RESUMEN
Colorectal cancer (CRC) is one of the most identified and deadly malignancies worldwide. It presents a serious challenge due to its quick growth, which finally culminates in severe malignancy. It is critical to improve the efficacy of berberine (BR) as an anticancer agent to overcome its limited bioavailability. Implementation of a novel, effective nanocarrier system of liponiosomes for BR (LipoNio.BR) can support mechanistic actions associated with its anti-CRC role. Following CRC induction in rats using 1,2 Dimethylhydrazine (40 mg DMH/kg/week), the potency and mechanistic actions of LipoNio.BR were assessed by evaluating the lesion severity and molecular mechanisms controlling oxidative stress, apoptosis, autophagy, and inflammatory responses, and conducting histopathological and immunohistochemistry examinations of colonic tissues. The results indicated that the severity of clinical signs comprising weight gain loss, increased diarrhea and rectal bleeding, and reduced survivability were greatly restored in the LipoNio.BR-treated group. LipoNio.BR remarkably reduced CRC development compared to FBR (free berberine), as it induced apoptosis via upregulating apoptotic genes (Bax and caspase3, increased up to 7.89 and 6.25-fold, respectively) and downregulating the anti-apoptotic gene Bcl-2 by 2.25-fold. LipoNio.BR mitigated the oxidative stress associated with CRC and maintained redox homeostasis. Notably, the excessive inflammatory response associated with CRC was prominently reduced following administration of LipoNio.BR [which decreased iterleukin (IL-B, IL-6), tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX2), inducible nitric oxide synthase (iNOS), proliferating cell nuclear antigen (PCNA), follistatin, and activin BA (beta-A) expression]. LipoNio.BR modulated the expression of nuclear factor kappa B (NF-κB) and mammalian target of rapamycin (mTOR), which impacted tumor vascularity (decreased Vascular endothelial growth factor (VEGF) expression by 2.36-fold). The severity of the histopathological alterations in the colonic tissues, including the development of neoplastic epithelium and the invasion of some neoplastic masses, was greatly reduced in the LipoNio.BR group compared to the FBR-(free berberine) administrated group. Following CRC induction, immunohistochemical staining revealed that the overexpression of cyclin and COX-2 in colonic tissues were suppressed in the LipoNio.BR group. Taken together, these findings suggest that LipoNio.BR has a potential role in reducing CRC progression to a greater extent compared to free BR and could be considered a promising and potent therapy against CRC.
Asunto(s)
Berberina , Neoplasias Colorrectales , Ratas , Animales , Berberina/farmacología , Berberina/uso terapéutico , Factor A de Crecimiento Endotelial Vascular/farmacología , FN-kappa B/metabolismo , Ciclooxigenasa 2/metabolismo , Ciclooxigenasa 2/farmacología , Ciclooxigenasa 2/uso terapéutico , Apoptosis , Neoplasias Colorrectales/patología , Modelos Teóricos , Mamíferos/metabolismoRESUMEN
Climate change is considered to be the primary cause of heat stress (HS) in broiler chickens. Owing to the unique properties of extracted polyphenols, resveratrol-loaded liposomal nanoparticles (Resv-Lipo NPs) were first explored to mitigate the harmful effects of HS. The dietary role of Resv-Lipo NPs in heat-stressed birds was investigated based on their growth performance, antioxidative potential, and the expression of heat shock proteins, sirtuins, antioxidant, immune, and muscle-building related genes. A total of 250 1-day-old Ross 308 broiler chickens were divided into five experimental groups (5 replicates/group, 10 birds/replicate) for 42 days as follows: the control group was fed a basal diet and reared in thermoneutral conditions, and the other four HS groups were fed a basal diet supplemented with Resv-Lipo NPsI, II, and III at the levels of 0, 50, 100, and 150 mg/kg diet, respectively. The results indicated that supplementation with Resv-Lipo NP improved the growth rate of the HS group. The Resv-Lipo NP group showed the most significant improvement in body weight gain (p < 0.05) and FCR. Additionally, post-HS exposure, the groups that received Resv-Lipo NPs showed restored functions of the kidney and the liver as well as improvements in the lipid profile. The restoration occurred especially at higher levels in the Resv-Lipo NP group compared to the HS group. The elevated corticosterone and T3 and T4 hormone levels in the HS group returned to the normal range in the Resv-Lipo NPsIII group. Additionally, the HS groups supplemented with Resv-Lipo NPs showed an improvement in serum and muscle antioxidant biomarkers. The upregulation of the muscle and intestinal antioxidant-related genes (SOD, CAT, GSH-PX, NR-f2, and HO-1) and the muscle-building genes (myostatin, MyoD, and mTOR) was observed with increasing the level of Resv-Lipo NPs. Heat stress upregulated heat shock proteins (HSP) 70 and 90 gene expression, which was restored to normal levels in HS+Resv-Lipo NPsIII. Moreover, the expression of sirtuin 1, 3, and 7 (SIRT1, SIRT3, and SIRT7) genes was increased (p < 0.05) in the liver of the HS groups that received Resv-Lipo NPs in a dose-dependent manner. Notably, the upregulation of proinflammatory cytokines in the HS group was restored in the HS groups that received Resv-Lipo NPs. Supplementation with Resv-Lipo NPs can mitigate the harmful impact of HS and consequently improve the performance of broiler chickens.
