Effects of benzo[a]pyrene and CYP19a1b knockdown on zebrafish development

Benzo[a]pyrene (BaP) is a ubiquitous environmental contaminant that is both an endocrine disruptor and a carcinogen. Aromatase (CYP19) is a key enzyme in steroidogenesis playing a key role in the hypothalamus-pituitary-gonad feedback loop. We hypothesized that BaP would negatively impact cyp19a1b expression in zebrafish, in turn, adversely affecting development and physiology. Here, we consider whether the toxicities observed following BaP exposure are comparable to those following a transient morpholino (MO)-mediated CYP19a1b knockdown or exposure to an aromatase inhibitor (fadrozole) during early development. One-cell zebrafish embryos were injected with a CYP19a1b-MO or control-MO. Other non-injected embryos were exposed to nominal waterborne concentrations of BaP (0, 10 or 50 ?g/L) and fadrozole (0, 10 or 50 ?g/L) for 96 hours post-fertilization (hpf). Real-time PCR shoboth BaP concentrations significantly decreased cyp19a1b expression in 96 hpf zebrafish larvae homogenates. Likewise, concentrations of E2 in 48 hpf whole body larval homogenates were significantly decreased by BaP, fadrozole and CYP19a1b-MO. Cumulative mortality of zebrafish larvae was significantly increased following BaP and fadrozole exposure and CYP19a1b knockdown compared to controls. Estradiol (E2, 10 nM) co-treatment rescued mortality mediated by 10 μg/L BaP, 10 μg/L fadrozole, and CYP19a1b-MO. In a treatment-blinded morphological assessment of larvae at 96 hpf, several phenotypes were negatively impacted by BaP, fadrozole, and CYP19a1b knockdown including body length, optic vesicle size, swim bladder inflation, pericardial and abdominal edema, and incidence of normal larval tail shape and these effects were reversed by exogenous E2-cotreatment. Decreased incidence of normal pectoral fins was only impacted by BaP exposure. In conclusion, certain adverse developmental outcomes caused by BaP exposure are at least in part related to BaP-mediated CYP19a1b inhibition

Moringa oleifera Lam. (family Moringaceae) leaf extract attenuates high-fat diet-induced dyslipidemia and vascular endothelium dysfunction in Wistar albino rats

Purpose: To investigate the protective effect of methanol extract of Moringa oleifera leaves (MEMO) in high-fat diet (HFD)-induced dyslipidemia and vascular endothelium dysfunction. Methods: Dose-dependent attenuating effect of MEMO was tested at doses of 200 and 400 mg/kg/day in an in vivo model of HFD-induced dyslipidemia using rats whereas vascular endothelial reactivity was assessed in isolated rat aorta using ex vivo organ bath setup. Results: MEMO administration in HFD-induced dyslipidemic rats for 3 consecutive weeks, resulted in significant decrease in rat body weight, LW/BW and RFPW/BW ratio when compared to rats treated with HFD only where an increase in body weight was observed. Decrease in the average daily feed intake and significant reductions in waist, Lee index and BMI was also observed after MEMO treatment in HFD-induced dyslipidemic rats. Lipid profile data indicate that HFD group showed significant increase in total cholesterol, triglyceride, LDL and VLDL levels while HDL levels decreased significantly. On the other hand, MEMO treatment improved lipid profile compared to HFD group. Ex-vivo isolated aorta results revealed that MEMO treatment reversed HFD-induced endothelium dysfunction when compared to SD group. Conclusion: MEMO treatment produces dose-dependent improvement in lipid profile and vascular endothelium protection, thereby rationalizing its traditional medicine use in the treatment of dyslipidemia and cardiovascular related endothelial disorders

Role of L- glutamine and crizanlizumab in sickle cell anaemia painful crisis reduction

BackgroundPatients with sickle cell disease, frequently ‎ suffer from intense painful episodes. Till recently hydroxyurea was the only available medical therapy that approved for reduction of painful episodes.AimsTo summarize the available data from randomized controlled trials that aim to evaluate the efficacy of newly approved L-‎glutamine‎ (alters redox state of red blood cells ‎‎[RBCs]) ‎and ‎crizanlizumab (‎(anti-P-selectin)‎)‎ ‎on vaso-occlusive episodes in Sickle cell disease ‎ patients.Methods PubMed, ‎Google Scholar, and EBSCO ‎ databases were ‎‎systematically search for relevant articles. The terms ‎ ‎ ‎ L-glutamine, sickle cell disease, sickle cell ‎anaemia,‎ ‎‎crizanlizumab ‎and vaso-occlusive episodes‎ were used.Results Out of Four-hundred seventy-two records, only three fulfilled the inclusion criteria. Two trials were aimed to evaluate the efficacy of L-glutamine therapy on the frequency of painful crises in sickle cell anaemia patients. Both studies showed that L-glutamine therapy significantly reduce the frequency of VOEs. Only one trial examined the ability of crizanlizumab on VOEs reduction, and showed crizanlizumab successful reduce the occurrence of VOEs.‎ConclusionNewer agent ‎with different mechanism of action, such as ‎L-glutamine, ‎and crizanlizumab may consider if ‎hydroxyurea not effective or not ‎tolerable

