SGLT2 inhibitor as a potential therapeutic approach in hyperthyroidism-induced cardiopulmonary injury in rats.

Hyperthyroidism-induced cardiac disease is an evolving health, economic, and social problem affecting well-being. Sodium-glucose cotransporter protein 2 inhibitors (SGLT2-I) have been proven to be cardio-protective when administered in cases of heart failure. This study intended to investigate the potential therapeutic effect of SGLT2-I on hyperthyroidism-related cardiopulmonary injury, targeting the possible underlying mechanisms. The impact of the SGLT2-I, dapagliflozin (DAPA), (1 mg/kg/day, p.o) on LT4 (0.3 mg/kg/day, i.p)-induced cardiopulmonary injury was investigated in rats. The body weight, ECG, and serum hormones were evaluated. Also, redox balance, DNA fragmentation, inflammatory cytokines, and PCR quantification in heart and lung tissues were employed to investigate the effect of DAPA in experimentally induced hyperthyroid rats along with histological and immunohistochemical examination. Coadministration of DAPA with LT4 effectively restored all serum biomarkers to nearly average levels, improved ECG findings, and reinstated the redox balance. Also, DAPA could improve DNA fragmentation, elevate mtTFA, and lessen TNF-α and IGF-1 gene expression in both organs of treated animals. Furthermore, DAPA markedly improved the necro-inflammatory and fibrotic cardiopulmonary histological alterations and reduced the tissue immunohistochemical expression of TNF-α and caspase-3. Although further clinical and deep molecular studies are required before transposing to humans, our study emphasized DAPA's potential to relieve hyperthyroidism-induced cardiopulmonary injury in rats through its antioxidant, anti-inflammatory, and anti-apoptotic effects, as well as via antagonizing the sympathetic over activity.

Differential effects of cancer modifying agents during radiation therapy on Ehrlich solid tumor-bearing mice: A comparative investigation of metformin and ascorbic acid.

BACKGROUND: This work was carried out to compare the modifying roles of ascorbic and metformin during Ehrlich (ESC) tumor-bearing mice irradiation. METHODS: Fifty Swiss albino male mice were segmented into seven groups, including one control group and six Ehrlich induced tumors treated with ascorbic, ascorbic plus radiation, metformin, metformin plus radiation, and radiation only. Many tests, including behavioral, biochemical, immunohistochemistry, gene expression, DNA fragmentation, oxidative stress markers, and EPR, were performed to interrogate the modifying effects on tumor and liver tissues. RESULTS: Remarkable apoptosis was found in metformin irradiated animals compared to irradiated ascorbic counterparts. The irradiated metformin mice showed the greatest reduction in PCNA. There was a significant reduction of DNA fragmentation in the liver tissues of the irradiated metformin group. Irradiated metformin and irradiated ascorbic acid animals showed a reduced signal of ERK as well as c-Fos genes. There was a tendency of metformin and metformin irradiated animals to reduce MDA levels in liver tissues. ESC-bearing mice treated with ascorbic or metformin showed an improvement in the spontaneous alternation percentage (SAP%) and improved short-term memory. There was also an improvement in long memory tests. CONCLUSIONS: The study added more preclinical evidence on the utility of metformin in cancer treatment during radiotherapy. Metformin was shown to reduce lipid peroxidation in irradiated healthy tissues, increase tumor cytotoxicity, downregulate critical pathways involved in tumor progression and proliferation, and enhance tumor apoptosis. Controlled clinical trials using metformin are highly warranted.

Selenium nanoparticles impart robust neuroprotection against deltamethrin-induced neurotoxicity in male rats by reversing behavioral alterations, oxidative damage, apoptosis, and neuronal loss.

This study investigated the neuroprotective role of selenium nanoparticles (SeNPs) on deltamethrin-induced neurotoxicity in rats. A total of 32 adult male Wister rats were allocated into the following four groups: 1) control, 2) deltamethrin (0.6 mg/kg), 3) SeNPs (0.5 mg/kg), and 4) deltamethrin + SeNPs. All agents were administered orally three times per week for 2 months. Locomotor behavior, anxiety-like behavior, biochemical parameters, including brain oxidative damage biomarkers (Malondialdehyde (MDA) and reduced glutathione (GSH)), brain acetylcholinesterase (AChE), and brain genotoxicity were evaluated. The gene expression levels of IGF-1 and Bcl2 were also determined. Moreover, a brain histopathological examination associated with the immunohistochemical determination of Bax in brain tissue was performed. Deltamethrin-intoxicated rats showed a reduction in the locomotor activity associated with a highly anxious state. They also displayed a disturbance in the brain redox state with a decrease in the brain AChE levels and a high DNA fragmentation percentage. Furthermore, they showed a decrement in the immunohistochemical GFAP levels as well as IGF-1 and Bcl2 gene expression levels with an increase in the immunohistochemical Bax levels. All these changes were confirmed by brain histopathology. Interestingly, SeNPs ameliorated all these changes and restored the normal brain architecture. In conclusion. SeNPs possess a potent medicinal activity due to their antioxidant and anti-inflammatory activity. Therefore, SeNPs can be a potential agent in ameliorating deltamethrin-induced neurotoxicity.

