STAT3 and Nrf2 pathways modulate the protective effect of verapamil on lung injury of diabetic rats

Objective. We aimed to assess the protective role of verapamil, L-type calcium channel blockers, against early lung damage in diabetic rats. Lung injury has recently been recognized as a consequent complication of diabetes mellitus. Hyperglycemia induces inflammatory changes in lung tissue early in the disease. Methods. Twenty four adult male rats were grouped into control, diabetic, diabetic treated with verapamil, and verapamil control. Streptozotocin (STZ) was used to induce diabetes. Oxidative parameters and antioxidative mechanisms were assessed in lung homogenate. Tumor necrosis factor alpha (TNFα) protein was measured as a pro-inflammatory mediator. Signal transducer and activator of transcription 3 (STAT3) gene expression and nuclear erythroid factor 2 (Nrf2) immunoexpression were screened. Results. The lung showed oxidative damage and inflammatory infiltration in STZ diabetic rats early at 2 weeks. The parameters significantly improved in lung tissue treated with verapamil. Histopathology of the lung tissue confirmed the results. Inhibition of STAT3/TNFα pathway was involved in the protection offered by verapamil. Activation of Nrf2 together with an increasing antioxidant capacity of diabetic lung significantly ameliorates the injury induced by diabetes. Conclusions. Verapamil afforded protection in diabetic lung injury. The protection was mediated by the anti-inflammatory and antioxidant effects of verapamil

Oxygen and hydrogen stable isotopes as recharge indicators, Central Nile Delta Quaternary aquifer, Egypt

This work aims to utilize oxygen and hydrogen stable isotopes as tracers for determining the groundwater sources of recharge in the central Nile delta. The analyzed water samples were collected from canals and drains as surface water, soil water and shallow, intermediate and deep zones of the groundwater. The isotopic data indicated that surface water samples have higher isotopic content than recent Nile river water (&#948 18O = 2.39‰ and &#9482 H = 22‰) which reflect the influence of an evaporation process that takes place in surface water bodies during its flow. Soil water samples were affected by evaporation process during water infiltration via soil. It was estimated that soil water samples have higher enrichment isotopic contents than groundwater and less than surface and recent Nile water. Studied groundwater is composed of mixed source from groundwater recharged before and that recharged after High Dam construction. Few groundwater samples have depleted isotopic content which suggested a mixing source between the rainwater and the Nile River water before High Dam construction. The evaporation is indicated in the shallow groundwater by the deviation away from the global meteoric line. In the deep groundwater, more deviation from global meteoric line was noticed which reflects the effect of mixing between freshwater and seawater. The intermediate groundwater samples average line showed an intermediate deviation indicating the effect of both evaporation and seawater intrusion

Fresh Azolla, Azolla pinnata as a Complementary Feed for Oreochromis niloticus: Growth, Digestive Enzymes, Intestinal Morphology, Physiological Responses, and Flesh Quality

Azolla is a potential fish feed ingredient due to its high nutritional value, abundant production, and low price. This study is aimed at evaluating the use of fresh green azolla (FGA) as a replacement ratio of the daily feed intake on the growth, digestive enzymes, hematobiochemical indices, antioxidant response, intestinal histology, body composition, and flesh quality of monosex Nile tilapia, Oreochromis niloticus (with an average initial weight of 108.0±5.0 g). Five experimental groups were used and differed in commercial feed replacement rates of 0% (T0), 10% (T1), 20% (T2), 30% (T3), and 40% (T4) with FGA for 70 days. Results showed that 20% replacement with azolla gave the highest values of growth performance and hematological parameters and the best feed conversion ratio, protein efficiency ratio, and fish whole body protein content. The highest levels of intestinal chymotrypsin, trypsin, lipase, and amylase were noted in 20% replacement with azolla. Fish fed diets with FGA levels of 10% and 40% showed the highest values for the thickness of the mucosa and submucosa layers among all treatments, respectively, while the length and width of the villi decreased significantly. No significant (P\u3e0.05) differences in the activities of serum alanine transaminase, aspartate transaminase, and creatinine were detected among treatments. The hepatic total antioxidant capacity and the activities of catalase and superoxide dismutase significantly (P\u3c0.05) increased while the activity of malonaldehyde decreased with increasing the replacement levels of FGA up to 20%. With increasing levels of dietary replacement with FGA, muscular pH, stored loss (%), and frozen leakage rate (%) were significantly decreased. Finally, it was concluded that the dietary replacement of 20% FGA or less may be considered a promising feeding protocol for monosex Nile tilapia, which may lead to high fish growth, quality, profitability, and sustainability for the tilapia production sector

