Curcumin nanogel and its efficacy against oxidative stress and inflammation in rat models of ischemic stroke.

Aim: The study was designed to develop and analyze curcumin nanoparticles. Methods: Curcumin nanoparticles were formulated and evaluated. Their efficacy in protecting against brain damage was investigated in a rat model of ischemic stroke, considering motor function, muscle strength and antioxidant enzyme activity. Results: Curcumin nanoparticles displayed a zeta potential of -55 ± 13.5 mV and an average particle size of 51.40 ± 21.70 nm. In ischemic stroke rat models, curcumin nanoparticle treatment significantly improved motor functions, and muscle strength and increased the activities of antioxidant enzymes like glutathione peroxidase, glutathione, glutathione S-transferase, superoxide dismutase and catalase, reducing oxidative stress and inflammation. Conclusion: Curcumin nanoparticles showed significant neuroprotective effects in ischemic stroke models.

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Hepatoprotective and Antioxidant Effects of Nanopiperine against Cypermethrin via Mitigation of Oxidative Stress, Inflammations and Gene Expression Using qRT-PCR.

Cypermethrin (Cyp) is a pyrethroid that has been associated with the toxicity of various organs. The aim of our study was to evaluate the hepatoprotective and antioxidant activities of nano-piperine (NP) against Cyp toxicity. Cyp (50 mg/kg) was administered orally in all animals of groups III-VI for 15 days. Groups IV-VI each received three doses of NP (125, 250, and 500 µg/kg/day) for 10 days after receiving the Cyp dosage, which was given after 1 h. A rise in serum biomarkers (ALT, AST, ALP, total protein, and albumin), which are indicators of toxicity alongside anomalous oxidative stress indices (lipid peroxidation (LPO), glutathione (GSH), superoxide dismutase (SOD) and catalase), was detected. After Cyp treatment, we observed upregulated cytokines, caspase expression, and histological analysis that the showed distortion of cell shape. However, the administration of NP dramatically reversed all of the Cyp-induced alterations, inducing reductions in serum marker levels, stress level, the production of cytokines, and caspase expression. Additionally, all of the histopathological alterations were minimized to values that were comparable to normal levels. The present findings suggested that NP exhibits potent antioxidant and anti-inflammatory activities that can protect rats' livers against Cyp-induced liver damage through hepatoprotective activities.

Cinnamon Oil Alleviates Acetaminophen-Induced Uterine Toxicity in Rats by Abrogation of Oxidative Stress, Apoptosis, and Inflammation.

Paracetamol, or acetaminophen (APAP), is one of the first-line medications that is used for fever and pain. However, APAP can induce uterine toxicity when overused. The mode of action of APAP toxicity is due to the production of free radicals. The main goal of our study is to determine uterine toxicity from APAP overdose and the antioxidative activity of cinnamon oil (CO) in female rats. The effect of different doses of CO (50-200 mg/kg b.w.) was assessed in the uterus toxicity induced by APAP. Additionally, the imbalance in oxidative parameters, interleukins, and caspases was evaluated for the protective effects of CO. A single dose of APAP (2 g/kg b.w.) resulted in uterus toxicity, indicated by a significant increase in the level of lipid peroxidation (LPO), inflammatory interleukins cytokines (IL-1 and 6), expression of caspases 3 and 9, and a marked change in uterus tissue architecture evaluated by histopathology. Co-treatment of CO resulted in a significant amelioration of all the parameters such as LPO, interleukins IL-1ß, IL-6, caspases 3 and 9 expression, and distortion of tissue architecture in a dose-dependent manner. Therefore, we can conclude that APAP-induced uterine injury due to oxidative stress can be restored by co-treatment with cinnamon oil (CO).

Neuroprotective Effects of Nano-Curcumin against Cypermethrin Associated Oxidative Stress and Up-Regulation of Apoptotic and Inflammatory Gene Expression in Rat Brains.

