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1.
Biol Res ; 57(1): 45, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982468

RESUMO

BACKGROUND: Diabetic neuropathy (DN) is recognized as a significant complication arising from diabetes mellitus (DM). Pathogenesis of DN is accelerated by endoplasmic reticulum (ER) stress, which inhibits autophagy and contributes to disease progression. Autophagy is a highly conserved mechanism crucial in mitigating cell death induced by ER stress. Chrysin, a naturally occurring flavonoid, can be found abundantly in honey, propolis, and various plant extracts. Despite possessing advantageous attributes such as being an antioxidant, anti-allergic, anti-inflammatory, anti-fibrotic, and anticancer agent, chrysin exhibits limited bioavailability. The current study aimed to produce a more bioavailable form of chrysin and discover how administering chrysin could alter the neuropathy induced by Alloxan in male rats. METHODS: Chrysin was formulated using PEGylated liposomes to boost its bioavailability and formulation. Chrysin PEGylated liposomes (Chr-PLs) were characterized for particle size diameter, zeta potential, polydispersity index, transmission electron microscopy, and in vitro drug release. Rats were divided into four groups: control, Alloxan, metformin, and Chr-PLs. In order to determine Chr- PLs' antidiabetic activity and, by extension, its capacity to ameliorate DN, several experiments were carried out. These included measuring acetylcholinesterase, fasting blood glucose, insulin, genes dependent on autophagy or stress in the endoplasmic reticulum, and histopathological analysis. RESULTS: According to the results, the prepared Chr-PLs exhibited an average particle size of approximately 134 nm. They displayed even distribution of particle sizes. The maximum entrapment efficiency of 90.48 ± 7.75% was achieved. Chr-PLs effectively decreased blood glucose levels by 67.7% and elevated serum acetylcholinesterase levels by 40% compared to diabetic rats. Additionally, Chr-PLs suppressed the expression of ER stress-related genes (ATF-6, CHOP, XBP-1, BiP, JNK, PI3K, Akt, and mTOR by 33%, 39.5%, 32.2%, 44.4%, 40.4%, 39.2%, 39%, and 35.9%, respectively). They also upregulated the miR-301a-5p expression levels by 513% and downregulated miR-301a-5p expression levels by 65%. They also boosted the expression of autophagic markers (AMPK, ULK1, Beclin 1, and LC3-II by 90.3%, 181%, 109%, and 78%, respectively) in the sciatic nerve. The histopathological analysis also showed that Chr-PLs inhibited sciatic nerve degeneration. CONCLUSION: The findings suggest that Chr-PLs may be helpful in the protection against DN via regulation of ER stress and autophagy.


Assuntos
Autofagia , Diabetes Mellitus Experimental , Neuropatias Diabéticas , Estresse do Retículo Endoplasmático , Flavonoides , Lipossomos , Animais , Flavonoides/farmacologia , Flavonoides/administração & dosagem , Autofagia/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Masculino , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Ratos , Neuropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/prevenção & controle , Polietilenoglicóis/farmacologia , Aloxano , Ratos Wistar , Ratos Sprague-Dawley
2.
Ecotoxicol Environ Saf ; 221: 112435, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34171690

RESUMO

The present work was designed to assess the potential ameliorative effect of thymol on the testicular toxicity caused by imidacloprid (IMI) in adult male rats. Forty adult male rats were allocated into four groups; control group was given corn oil, thymol-treated group (30 mg/kg b.wt), IMI-treated group (22.5 mg/kg b.wt), and IMI + thymol-treated group. All administrations were done by gavage every day for duration of 56 days. As a result, the IMI exposure caused a significant decline in the body weight change, reproductive organ weights, sperm functional parameters, and serum level of testosterone, widespread histological alterations, and apoptosis in the testis. Additionally, the IMI-treated rats exhibited a remarkable increment in the serum levels of follicle stimulating hormone and luteinizing hormone. Also, IMI induced testicular oxidative stress, as indicated by elevated malondialdehyde (MDA) levels and a marked decline in the activity of antioxidant enzymes and reduced glutathione (GSH), and total antioxidant capacity (TAC) levels. Moreover, IMI treatment significantly downregulated the mRNA expression of steroidogenic genes and proliferating cell nuclear antigen (PCNA) immunoexpression in the testicular tissue. However, thymol co-administration significantly mitigated the IMI-induced toxic effects. Our findings suggested that IMI acts as a male reproductive toxicant in rats and thymol could be a potential therapeutic option for IMI reprotoxic impacts.


