Quercetin attenuated ischemic stroke induced neurodegeneration by modulating glutamatergic and synaptic signaling pathways.

Ischemic strokes originate whenever the circulation to the brain is interrupted, either temporarily or permanently, resulting in a lack of oxygen and other nutrients. This deprivation primarily impacts the cerebral cortex and striatum, resulting in neurodegeneration. Several experimental stroke models have demonstrated that the potent antioxidant quercetin offers protection against stroke-related damage. Multiple pathways have been associated with quercetin's ability to safeguard the brain from ischemic injury. This study examines whether the administration of quercetin alters glutamate NMDA and GluR1 receptor signaling in the cortex and striatum 72 h after transient middle cerebral artery occlusion. The administration of 10 mg/kg of quercetin shielded cortical and striatal neurons from cell death induced by ischemia in adult SD rats. Quercetin reversed the ischemia-induced reduction of NR2a/PSD95, consequently promoting the pro-survival AKT pathway and reducing CRMP2 phosphorylation. Additionally, quercetin decreased the levels of reactive oxygen species and inflammatory pathways while increasing the expression of the postsynaptic protein PSD95. Our results suggest that quercetin may be a promising neuroprotective drug for ischemic stroke therapy as it recovers neuronal damage via multiple pathways.

Protective effect of metformin on rat diabetic retinopathy involves suppression of toll-like receptor 4/nuclear factor-k B expression and glutamate excitotoxicity.

Microvascular complications of diabetes mellitus are progressively significant reasons for mortality. Metformin (MET) is considered as the first-line therapy for type 2 diabetes patients, and may be especially beneficial in cases of diabetic retinopathy although the precise mechanisms of MET action are not fully elucidated. The current study was designed to inspect the antioxidant and modulatory actions of MET on DRET in streptozotocin-induced diabetic rats. The effect of MET on the toll-like receptor 4/nuclear factor kappa B (TLR4/NFkB), inflammatory burden and glutamate excitotoxicity was assessed. Twenty-four male rats were assigned to four experimental groups: (1) Vehicle group, (2) Diabetic control: developed diabetes by injection of streptozotocin (60 mg/kg, i.p.). (3&4) Diabetic + MET group: diabetic rats were left for 9 weeks without treatment and then received oral MET 100 and 200 mg/kg for 6 weeks. Retinal samples were utilized in biochemical, histological, immunohistochemical and electron microscopic studies. MET administration significantly decreased retinal level of insulin growth factor and significantly suppressed the diabetic induced increase of malondialdehyde, glutamate, tumor necrosis factor-α and vascular endothelial growth factor (VEGF). Further, MET decreased the retinal mRNA expression of NFkB, tumor necrosis factor-α and TLR4 in diabetic rats. The current findings shed the light on MET's efficacy as an adjuvant therapy to hinder the development of diabetic retinopathy, at least partly, via inhibition of oxidative stress-induced NFkB/TLR4 pathway and suppression of glutamate excitotoxicity.

Chemopreventive effect of α-hederin/carboplatin combination against experimental colon hyperplasia and impact on JNK signaling.

Colon cancer is the commonest cancer worldwide. α-Hederin is a monodesmosidic triterpenoid saponin possessing diverse pharmacological activities. The running experiment was designed to test the chemopreventive activity of α-hederin when used as an adjuvant to carboplatin in an experimental model of mouse colon hyperplasia induced by 1,2-dimethylhydrazine (DMH). Fifty male Swiss albino mice were classified into five groups: group (I): saline group, group (II): DMH-induced colon hyperplasia control group, group (III): DMH + carboplatin (5 mg/kg) group, group (IV): DMH + α-hederin (80 mg/kg) group, and group (V): DMH + carboplatin (5 mg/kg)+α-hederin (80 mg/kg) group. Analyzing of colonic tissue indicated that the disease control group showed higher colon levels of phospho-PI3K to total-PI3K, phospho-AKT to total-AKT and cyclin D1 concurrent with lower phospho-JNK/total JNK ratio and caspase 3. However, treatment with α-hederin, in combination with carboplatin, favorably ameliorated phosphorylation of PI3K/AKT/JNK proteins, increased colon caspase 3 and downregulated cyclin D1. Microscopically, α-hederin, in combination with carboplatin, produced the most reduction in the histologic hyperplasia score, enhanced the goblet cell survival in periodic acid Schiff staining and reduced proliferation (Ki-67 immunostaining) in the current colon hyperplasia model. Collectively, the current study highlighted for the first time that using α-hederin as an adjuvant to carboplatin enhanced its chemopreventive activity, improved JNK signaling and increased apoptosis. Hence, further studies are warranted to test α-hederin as a promising candidate with chemotherapeutic agents in treating colon cancer.