RESUMEN
The aim of the present study was to prepare and characterize nanocomposite films to improve the treatment of skin wounds by applying the film as a bandage. To modify chitosan (Cs) and to prepare nanocomposites, a mixture between titanium dioxide nanoparticles (TiO2 NPs) was performed at different concentrations (2, 5, 10 and 15 wt%) and oleic acid (OA). The thin nanocomposite films were prepared by using casting method. The prepared films (Cs, Cs/TiO2 NPs, Cs/OA and Cs/OA/TiO2 NPs) were described by water absorption (swelling study) and biological degradation. Physico-chemical characterizations of Cs, Cs/OA, Cs/TiO2 NPs and Cs/OA/TiO2 NPs (with only 15 wt% TiO2 NPs) films were determined by X-ray diffraction, transmission high-resolution electron microscopy, field emission scanning electron microscopy, thermal analysis and Fourier transform infrared spectroscopy as well as their mechanical properties. Antimicrobial activity against microorganisms has been studied to assess activity against bacteria. The prepared nanocomposite films showed good antimicrobial activity for both Gram-positive and Gram-negative bacteria. The therapeutic effects of Cs-TiO2 NPs-oleic acid nanocomposites on healing excision wounds were studied in rat animal model. The data obtained revealed that groups treated with nanocomposites showed enhancement wound closure and speed up wound healing time.
Asunto(s)
Quitosano/química , Nanocompuestos/química , Nanoestructuras/química , Ácido Oléico/química , Titanio/química , Animales , Antibacterianos/farmacología , Materiales Biocompatibles , Femenino , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Polímeros , Ratas , Cicatrización de Heridas/efectos de los fármacosRESUMEN
PURPOSE: To evaluate the efficacy of persimmon leaf extract (PL (as a rich plant source) in modulation of radiation-induced liver injury and some metabolic variations in gamma-irradiated rats. MATERIALS AND METHODS: PL at a dose of 1000 mg/kg body weight (P1000) was administered to male albino rats via gastric intubation for 15 days after whole body γ-irradiation (6 Gy). RESULTS: Irradiated rats showed significant decreases in hepatic glutathione content (GSH), superoxide dismutase (SOD), catalase (CAT) and xanthine dehydrogenase (XDH) activities with significant increases in malondialdehyde (MDA) level and xanthine oxidase (XO) activity designating oxidative stress. In parallel significant increases in serum aspartate and alanine transaminase (AST, ALT), alkaline phosphatase (ALP), γ-glutamyl-transferase (GGT) activities and bilirubin content were recorded indicating liver injury. In addition, hyperglycemia, hypoinsulinemia and dyslipidemia (elevated total cholesterol, triglycerides, low density lipoprotein-cholesterol and Atherogenic Index and decreased high density lipoprotein-cholesterol) were recorded. PL treatment has significantly attenuated radiation-induced oxidative stress in hepatic tissues concomitant with significant amelioration of liver function and metabolic disturbances. CONCLUSION: It is concluded that PL may have therapeutic potential to alleviate the severity of radiation-induced liver injury, hyperglycemia, hypoinsulinemia and dyslipidemia.
Asunto(s)
Diospyros/química , Hepatopatías/etiología , Hepatopatías/metabolismo , Hepatopatías/prevención & control , Estrés Oxidativo/efectos de la radiación , Extractos Vegetales/administración & dosificación , Traumatismos por Radiación/prevención & control , Animales , Relación Dosis-Respuesta en la Radiación , Rayos gamma/efectos adversos , Masculino , Hojas de la Planta/química , Dosis de Radiación , Traumatismos por Radiación/etiología , Traumatismos por Radiación/metabolismo , Protectores contra Radiación/administración & dosificación , Ratas , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate the impact of oral administration of purslane (Portulaca oleracea) extract or fish oil and their co-treatments in the modulation of radiation-induced damage. MATERIAL AND METHODS: Purslane (P) (400 mg/kg body weight) or fish oil (Fo) (60 mg/kg body weight) was administrated to male albino rats via gastric intubation for 15 days after whole body exposure to a single dose of 6 Gy gamma rays. The animals were sacrificed after the elapse of 15 days. RESULTS: The results revealed that irradiation induced a significant elevation of total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-c), and atherogenic index: TC/high density lipoprotein cholesterol (HDL-c) in addition to aspartate and alanine transaminase (AST, ALT), alkaline phophatase (ALP), bilirubin, as well as urea, creatinine and uric acid. Moreover, liver, kidney and heart malondialdehyde (MDA) was significantly elevated, whereas nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT) and HDL-c were depressed. Purslane and/or fish oil treatment significantly attenuated lipids alteration, liver and kidney functions as well as oxidative stress in irradiated rats. The results pointed out that dietary fish oil supplementation, at adequate doses, may provide a cushion for a prolonged therapeutic option against radiation-induced damage without harmful side-effects. CONCLUSION: It could be concluded that purslane extract and fish oil may have therapeutic potential to improve hepatic and renal functions as well as oxidative stress in irradiated rats. Moreover, their co-administration showed a better improved liver function.