Neuroprotective potential of Afzelin: A novel approach for alleviating catalepsy and modulating Bcl-2 expression in Parkinson's disease therapy

The lost dopaminergic neurons in the brain prevent mobility in Parkinson's disease (PD). It is impossible to stop the disease's progress by means of symptoms management. Research focuses on oxidative stress, mitochondrial dysfunction, and neuronal degeneration. Exploration of potential neuroprotective drugs against prosurvival B-cell lymphoma 2 (Bcl-2) protein is ongoing. An investigable cause behind PD, as well as preventive measures, could be discovered considering the association between such behavioural manifestations (cataleptic behaviours) and PD. The compound Afzelin, known to guard the nervous system, was chosen for this study. The study was done on rats divided into six different groups. First, there was a control group. The other group was treated with Reserpine (RES) (1 mg/kg). The third group received RES (1 mg/kg) and levodopa (30 mg/kg). The remaining three groups were given RES (1 mg/kg) in conjunction with Afzelin at the following doses: 5 mg/kg, 10 mg/kg, and 20 mg/kg. Cataleptic behavior and mobility in rats was assessed using the rotarod, open field, and modified forced-swim tests. thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), biogenic amines, and Bcl-2 level in rat tissue homogenates were considered. According to the study's findings, the rats treated through co-administration of RES and Afzelin improved significantly in their cataleptic behaviours and locomotor activity. In addition, administering Afzelin itself caused Bcl-2 expression, which could have some neuroprotection properties. This study provides meaningful information on the effectiveness of Afzelin in handling catalepsy and other degenerative neurologic disorders. As a result, other studies need to be conducted to establish the reasons behind the reactions and determine the long-term effects of Afzelin on these conditions

Cymbopogon Proximus Essential Oil Protects Rats against Isoproterenol-Induced Cardiac Hypertrophy and Fibrosis

Cardiac hypertrophy is an independent risk factor of many cardiovascular diseases. Several cardiovascular protective properties of Cymbopogon proximus have been reported. However, no reports investigating the direct effect of C. proximus essential oil on the heart are available. The goal of this study was to explore the cardioprotective effect of C. proximus on cardiac hypertrophy and fibrosis. Male albino rats were administered C. proximus essential oil in the presence or absence of hypertrophic agonist isoproterenol. Cardiac hypertrophy and fibrosis were assessed using real-time polymerase chain reaction (PCR) and histological examination. Pre- treatment of rats with C. proximus decreased the ratio of heart weight to body weight and gene expression of hypertrophy markers atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-myosin heavy chain (β-MHC), which were induced by isoproterenol. Moreover, C. proximus prevented the increase in gene expression of fibrosis markers procollagen I and procollagen III and alleviated the collagen volume fraction caused by isoproterenol. The pre- treatment with C. proximus essential oil conferred cardio-protection against isoproterenol- induced cardiac hypertrophy and fibrosis

Ameliorative Effects of Isoeugenol and Eugenol against Impaired Nerve Function and Inflammatory and Oxidative Mediators in Diabetic Neuropathic Rats

Diabetic polyneuropathy is characterized by structural abnormalities, oxidative stress, and neuroinflammation. The current study aimed to determine the antinociceptive effects of isoeugenol and eugenol and their combinations in neuropathic pain resulting from streptozotocin (STZ)-induced diabetes and neuroinflammation. Female SD rats were categorized into normal control, diabetic control, and treatment groups. On the 28th day and 45th day, behavioral studies (allodynia and hyperalgesia) were performed to analyze the development and protection of diabetic polyneuropathy. The levels of inflammatory and oxidative mediators, such as superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), catalase, reduced glutathione, and thiobarbituric acid reactive substances (TBARS), were estimated. In addition, the level of nerve growth factor (NGF) was estimated at the end of the study in different groups. The anti-NGF treatment decreased its upregulation in the dorsal root ganglion significantly. The results showed that isoeugenol, eugenol, and their combination have therapeutic potential against neuronal and oxidative damage induced by diabetes. In particular, both compounds significantly affected behavioral function in treated rats and showed neuroprotection against diabetic neuropathy, and their combination had synergistic effects

Possible Synergistic Antidiabetic Effects of Quantified Artemisia judaica Extract and Glyburide in Streptozotocin-Induced Diabetic Rats via Restoration of PPAR-α mRNA Expression

