Comparing the effect of intravenous versus intracranial grafting of mesenchymal stem cells against parkinsonism in a rat model: Behavioral, biochemical, pathological and immunohistochemical studies.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases worldwide. Currently applied therapeutic protocols are limited to improve the motor functions of patients. Therefore, seeking alternative regimes with better therapeutic impact is crucial. This study aims to validate the therapeutic impact of mesenchymal stem cell injection using two delivery methods, intracranial administration and intravenous administration, on rotenone (ROT)-induced PD model in rats. Our work included behavioral, biochemical, histological, and molecular investigations. Open field test (OFT) and rotarod tests were applied. Important oxidative stress, antioxidant and proinflammatory markers were monitored. Substantia Nigra and Striatum tissues were examined histologically and the molecular expression of DOPA decarboxylase, Tyrosine hydroxylase, and α-synuclein in neurons in these tissues were investigated. Our results showed that MSC grafting improved motor and memory impairments and oxidative stress status that were observed after ROT administration. Additionally, BM-MSCs application restored SOD and CAT activities and the levels of DA, L-Dopa, IL6, IL1ß, and TNFα. Moreover, MSC grafting overwhelmed the pathological changes induced by ROT and normalized the expression of Tyrosine hydroxylase, DOPA decarboxylase, and α-synuclein towards the control values in the Nigral and Striatal tissues of male rats. Conclusively, both administration routes improved motor function, protection of the nigrostriatal system, and improved striatal dopamine release. The observed beneficial effect of applying MSCs suggests potential benefits in clinical applications. No significant differences in the outcomes of the treatment would favor a certain way of MSC application over the other. However, the intravenous delivery method seems to be safer and more feasible compared to the intrastriatal method.

Ginkgo biloba extract protects against tartrazine-induced testicular toxicity in rats: involvement of antioxidant, anti-inflammatory, and anti-apoptotic mechanisms.

The use of additives, especially colorants, in food and pharmaceutical industry is increasing dramatically. Currently, additives are classified as contaminants of emerging concern (CECs). Concerns have been raised about the potential hazards of food additives to reproductive organs and fertility. The present study investigates the reproductive toxicity of tartrazine (TRZ), a synthetic colorant, in male rats and aims to explore the curative effect of Ginkgo biloba extract (EGb) against TRZ-induced testicular toxicity. Twenty-four rats were divided into four groups: the control (0.5 ml distilled water), the EGb group (100 mg/kg EGb alone), the TRZ group (7.5 mg/kg TRZ alone), and the TRZ-EGb group (7.5 mg/kg TRZ plus 100 mg/kg EGb). The doses were administered orally in distilled water once daily for 28 days. Toxicity studies of TRZ investigated testicular redox state, serum gonadotropins, and testosterone levels, testicular 17 ß-hydroxysteroid dehydrogenase activity, sperm count and quality, levels of inflammatory cytokines, and caspase-3 expression as an apoptotic marker. Also, histopathological alterations of the testes were examined. TRZ significantly affected the testicular redox status as indicated by the increase in malondialdehyde and the decrease in reduced glutathione, superoxide dismutase, and catalase. It also disrupted serum gonadotropins (follicle stimulating hormone and luteinizing hormone) and testosterone levels and the activity of testicular 17ß-hydroxysteroid dehydrogenase. Additionally, TRZ adversely affected sperm count, motility, viability, and abnormality. Levels of tumor necrosis factor-α, interleukin-1ß, interleukin-6, and expression of caspase-3 were increased in the testes. Histopathological examination of the testes supported the alterations mentioned above. Administration of EGb significantly ameliorated TRZ-induced testicular toxicity in rats. In conclusion, EGb protected against TRZ-induced testicular toxicity through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms.

Characterization and biological applications of gonadal extract of Paracentrotus lividus collected along the Mediterranean coast of Alexandria, Egypt.