Quercetin Alleviates the Immunotoxic Impact Mediated by Oxidative Stress and Inflammation Induced by Doxorubicin Exposure in Rats.

Doxorubicin (DOX) is a chemotherapeutic agent against hematogenous and solid tumors with undesirable side effects including immunosuppression. Quercetin (QUR), a natural flavonoid abundant in fruits and vegetables, has a potent antioxidant activity. The aim of the current study was to assess the impact of QUR on DOX-induced hematological and immunological dysfunctions in a rodent model. Randomly grouped rats were treated as follows: control, QUR alone (50 mg/kg for 15 days per os), DOX alone (2.5 mg/kg I/P, three times a week, for two weeks), and co-treated rats with QUR for 15 days prior to and concomitantly with DOX (for two weeks), at the doses intended for groups two and three. DOX alone significantly disrupted the erythrogram and leukogram variables. Serum immunoglobulin (IgG, IgM, and IgE) levels and the activities of catalase (CAT) and superoxide dismutase (SOD) in spleen were declined. The DNA damage traits in spleen were elevated with an upregulation of the expression of the apoptotic markers (p53 and Caspase-3 genes) and the proinflammatory cytokines (IL-6 and TNF-α genes), while the expression of CAT gene was downregulated. These biochemical changes were accompanied by morphological changes in the spleen of DOX-treated rats. Co-treatment with QUR abated most of the DOX-mediated alterations in hematological variables, serum immunoglobulins, and spleen antioxidant status, pro-inflammatory and apoptotic responses, and histopathological alterations. In essence, these data suggest that QUR alleviated DOX-induced toxicities on the bone marrow, spleen, and antibody-producing cells. Supplementation of chemotherapy patients with QUR could circumvent the DOX-induced inflammation and immunotoxicity, and thus prevent chemotherapy failure.

Astaxanthin Mitigates Thiacloprid-Induced Liver Injury and Immunotoxicity in Male Rats.

Thiacloprid (TCP) is a widely used neonicotinoid insecticide with a probable toxic hazard to animals and human beings. This hazard has intensified the demand for natural compounds to alleviate the expected toxic insults. This study aimed at determining whether astaxanthin (ASX) could mitigate the hepatotoxic effect of TCP and diminish its suppressive effect on immune responses in rats. Animals received TCP by gavage at 62.1 mg/kg (1/10th LD50) with or without ASX at 40 mg/kg for 60 days. Intoxicated rats showed modulation of serum transaminases and protein profiles. The hemagglutination antibody titer to sheep red blood cells (SRBC) and the number of plaque-forming cells in the spleen were reduced. The cell-mediated immunity and phagocytosis were suppressed, while serum interleukins IL-1ß, IL-6, and IL-10 were elevated. Additionally, malondialdehyde, nitric oxide, and 8-hydroxy-2'-deoxyguanosine levels were increased in the liver, spleen, and thymus, with depletion of glutathione and suppression of superoxide dismutase and catalase activities. The expressions of inducible nitric oxide synthase and the high mobility group box protein 1 genes were upregulated with histomorphological alterations in the aforementioned organs. Cotreatment with ASX markedly ameliorated the toxic effects of TCP, and all markers showed a regression trend towards control values. Collectively, our data suggest that the protective effects of ASX on the liver and immune system of TCP-treated animals depend upon improving the antioxidant status and relieving the inflammatory response, and thus it may be used as a promising therapeutic agent to provide superior hepato- and immunoprotection.

Epidemiological and genetic characteristics of asymptomatic canine leishmaniasis and implications for human Leishmania infections in Egypt.

Leishmaniasis is a neglected zoonotic disease that poses significant veterinary and public health risks in developing countries. Dogs act as a reservoir host for leishmaniasis transmitted to humans. A total of 108 human cases of cutaneous leishmaniasis (CL) were identified in the Al-Houd Al-Marsoud Hospital in Cairo, Egypt, during 2018. Blood samples and skin biopsies were collected for further examination. Blood samples from 96 asymptomatic dogs were collected. All samples were subjected to molecular and phylogenetic analysis. Quantitative RT-PCR was used to measure the expression of genes related to mTOR signalling and inflammation in blood and tissue samples. The distribution pattern of human cases pointed to an endemic focus in North Sinai (66.67%). The prevalence of asymptomatic canine leishmaniasis was 66.60%. Histopathological examination of human skin lesions revealed a severe granulomatous inflammatory reaction, necrosis and ulceration. Moreover, leishmanial amastigotes could be detected in human tissue samples. Phylogenetic analysis revealed 100% identity of human isolates to Leishmania tropica (MN453682), and dog isolates to Leishmania infantum (MN453673), with 94.9% similarity between the two isolates. Gene expression related to mTOR signalling and inflammation in both species' samples confirmed a significant alteration of EIF4EBP1, CCR4 and INF-γ expression compared with control groups. In Egypt, increased incidence of asymptomatic carrier dogs acting as a significant reservoir host for Leishmania poses a public health hazard. Findings warrant further epidemiological investigation of CL in Egypt, as well as additional study of parasite differentiation and gene regulation.

