Enhanced wound healing potential of arabincoside B isolated from Caralluma Arabica in rat model; a possible dressing in veterinary practice.

BACKGROUND: Wound management is a critical procedure in veterinary practice. A wound is an injury that requires the body's cells' alignment to break down due to external assault, such as trauma, burns, accidents, and diseases. Re-epithelization, extracellular matrix deposition, especially collagen, inflammatory cell infiltration, and development of new blood capillaries are the four features that are used to evaluate the healing process. Using a natural extract for wound management is preferred to avoid the side effects of synthetic drugs. The current study aimed to assess the effect of major pregnane glycoside arabincoside B (AR-B) isolated from Caralluma arabica (C. arabica) for the wound healing process. METHOD: AR-B was loaded on a gel for wound application. Rats were randomly distributed into six groups: normal, positive control (PC), MEBO®, AR-B 0.5%, AR-B 1%, and AR-B 1.5%, to be 6 animals in each group. Wounds were initiated under anesthesia with a 1 cm diameter tissue needle, and treatments were applied daily for 14 days. The collected samples were tested for SOD, NO, and MDA. Gene expression of VEGF and Caspase-3. Histopathological evaluation was performed at two-time intervals (7 and 14 days), and immunohistochemistry was done to evaluate α -SMA, TGF-ß, and TNF-α. RESULT: It was found that AR-B treatment enhanced the wound healing process. AR-B treated groups showed reduced MDA and NO in tissue, and SOD activity was increased. Re-epithelization and extracellular matrix deposition were significantly improved, which was confirmed by the increase in TGF-ß and α -SMA as well as increased collagen deposition. TNF-α was reduced, which indicated the subsiding of inflammation. VEGF and Caspase-3 expression were reduced. CONCLUSION: Our findings confirmed the efficiency of AR-B in enhancing the process of wound healing and its potential use as a topical wound dressing in veterinary practice.

Evaluating the potential impact of sodium-glucose cotransporter-2 inhibitor "canagliflozin" on the hepatic damage triggered by hypertension in rats.

Hypertension (HTN) is a prevalent chronic disease. HTN and liver disease association is extensively noted. Thus, finding a medication that can alleviate HTN and its accompanying liver insult would be promising. This study investigated the potential impacts of canagliflozin "sodium-glucose cotransporter-2 inhibitor" on the liver of the Nω-nitro-L-arginine methyl ester (L-NAME)-induced HTN rat model. Twenty-four adult male rats were divided into four groups; negative control group, canagliflozin group, L-NAME group: 50 mg/kg of L-NAME was injected daily for 5 weeks and L-NAME + canagliflozin group: 1 week after L-NAME injection both L-NAME + canagliflozin (40 mg/kg) were given concomitantly daily for further 4 weeks. Liver functions, serum lipid profile, hepatic oxidative/nitrative stress biomarkers, gene expression of lipogenic enzymes, B-cell lymphoma 2 (Bcl2), and DNA fragmentation, were measured. Besides, hepatic histology and immunohistochemistry of nuclear factor kappa B (NF-κB) and endothelial nitric oxide synthase (eNOS) were assessed. Canagliflozin improved hepatic lipogenesis via the downregulation of fatty acid synthase (FAS) and transcriptional regulatory element binding protein 1c (SREBP1c) genes leading to an improved serum lipid profile. Further, canagliflozin modified the eNOS/inducible nitric oxide synthase (iNOS) pathway and decreased the NF-κB immunoreactivity besides restoring the oxidants-antioxidants balance; increased reduced glutathione concomitant with declined malondialdehyde. This improvement of the liver was mirrored by the significant restoration of liver architecture and confirmed by the preserved liver DNA content and upregulation of the antiapoptotic Bcl2 mRNA level and attenuation of the alanine transaminase, aspartate aminotransferase. In conclusion, canagliflozin is a promising anti-hypertensive and hepatic-supportive medication. RESEARCH HIGHLIGHTS: Canagliflozin's antioxidant, anti-inflammatory, anti-lipogenic, and antiapoptotic characteristics mitigate remote liver compromise caused by hypertension. Canagliflozin can be exploited as a hepatoprotective and antihypertensive medication.

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.

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.