Marine invertebrates represent a valuable reservoir of pharmaceutical bioactive compounds with potential relevance to various medical applications. These compounds exhibit notable advantages when compared to their terrestrial counterparts, in terms of their potency, activity, and mechanism of action. Within this context, the present work aimed to extract, chemically characterize, and investigate the bioactivity of the gonadal extract of the sea urchin Paracentrotus lividus (P. lividus) collected along the Mediterranean coast of Alexandria, Egypt. Fractions of the gonadal extract were characterized by Spectrophotometry and gas chromatography-mass spectrometry (GC-MS), and their bioactivities were investigated in vitro. The analysis supported the extract richness of carotenoids and bioactive compounds. The extract showed promising anticancer activity against three different breast cancer cell lines with different levels of aggressiveness and causative factors, namely MDA-MB-231, MDA-MB-453, and HCC-1954. Gene expression analysis using RT-qPCR showed that P. lividus extract inhibited the expression of crucial factors involved in cell cycle regulation and apoptosis. In addition, the extract significantly inhibited the lipo-polysaccharides (LPS) induced inflammation in the RAW264.7 macrophage cell line and exerted anti-bacterial activity against the Gram-negative bacteria Klebsiella pneumoniae and Pseudomonas aeruginosa. Collectively, these results demonstrated the chemical richness and the wide-scale applicability of P. lividus gonadal extract as an anti-cancer, anti-bacterial, and anti-inflammatory natural extract.

Photomodulatory effects in the hypothalamus of sleep-deprived young and aged rats.

Insufficient sleep is associated with impaired hypothalamic activity and declined attentional performance. In this study, alterations in the hypothalamus of REM sleep-deprived (SD) young and aged rats, and the modulatory effect of near-infrared (NIR) laser were investigated. Forty-eight male Wistar rats (24 young at 2 months and 24 senile at 14 months) were divided into three groups: the control, the SD group subjected to 72 hr of sleep deprivation, and the transcranial-NIR laser-treated (TLT) group subjected to SD for 72 hr and irradiated with 830 nm laser. The hypothalamic levels of oxidative stress, inflammatory biomarkers, antioxidant enzymes, mitochondrial cytochrome C oxidase (CCO), apoptotic markers (BAX, BCL-2), and neuronal survival-associated genes (BDNF, GLP-1) were evaluated. Furthermore, the hypothalamic tissue alterations were analyzed via histological examination. The results revealed that TLT treatment has enhanced the antioxidant status, prevented oxidative insults, suppressed neuroinflammation, regulated CCO activity, reduced apoptotic markers, and tuned the survival genes (BDNF & GLP-1) in hypothalamic tissue of SD young and aged rats. Microscopically, TLT treatment has ameliorated the SD-induced alterations and restored the normal histological features of hypothalamus tissue. Moreover, the obtained data showed that SD and NIR laser therapy are age-dependent. Altogether, our findings emphasize the age-dependent adverse effects of SD on the hypothalamus and suggest the use of low-laser NIR radiation as a potential non-invasive and therapeutic approach against SD-induced adverse effects in young and aged animals.

L-methionine protects against nephrotoxicity induced by methotrexate through modulation of redox status and inflammation.

Objective: Methotrexate (MTX) is a drug used in the treatment of cancer and autoimmune disorders; however, its clinical use is limited because of serious side effects including renal toxicity. This study aimed to investigate the protective effect of Lmethionine (L-Met) on MTX toxicity in the kidneys of rats.Methods: Thirty male rats were divided equally into five groups: control (saline), Met400 (400 mg/kg L-Met), MTX (20 mg/kg MTX), MTX-Met300 (300 mg/kg L-Met and 20 mg/kg MTX), and MTX-Met400 (400 mg/kg L-Met and 20 mg/kg MTX). Rats were euthanized one day after the last dose administration (day 16) and serum and renal tissue samples were collected. Renal function and injury indices, oxidative stress/antioxidant indices and proinflammatory cytokines were evaluated.Results: The results showed that L-Met could effectively counteract the nephrotoxic effects of MTX, in a dose-related manner, by improving most of the tested parameters. Furthermore, the higher dose of L-Met was able to restore several parameters to normal levels. In addition, investigation of MTX-induced hematological changes revealed a corrective potential of L-Met.Conclusion: L-Met can be an effective adjuvant therapy to modulate renal toxicity associated with MTX because of its antioxidant and antiinflammatory effects.

