Moringa oleifera leaves ethanolic extract counteracts cortical neurodegeneration induced by aluminum chloride in rats.

Background: Aluminum, a well-recognized neurotoxin, is implicated in various neurodegenerative disorders. Moringa oleifera (M. oleifera), known as a miracle tree, is utilized as a functional food and nutritional supplement. This study investigates the potential preventive effects of M. oleifera extract on aluminum chloride (AlCl3)-induced cortical neurodegeneration in rats. Materials and methods: Therefore, 24 adult male Wistar rats were randomly divided into four distinct groups: negative control, M. oleifera extract (MOE), AlCl3, and AlCl3 + MOE. Treatments were administered orally for 28 consecutive days. Cognitive performance, brain oxidative/nitrosative stress, neuroinflammation, apoptotic-cell death, and associated histopathological alterations were assessed. Results: Our results showed that MOE improved spatial learning and memory, enhanced antioxidant superoxide dismutase enzyme activity, antagonized nitrosative stress, reduced inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6), decreased caspase-3, increased Bcl-2, and facilitated repair of cortical and hippocampal structures. Conclusions: We concluded that MOE exhibits protective effects against cortical neurodegeneration, making it a promising supplement to counteract aluminum-induced neurotoxic effects.

Repurposing of carvedilol to alleviate bleomycin-induced lung fibrosis in rats: Repressing of TGF-ß1/α-SMA/Smad2/3 and STAT3 gene expressions.

Idiopathic pulmonary fibrosis (IPF) is the most widely studied interstitial lung disease. IPF eventually leads to respiratory insufficiency, lung cancer, and death. Carvedilol (CAR) is a third-generation ß-adrenergic receptor antagonist with an α1-blocking effect. CAR demonstrates antifibrotic activities in various experimental models of organ fibrosis. AIMS: This work is designed to explore the possible alleviating effects of CAR on bleomycin (BLM)-induced lung fibrosis in rats. MAIN METHODS: The BLM rat model of lung fibrosis was achieved by intratracheal delivery of a single dose of 5 mg/kg of BLM. Seven days following BLM injection, either prednisolone or CAR was orally administered at doses of 10 mg/kg once daily for 21 days to the rats. The actions of CAR were evaluated by lung oxidant/antioxidant parameters, protein concentration and total leucocyte count (TLC) in bronchoalveolar lavage fluid (BALF), fibrosis regulator-related genes along with the coexistent lung histological changes. KEY FINDINGS: CAR effectively decreased lung malondialdehyde level, increased superoxide dismutase activity, declined both protein concentration and TLC in BALF, downregulated TGF-ß1/α-SMA/Smad2/3 and STAT3 gene expressions, and repaired the damaged lung tissues. SIGNIFICANCE: CAR conferred therapeutic potential against BLM-induced lung fibrosis in rats, at least in part, to its antioxidant, anti-inflammatory, and antifibrotic activities. CAR could be utilized as a prospective therapeutic option in patients with lung fibrosis in clinical practice.

Critical Hypermagnesemia in Preeclamptic Women Under a Magnesium Sulfate Regimen: Incidence and Associated Risk Factors.

Magnesium sulfate is used as prophylaxis and treatment of severe preeclampsia/eclampsia, albeit its safety and toxicity are a concern. We designed this study to estimate the incidence of critical hypermagnesemia in severely preeclamptic women under a magnesium sulfate regimen at 8 h following its administration and to identify the associated risk factors as the primary outcomes. Also, secondary outcomes were to compare baseline characteristics, laboratory findings, and maternal-neonatal complications stratified by the baseline serum magnesium (Mg2+) in those women, and to assess the degree of agreement between patellar reflex and serum Mg2+ concentration 8 h following magnesium sulfate administration. We conducted a retrospective study including severely preeclamptic women receiving magnesium sulfate from June 2016 to May 2021. We enrolled 429 women in the study. Two-hundred sixty-one (60.8%) of the included women developed critical hypermagnesemia. Preeclamptic women with high baseline serum Mg2+ concentration demonstrated significantly affected renal functions, hepatic transaminase activities, and low platelet count as well as more reported maternal complications compared to those with low baseline serum Mg2. Multivariable logistic regression revealed that a lower gestational age, a higher uric acid concentration, and a higher baseline serum Mg2+ concentration were independently associated with an increased risk of critical hypermagnesemia. The agreement between deep tendon reflex assessment and serum Mg2+ concentration was slight although not significant. The maternal-neonatal outcomes were non-significant in women with critical hypermagnesemia. More vigilant monitoring through assessment of both serum Mg2+ concentration and deep tendon reflex should be considered especially in high-risk women.

Crocin averts functional and structural rat hepatic disturbances induced by copper oxide nanoparticles.