Several members of the genus Artemisia are used in both Western and African traditional medicine for the control of diabetes. A considerable number of diabetic patients switch to using oral antidiabetic drugs in combination with certain herbs instead of using oral antidiabetic drugs alone. This study examined the effect of Artemisia judaica extract (AJE) on the antidiabetic activity of glyburide (GLB) in streptozotocin (STZ)-induced diabetes. Forty-two male Wistar rats were divided into seven equal groups. Normal rats of the first group were treated with the vehicle. The diabetic rats in the second–fifth groups received vehicle, GLB (5 mg/kg), AJE low dose (250 mg/kg), and AJE high dose (500 mg/kg), respectively. Groups sixth–seventh were treated with combinations of GLB plus the lower dose of AJE and GLB plus the higher dose of AJE, respectively. All administrations were done orally for eight weeks. Fasting blood glucose (FBG) and insulin levels, glycated hemoglobin (HbA1c) percentage, serum lipid profile, and biomarkers of oxidative stress were estimated. The histopathological examination of the pancreas and the immunohistochemical analysis of anti-insulin, anti-glucagon, and anti-somatostatin protein expressions were also performed. The analysis of the hepatic mRNA expression of PPAR-α and Nrf2 genes were performed using quantitative RT-PCR. All treatments significantly lowered FBG levels when compared with the STZ-control group with the highest percentage reduction exhibited by the GLB plus AJE high dose combination. This combination highly improved insulin levels, HbA1c, and lipid profile in blood of diabetic rats compared to GLB monotherapy. In addition, all medicaments restored insulin content in the β-cells and diminished the levels of glucagon and somatostatin of the α- and δ-endocrine cells in the pancreatic islets. Furthermore, the GLB plus AJE high dose combination was the most successful in restoring PPAR-α and Nrf2 mRNA expression in the liver. In conclusion, these data indicate that the GLB plus AJE high dose combination gives greater glycemic improvement in male Wistar rats than GLB monotherapy

Brain Targeting by Intranasal Drug Delivery: Effect of Different Formulations of the Biflavone “Cupressuflavone” from Juniperus sabina L. on the Motor Activity of Rats

The polar fractions of the Juniperus species are rich in bioflavonoid contents. Phytochemical study of the polar fraction of Juniperus sabina aerial parts resulted in the isolation of cupressuflavone (CPF) as the major component in addition to another two bioflavonoids, amentoflavone and robustaflavone. Biflavonoids have various biological activities, such as antioxidant, anti-inflammatory, antibacterial, antiviral, hypoglycemic, neuroprotective, and antipsychotic effects. Previous studies have shown that the metabolism and elimination of biflavonoids in rats are fast, and their oral bioavailability is very low. One of the methods to improve the bioavailability of drugs is to alter the route of administration. Recently, nose-to-brain drug delivery has emerged as a reliable method to bypass the blood–brain barrier and treat neurological disorders. To find the most effective CPF formulation for reaching the brain, three different CPF formulations (A, B and C) were prepared as self-emulsifying drug delivery systems (SEDDS). The formulations were administered via the intranasal (IN) route and their effect on the spontaneous motor activity in addition to motor coordination and balance of rats was observed using the activity cage and rotarod, respectively. Moreover, pharmacokinetic investigation was used to determine the blood concentrations of the best formulation after 12 h. of the IN dose. The results showed that formulations B and C, but not A, decreased the locomotor activity and balance of rats. Formula C at IN dose of 5 mg/kg expressed the strongest effect on the tested animals

Europinidin Inhibits Rotenone-Activated Parkinson’s Disease in Rodents by Decreasing Lipid Peroxidation and Inflammatory Cytokines Pathways

Background: Europinidin is a derivative of delphinidin obtained from the plants Plumbago Europea and Ceratostigma plumbaginoides. This herb has wide medicinal applications in treating various diseases but there are very few studies available on this bioactive compound. Considering this background, the present study is designed for the evaluation of Europinidin against Parkinson’s disease. Aim: The investigation aims to assess the effect of Europinidin in the rotenone-activated Parkinson’s paradigm. Methods: To evaluate neuroprotective activity, rotenone (1.5 mg/kg s.c) and europinidin (10 mg/kg and 20 mg/kg) was administered in rats for 21 days. The behavioural parameters were performed before sacrificing the rats. On the 22nd day, all the rats were assessed for biochemical markers (SOD, GSH, MDA, Catalase), neurotransmitter levels (Dopamine, 5-HIAA, DOPAC, and HVA levels), and neuroinflammatory markers (IL-6, IL-1β and TNF-α). Results: It was found that rotenone produced significant (p < 0.001) oxidative damage, a cholinergic deficit, dopaminergic loss, and a rise in neuroinflammatory markers in rats. Conclusion: The study concludes that europinidin possesses anti-oxidant and anti-inflammatory properties. The results suggest the therapeutic role of europinidin against rotenone-activated behavioural, biochemical, and neuroinflammatory alterations in rats