Molecular mechanisms underlying the potential neuroprotective effects of Trifolium pratense and its phytoestrogen-isoflavones in neurodegenerative disorders.

Neurodegenerative disorders are heterogeneous, debilitating, and incurable groups of brain disorders that have common features including progressive degeneration of the structure and function of the nervous system. Phytoestogenic-isoflavones have been identified as active compounds that can modulate different molecular signaling pathways related to the nervous system. The main aim is to shed the light on the molecular mechanisms followed by phytoestrogen-isoflavones profound in the Trifolium pratense and discuss the latest pharmacological findings in the treatment of neurodegenerative disorders. Data were collected using different databases. The search terms used included "Phytoestrogens," "Isoflavones," "neurodegenerative disorders," "Neuronal plasticity," etc., and combinations of these keywords. As a result, this review article mainly demonstrates the potential neuroprotective properties of phystoestrogen-isoflavones present in the Trifolium pratense (Red clover), particularly in neurodegenerative disorders. Phytochemical studies have shown that Trifolium pratense mainly includes more than 30 isoflavone compounds. Among them, phytoestrogen-isoflavones, such as biochanin A, daidzein, formononetin, genistein (Gen), etc.,are characterized by potent neuroprotective properties against different neurodegenerative disorders. There are preclinical and clinical scientific evidence on their mechanisms of action involve molecular interaction with estrogenic receptors, anti-inflammatory, anti-oxidative, antiapoptotic, autophagic inducing, and so on. phytoestrogen-isoflavones are the major bioactive components in the Trifolium pratense that exhibit therapeutic efficacy in the case of neurodegenerative disorders. This review provides detailed molecular mechanisms targeted by phytoestrogen-isoflavones and experimental key findings for the clinical use of prescriptions containing Trifolium pratense-derived isoflavones for the treatment of neurodegenerative disorders.

Analysis of Melatonin-Modulating Effects Against Tartrazine-Induced Neurotoxicity in Male Rats: Biochemical, Pathological and Immunohistochemical Markers.

Tartrazine (E-102) is one of the most widely used artificial food azo-colors that can be metabolized to highly sensitizing aromatic amines such as sulphanilic acid. These metabolites are oxidized to N-hydroxy derivatives that cause neurotoxicity. Melatonin is a neurohormone. That possesses a free-radical scavenging effect. The present work was mainly designed to evaluate the possible ameliorative role of melatonin against tartrazine induced neurotoxicity in cerebral cortex and cerebellum of male rats. Adult male rats were administered orally with tartrazine (7.5 mg/kg) with or without melatonin (10 mg/kg) daily for four weeks. The data revealed that tartrazine induced redox disruptions as measured by significant (p < 0.05) increased malondialdehyde (MDA) level and inhibition of (GSH) concentration and catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) antioxidant enzyme activities. Besides, brain acetyl cholin (Ach) and gamma-aminobutyric acid (GABA) were elevated while, dopamine (DA) was depleted in trtrazine -treated rats. Moreover, tartrazine caused a significant (p < 0.05) increase in the brain interleukin-6 (IL-6), interleukin-1ß (IL-1 ß) and tumor necrosis factor-α (TNFα). At the tissue level, tartrazine caused severe histopathological changes in the cerebellum and cerebral cortex of rats. The immunohistochemical results elucidated strong positive expression for Caspase-3 and GFAP and weak immune reaction for BcL2 and synaptophysin in tatrazine- treated rats. The administration of melatonin to tartrazine -administered rats remarkably alleviated all the aforementioned tartrzine-induced effects. It could be concluded that, melatonin has a potent ameliorative effect against tartrazine induced neurotoxicity via the attenuation of oxidative/antioxidative responses.