Cypermethrin (CPM) is the most toxic synthetic pyrethroid that has established neurotoxicity through oxidative stress and neurochemical agitation in experimental rats. The toxic effects are supposed to be mediated by modifying the sodium channels, reducing Na-K ATPase, acetylcholine esterase (AchE), and monoamine oxidase (MAO). The use of curcumin nanoparticles (NC) that have potent antioxidant, anti-inflammatory and antiapoptotic properties with improved bioavailability attenuates neurotoxicity in rat brains. To test this hypothesis, animals were divided into five groups, each having six animals. Group-I control received vehicle only, while Group-II was treated with 50 mg/kg CPM. Group-III and Group-IV received both CPM and NC 2.5 mg/kg and 5 mg/kg, respectively. Group-V received 5 mg of NC alone. The CPM and NC were given by oral route. Afterwards, brain antioxidant status was measured by assessing lipid peroxidation (LPO), 4-HNE, glutathione reduced (GSH), antioxidant enzyme catalase, and superoxide dismutase (SOD) along with neurotoxicity markers Na-K ATPase, AchE, and MAO. Inflammation and apoptosis indices were estimated by ELISA, qRT-PCR, and immunohistochemistry, while morphologic changes were examined by histopathology. Observations from the study confirmed CPM-induced neurotoxicity by altering Na-K ATPase, AchE, and MAO, and by decreasing the activity of antioxidant enzymes and GSH. Oxidative stress marker LPO and the level of inflammatory interleukins IL-6, IL-1ß, and TNF-α were notably high, and elevated expressions of Bax, NF-kB, and caspase-3 and -9 were reported in CPM group. However, NC treatment against CPM offers protection by improving antioxidant status and lowering LPO, inflammation, and apoptosis. The neurotoxicity marker's enzyme successfully attenuated after NC treatment. Therefore, this study supports the administration of NC effectively ameliorated CPM-induced neurotoxicity in experimental rats.

Hepatoprotective Effect of Curcumin Nano-Lipid Carrier against Cypermethrin Toxicity by Countering the Oxidative, Inflammatory, and Apoptotic Changes in Wistar Rats.

This study investigated the potential hepatoprotective activity of curcumin-incorporated nano-lipid carrier (Cur-NLC) against cypermethrin (Cyp) toxicity in adult Wistar male rats. All animals in groups III, IV, V, and VI were subjected to Cyp (50 mg/kg) toxicity for 15 days. Three different doses of Cur-NLC (1, 2.5, and 5 mg/kg/day) were administered orally for 10 days. The toxic effects were evaluated considering the increases in serum hepatic biomarkers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein and albumin, and lipid peroxidation (LPO), as well as a decrease in antioxidative activity (reduced glutathione (GSH), superoxide dismutase (SOD), and catalase) and the upregulation of inflammatory cytokines (IL-1ß, IL-6, and TNF-α). Immunohistochemistry studies of proteins (NF-κB, Apaf-1, 4-HNE, and Bax) showed enhanced expression, and histopathological examination revealed architectural changes in liver cells, indicating liver toxicity in animals. Toxicity was determined by quantitative and qualitative determinations of DNA fragmentation, which show massive apoptosis with Cyp treatment. The administration of Cur-NLC significantly ameliorates all changes caused by Cyp, such as a decrease in the levels of serum liver markers, an increase in antioxidative parameters, a decrease in expression of inflammatory cytokines (IL-1ß, IL-6, TNF-α, and NF-κB), and apoptosis (caspases-3, 9, Apaf-1, 4-HNE, and Bax), according to calorimetric and immunohistochemistry studies. The smear-like pattern of DNA is ameliorated similarly to the control at a high dose of Cur-NLC. Furthermore, all histopathological changes were reduced to a level close to the control. In conclusion, Cur-NLC could be a potent nutraceutical that exhibits a hepatoprotective effect against Cyp-induced hepatotoxicity in rats.

Role of cinnamon oil against acetaminophen overdose induced neurological aberrations through brain stress and cytokine upregulation in rat brain.

Acetaminophen (APAP) is a well-known antipyretic and analgesic medicine. It is safe at therapeutic suggested level while overdose initiates oxidative stress and inflammation mediated neurochemical alteration in the brain. The aim of this study was to investigate the role of cinnamon oil (CO), which possesses potent antioxidant and anti-inflammatory activities against an overdose of APAP that induced oxidative stress and inflammation in male albino rats. APAP treated rats showed significant elevation of thiobarbituric acid-reactive substances (TBARS) and decreased level of GSH in brain tissue, which is recognized as a biomarker of oxidative stress. Antioxidant enzymes GPx, GR, SOD, and CAT activity was depleted in APAP group along with neurotoxicity biomarkers such as Na+-K+-ATPase and increased activity of acetylcholinesterase (AchE), monoamine oxidase (MAO), and upregulated pro-inflammatory cytokine was observed. CO significantly protected the diminished activity of the antioxidant enzyme and suppressed the upregulated cytokines in brain tissue. CO also attenuated the activity of neurotoxicity biomarker enzyme, decreased TBARS content, and an increased level of GSH. The present findings perceptibly confirmed that the nutraceutical property of CO ameliorates APAP induced oxidative stress and inflammation. Therefore, our findings suggested that CO could be an alternative nutraceutical substitute in APAP overdose poisoning.

