RESUMEN
Melamine and its analogues are illegally added to raise the apparent protein content in foods. The elevated concentrations of these compounds cause adverse effects in humans and animals. In this contribution, the protective effects of the synthesized starch-stabilized selenium nanoparticles (Se-NPs@starch) on melamine-induced hepato-renal toxicity have been systematically investigated. The Se-NPs@starch were characterized by X-ray photoelectron spectroscopy (XPS) analysis, energy dispersive spectroscopy (EDS) mapping analysis, TEM, and FT-IR. Starch plays a crucial role in the stabilization and dispersion of Se NPs, as noticed from the TEM and EDS investigations. Furthermore, the atomic ratio of Se distribution over the starch surface is approximately 1.67%. The current study was conducted on four groups of adult male rats, and the oral daily treatments for 28 days were as follows: group I served as control, group II received Se-NPs@starch, group III was exposed to melamine, while group IV was treated with melamine and Se-NPs@starch. The results reveal a significant alteration in the histoarchitecture of both hepatic and renal tissues induced by melamine. Furthermore, elevated liver and kidney function markers, high malondialdehyde, and increased expression levels of apoptosis-related genes besides a reduction in GSH and expression levels of antioxidant genes were observed in the melamine-exposed group. Interestingly, the administration of the Se-NPs@starch resulted in remarkable protection of rats against melamine-induced toxicity through increasing the antioxidant capacity and inhibiting oxidative damage. Collectively, this study provides affordable starch-stabilized Se-NPs with potent biological activity, making them auspicious candidates for prospective biomedical applications.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Nanopartículas/química , Selenio/química , Almidón/química , Triazinas/toxicidad , Animales , Apoptosis , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Riñón/efectos de los fármacos , Riñón/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Nanopartículas/uso terapéutico , Estrés Oxidativo , RatasRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Chickpea was used in both greek and indian traditional medicine for hormonal related conditions as menstrual induction, acceleration of parturation, treatment of retained placenta and stimulation of lactation. Chickpea (Cicer arietinum) sprout isoflavone isolates exhibited reasonable estrogenic activities. Isoflavones, a subtype of phytoestrogens, are plant derivatives with moderate estrogenic activity that tend to have protective effects on hormonal and metabolic abnormalities of women with polycystic ovary syndrome (PCOS). AIM OF THE STUDY: In this study, we investigated the effect of UPLC/ESI-MS characterized Cicer arietinum L. seeds ethanol extract (CSE) on ovarian hormones, oxidative response and ovarian histological changes on induced PCOS rat model. MATERIALS AND METHODS: Thirty-five rats were divided into five groups including negative control, PCOS, and treatment groups. PCOS was induced using letrozole (1 mg/kg) daily orally for 21 days. Each treatment group was treated with one of the following for 28 days after induction of PCOS: clomiphene citrate (1 mg/kg), and CSE at 250 and 500 mg/kg. Ovaries and uteri were excised, weighed and their sections were used for quantitative real-time reverse transcriptase polymerase chain reaction, antioxidant assays and histomorphometric study of the ovaries. The antioxidant assays, histopathological examination, hormonal and metabolic profiles, and Cyp11a1(steroidogenic enzyme) mRNA expression were measured. RESULTS: In all treatment groups, ovarian weight was significantly decreased despite having no significant effect on uterine weight. Histomorphometric study in the treatment groups revealed a significant decrease in the number and diameter of cystic follicles, a significant increase in granulosa cell thickness while, thickness of theca cells was significantly decreased when compared to PCOS. Hormone levels, metabolic profile and antioxidant status were improved in the treatment groups. Moreover, Cyp11a1 mRNA expression was significantly downregulated in the treatment groups compared to PCOS. CONCLUSIONS: In the current study, CSE enhanced the reproductive and metabolic disorders which were associated with PCOS induction. For the first time, we have highlighted the effect of CSE in treating PCOS and its associated manifestations.
