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1.
Trop Anim Health Prod ; 56(2): 62, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38278967

RESUMO

A feeding trial was conducted to assess the effect of partial replacement of dietary soybean meal by three plant protein sources: coconut, rocket seed, and black cumin meals with their combination in the presence or absence of nano-chitosan (NCH) on growth performance and immune response in broiler chickens. Five starter and grower diets were formulated and used from 1 to 42 days of age. The NCH was added to starter and grower diets at 1.0 g/kg. Five-hundred-fifty-day-old Arbor Acres Plus broiler chicks were randomly divided into ten treatments with five equal replications. Final body weight (FBW), body weight gain (BWG), feed intake (FI), feed conversion ratio (FCR), and blood plasma parameters were investigated. Histological aspects of lymphoid organs (thymus: T, bursa of Fabricius: B, and spleen: S) were characterized. Apart from added NCH, the FBW, BWG, and FCR of broilers fed the diets containing the tested plant proteins were significantly superior to the control ones. However, FI of birds fed the diets containing CM alone or combined with RSM plus BCM was significantly reduced. All experimental broilers displayed high plasma levels of IgG compared with the control group. There were significant increases in plasma concentrations of IgM, IgA, and T4 for groups that fed the diets containing RSM, BCM, and mixture of CM, RSM, and BCM compared with their controls. The T3 levels of broilers fed the tested plant proteins were significantly increased compared with the controls. Aside from plant protein source, broilers fed the NCH-enriched diets achieved significant increases in levels of IgM, TAC, and FSH and activities of CAT and SOD but reduced the MDA level compared with control. The interactions between plant protein source and added nano-chitosan were not interrelated. Furthermore, CM, RSM, and BCM can be used as complementary dietary proteins singly or combined with NCH with no adverse effects on growth performance. Addition of NCH molecules has a positive effect on live body weight and increases feed intake compared with control chicks.


Assuntos
Galinhas , Dieta , Animais , Dieta/veterinária , Peso Corporal , Aumento de Peso , Proteínas Alimentares/metabolismo , Imunidade , Proteínas de Plantas/metabolismo , Imunoglobulina M , Ração Animal/análise , Suplementos Nutricionais , Fenômenos Fisiológicos da Nutrição Animal
2.
Pestic Biochem Physiol ; 194: 105492, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37532318

RESUMO

Nanomaterials have been produced with the use of bio-nanotechnology, which is a low-cost approach. Currently, research is being conducted to determine whether actinomycetes isolated from Egyptian soil can biosynthesize Ag nanoparticles (Ag NPs) and characterized by using the following techniques: Transmission electron microscopy (TEM), Dynamic light scattering (DLS), Fourier transforms infrared (FT-IR), Energy-dispersive X-ray spectroscopy (EDX), UV-Vis spectroscopy and X-ray diffraction (XRD). The most promising actinomycetes isolate were identified, morphologically, biochemically, and molecularly. Streptomyces avermitilis Azhar A.4 was found to be able to reduce silver metal nanoparticles from silver nitrate in nine isolates collected from Egyptian soil. Toxicity of biosynthesized against 2nd and 4th larval instar of Agrotis ipsilon (Hufn.) (Lepidoptera: Noctuidae) was estimated. In addition, activity of certain vital antioxidant and detoxifying enzymes as well as midgut histology of treated larvae were also investigated. The results showed appositive correlations between larval mortality percentage (y) and bio-AgNPs concentrations (x) with excellent (R2). The 4th larval instar was more susceptible than 2nd larval instar with LC50 (with 95% confirmed limits) =8.61 (2.76-13.89) and 26.44(13.25-35.58) ppml-1, respectively of 5 days from treatment. The initial stages of biosynthesized AgNps exposure showed significant increases in carboxylesterase (CarE) and peroxidases (PODs) activity followed by significant suppression after 5 days pos-exposure. While protease activity was significantly decreased by increasing time post-exposure. Midgut histology showed abnormality and progressive damage by increasing time post exposure leading to complete destruction of midgut cells after 5 days from exposure. These results make biosynthesized AgNPs an appropriate alternative to chemical insecticide in A. ipsilon management.