Neuropathological and Cognitive Effects Induced by CuO-NPs in Rats and Trials for Prevention Using Pomegranate Juice.

Copper oxide nanoparticles (CuO-NPs) are extensively utilized in several industries and in pharmaceutical production. This excess exposure elevates the concern about its expected poisonous impacts on humans and animals. Pomegranate juice (PJ) is a natural source of polyphenols and exhibits potent antioxidant activities. Our experiment intended to explore the neurobehavioral and toxicopathological impacts of CuO-NPs and to explain the mechanistic role of PJ to reduce their toxicity. Thirty Wistar albino rats received the subsequent materials through oral gavage, every day for 28d: (1) normal saline, (2) 3 mL/kg bwt PJ, (3) 6 mL/kg bwt PJ, (4) 300 mg/kg bwt CuO-NPs, (5) CuO-NPs + 3 mL/kg bwt PJ, (6) CuO-NPs + 6 mL/kg bwt PJ. Continuous exposure to CuO-NPs caused a significant elevation of MDA levels and reduction of total antioxidant capacity associated with remarkable pathological alterations in all brain regions including cerebrum, hippocampus and cerebellum. Progressive decline of memory along with cognitive and psychiatric disturbances were observed in rats exposed to CuO-NPs not in PJ co-treated rats. Continuous exposure to CuO-NPs caused over expression of the immunohistochemical markers of caspase-3, iNOS and GFAP altogether with DAN fragmentation and down-regulation of HO-1 and Nrf2 gene in the whole brain tissues. Conversely, rats co-treated with PJ showed dose dependent improvements in the entire toxicological, behavioral, and pathological parameters. We showed that PJ had the ability to reduce the oxidative stress damage via up-regulation of HO-1 and Nrf2 genes in the brain. So that PJ had the ability to protect the brain and DNA from further damage.

Antimicrobial action of autologous platelet-rich plasma on MRSA-infected skin wounds in dogs.

Effective antimicrobial preparations, other than antibiotics, are important for the treatment of potentially fatal drug-resistant infections. Methicillin-resistant Staphylococcus aureus (MRSA) is one of the leading causes of hospital-acquired and post- operative infections. Fortunately, the antimicrobial properties of platelet-rich plasma (PRP) against various microorganisms enable its potential use as an alternative to conventional antibiotics. The present work was designed to evaluate the hypothesized antimicrobial activity of PRP against MRSA infected skin wounds. Six adult male dogs were divided equally into control and PRP groups. Unilateral circular full-thickness skin wounds were created then a MRSA suspension was injected locally. Treatment started at 1st week post infection with subcutaneous infiltration of autologous activated PRP every week in the PRP group and with topical application of clindamycin cream twice daily in the control group. PRP decreased wound size and significantly increased wound contractility and re-epithelization, as confirmed by histopathological and immunohistochemical findings. Also PRP treated group showed significant decrease in ROS and redox imbalance with over expression of the TNF-α and VEGFA genes that indicate angiogenesis and maximum antibacterial activity after three weeks. In conclusion, CaCl2-activated PRP exhibited antimicrobial activity against MRSA infection, which improved the infected wound healing re-epithelization and granulation tissue formation.

Burn-Induced Multiple Organ Injury and Protective Effect of Lutein in Rats.

Thermal injury may lead to multiple organ dysfunction through release of proinflammatory mediators and reactive oxygen radicals. This study investigated the effects of thermal injury on remote organs of rats and the possible protective effect of lutein. Thermal trauma was induced in the back of rats by exposing them to 90 °C bath for 10 s. Rats were sacrificed 48 h after burn, and blood samples were collected to monitor liver and kidney functions. Tissue samples from liver, kidneys, and lungs were taken for studying oxidative stress parameters, gene expressions of TNF-α and Casp-3, besides histopathological examination. Skin scald injury caused significant elevations of liver and kidney function biomarkers in the serum. In tissue samples, increments of MDA, GPx, and 8-OHdG were recorded while GSH level and the activities of CAT and SOD were suppressed. The expressions of TNF-α and caspase-3 mRNA were increased, and histopathological results revealed remote organ injury. Oral administration of lutein (250 mg/kg) resulted in amelioration of the biochemical and molecular changes induced by burn as well as the histopathological alterations. According to the findings of the present study, lutein possesses anti-oxidant, anti-inflammatory, and anti-apoptotic effects that protect against burn-induced damage in remote organs.