Assuntos
Apoptose/genética , Neonicotinoides/toxicidade , Nitrocompostos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Testículo/efeitos dos fármacos , Timol/farmacologia , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Espermatozoides/efeitos dos fármacos , Testosterona/sangue
3.
ACS Omega ; 7(41): 36865-36872, 2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36278044

RESUMO

Diabetes mellitus (DM) is a category of metabolic illness characterized by high blood sugar levels and insufficient pancreatic insulin production or activity within the body. The most common type of diabetes is type II diabetes, which is a metabolic condition characterized by insulin resistance and pancreatic islet ß-cell failure, resulting in hyperglycemia. The goal of this study was to examine the anti-diabetic implications of zinc oxide nanoparticles (ZnO NPs) and/or pyrazolopyrimidine in type II diabetic rats. Rats with a weight of 150 ± 20 g were used. Animals were divided into five groups as follows: group 1: control, group 2: type II diabetic rats, group 3: diabetic rats received ZnO NPs (10 mg/kg/orally/day), group 4: diabetic rats received pyrazolopyrimidine (5 mg/kg/orally/day), and group 5: diabetic rats received ZnO NPs (10 mg/kg/orally/day) + pyrazolopyrimidine (5 mg/kg/orally/day), respectively, for 30 days. The results indicated that serum glucose, total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein-cholesterol (LDL-c), very low-density lipoprotein-cholesterol (VLDL-c), malondialdehyde, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha PGC-1α mRNA expressions were increased in the diabetic group versus the control group, while serum insulin, high-density lipoprotein-cholesterol (HDL-c), superoxide dismutase (SOD), and carnitine palmitoyltransferase 1A (CPT1A) mRNA expression levels were decreased. These parameters were reserved in the treated groups (ZnO NPs, pyrazolopyrimidine, and ZnO NPs + pyrazolopyrimidine). This study proved that ZnO NPs and pyrazolopyrimidine had an ameliorative effect on blood glucose levels, antioxidant status, lipid profile, liver function enzymes, and mRNA expression of hepatic genes.

4.
Environ Sci Pollut Res Int ; 27(24): 30426-30436, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32462624

RESUMO

Fluoride is widely distributed in the environment and has been associated with the development of different health hazards in animals and humans. Argan oil (AO) is a natural vegetable oil with various beneficial pharmacological effects. This study was designed to investigate the potential protective effect of AO supplementation as pre-treatment or co-treatment on sodium fluoride (NaF)-induced nephrotoxicity in rats. Male Sprague Dawley rats (n = 50) were randomly assigned to one of five equal groups: control group, AO-treated group (6 ml/kg b.wt.), NaF-treated group (20 mg/kg b.wt.), pre-treated group, and co-treated group. All rats were daily administered by oral gavage for duration of 30 days. The results showed that AO administration significantly improved renal function and antioxidant status and decreased the lipid peroxidation in NaF-treated rats. Additionally, AO normalized the renal levels of inflammatory markers and mRNA expression level of the intermediate filament protein genes, indicating NaF-induced podocyte damage was ameliorated. Histopathological evaluation of the kidney confirmed the before mentioned biochemical results. AO counteracted the nephrotoxic effects of NaF in rats particularly at co-exposure. These results concluded that AO administration exhibited a significant nephroprotective effect against renal injury induced by NaF in rats.