Assuntos
Actinobacteria , Nanopartículas Metálicas , Animais , Nanopartículas Metálicas/toxicidade , Nanopartículas Metálicas/química , Actinomyces , Espectroscopia de Infravermelho com Transformada de Fourier , Prata/toxicidade , Larva , Extratos Vegetais/farmacologia , Antibacterianos/farmacologia
3.
Anim Biotechnol ; 34(8): 3519-3532, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36688617

RESUMO

Effects of dietary inclusion of spirulina platensis (SP) and selenium nanoparticles (SeNPs) combination (SP-SeNPs) on the reproductive performance in vivo and in vitro, reproductive and metabolic hormones, hemato-bichemical parameters, oxidative stress, and immunity of heat-stressed doe rabbis were evaluated. All supplements significantly increased live litter size at birth and weaning, viability rate at birth, hemoglobin and red blood cells, and plasma T3, T4, insulin, total proteins and albumin compared with control. Plasma estradiol 17-ß (pre-mating), progesterone (mid-pregnancy), and prolactin (day -7 postpartum) were significantly increased only by SeNPs (0.3, 0.4, and 0.5 mg/kg). All dietary supplements significantly reduced WBCs, cortisol, lipid profile, and improved liver and kidney functions. Immunoglobulins levels, antioxidants capacity were significantly increased, superoxide dismutase was increased by SeNPs (0.4 and 0.5 mg/kg), while malondialdehyde was reduced by 0.3, 0.4 and 0.5 SeNPs mg/kg. Sexual receptivity, pregnancy rate, viability rate at weaning, ovulation rate, and embryo quality were significantly increased by increasing SeNPs above 0.1 mg, while embryo yield was increased by >0.2 mg SeNPs/kg. A combination of SP and SeNPs, could be potentially used as a strong antioxidant to enhance heat regulation and doe rabbit reproduction via improving reproductive and metabolic hormones, antioxidant status and immunological parameters.


Assuntos
Nanopartículas , Selênio , Spirulina , Gravidez , Feminino , Coelhos , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Selênio/farmacologia , Spirulina/metabolismo , Reprodução , Estresse Oxidativo , Hormônios/farmacologia , Resposta ao Choque Térmico
4.
Antioxidants (Basel) ; 11(11)2022 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-36358523

RESUMO

Aging is a naturally occurring physiological process with a deleterious impact on various body organs and humans' well-being. The aging population is increasing worldwide, which imposes the need for the exploration of nutritional options that can intercept the impact of the aging processed on various body organs. Vitamin K2 (VK2) is a fat-soluble vitamin with emerging evidence on its therapeutic merits. In the current study, natural aging induced a significant liver deterioration with a disrupted Keap-1/Nrf-2/HO-1 axis and increased COX-2, iNOS and TNF-α expression and apoptotic and fibrotic changes. VK2 administration, on the other hand, improved the biochemical indices of liver function (total protein, albumin, ALT and AST); the suppressed hepatic expression of Keap-1 and increased the hepatic expression of Nrf-2 with a parallel increase in the hepatic activity of HO-1. Subsequently, the liver content and hepatic expression of TNF-α, COX-2 and iNOS were significantly retracted. In context, the liver content and hepatic expression of the fibrotic biomarkers TGFß and TIMP significantly retracted as well. Moreover, the TUNEL assay confirmed the retraction of liver apoptotic changes. Of notice, electron transmission microscope examination confirmed the preservation of mitochondrial functions and preservation of the ultra-microscopical structures. In conclusion, the VK2-mediated interception of aging-induced Keap-1/Nrf-2/HO-1 signaling suppressed the hepatic contents of inflammatory and fibrotic biomarkers, as well as apoptotic changes with preservation of the hepatic architectural and functional status. VK2 can be presumed to be an effective nutritional supplement to the aging population to spare the liver, amongst other body organs, against aging-induced deleterious injury.