Renoprotective effects of cinnamon oil against APAP-Induced nephrotoxicity by ameliorating oxidative stress, apoptosis and inflammation in rats.

Acetaminophen (APAP) is used as a primary medication in relieving moderate pain and fever. However, APAP is associated with toxic effects in renal tissue that appear because of its free radicals property. The principle goal of the present work is to assess the kidney damage by APAP and its restore antioxidative property of cinnamon oil (CO). Animals were distributed into six animals each in six groups. Rats were administered with three varying doses of CO from 50 to 200 mg/kg b.w. respectively and only a single dose of APAP. APAP induced an alteration in serum biochemical markers, imbalance in oxidative parameters, morphological changes in kidney tissue along with increased interleukins cytokines (IL-1ß & 6) and caspase (3, 9) levels. CO administration significantly ameliorates all the parameters and histopathological changes were restored. Moreover, it also restored the activities of antioxidative enzymes. Our work proved that an variance of oxidative markers in the kidney by APAP is ameliorated by CO in rats. Thus, CO could be used in reducing APAP-induced nephrotoxicity.

Nanoparticles of resveratrol attenuates oxidative stress and inflammation after ischemic stroke in rats.

Resveratrol is a nutraceutical compound that has exciting pharmacological potential in different diseases, including stroke. Due to its low bioavailability, the efficacy of resveratrol is minimal. Hence, the present study is aimed to synthesize and characterize nanoparticles of resveratrol (NR) followed by evaluating the neuroprotective role and elucidate the mechanism of NR in a rat model of middle cerebral artery occlusion (MCAO). Male Wistar rats (280-300 g) were pretreated with various doses (125 µg, 250 µg, and NR 500 µg; once daily, i.p.) of NR or vehicle (nanostructured lipid carriers) for 10 days. MCAO was performed for 2 h followed by reperfusion of 22 h. After 24 h of MCAO, animals were tested for the neurological outcome and were sacrificed for the analysis of infarct volume, oxidative, inflammatory, and apoptotic markers. NR-treated rats showed a substantial reduction in infarction compared to saline controls in parallel with improved motor and cognitive function. Further, NR pretreatment ameliorated oxidative stress markers and attenuated activities of antioxidant enzymes and Na+ K+ ATPase. The enhanced activities of caspases -3 and -9 and cytokines: interleukin-1ß, and -6, and tumor necrosis factor-ɑ) in the MCAO group were significantly protected with the treatment of 500 µg of NR. Taken together, these data indicate that inhibition by NR has therapeutic potential in the ischemic stroke model. Further investigations into the therapeutic efficacy and post-treatment protocols are needed to confirm whether NR treatment could be a promising candidate for a stroke.

Pharmacological melioration by Selenium on the toxicity of tellurium in neuroendocrine centre (Pituitary Gland) in male wistar rats: A mechanistic approach.

PURPOSE: The present research was designed to evaluate the toxicity of tellurium and its prevention by selenium on the pituitary gland in male Wistar rats. METHODS: 30 rats were used weighing 200-250 gm, and randomly divided them into five groups. Each group contained an equal number of animals. Group-1 was nominated as control group. Group-2 received an intraperitoneal dose of selenium 0.3  mg per kg body wt. Group-3 was administered with tellurium 4.15 mg per kg body wt. Group-4 was given low-dose (L) of both selenium 0.15 and tellurium 2.075, Group-5 was given High-dose (H) of both selenium 0.3 and tellurium 4.15 mg/kg body wt. orally once in a day. After 15 days of dosing, the behavioral activities- motor co-ordination rotarod and grip strength test were measured. On 16th-day animals were sacrificed and activity of LPO, GSH, caspase-3, caspase-9, GPx, GR, SOD, catalase, and AChE were performed on the pituitary gland as per standard method reported. RESULTS: Se when given together with Te, significantly protects the motor coordination up to 32.5%, and also protects the grip strength up to 75% in group 4 and 5 respectively as compared to group- 3. Se + Te treatment protects the activity of TBARS up to 48.68% and GSH is 58%. As compared to control, it protects caspase-3 up to 118% and caspase-9 up to 83%. The level of AChE was also observed to be modulated by the administration of Se in Group- 4 and 5. Se + Te protected AChE up to 28.6%. Similar findings were observed for the biochemical activities of GPx (140% protection), SOD (458%), GR (159%), and catalase (95%) activities that were protected significantly Se + Te in Group- 4 and 5. CONCLUSION: Selenium dose-dependently protects behavioral activities. It also protects apoptosis, oxidative stress, and AChE activities in the pituitary gland.