Paeonol Attenuates Methotrexate-Induced Cardiac Toxicity in Rats by Inhibiting Oxidative Stress and Suppressing TLR4-Induced NF-κB Inflammatory Pathway

Methotrexate (MTX) is a commonly used chemotherapeutic agent. Oxidative stress and inflammation have been proved in the development of MTX toxicity. Paeonol is a natural phenolic compound with various pharmacological activities including antioxidant and anti-inflammatory properties. The aim of the present study was to evaluate the protective effect of paeonol against MTX-induced cardiac toxicity in rats and to evaluate the various mechanisms that underlie this effect. Paeonol (100 mg/kg) was administered orally for 10 days. MTX cardiac toxicity was induced at the end of the fifth day of the experiment, with or without paeonol pretreatment. MTX-induced cardiac damage is evidenced by a distortion in the normal cardiac histological structure, with significant oxidative and nitrosative stress shown as a significant increase in NADPH oxidase-2, malondialdehyde, and nitric oxide levels along with a decrease in reduced glutathione concentration and superoxide dismutase activity compared to the control group. MTX-induced inflammatory effects are evidenced by the increased cardiac toll-like receptor 4 (TLR4) mRNA expression and protein level as well as increased cardiac tumor necrosis factor- (TNF-) α and interleukin- (IL-) 6 levels along with increased nuclear factor- (NF-) κB/p65 immunostaining. MTX increased apoptosis as shown by the upregulation of cardiac caspase 3 immunostaining. Paeonol was able to correct the oxidative and nitrosative stress as well as the inflammatory and apoptotic parameters and restore the normal histological structure compared to MTX alone. In conclusion, paeonol has a protective effect against MTX-induced cardiac toxicity through inhibiting oxidative and nitrosative stress and suppressing the TLR4/NF-κB/TNF-α/IL-6 inflammatory pathway, as well as causing an associated reduction in the proapoptotic marker, caspase 3

Tramadol Induced Adrenal Insufficiency: Histological, Immunohistochemical, Ultrastructural, and Biochemical Genetic Experimental Study

Tramadol is a synthetic, centrally acting analgesic. It is the most consumed narcotic drug that is prescribed in the world. Tramadol abuse has dramatically increased in Egypt. Long term use of tramadol can induce endocrinopathy. So, the aim of this study was to analyze the adrenal insufficiency induced by long term use of tramadol in experimental animals and also to assess its withdrawal effects through histopathological and biochemical genetic study. Forty male albino rats were used in this study. The rats were divided into 4 groups (control group, tramadol-treated group, and withdrawal groups). Tramadol was given to albino rats at a dose of 80 mg/kg body weight for 3 months and after withdrawal periods (7–15 days) rats were sacrificed. Long term use of tramadol induced severe histopathological changes in adrenal glands. Tramadol decreased the levels of serum cortisol and DHEAS hormones. In addition, it increased the level of adrenal MDA and decreased the genetic expression of glutathione peroxidase and thioredoxin reductase in adrenal gland tissues. All these changes started to return to normal after withdrawal of tramadol. Thus, it was confirmed that long term use of tramadol can induce severe adrenal insufficiency

Modified Adenovirus Reduces De Novo Peritoneal Adhesions in Rats and Limits Off-Target Transfection. Role of EZH2 in Adhesion Formation