5.
J Dermatolog Treat ; 33(3): 1617-1622, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-33390056

RESUMO

BACKGROUND: Controlling psoriasis with various systemic treatments, including methotrexate, may significantly decrease associated cardiovascular risk problems. OBJECTIVE: To assess the value of vitamin D supplementation on clinical response as well as changes in cardiovascular risk parameters in psoriasis patients treated with methotrexate. METHODS: This prospective randomized comparative study included 30 patients with moderate to severe psoriasis divided randomly to receive either methotrexate alone (Mtx) or methotrexate plus intramuscular vitamin D (MtxD) for 3 months. Lipid profile, HsCRP, carotid intima-media thickness (CIMT) and blood pressure (BP) measurements were recorded before and after the therapy. RESULTS: At end of study period, significant clinical improvement in both groups was observed. CIMT and systolic BP decreased in both groups but only statistically significant in Mtx group. HsCRP decreased in both groups but didn't reach statistical significance. We also observed, an increase in triglycerides and cholesterol levels in the Mtx group with the latter decreasing in the combined Mtx and vitamin D therapy group. CONCLUSION: Treating psoriasis with methotrexate may decrease cardiovascular disease risk factors. Adding vitamin D supplementation to methotrexate may protect lipid homeostasis, specifically cholesterol and triglycerides.


Assuntos
Doenças Cardiovasculares , Metotrexato , Psoríase , Vitamina D , Proteína C-Reativa , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Espessura Intima-Media Carotídea , Colesterol/sangue , Suplementos Nutricionais , Fatores de Risco de Doenças Cardíacas , Humanos , Lipídeos , Metotrexato/uso terapêutico , Estudos Prospectivos , Psoríase/complicações , Psoríase/tratamento farmacológico , Triglicerídeos/sangue , Vitamina D/uso terapêutico
6.
J Dermatolog Treat ; 33(4): 2358-2363, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34376113

RESUMO

BACKGROUND: Growing evidence suggests the important role of IL-36 in the pathogenesis of psoriasis. Cathepsin G is a neutrophil-derived protease that can activate IL-36γ. OBJECTIVE: To assess the expression of IL-36γ and cathepsin G in psoriasis and to quantify the impact of treatment with narrow-band ultraviolet B phototherapy (NB-UVB) on their levels. METHODS: This case-control study involved 26 patients with moderate-severe psoriasis and 25 healthy volunteers. Psoriasis patients eligible for phototherapy received 24 NB-UVB sessions. Punch skin biopsies were obtained from all participants at recruitment and after phototherapy from patients. Real-time PCR was utilized for quantitative assessment of IL-36γ and cathepsin G expression in tissue samples. RESULTS: The expression of IL-36γ and cathepsin G was significantly higher in psoriasis before NB-UVB therapy compared to controls (p < .001). Both proteins decreased significantly with clinical improvement following NB-UVB therapy compared to baseline (p < .001). However, their expression after treatment was still higher than controls (p < .001). CONCLUSION: IL-36γ and cathepsin G expression is upregulated in psoriatic lesions, supporting their role as mediators of inflammation in psoriasis. Downregulation of IL-36γ and cathepsin G is a possible mechanism for psoriasis improvement after NB-UVB therapy. IL-36 and cathepsin G can be considered as therapeutic targets for psoriasis.


Assuntos
Catepsina G/metabolismo , Interleucina-1/metabolismo , Psoríase , Terapia Ultravioleta , Estudos de Casos e Controles , Regulação para Baixo , Humanos , Interleucinas , Fototerapia , Psoríase/patologia , Psoríase/radioterapia
7.
Poult Sci ; 100(2): 675-684, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33518121

RESUMO

In the present study, 200 Brown commercial egg-type layers (60 wk old) were used to study the effects of different levels of ecofriendly synthesis of calcium (Ca) nanoparticles (0.0, 0.50, 1.0, and 1.5 g/kg diet) with biocompatible Sargassum latifolium algae extract (SL-CaNps) on exterior egg quality traits, electronic microscopic view of eggshells, Ca and phosphorus (P) retention, serum Ca and P concentrations, and the histology of the uterus. Hens fed with dietary SL-CaNps powder had higher egg weight and shell weight % values than those of the control group. All SL-CaNps treatment groups had the greatest values of shell weight per unit surface area and shell thickness. Dietary supplementation of SL-CaNps at graded levels up to 1.5 g/kg diet had higher serum Ca and inorganic P levels than that of the control. Laying hens fed with SL-CaNps-added diets had beneficial effects on shell ultrastructure in terms of well-developed palisade and mammillary layers. The numbers of apical cells along the branched tubular gland were greater in SL-CaNps-treated groups than those of control. Conclusively, supplementing SL-CaNps powder up to 1.5 g/kg to the diet of laying hens improved eggshell thickness, shell weight% and shell weight per unit surface and has no adverse effect on their eggshell quality or electronic microscopic view of their eggshell.