Background: Exposure to nanoparticles became inevitable in our daily life due to their huge industrial uses. Copper oxide nanoparticles (CuONPs) are one of the most frequently utilized metal nanoparticles in numerous applications. Crocin (CRO) is a major active constituent in saffron having anti-inflammatory and antioxidant potentials. Objectives: We designed this study to explore the probable defensive role of CRO against CuONPs-induced rat hepatic damage. Materials and methods: Therefore, 24 adult rats were randomly distributed into 4 equal groups as negative control, CRO, CuONPs, and co-treated CuONPs with CRO groups. All treatments were administered for 14 days. The hepatotoxic effect of CuONPs was evaluated by estimation of hepatic alanine aminotransferase and aspartate aminotransferase enzymes, hepatic oxidative malondialdehyde and antioxidant glutathione reduced, serum levels of inflammatory biomarkers (tumor necrosis factor-alpha, interleukin-1-beta, and nuclear factor kappa B), and expression of the apoptotic BAX in hepatic tissues; in addition, histopathological examination of the hepatic tissues was conducted. Results: We found that concurrent CRO supplement to CuONPs-treated rats significantly averted functional and structural rat hepatic damage as documented by decreased hepatic enzymes activities, restored hepatic oxidant/antioxidant balance, decreased serum levels of inflammatory biomarkers, reversed BAX-mediated apoptotic cell death in hepatic tissues along with repair of CuONPs-induced massive hepatic structural and ultrastructural alterations. Conclusions: It is concluded that combined CRO supplement to CuONPs-treated rats improved hepatic function and structure by, at least in part, antioxidant, anti-inflammatory, and antiapoptotic mechanisms.

Targeting Colorectal Cancer Cells with Niosomes Systems Loaded with Two Anticancer Drugs Models; Comparative In Vitro and Anticancer Studies.

Colorectal cancer (CRC) is considered one of the most commonly diagnosed malignant diseases. Recently, there has been an increased focus on using nanotechnology to resolve most of the limitations in conventional chemotherapy. Niosomes have great advantages that overcome the drawbacks associated with other lipid drug delivery systems. They are simple, cheap, and highly stable nanocarriers. This study investigated the effectiveness of using niosomes with their amphiphilic characteristics in the incorporation of both hydrophilic and hydrophobic anticancer drugs for CRC treatment. METHODS: Drug-free niosomes were formulated using a response surface D-optimal factorial design to study the cholesterol molar ratio, surfactant molar ratio and surfactant type effect on the particle size and Z-potential of the prepared niosomes. After numerical and statistical optimization, an optimized formulation having a particle size of 194.4 ± 15.5 nm and a Z-potential of 31.8 ± 1.9 mV was selected to be loaded with Oxaliplatin and Paclitaxel separately in different concentrations. The formulations with the highest entrapment efficiency (EE%) were evaluated for their drug release using the dialysis bag method, in vitro antitumor activity on HT-29 colon cancer cell line and apoptosis activity. RESULTS: Niosomes prepared using d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) at a molar ratio 4, cholesterol (2 molar ratio) and loaded with 1 molar ratio of either Oxaliplatin or Paclitaxel provided nanosized vesicles (278.5 ± 19.7 and 251.6 ± 18.1 nm) with a Z-potential value (32.7 ± 1.01 and 31.69 ± 0.98 mV) with the highest EE% (90.57 ± 2.05 and 93.51 ± 2.97) for Oxaliplatin and Paclitaxel, respectively. These formulations demonstrated up to 48 h drug release and increased the in vitro cytotoxicity and apoptosis efficiency of both drugs up to twice as much as free drugs. CONCLUSION: These findings suggest that different formulation composition parameters can be adjusted to obtain nanosized niosomal vesicles with an accepted Z-potential. These niosomes could be loaded with either hydrophilic drugs such as Oxaliplatin or hydrophobic drugs such as Paclitaxel. Drug-loaded niosomes, as a unique nanomicellar system, could enhance the cellular uptake of both drugs, resulting in enhanced cytotoxic and apoptosis effects against HT-29 colon cancer cells. Oxaliplatin-niosomes and Paclitaxel-niosomes can be considered promising alternative drug delivery systems with enhanced bioavailability of these two anticancer drugs for colorectal cancer treatment.

Naringenin alleviates hepatic injury in zinc oxide nanoparticles exposed rats: impact on oxido-inflammatory stress and apoptotic cell death.

Human exposure to nanoparticles became unavoidable secondary to their massive involvement in a multitude of industrial applications. Zinc oxide nanoparticles (ZnONPs) are one of the most commonly used metal oxide nanoparticles in biological applications. Naringenin (NAR), a citrus-derived flavonoid, has favorable biological properties that promote human health. The present study was carried out to investigate the possible defensive role of NAR versus ZnONPs provoked hepatic injury in rats through an evaluation of liver enzymes, hepatic biomarkers of oxidative stress, inflammatory process, apoptotic cell death along with histopathological examination of liver tissue. Therefore, 32 adult rats were randomly divided into four equal groups as control, NAR, ZnONPs and co-treated ZnONPs with NAR groups. All treatments were administered for 14 days. Our results showed that ZnONPs induced hepatic injury as documented by the marked increased in hepatic enzymes activities, disturbed hepatic oxidant/antioxidant balance, increased hepatic inflammatory reactions, in addition to, extensive hepatic morphological alterations, marked collagen fibers accumulation as well as overexpression of apoptotic BAX and the noticeable intensified positive nuclear staining for nuclear factor Kabba-b in hepatic tissues. Concurrent NAR supplement to ZnONPs- treated rats significantly declined liver enzymes activities, restored oxidant/antioxidant balance, reversed inflammation, induced fewer collagen fibers accumulation, and antagonized BAX-mediated apoptotic cell death in hepatic tissues. We concluded that concurrent NAR supplement to ZnONPs treated rats improved hepatic function and structure by its antioxidant, anti-inflammatory and antiapoptotic potentials.