Aim of the study: Adenovector encoding tissue plasminogen activator (tPA) was shown to reduce experimental peritoneal adhesion. We investigated the targeting potential of our modified adenovector, its ability to reduce adhesions and the epigenetic role of histone methyltransferase EZH2 in adhesion formation. Materials and methods: Control lacZ, nonmodified tPA or modified tPA vectors were instilled in the peritoneal cavity after injury in de novo adhesions or after lysis of adhesions in recurrent adhesions. Adhesion severity was scored and adhesions and liver tissues were examined for adenovirus E4 gene and tPA mRNA expression. Levels of tPA, plasminogen activator inhibitor-1 (PAI-1), transforming growth factor-β1 (TGF-β1), and EZH2 expression were measured. Results: E4 transcripts were detected in adhesions of nonmodified and modified and in livers of nonmodified but not in livers of modified de novo adhesions. Both nonmodified (p = 0.021) and modified vectors (p = 0.036) reduced the severity of de novo adhesions compared to lacZ vector. Levels of tPA in nonmodified (p = 0.021) and modified adhesions (p = 0.001) were elevated while PAI-1 (p = 0.013 and p = 0.001, respectively) and TGF-β1 levels (p = 0.002 and p = 0.016, respectively) were reduced compared with lacZ group. All vectors were not expressed in recurrent adhesions and severity score were not different among groups. EZH2 levels were elevated in de novo nontreated (p = 0.001) and was further increased in recurrent (p = 0.001) nontreated adhesions compared with noninjured peritoneum. Conclusion: Modified adenovirus successfully targeted de novo adhesions but not liver tissues and reduced the severity of de novo adhesions. EZH2 is involved in the development and progression of peritoneal adhesions

Evaluation of Groundwater Sensitivity to Pollution Using GIS-Based Modified DRASTIC-LU Model for Sustainable Development in the Nile Delta Region

The groundwater resources in the Nile Delta region are an important resource for freshwater because of rising water demand due to anthropogenic activities. The goal of this study is to quantify groundwater sensitivity to pollution in the Nile Delta by a modified GIS-based DRASTIC-LU model. In this study, we utilized two types of modified DRASTIC-LU models, generic and pesticide, to determine the groundwater vulnerability rates to contamination. The results of the generic DRASTIC-LU model showed that the research region, except for the northwestern part with moderate vulnerability of 3.38%, is highly and very highly vulnerable to pollution with 42.69 and 53.91%, respectively. Results from the pesticide DRASTIC-LU model, on the other hand, also confirmed that, except for the northwestern and southern parts with a moderate vulnerability of 9.78%, most the Nile Delta is highly and very highly vulnerable with 50.68 and 39.53%, respectively. A validation of the model generated was conducted based on nitrate concentrations in the groundwater and a sensitivity analysis. Based on the nitrate analysis, the final output map showed a strong association with the pesticide vulnerability model. Examining the model sensitivity revealed that the influence of depth to water and net recharge were the most important factors to consider

Evaluation of Groundwater Sensitivity to Pollution Using GIS-Based Modified DRASTIC-LU Model for Sustainable Development in the Nile Delta Region

The groundwater resources in the Nile Delta region are an important resource for freshwater because of rising water demand due to anthropogenic activities. The goal of this study is to quantify groundwater sensitivity to pollution in the Nile Delta by a modified GIS-based DRASTIC-LU model. In this study, we utilized two types of modified DRASTIC-LU models, generic and pesticide, to determine the groundwater vulnerability rates to contamination. The results of the generic DRASTIC-LU model showed that the research region, except for the northwestern part with moderate vulnerability of 3.38%, is highly and very highly vulnerable to pollution with 42.69 and 53.91%, respectively. Results from the pesticide DRASTIC-LU model, on the other hand, also confirmed that, except for the northwestern and southern parts with a moderate vulnerability of 9.78%, most the Nile Delta is highly and very highly vulnerable with 50.68 and 39.53%, respectively. A validation of the model generated was conducted based on nitrate concentrations in the groundwater and a sensitivity analysis. Based on the nitrate analysis, the final output map showed a strong association with the pesticide vulnerability model. Examining the model sensitivity revealed that the influence of depth to water and net recharge were the most important factors to consider