results in considerable amounts of side-products, such as grape seeds, walnut shells, spent coffee grounds, and harvested tomato plants. These materials are still rich in valuable and biologically active substances and therefore of interest from the perspective of waste management and "up-cycling". In contrast to traditional, often time consuming and low-value uses, such as vermicomposting and anaerobic digestion, the complete conversion into nanosuspensions unlocks considerable potentials of and new applications for such already spent organic materials without the need of extraction and without producing any additional waste. In this study, nanosuspensions were produced using a sequence of milling and homogenization methods, including High Speed Stirring (HSS) and High Pressure Homogenization (HPH) which reduced the size of the particles to 200-400 nm. The resulting nanosuspensions demonstrated nematicidal and antimicrobial activity and their antioxidant activities exceeded the ones of the bulk materials. In the future, this simple nanosizing approach may fulfil several important objectives, such as reducing and turning readily available waste into new value and eventually closing a crucial cycle of agricultural products returning to their fields - with a resounding ecological impact in the fields of medicine, agriculture, cosmetics and fermentation. Moreover, up-cycling via nanosizing adds an economical promise of increased value to residue-free waste management.


Assuntos
Manipulação de Alimentos , Nanotecnologia , Gerenciamento de Resíduos , Agricultura , Café , Fermentação
10.
J Basic Clin Physiol Pharmacol ; 28(2): 123-131, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-27861138

RESUMO

BACKGROUND: The folkloric use of Bonny light crude oil (BLCO) in the treatment of gastrointestinal disorders and as an anti-poison is a generally acceptable practice in the Niger Delta area of Nigeria. The testicular dysfunction induced by BLCO exposure is of public concern with a view to its folkloric usage. The present study investigated the effects of BLCO exposure and withdrawal on the levels of testicular stress proteins and apoptosis-related proteins in rats. METHODS: Adult male Wistar rats were exposed to 800 mg/kg body weight of BLCO for 7 days. One-half of the rats in each group were sacrificed on day 8, while the remaining one-half stayed an additional 45 days without treatment. RESULTS: Western blot analysis showed that administration of BLCO resulted in a significant increase in the levels of stress proteins and apoptosis-related proteins by 50% and above relative to control, except cytosolic nuclear factor-κB (NF-κB), which decreased significantly relative to control. This was followed by a concomitant increase in the expression of caspase-3, FasL, and NF-κB by immunofluorescence staining within the testicular germ cells. Apoptosis showed a significant increase in TUNEL-positive cells. Following withdrawal of treatment, BLCO-mediated alteration in stress proteins and induction of apoptosis persisted relative to control. CONCLUSIONS: Collectively, BLCO induced irreversible alteration in testicular stress proteins and apoptosis in rats within the time course of investigation. These findings highlight the potential long-term adverse effects of BLCO on individuals unduly exposed to BLCO.


Assuntos
Apoptose/fisiologia , Proteínas de Choque Térmico/biossíntese , Mediadores da Inflamação/metabolismo , Petróleo/toxicidade , Síndrome de Abstinência a Substâncias/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo , Animais , Apoptose/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Síndrome de Abstinência a Substâncias/patologia , Testículo/patologia
11.
Drug Chem Toxicol ; 39(4): 424-31, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26821606

RESUMO

Studies have shown the reproductive effects of Bonny Light crude oil (BLCO) via the mechanism of oxidative stress and testicular apoptosis. We investigated the protective role of quercetin and vitamin E on BLCO-induced testicular apoptosis. Experimental rats were divided into four groups of four each. Animals were orally administered 2 ml/kg corn oil (control: group 1), BLCO-800 mg/kg body weight + 10 mg/kg quercetin (group 2), BLCO-800 mg/kg body weight + 50 mg/kg vitamin E (group 3) and BLCO-800 mg/kg body weight only (group 4) for 7 d. Protein levels of caspase 3, FasL, NF-kB, steroidogenic acute regulatory protein and stress response proteins were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Immunofluorescence staining was used to quantify the expression of caspase 3, FasL and NF-kB. Apoptosis was quantified by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. Administration of BLCO resulted in a significant increase in the levels of stress response proteins and apoptosis-related proteins by 50% and above after 7 d following BLCO exposure and a concomitant increase in expression of caspase 3, FasL and NF-kB expression by immunofluorescence staining. Apoptosis showed a significant increase in TUNEL positive cells. Co-administration with quercetin or vitamin E reversed BLCO-induced apoptosis and levels of stress protein, relative to control. These findings suggest that quercetin and vitamin E may confer protection against BLCO-induced testicular oxidative stress-related apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Proteínas de Choque Térmico/metabolismo , Petróleo/toxicidade , Fosfoproteínas/metabolismo , Quercetina/farmacologia , Testículo/efeitos dos fármacos , Vitamina E/farmacologia , Animais , Marcação In Situ das Extremidades Cortadas , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Testículo/patologia
12.
J Basic Clin Physiol Pharmacol ; 26(3): 223-31, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25046308