Assuntos
Cálcio/administração & dosagem , Galinhas/fisiologia , Casca de Ovo/ultraestrutura , Ovos/normas , Nanopartículas , Sargassum/química , Fatores Etários , Ração Animal/análise , Animais , Galinhas/anatomia & histologia , Dieta/veterinária , Suplementos Nutricionais , Feminino , Microscopia Eletrônica de Varredura/veterinária , Microscopia Eletrônica de Transmissão/veterinária , Distribuição Aleatória , Espectrofotometria Ultravioleta/métodos , Espectrofotometria Ultravioleta/veterinária
8.
Photodermatol Photoimmunol Photomed ; 37(4): 306-312, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33404131

RESUMO

BACKGROUND: Despite exhaustive research, melanocyte disappearance and the evolution of vitiligo remain enigmatic, and although multi-factorial, oxidative stress appears as a major player. The role of cutaneous cholinergic system in vitiligo pathogenesis has also been reported in some studies. OBJECTIVE: To evaluate and correlate the influence of phototherapy on cutaneous cholinergic system and oxidative stress in vitiligo. METHODS: Acetyl choline (ACh), its receptors; nicotinic (nAChR) and muscarinic (mAChR); acetylcholine esterase (AChE) and H2 O2 levels were estimated in de-pigmented and re-pigmented lesions of 30 vitiligo patients before and after NB-UVB phototherapy and in 30 controls. ACh and H2 O2 levels were measured by colorimetry. AChE and acetylcholine receptors expression were measured by quantitative real-time PCR. RESULTS: Mean ACh and H2 O2 levels were significantly higher in vitiligo lesions before NB-UVB (P < .001) whereas AChE enzyme level was significantly lower (P < .001) compared to both re-pigmented and control skin. Additionally, mean mAChR was significantly higher and mean nAChR was significantly lower in vitiligo lesions before NB-UVB versus controls and re-pigmented skin (P < .001). Also, H2 O2 and AChE showed negative correlation whereas ACh and mAChR showed significant positive correlation. Although all the studied parameters showed significant changes after treatment and subsequent re-pigmentation, a significant difference continued to exist between all vitiligo skin and controls. CONCLUSION: Cholinergic system is strongly involved in vitiligo pathogenesis through H2 O2 inhibition of AChE which could be reversed by NB-UVB. Moreover, the strong activation of mAChRs may reflect genetic and/or acquired errors, direct up-regulation by ACh and H2 O2 or both.


Assuntos
Terapia Ultravioleta , Vitiligo , Colinérgicos , Humanos , Estresse Oxidativo , Pele , Resultado do Tratamento
9.
J Adv Res ; 28: 27-33, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33364042

RESUMO

In type 2 diabetes mellitus (T2DM), hyperglycemia leads to oxidative insult. Vitamins A and E have antioxidant potentials and may help in managing diabetes. The combined effect of high-dose vitamin A plus E supplementation with and without zinc on T2DM, has never been examined. Thus, this study aimed to evaluate and compare the effect of high-dose vitamin A plus E supplementation (AE) versus high-dose vitamin A plus E with zinc (AEZ), on different diabetic parameters. Ninety-eight patients with T2DM were randomized to receive either: 50,000 IU vitamin A and 100 mg vitamin E (AE group, N = 36), an equivalent dose of vitamin A and E combined with 25 mg zinc (AEZ group, N = 35), or no supplements (control group, N = 27) for three months. Compared to control, AEZ group showed significant reductions in fasting blood glucose, 2 h postprandial blood glucose, and glycated hemoglobin (HbA1c) with significant increases in homeostasis model assessment of beta-cell function and difference value of fasting insulin. Two hair loss cases were recorded in both treated groups. Although vitamin A needs dose moderation, these results suggest that, high-dose vitamin A plus E supplementation combined with zinc may improve glycemic control, ß-cell function, and insulin secretion in adults with T2DM.