Altered testicular morphology and oxidative stress induced by cadmium in experimental rats and protective effect of simultaneous green tea extract / Morfología testicular alterada y stress oxidativo inducido por cadmio en ratas de experimentación y el efecto protector del extracto simultáneo del té verde

Cadmium (Cd), is an environmental and industrial pollutant that affects the male reproductive system. Cd induces its effect by affecting tissue antioxidant enzyme systems. Green tea extract (GTE) is an antioxidant and free radicals scavenger and has a chelating property. The purpose of this study was to investigate the protective effect of GTE against testes damage induced by Cd. Four groups of male rats, were utilized as following: Controls, GTE treated, Cd treated and Cd + GTE, treated rats at the same doses. The rats received GTE and or Cd orally in drinking water. After 5 weeks, the animals were sacrificed and testes were removed for microscopic and Biochemical evaluation. The levels of lipid peroxides (LPO) and glutathione (GSH) were detected in the tissue homogenates of rat testes. The current study showed marked morphological changes in the form of swelling, congestion, hemorrhage and necrosis in testes of rats treated with Cd alone. However, the rats treated with Cd+GTE showed milder edema, congestion and minute foci of necrosis in the testes. The LPO levels were significantly higher as compared to control and of GSH were significantly lower in Cd-treated rats but when GTE was co-administrated with Cd, there was an effective reduction in oxidative stress as shown by a significant rise of GSH level. In conclusion, the rats received GTE + Cd could enhance antioxidant/ detoxification system which consequently reduced the oxidative stress in rat testes. The beneficial effect of GTE is thus potentially reducing Cd toxicity and tissue damage.

El cadmio (Cd), es un contaminante del medio ambiente e industrial que afecta al sistema reproductivo masculino. Cd induce su efecto por afección de los sistemas enzimáticos antioxidantes de los tejidos. El extracto de té verde (ETV) es un antioxidante y buscador de radicales libres y tiene una propiedad quelante. El objetivo de este estudio fue investigar el efecto protector de ETV contra daños provocado por Cd a los testículos. Cuatro grupos de ratas macho, se utilizaron: Controles, tratados con ETV, tratados con Cd y tratados con Cd + ETV, todas las ratas tratadas con las mismas dosis. Las ratas recibieron ETV o Cd por vía oral en el agua potable. Después de 5 semanas, los animales fueron sacrificados y los testículos fueron retirados para la evaluación microscópica y bioquímica. Los niveles de peróxidos lípidos (LPO) y de glutation (GSH) fueron detectados en el tejido homogenizado de rata testículos. El estudio demostró marcados cambios morfológicos como inflamación, congestión, hemorragia y necrosis en los testículos de las ratas tratadas solamente con Cd. Sin embargo, las ratas tratadas con Cd + ETV mostraron leves signos de edema, congestión y focos de necrosis en los testículos. Los niveles de LPO fueron significativamente mayores en comparación con el control y la de GSH fue significativamente menor en las ratas tratadas con Cd, pero cuando ETV fue co-administrado con Cd, hubo una reducción efectiva en el estrés oxidativo, como lo demuestra el aumento significativo del nivel de GSH. En conclusión, las ratas recibieron GTE + Cd que podría aumentar el sistema antioxidante / desintoxicación, por tanto, reducir el estrés oxidativo en los testículos de ratas. El efecto beneficioso de GTE es reducir la toxicidad y el daño tisular causado Cd.