Asunto(s)
Cicer/química , Letrozol/toxicidad , Fitoterapia , Extractos Vegetales/uso terapéutico , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Animales , Inhibidores de la Aromatasa/toxicidad , Enzima de Desdoblamiento de la Cadena Lateral del Colesterol/genética , Enzima de Desdoblamiento de la Cadena Lateral del Colesterol/metabolismo , Clomifeno/uso terapéutico , Relación Dosis-Respuesta a Droga , Antagonistas de Estrógenos/uso terapéutico , Femenino , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Tamaño de los Órganos , Ovario/patología , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Síndrome del Ovario Poliquístico/inducido químicamente , Distribución Aleatoria , RatasRESUMEN
BACKGROUND: Complementary remedies such as the Chinese herb 'Sheng Ma' (Black cohosh; Actaea racemosa 'AR') are being sought to overcome the shortcomings of conventional hormonal and surgical therapies developed for the treatment of polycystic ovary syndrome (PCOS). However, AR-induced hepatotoxicity necessitates a cautionary warning to be labeled on its products as recommended by the United States Pharmacopeia, where four out of seven hepatotoxic cases in Sweden were possibly associated with black cohosh products. METHODS: We investigated the effects, safety, and molecular targets of black cohosh ethanolic extract and/or vitamin C on ovarian functionality and oxidative response in hyperandrogenism-induced PCOS rats. A well-established rat model using oral letrozole, daily, for 21 days was employed. The rats then received the AR extract with and without vitamin C for 28 days. The hormonal evaluation, antioxidant status, histopathological examination, immunohistochemical analysis, cell proliferation, and the expression ratio of the aromatase (Cyp19α1) gene were evaluated. Additionally, holistic profiling of the AR arsenal of secondary metabolites was performed using ultra-high-performance liquid chromatography (UHPLC) coupled with quadrupole high-resolution time of flight mass spectrometry (QTOF-MS). RESULTS: Beneficial effects were exerted by AR in PCOS rats as antioxidant status, hormonal profile, lipid profile, glucose level, liver functions, and the induced Ki-67 expression in the granulosa, theca cell layers and interstitial stromal cells were all improved. Notably, the combination of AR with vitamin C was not only more effective in reversing the dysregulated levels of testosterone, luteinizing hormone, and mRNA level of Cyp19α1 gene in the PCOS rat, but also safer. The combination regulated both ovarian and hepatic malondialdehyde (MDA) and glutathione (GSH) levels with histological improvement observed in the liver and ovaries. In addition, the untargeted metabolomic profiling enabled the identification of 61 metabolites allocated in five major chemical classes. CONCLUSION: This study demonstrated the benefit of the combinatorial effects of AR and vitamin C in mitigating the reproductive and metabolic disorders associated with PCOS with the elimination of AR hepatotoxic risk.
RESUMEN
The present study was led to investigate the defensive role of Terminalia laxiflora extract (TLE) on fipronil (FPN) induced hepatotoxicity and nephrotoxicity in male rats. Rats were administered with TLE (100 mg/kg) against the renal toxicity and hepatotoxicity induced by administration of FPN (10.5 mg/kg) for 30 days. At the end of the experimental period, the serum, liver, and kidneys were harvested and assessed for subsequent analysis. FPN administration to rats resulted in a significant elevation of serum transaminases, urea, and creatinine. Also, FPN-treated groups exhibited a marked reduction in total protein and albumin levels. Compared with the control group, the level of malondialdehyde (MDA) was elevated in groups treated with FPN, whereas superoxide dismutase (SOD), catalase (CAT) activities, and glutathione levels were distinctly reduced in this group. Significant increases in genomic DNA fragmentation and the expression level of the caspase-3 gene were also recorded. The biochemical result was supported by histopathological findings. Co-administration of TLE along with FPN significantly diminished the liver and kidney function tests decreased the level of lipid peroxidation, and enhanced all the antioxidant enzymes, while also diminishing the expression of caspase-3 and DNA laddering, indicating amelioration of DNA damage. These results indicate that TLE plays a vital role in diminishing FPN-induced hepatotoxicity and nephrotoxicity.
Asunto(s)
Terminalia , Animales , Antioxidantes , Glutatión , Riñón , Peroxidación de Lípido , Masculino , Estrés Oxidativo , Extractos Vegetales , Pirazoles , Ratas , Ratas Wistar , Superóxido DismutasaRESUMEN
The accidental spilling of petroleum oils into natural water resources expose fishes in the effluent area to serious problems.. Oreochromis niloticus were used in the current study as a model to investigate the toxicity of used engine oil and to evaluate the protective role of vitamin C against this toxicity. The oil concentration used in this study was previously determined to be 0.25â¯ml/l by 96 h-LC50. After 21 days of engine oil exposure, haematological and biochemical analyses revealed significant reduction in RBCs counts, haemoglobin concentrations and total proteins. However, ALT, AST and glucose levels were significantly increased by the end of the experiment indicating the damaging effects of the oil on fish tissues. Oxidative stress biomarkers were also measured; liver CAT activity was significantly decreased in the oil exposed group compared to control group, while MDA levels were significantly elevated. Histopathological examination showed the presence of several alterations in hepatic and branchial tissues in exposed group compared to the control group. Significant elevations in CYP1 A1 mRNA expression levels in hepatic tissue were also detected in the group exposed to used engine oil compared to the control group. However, supplementation of fishexposed to used engine oil with vitamin Csignificantly enhance the biochemical, oxidative and histological parameters.