Astragalus species: Phytochemistry, biological actions and molecular mechanisms underlying their potential neuroprotective effects on neurological diseases.

Neurodegenerative and neuropsychiatric illnesses are prevalent and life-threatening disorders characterized by a wide range of clinical syndromes and comorbidities, all of which have complex origins and share common molecular pathomechanisms. Although the pathophysiology of neurological illnesses is not completely understood, researchers have discovered that several ion channels and signalling pathways may have played a role in disease pathogenesis. Active substances from Astragalus sp. are being employed for nutrition, and their usefulness in the treatment of neurological illnesses is receiving more attention. Because their extracts and active components exert different pharmacological effects on a variety of ailments, they have a long history of usage as a cure for various diseases. This review summarizes the research work on Astragalus and their biologically active constituents as potential candidates for the protection against and treatment of neurodegenerative and neuropsychiatric disorders to show the potential efficacy of Astragalus sp. and its active ingredients in treating some neurological diseases. Simultaneously, the chemical structures of these active compounds, their sources, biological properties, and mechanisms are also listed. In ethnopharmacological applications, Astragalus membranaceus and spinosus have been studied as traditional medicines worldwide. The chemical constituents of Astragalus species mainly comprise terpenoids, flavonoids, and polysaccharides. The extracts and phytochemical compounds of Astragalus species exhibit various pharmacological activities, including antioxidant, anti-inflammatory, anticancer, antitumor, anticonvulsive, immunomodulatory, and other activities. Based on the current literature, we conclude that Astragalus is a promising dietary herb with multiple potential signal modulating applications that mainly include the modulation of neurotransmitters and receptors, anti-inflammatory activities, inhibition of amyloid aggregation, induction of myelin sheath repair and neurogenesis, as well as activation of the signalling pathways relevant to neurological diseases.

Asprosin in health and disease, a new glucose sensor with central and peripheral metabolic effects.

Adipose tissue malfunction leads to altered adipokine secretion which might consequently contribute to an array of metabolic diseases spectrum including obesity, diabetes mellitus, and cardiovascular disorders. Asprosin is a novel diabetogenic adipokine classified as a caudamin hormone protein. This adipokine is released from white adipose tissue during fasting and elicits glucogenic and orexigenic effects. Although white adipose tissue is the dominant source for this multitask adipokine, other tissues also may produce asprosin such as salivary glands, pancreatic B-cells, and cartilage. Significantly, plasma asprosin levels link to glucose metabolism, lipid profile, insulin resistance (IR), and ß-cell function. Indeed, asprosin exhibits a potent role in the metabolic process, induces hepatic glucose production, and influences appetite behavior. Clinical and preclinical research showed dysregulated levels of circulating asprosin in several metabolic diseases including obesity, type 2 diabetes mellitus (T2DM), polycystic ovarian syndrome (PCOS), non-alcoholic fatty liver (NAFLD), and several types of cancer. This review provides a comprehensive overview of the asprosin role in the etiology and pathophysiological manifestations of these conditions. Asprosin could be a promising candidate for both novel pharmacological treatment strategies and diagnostic tools, although developing a better understanding of its function and signaling pathways is still needed.

Therapeutic effects of astragaloside IV and Astragalus spinosus saponins against bisphenol A-induced neurotoxicity and DNA damage in rats.