Assuntos
Estresse Oxidativo , Fluoreto de Sódio , Animais , Antioxidantes , Humanos , Inflamação , Filamentos Intermediários , Rim , Masculino , Óleos de Plantas , Ratos , Ratos Sprague-Dawley , Ratos Wistar
5.
Compr Physiol ; 8(4): 1253-1290, 2018 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-30215860

RESUMO

The sexual dimorphism in human body fat distribution suggests a causal role for sex hormones. This is of particular importance when considering the role of excess visceral adipose tissue accumulation as a critical determinant of obesity-related cardiometabolic alterations. Scientific literature on the modulation of body fat distribution by androgens in humans is abundant, remarkably inconsistent and difficult to summarize. We reviewed relevant literature on this topic, with a particular emphasis on androgen replacement, androgen effects on selected parameters of adipose tissue function and adipose tissue steroid-converting enzymes. In men, low androgenic status mostly reflected by reduced total testosterone is a frequent feature of visceral obesity and the metabolic syndrome. Regarding testosterone therapy, however, studies must be appreciated in the context of current controversies on their cardiovascular effects. Analyses of available studies suggest that decreases in waist circumference in response to testosterone are more likely observed in men with low levels of testosterone and high BMI at study onset. In women with androgen excess, higher testosterone and free testosterone levels are fairly consistent predictors of increased abdominal and/or visceral adipose tissue accumulation, which is not the case in nonhyperandrogenic women. Regarding mechanisms, androgens decrease adipogenesis and markers of lipid storage in vitro in men and women. Evidence also suggest that local steroid transformations by adipose tissue steroid-converting enzymes expressed in a depot-specific fashion may play a role in androgen-mediated modulation of body fat distribution. Accumulating evidence shows that androgens are critical modulators of body fat distribution in both men and women. © 2018 American Physiological Society. Compr Physiol 8:1253-1290, 2018.


Assuntos
Adiposidade , Androgênios/metabolismo , Tecido Adiposo/metabolismo , Feminino , Humanos , Masculino
6.
J Steroid Biochem Mol Biol ; 147: 56-69, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25448733

RESUMO

Over the past decade, adipose tissues have been increasingly known for their endocrine properties, that is, their ability to secrete a number of adipocytokines that may exert local and/or systemic effects. In addition, adipose tissues have long been recognized as significant sites for steroid hormone transformation and action. We hereby provide an updated survey of the many steroid-converting enzymes that may be detected in human adipose tissues, their activities and potential roles. In addition to the now well-established role of aromatase and 11ß-hydroxysteroid dehydrogenase (HSD) type 1, many enzymes have been reported in adipocyte cell lines, isolated mature cells and/or preadipocytes. These include 11ß-HSD type 2, 17ß-HSDs, 3ß-HSD, 5α-reductases, sulfatases and glucuronosyltransferases. Some of these enzymes are postulated to bear relevance for adipose tissue physiology and perhaps for the pathophysiology of obesity. This elaborate set of steroid-converting enzymes in the cell types of adipose tissue deserves further scientific attention. Our work on 20α-HSD (AKR1C1), 3α-HSD type 3 (AKR1C2) and 17ß-HSD type 5 (AKR1C3) allowed us to clarify the relevance of these enzymes for some aspects of adipose tissue function. For example, down-regulation of AKR1C2 expression in preadipocytes seems to potentiate the inhibitory action of dihydrotestosterone on adipogenesis in this model. Many additional studies are warranted to assess the impact of intra-adipose steroid hormone conversions on adipose tissue functions and chronic conditions such as obesity, diabetes and cancer.


Assuntos
Tecido Adiposo/enzimologia , Hidroxiesteroide Desidrogenases/metabolismo , Esteroides/metabolismo , Tecido Adiposo/metabolismo , Animais , Distribuição da Gordura Corporal , Humanos , Obesidade/enzimologia , Obesidade/metabolismo
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