Asunto(s)
Ácido Ascórbico/farmacología , Cíclidos , Branquias/efectos de los fármacos , Hígado/efectos de los fármacos , Petróleo/toxicidad , Animales , Análisis Químico de la Sangre , Cíclidos/sangre , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Branquias/patología , Branquias/ultraestructura , Estado de Salud , Histocitoquímica , Hígado/patología , Hígado/ultraestructura , Microscopía Electrónica de Transmisión , Estrés Oxidativo/efectos de los fármacosRESUMEN
Lead (Pb) is a ubiquitous environmental and industrial pollutant with worldwide health problems. The present study was designed to investigate the neurotoxic effects of Pb in albino rats and to evaluate the ameliorative role of garlic as well as Spirulina maxima against such toxic effects. Forty adult male rats were used in this investigation (10 rats/group). Group I: served as control, Group II: rats received lead acetate (100 mg/kg), Group III: rats received both lead acetate (100 mg/kg) and garlic (600 mg/kg) and Group IV: rats received both lead acetate (100 mg/kg) and spirulina (500 mg/kg) daily by oral gavage for one month. Exposure to Pb acetate adversely affected the measured acetyl cholinesterase enzyme activity, oxidative stress and lipid peroxidation parameters as well as caspase-3 gene expression in brain tissue (cerebrum and cerebellum). Light and electron microscopical examination of the cerebrum and cerebellum showed various lesions after exposure to Pb which were confirmed by immunohistochemistry. On the other hand, administration of garlic and spirulina concomitantly with lead acetate ameliorated most of the undesirable effects. It could be concluded that, the adverse effects induced by lead acetate, were markedly ameliorated by co-treatment with S. maxima more than garlic.
Asunto(s)
Apoptosis/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Caspasa 3/metabolismo , Ajo , Plomo/toxicidad , Fármacos Neuroprotectores/administración & dosificación , Spirulina , Animales , Encéfalo/patología , Encéfalo/ultraestructura , Expresión Génica , Masculino , Estrés Oxidativo , Extractos Vegetales/administración & dosificación , RatasRESUMEN
The extensive use of fipronil (FPN) may trigger hazards to more than insects. The present investigation was carried out to evaluate the abrogating role of Terminalia laxiflora (TL) methanol extract (TLE) against the neurotoxic effects provoked by FPN. Fourty male albino rats were assigned into four equal groups. The first group served as control, the second one was orally administered FPN (10.5 mg/kg BW), the third group was given combination of FPN and TLE) (100 mg/kg BW), and the fourth one was orally given TLE. Our findings highlighted the efficacy of TLE as a neuroprotectant through a significant reduction in malondialdehyde (MDA) content by 25.8%, elevations of the reduced glutathione (GSH) level, catalase (CAT,) and superoxide dismutase (SOD) activities by 30.9, 41.2, and 48.2% respectively. Consequently, the relative mRNA levels of both Bax and caspase-3 were down-regulated by 40.54% and caspase-3 by 30.35% compared with the control group. Moreover, restoration of the pathological tissue injuries were detected. In conclusion, TLE proved to be a potent neuroprotective agent against the FPN-induced toxicity.
Asunto(s)
Síndromes de Neurotoxicidad/prevención & control , Extractos Vegetales/farmacología , Pirazoles/toxicidad , Terminalia/química , Animales , Caspasa 3/genética , Caspasa 3/metabolismo , Catalasa/metabolismo , Glutatión/metabolismo , Insecticidas/toxicidad , Masculino , Malondialdehído/metabolismo , Metanol/química , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacología , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/metabolismo , Extractos Vegetales/química , Ratas , Superóxido Dismutasa/metabolismoRESUMEN
The current study was conducted to test the possible ameliorative role of selenium nanoparticles (Se-NPs) against oxidative damage of Leyding cells induced by di-n-butyl phthalate (DBP) in pre-pubertal male rat offspring. Forty-two pregnant female rats treated from gestation day (GD) 12 to postnatal day (PND) 14 day with two doses of Se-NPs (0.2 and 0.5 mg/kg/d) against developmental testicular toxicity induced by DBP (500 mg/kg/d). At PND 25 serum and testes of offspring were collected. Serum LH, the Leydig cells performance [total serum testosterone, LH and testosterone (LH/T) ratio, relative gene expression of insulin-like growth factor-3 (INSL3) and mineralocorticoid receptor (MR)], oxidative stress biomarker malondialdehyde (MDA) and antioxidant machinery [reduced glutathione (GSH), and the relative gene expression of antioxidant enzymes: superoxide dismutase (SOD), glutathione peroxidase (GPx)] were estimated in all groups. The obtained results revealed that maternal exposure to DBP significantly reduced total serum testosterone level, relative mRNA expression of INSL3 and MR genes with observed testicular damage revealed by increasing MDA and depressed levels of GSH and antioxidant enzymes. The histopathological changes include necrosis and desquamation of spermatogoneal cells. Co-administration of Se-NPs high dose along with DBP significantly increased serum testosterone, improved LH/T ratio and the relative mRNA expression of INSL3 and MR genes, decreased the level of MDA, and also improved all the antioxidant enzymes expression levels. In conclusion, Se-NPs could be a potent maternal prophylactic agent against the reduced total serum testosterone level and oxidative damage of Leydig cells induced by DBP via reducing the lipid peroxidation (LPO) and enhancing the antioxidant state in pre-pubertal male rat offspring.