BACKGROUND: Bisphenol A (BPA) is an endocrine disruptor to which humans are often subjected during daily life. This study aimed to investigate the ameliorative effect of astragaloside IV (ASIV) or saponins extracted from Astragalus spinosus (A. spinosus) against DNA damage and neurotoxic effects induced by BPA in prefrontal cortex (PFC), hippocampal and striatal brain regions of developing male rats. MATERIALS AND METHODS: Juvenile PND20 (pre-weaning; age of 20 days) male Sprague Dawley rats were randomly and equally divided into four groups: control, BPA, BPA+ASIV and BPA+A. spinosus saponins groups. Bisphenol A (125 mg/kg/day) was administrated orally to male rats from day 20 (BPA group) and along with ASIV (80 mg/kg/day) (BPA+ASIV group) or A. spinosus saponin (100 mg/kg/day) (BPA+ A. spinosus saponins group) from day 50 to adult age day 117. RESULTS: Increased level of nitric oxide (NO) and decreased level of glutamate (Glu), glutamine (Gln), glutaminase (GA) and glutamine synthetase (GS) were observed in the brain regions of BPA treated rats compared with the control. On the other hand, co-administration of ASIV or A. spinosus saponin with BPA considerably improved levels of these neurochemicals. The current study also revealed restoration of the level of brain derived neurotrophic factor (BDNF) and N-methyl-D-aspartate receptors (NR2A and NR2B) gene expression in BPA+ ASIV and BPA+A. spinosus saponins groups. The co-treatment of BPA group with ASIV or A. spinosus saponin significantly reduced the values of comet parameters as well as the intensity of estrogen receptors (ERs) immunoreactive cells and improved the histological alterations induced by BPA in different brain regions. CONCLUSION: It could be concluded that ASIV or A. spinosus saponins has a promising role in modulating the neurotoxicity and DNA damage elicited by BPA.

Oral Supplements of Ginkgo biloba Extract Alleviate Neuroinflammation, Oxidative Impairments and Neurotoxicity in Rotenone-Induced Parkinsonian Rats.

BACKGROUND: Ginkgo biloba extract (GbE) is known to contain several bioactive compounds and exhibits free radical scavenging activity. Parkinson's Disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons and is associated with oxidative stress, neuroinflammation and apoptosis. OBJECTIVE: The current study aimed to investigate the neuroprotective effect of GbE in a rat model of PD induced by rotenone (ROT; a neurotoxin). METHODS: Twenty-four male albino rats were randomly divided into four groups of six rats each: normal control, GbE treated, toxin control (ROT treated) and GbE+ROT group. RESULTS: Oral administration of ROT (2.5 mg/kg b.w.) for 50 days caused an increased generation of lipid peroxidation products and significant depletion of reduced glutathione, total thiol content and activities of enzymatic antioxidants, i.e., superoxide dismutase and glutathione peroxidase in the brains of treated rats. Furthermore, ROT caused an elevation in acetylcholinesterase, interleukin-1ß, interleukin- 6 and tumor necrosis factor-α and a significant reduction in dopamine in the stratum and substantia nigra. Immunohistochemical results illustrated that ROT treatment reduced the expression of tyrosine hydroxylase (TH). GbE treatment (150 mg/kg b.w./day) significantly reduced the elevated oxidative stress markers and proinflammatory cytokines and restored the reduced antioxidant enzyme activities, DA level and TH expression. These results were confirmed by histological observations that clearly indicated a neuroprotective effect of GbE against ROT-induced PD. CONCLUSION: GbE mitigated ROT-induced PD via the inhibition of free-radical production, scavenging of ROS, and antioxidant enhancement.

Soybean isoflavone ameliorates cognitive impairment, neuroinflammation, and amyloid ß accumulation in a rat model of Alzheimer's disease.