10.
Int Immunopharmacol ; 87: 106813, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32707499

RESUMO

The prevalence of diabetes mellitus (DM) drastically increases worldwide. Persistent hyperglycemia affects body microvasculature causing injuries to kidney producing diabetic nephropathy (DNE). Manifestation of these microvascular complications is associated with disturbed redox homeostasis. The current study evaluated the effect of isoliquiritigenin (ISLQ), a bioactive chalcone found in licorice which is known for its antioxidant effect, on diabetes-induced renal injury. DM was prompted in male rats by streptozotocin (STZ, 50 mg/kg, intraperitoneally). ISLQ was administrated by oral gavage for 8 weeks at a dose (20 mg/kg/day). Features of renal injury were observed in kidneys of diabetic rats including, albuminuria and deteriorated renal function. Renal dysfunction was associated with reduced sirtuin-1 (Sirt-1) expression, increased renal oxidative stress, nucleotide-binding domain and leucine-rich repeat containing protein-3 (NLRP3), nuclear factor-κB (NFκB) and inflammatory cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α). Moreover, there was significant downregulation of anti-inflammatory cytokine interleukin-10 (IL-10), glomerular and tubular injury and collagen accumulation. ISLQ administration preserved renal function and architecture, restored Sirt1 and renal oxidant-antioxidant balance, dampened inflammation and attenuated collagen accumulation. It can be inferred that ISLQ possess a protective effect and could have a potential as a food supplement to halt development and progression of DNE.


Assuntos
Anti-Inflamatórios/uso terapêutico , Chalconas/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Rim/patologia , Animais , Glycyrrhiza , Humanos , Masculino , Modelos Animais , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos , Ratos Sprague-Dawley , Sirtuína 1/genética , Sirtuína 1/metabolismo
11.
Chem Biol Interact ; 315: 108897, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31726037

RESUMO

Type 2 diabetes mellitus (T2DM) is a disease with a drastically growing worldwide prevalence. It is usually associated with numerous complications of which; diabetic nephropathy (DN); is a main complication of microvasculature and more seriously, a common cause of end-stage renal disease (ESRD). Unfortunately, both the lack of a definitive remedy alongside the economic and the social burden on DN patients enforces considerable impetus for developing alternative therapies. IL-33 is a newly discovered member of the IL-1 cytokine family. IL33/ST2 signaling plays a crucial role in acute and chronic kidney diseases. Calycosin is an isoflavone with reported IL33 signaling inhibitory activity. The present study aimed to investigate if calycosin possess renal protective effect in high-fat diet/STZ-induced T2DM model and to clarify the potential underlying mechanisms. HFD-STZ control rats showed functional and structural renal damage confirmed by increased serum creatinine, blood urea nitrogen and albuminuria associated with marked renal glomerulosclerosis and interstitial fibrosis. Initiation of inflammation, oxidative stress, and fibrosis was evident as depicted by elevated renal levels of IL33/ST2 mRNA as well as increased renal NF-κBp65, TNF-α, IL-1ß, MDA, and TGF-ß contents with suppressed Nrf2 and TAC. Calycosin treatment markedly improved the aforementioned makers of renal injury and dysfunction, modulated IL33/ST2 signaling, inflammatory cytokines, oxidative stress and fibrotic processes. This was accompanied by improvement of T2DM-induced renal ultramicroscopic and histopathological alterations.