Asunto(s)
Nanopartículas , Estrés Oxidativo/efectos de los fármacos , Selenio/farmacología , Testículo/efectos de los fármacos , Animales , Antioxidantes/metabolismo , Dibutil Ftalato/toxicidad , Relación Dosis-Respuesta a Droga , Femenino , Glutatión Peroxidasa/metabolismo , Insulina/genética , Células Intersticiales del Testículo/efectos de los fármacos , Células Intersticiales del Testículo/patología , Peroxidación de Lípido/efectos de los fármacos , Hormona Luteinizante/sangre , Masculino , Malondialdehído/metabolismo , Tamaño de la Partícula , Proteínas/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Selenio/administración & dosificación , Superóxido Dismutasa/metabolismo , Testículo/patología , Testosterona/sangreRESUMEN
In the present study, we investigated the protective effect of an aqueous extract of green tea leaves (GTE) against neurotoxicity and oxidative damage induced by deltamethrin (DM) in male rats. Four different groups of rats were used: the 1st group was the vehicle treated control group, the 2nd group received DM (0.6 mg/kg BW), the 3rd group received DM plus GTE, and the 4th received GTE alone (25 mg/kg BW). The brain tissues were collected at the end of the experimental regimen for subsequent investigation. Rats that were given DM had a highly significant elevation in MDA content, nitric oxide concentration, DNA fragmentation and expression level of apoptotic genes, TP53 and COX2. Additionally, a significant reduction in the total antioxidant capacity in the second group was detected. The findings for the 3rd group highlight the efficacy of GTE as a neuro-protectant in DM-induced neurotoxicity through improving the oxidative status and DNA fragmentation as well as suppressing the expression of the TP53 and COX2 genes. In conclusion, GTE, at a concentration of 25mg/kg/day, protected against DM-induced neurotoxicity through its antioxidant and antiapoptotic influence; therefore, it can be used as a protective natural product against DM-induced neurotoxicity.
Asunto(s)
Apoptosis/efectos de los fármacos , Encéfalo/efectos de los fármacos , Insecticidas/toxicidad , Nitrilos/toxicidad , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Piretrinas/toxicidad , Animales , Encéfalo/metabolismo , Encéfalo/patología , Fragmentación del ADN/efectos de los fármacos , Masculino , Ratas , TéRESUMEN
BACKGROUND: The safety of Deltamethrin (DM) has been raised as a point of concern. The current investigation was envisaged to explore the responsiveness of oxidative stress parameters, DNA fragmentation and expression levels of TP53, cycloxygenase 2 (COX2) and cytochrome p4502E1 (CYP2E1) as toxicological endpoint in rats treated with DM. as well as attention was provided to the neuroprotective effect of vitamin E (VE). METHODS: Four different groups of rats were used in this study, group I served as control, group II received DM (0.6 mg/kg BW), group III received both DM plus VE and finally group IV received VE only (200 mg/kg BW). The treatment regimen was extending for one month for all groups and the brain tissues were collected for further analysis. RESULTS: The obtained results showed a highly statistically significant increase in lipid peroxidation (LPO) content, nitric oxide concentration, and DNA fragmentation percentage and expression level of CYP2E1, TP53 and COX2 genes, in addition statistical significant reduction in total antioxidant capacity in DM treated group as compared to control were detected. Oral administration of VE attenuated the neurotoxic effects of DM through improvement of oxidative status, DNA fragmentation percentage and suppressing the expression level of CYP2E1, TP53 and COX2 genes. CONCLUSION: From this study we concluded that VE supplementation has beneficial impacts on DM neurotoxicity in rats through its antioxidant and antiapoptotic properties.