Oxidative stress and neuroinflammatory changes appear to be the early events involved in AD's development and progression. The present study was designed to assess the effect of soybean isoflavone extract (SIFE) against colchicine-induced cognitive dysfunction and oxidative stress in male rats.Fifty adult male Wistar albino rats were divided into five groups: control, ACSF-treated group, soybean isoflavones (SIF)-treated group, colchicine (COL)-treated group, and SIF + COL-treated group. We found that an intracerebroventricular (icv) injection of a single dose of colchicine (7.5 µg/rat bilaterally) resulted in learning deficits in rats subjected to the Morris water maze task associated with marked oxidative damage and decreased acetyl cholinesterase (AChE) activity. In addition, COL caused significant increase in amyloid beta peptide 1-42 (ß, amyloid 1-42) interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNFα), cyclooxygenase-2 (COX-2) and TNF-α genes expression in the brain, and glial fibrillary acidic protein (GFAP) in cortical astrocytes in the brain cortex.Treatment with SIFE (80 mg/kg b.wt) daily for 14 days followed by a single dose of COL significantly reduced the elevated oxidative stress parameters and restored the reduced antioxidant activities. Besides, the administration of SIFE reversed the overproduction of ß, amyloid 1-42, pro-inflammatory cytokines, and GFAP in the brain. The obtained results were confirmed by histological observations that clearly indicate a neuroprotective effect of SIF against AD.

Protective effect of Nigella sativa seeds against spermatocyte chromosomal aberrations and genotoxicity induced by carbon tetrachloride in mice.

Nigella sativa is a well-known dietary antioxidant and a valuable inhibitor of clastogenesis and carcinogenesis. The purpose of the present work was to investigate the effects of N. sativa seeds against chromosomal aberrations in primary spermatocytes and early embryonic lethality induced by CCl4 hepatotoxin in Swiss albino mice. One hundred male Swiss albino mice were randomly divided into five groups. Groups I, II, and III received only normal saline, olive oil, and aqueous suspension of N. sativa seeds (50 mg/kg b.w.), while groups IV and V were orally given CCl4 dissolved in olive oil at a dose level of 1.9 (» LD50) alone and with aqueous suspension of N. sativa seeds (50 mg/kg b.w.) alternately. Aqueous extract of N. sativa significantly reduced the elevated frequency of chromosomal aberrations induced by CCl4 in mouse primary spermatocytes. For the male-dominant lethal test, four males from each group (control and experimental) were used and each male was mated for 13 days to two untreated virgin females. On days 14-16 after breeding, all the females were evaluated for incidence of pregnancy, live implants, and fetal deaths. Treatment with 1/4 LD50 of CCl4 induced positive dominant lethal mutation, reflecting a high rate of deformations in male germ cells. Interestingly, no dominant lethal mutations were recorded in females mated to male mice treated with CCl4 plus N. sativa. Under the experimental conditions of this study, our results highlight the beneficial role of N. sativa against CCl4-induced mutagenicity.

Biochemical and histopathological changes in liver of the Nile tilapia from Egyptian polluted lakes.

The aim of the present study was to analyze the impact of environmental contamination on oxidative stress and histopathologic biomarkers in liver of the Nile tilapia, Oreochromis niloticus, collected from four sites that differ in their extent of pollution load, including heavy metals: the southeast basin (SEB), main basin (MB), and northwest basin (NWB) of Lake Mariut as well as Boughaz El-Maadiya, a channel in Lake Edku. The SEB was the less-impacted site, and thus considered as a reference. High concentrations of heavy metals (cadmium, copper, iron, lead, zinc, and manganese) were detected in fish liver at sites with anthropogenic pressure. All biomarkers, lipid peroxidation (in the MB, NWB, and Lake Edku), superoxide dismutase (in the MB and NWB), and glutathione peroxidase, and reduced glutathione (in the NWB) were found to be significantly higher compared to the reference values. Catalase, glutathione reductase, and glucose-6-phosphate dehydrogenase showed a varied response and displayed significantly lower activities in the polluted sites. Certain hepatic lesions, detected microscopically, were stimulated in fish from the MB and NWB, reflecting the high contamination of these areas. These included foci of necrosis, melanomacrophage infiltration, congestion, nuclear pyknosis, and extensive vacuolation corresponding to relatively higher lipid content. Overall, our results suggest that the selected biomarkers are useful for the assessment of pollution impacts in natural aquatic environments influenced by multiple pollution sources. The existence of chronic background pollution of the test sites implies that the observed biomarker responses cannot be solely attributed to heavy metals.