RESUMO

BACKGROUND: Mounting experimental evidence highlights the testicular and neuronal toxicity of environmental/industrial chemicals in experimental animals via the mechanism involving oxidative damage. Nigerian Bonny Light crude oil (BLCO) has been reported to exhibit reproductive and neuronal toxicity in male rats. Studies have shown that vitamin E and quercetin protect rat neuronal and testicular cells from environmental chemical-induced oxidative damage. We investigated the possible protective role of quercetin and vitamin E in BLCO induced-neuronal and testicular toxicity. METHODS: Male rats were administered BLCO at doses of 400 and 800 mg/kg body wt/day p.o. three times/week for 6 weeks. Other groups were co-administered BLCO (400 and 800 mg/kg body wt/day p.o.) with/without vitamin E (50 mg/kg body wt/day p.o.) or quercetin (10 mg/kg body wt/day p.o.) three times/week for 6 weeks, respectively. RESULTS: Semen quality deteriorated, testosterone and luteinizing hormone (LH) levels were significantly decreased, and follicle stimulating hormone (FSH) increased following BLCO reatment. There was a significant decline in the activities of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and glutathione-S-transferase (GST) with concomitant increased levels of lipid peroxidation and activities of xanthine oxidase (XO) in a dose-dependent manner, in testes and brain of rats. Co-administration with vitamin E or quercetin reversed BLCO-induced neuronal and testicular toxicity by preventing oxidative stress, improving sperm quality, and restoring hormonal levels relative to controls. CONCLUSIONS: BLCO altered reproductive indices and induced neuronal toxicity via the mechanism of oxidative stress. Quercetin and vitamin E showed possible chemoprotection against the toxicity.


Assuntos
Neurônios/efeitos dos fármacos , Petróleo/efeitos adversos , Quercetina/administração & dosagem , Testículo/efeitos dos fármacos , Vitamina E/administração & dosagem , Animais , Antioxidantes/administração & dosagem , Catalase/metabolismo , Hormônio Foliculoestimulante/metabolismo , Glutationa/metabolismo , Glutationa Transferase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Hormônio Luteinizante/metabolismo , Masculino , Neurônios/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Análise do Sêmen/métodos , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Testículo/metabolismo , Testosterona/metabolismo , Xantina Oxidase/metabolismo
13.
Environ Toxicol ; 30(2): 242-52, 2015 02.
Artigo em Inglês | MEDLINE | ID: mdl-24106129

RESUMO

In the past few decades, there has been much concern about the adverse health effects of environmental contaminants in general and Crude Oil in particular around the Niger Delta region of Nigeria where all the crude Oil exploration is taking place. Studies have shown the repro-toxic effects of Bonny-light crude oil (BLCO). However, the insight into the mechanisms of gonadal toxicity induced by BLCO is not well known. In this study, we sought to elucidate the mechanism(s) underpinning the gonadal effects within hours of exposure to BLCO. Experimental rats were divided into five groups of four each. Animals were orally administered with a single dose of BLCO (800 mg/kg body weight) and killed at 0, 6, 12, 24, and 72 h post-treatment. The levels and time-course of induction of stress response proteins and apoptosis-related proteins like cytochorome C, caspase 3 and procaspase 9, Fas-FasL, NF-kB and TNF-α were determined to assess sequential induction of apoptosis in the rat testis. DNA damage was assessed by TUNEL assay. Administration of BLCO resulted in a significant increase in the levels of stress response proteins and apoptotis- related proteins as early as 6 h following exposure. Time-dependent elevations in the levels of the proteins were observed. The DNA damage was measured and showed time-dependent increase in the TUNEL positive cells of testicular cells. The study demonstrates induction of testicular apoptosis in adult rats following exposure to a single dose of BLCO.


Assuntos
Apoptose/efeitos dos fármacos , Caspase 3/efeitos dos fármacos , Proteínas de Choque Térmico/biossíntese , Petróleo/toxicidade , Testículo/metabolismo , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Dano ao DNA , Poluentes Ambientais/toxicidade , Marcação In Situ das Extremidades Cortadas , Masculino , Nigéria , Ratos , Ratos Wistar , Testículo/efeitos dos fármacos
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