Assuntos
Fibrose/tratamento farmacológico , Interleucina-33/metabolismo , Isoflavonas/farmacologia , Rim/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Receptores de Interleucina-1/metabolismo , Animais , Citocinas/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Dieta Hiperlipídica/efeitos adversos , Fibrose/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Rim/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Estreptozocina/farmacologia
12.
Can J Physiol Pharmacol ; 95(4): 420-426, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28112972

RESUMO

Drug-induced hepatotoxicity is one of the most commonly encountered obstacles in the field of medical practice. Sodium valproate (VPA) is among many drugs with reported hepatotoxic effects. Sulforaphane (SFN) is a thiol compound found in wide abundance in cruciferous plants that has numerous reported therapeutic efficacies. The current investigation sheds light on the potential hepatoprotective effect of SFN against VPA-induced liver injury in rats. Twice daily VPA (700 mg/kg, i.p.) for 7 days induced significant biochemical alterations and hepatic histopathological damage. SFN (0.5 mg/kg, orally) for 7 days significantly boosted liver function biomarkers; it reduced serum alanine transaminase, aspartate aminotransferase, and alkaline phosphatase, and restored serum albumin concentration in a significant manner. Meanwhile, SFN significantly mitigated VPA-induced histopathological alterations. To highlight the mechanisms implicated in the observed hepatoprotective action, hepatic malondialdehyde and tumour necrosis factor α content significantly declined with concomitant increase in hepatic heme oxygenase-1 content and glutathione concentration with SFN treatment. In conclusion, SFN can significantly ameliorate VPA-induced hepatotoxicity and liver injury primarily by direct association between antioxidant and anti-inflammatory properties.


Assuntos
Anticarcinógenos/uso terapêutico , Anticonvulsivantes/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Isotiocianatos/uso terapêutico , Compostos Fitoquímicos/uso terapêutico , Ácido Valproico/efeitos adversos , Alanina Transaminase/sangue , Animais , Anti-Inflamatórios/uso terapêutico , Anticonvulsivantes/uso terapêutico , Antioxidantes/uso terapêutico , Aspartato Aminotransferases/sangue , Biomarcadores/análise , Brassica/química , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Epilepsia/tratamento farmacológico , Glutationa/metabolismo , Heme Oxigenase-1/metabolismo , Humanos , Testes de Função Hepática , Masculino , Malondialdeído/metabolismo , Ratos , Ratos Sprague-Dawley , Sulfóxidos , Fator de Necrose Tumoral alfa/metabolismo , Ácido Valproico/uso terapêutico
13.
J Physiol Biochem ; 71(4): 635-48, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26293752

RESUMO

Diabetes mellitus is an ever growing world-wide health problem. The patient has to stick to a firm life-long therapeutic regimen, otherwise diabetic complications will develop. Diabetic nephropathy (DN) is one of the most common diabetic complications and it requires careful medical attendance. Nilotinib hydrochloride is a protein tyrosine kinase inhibitor reported to have numerous therapeutic efficacies besides being an anticancer. In the current study, single I.P. streptozotocin (50 mg/kg) injection was used to induce type I diabetes mellitus in male Sprague-Dawley rats. After 8 weeks, significant deterioration of renal function with urinary excretion of nephrin, podocalyxin, and albumin was observed. Daily oral administration of nilotinib (20 mg/kg) for 8 weeks significantly improved signs of DN on all investigated scales. On a biochemical scale, kidney functions, albuminuria, urinary nephrin, podocalyxin excretion, and host oxidant/antioxidant balance significantly improved. Kidney content of nitric oxide, expression of toll-like receptors 4 and NF-κB/p65 activity significantly declined as well. On a histopathological scale, α-smooth muscle actin and nestin expression significantly declined. Meanwhile, area of fibrosis significantly declined as seen with significant reduction in accumulation of extracellular matrix components and kidney content of collagen. Ultimately, such improvements were accompanied by significant restoration of normal kidney physiology and function. In conclusion, nilotinib can hinder progression of DN through various mechanisms. Reduction of oxidative stress, enhancement of host antioxidant defense system, reduction of inflammation, angiogenesis, tissue hypoxia, and pro-fibrogenic biomarker expression can be implicated in the beneficial therapeutic outcome observed with nilotinib therapy.


Assuntos
Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/tratamento farmacológico , Rim/patologia , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Animais , Nitrogênio da Ureia Sanguínea , Colágeno/metabolismo , Creatinina/sangue , Avaliação Pré-Clínica de Medicamentos , Glutationa/metabolismo , Hidroxiprolina/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Receptor 4 Toll-Like/metabolismo , Fator de Transcrição RelA/metabolismo
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