L-carnitine suppresses cisplatin-induced renal injury in rats: impact on cytoskeleton proteins expression.

We designed this work to examine the curative role of L-carnitine (LCAR) in a rat model of cisplatin (CDDP)-induced kidney injury. We induced kidney injury in rats by a single intraperitoneal injection of 5 mg/kg of CDDP. Fifteen days post injection, rats were orally supplemented with 354 mg/kg of LCAR for another 15 days. Kidney tissues were subjected to histo-biochemical analysis along with mRNA gene expression quantification for cytoskeleton proteins encoding genes (vimentin, nestin, and connexin 43) by real-time reverse transcription polymerase chain reaction. LCAR reversed CDDP-induced renal structural and functional impairments. LCAR significantly declined serum urea and creatinine concentrations, restored oxidant/antioxidant balance, reversed inflammation, and antagonized caspase 3-mediated apoptotic cell death in renal tissues. Moreover, LCAR effectively down-regulated cytoskeleton proteins mRNA levels, reflecting amelioration of CDDP-provoked podocyte injury. We concluded that LCAR has a favorable therapeutic utility against CDDP-induced kidney injury.

Extracellular vesicles derived from bone marrow mesenchymal stem cells repair functional and structural rat adrenal gland damage induced by fluoride.

The adrenal glands have striking morpho-biochemical features that render them vulnerable to the effects of toxins. AIMS: This study was conducted to explore the therapeutic utility of extracellular vesicles derived from bone marrow mesenchymal stem cells (BMSC-EVs) against fluoride-induced adrenal toxicity. MATERIALS AND METHODS: The work included isolation and further identification of BMSC-EVs by transmission electron microscopy and flow cytometric analysis. Adrenal toxicity in rats was induced by oral administration of 300 ppm of sodium fluoride (NaF) in drinking water for 60 days followed by a single dose injection of BMSC-EVs. The effects of BMSC-EVs against NaF was evaluated by adrenal oxidant/antioxidant biomarkers, hormonal assay of plasma adrenocorticotrophic hormone (ACTH) and corticosterone (CORT) and mRNA gene expression quantitation for adrenal cortical steroidogenic pathway-encoding genes. Histopathological examination of the adrenal tissue was performed. KEY FINDINGS: BMSC-EVs were effectively isolated and characterized. NaF exposure decreased adrenal superoxide dismutase and catalase activities, increased adrenal malondialdehyde levels, elevated plasma ACTH, diminished CORT concentrations and downregulated the adrenal cortical steroidogenic pathway-encoding genes. In addition, NaF-induced marked adrenal histopathological lesions. SIGNIFICANCE: BMSC-EVs treatment repaired damaged adrenal tissue and recovered its function greatly following NaF consumption. BMSC-EVs reversed the toxic effects of NaF and reprogramed injured adrenal cells by activating regenerative processes.

Possible healing effects of Salvadora persica extract (MISWAK) and laser therapy in a rabbit model of a caustic-induced tongue ulcers: histological, immunohistochemical and biochemical study.

Caustic ingestion is a potentially detrimental event that can cause serious devastating damage on contact with tissues. Local exposure is associated with severe pain, swelling and ulceration. Caustics-induced oral ulcers can be painful enough to compromise the patient's quality of life. Treatment of oral ulcers is crucial in clinical practice. Albeit, some ulcers do not respond adequately to the conventional treatment. The current study was conducted to evaluate the potential healing effects of topical Salvadora persica (SP) extract, low-level laser (LLL) and high-level laser (HLL) therapies in a rabbit model of caustic-induced tongue ulcers and explore the underlying mechanisms. Fifty male rabbits with a caustic induced tongue ulcers were included in the study. Rabbits were equally divided into four groups: positive control (ulcer) group, SP, LLL and HLL groups in addition to the negative control (healthy) group. All treatments were given thrice weekly for 14 days. Results showed that acetic acid-induced tongue ulcers caused extensive structural tongue damage secondary to overexpression of apoptotic BAX, pathological angiogenesis indicated by VEGF overexpression, marked collagen fibers deposition as well as upregulation of tissue pro-inflammatory TNF-α and upregulation of tissue anti-inflammatory IL-10. The healing potential of topical SP, LLL and HLL therapy are mostly comparable. In conclusion, acetic acid-induced extensive tongue damage. Topical SP extract, LLL and HLL are equally effective therapies against caustics-induced tongue ulcers. However, we recommend SP extract, owing to its safety, non-invasiveness, availability and low cost.