Brain-targeted glycyrrhizic-acid-loaded surface decorated nanoparticles for treatment of cerebral ischaemia and its toxicity assessment.

OBJECTIVE: Enhancement of CS-GA-PCL-NPs (Glycyrrhizic Acid-encapsulated-chitosan-coated-PCL-Nanoparticles) bioavailability in brain. METHODS: Double emulsification solvent evaporation method in order to develop CS-PCL-NPs (Chitosan-coated-PCL-Nanoparticles) followed by characterization of particle size and distribution, zeta potential, encapsulation efficiency and drug release (in vitro). To determine drug-uptake and its pharmacokinetic profile in brain as well as plasma, UHPLC (triple quadrupole Q-trap) MS/MS method was developed and optimized for CS-GA-PCL-NPs as well as to follow-up examined effective role of optimized NPs in reduction of all brain injury parameters after MCAO through the grip strength, locomotor activity, inflammatory cytokines levels, measurement of infarction volume and histopathological changes in neurons with safety/toxicity after i.n. in animals. RESULTS: The developed NPs showed an average particle size, entrapment efficiency with PDI (polydispersity index) of 201.3 ± 4.6 nm, 77.94 ± 5.01% and 0.253 ± 0.019, respectively. Higher mucoadhesive property for CS-GA-PCL-NPs as compared to conventional and homogenized nanoformulations was observed whereas an elution time of 0.37 min and m/z of 821.49/113.41 for GA along with an elution time of 1.94 min and m/z of 363.45/121.40 was observed for hydrocortisone i.e. Internal standard (IS). Similarly, %CV i.e. inter and intra assay i.e. 0.49-4.41%, linear dynamic range (10-2000 ng/mL) and % accuracy of 90.00-99.09% was also observed. AUC0-24 with augmented Cmax was noted (**p < .01), in Wistar rat brain as compared to i.v. treated group during pharmacokinetics studies. In MCA-occluded rats, enhanced neurobehavioral activity i.e. locomotor and grip strength along with a decrease in cytokines level (TNF-α and IL-1ß) was observed, following i.n. administration. CONCLUSIONS: CS-coated-GA-loaded-PCL-NPs when administered i.n. enhanced the bioavailability of the drug in rat brain as compared to i.v. administration. The observation from toxicity study concludes; the developed NPS are safe and free of any health associated risk.

Current Progress on Peroxisome Proliferator-activated Receptor Gamma Agonist as an Emerging Therapeutic Approach for the Treatment of Alzheimer's Disease: An Update.

Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder, characterized by the deposition of amyloid-ß within the brain parenchyma resulting in a significant decline in cognitive functions. The pathophysiological conditions of the disease are recognized by the perturbation of synaptic function, energy and lipid metabolism. In Addition deposition of amyloid plaques also triggers inflammation upon the induction of microglia. Peroxisome proliferatoractivated receptors (PPARs) are ligand-activated transcription factors known to play important role in the regulation of glucose absorption, homeostasis of lipid metabolism and are further known to involved in repressing the expression of genes related to inflammation. Therefore, agonists of this receptor represent an attractive therapeutic target for AD. Recently, both clinical and preclinical studies showed that use of Peroxisome proliferator-activated receptor gamma (PPARγ) agonist improves both learning and memory along with other AD related pathology. Thus, PPARγ signifies a significant new therapeutic target in treating AD. In this review, we have shed some light on the recent progress of how, PPARγ agonist selectively modulated different cellular targets in AD and its amazing potential in the treatment of AD.

Oxidative Stress and Anti-oxidants in Pre and Post-operative Cases of Breast Carcinoma.

OBJECTIVES: To investigate the existence of oxidative stress in the sera of patients with breast cancer and its effects on the consequent breast cancer. MATERIALS AND METHODS: This study included 50 control volunteers, 50 patients with breast cancer, and 50 patients with post-operative breast cancer. Patients with pre-operative cancer were clinically and histopathologically diagnosed for breast carcinoma with stage 0, not having therapeutic history. The control 50 healthy female volunteers had the same socio-economic status, and no history of any cancer. After obtaining consent, venous blood was collected from the volunteers by vein puncture using a 10 mL sterile disposable syringe and needle. About 8 mL of blood was collected, 4 mL of which was poured into a heparinized bulb and 4 mL was allowed to clot. The levels of MDA, NO, GSH, and activities of RBC-SOD (in RBC lysate), NOS, copper and zinc GPx, and CAT, and vitamins A, C, and E metabolites were measured in the sera of each group. RESULTS: The activities of RBC-SOD and the levels of MDA, NO, as well as the NOS were significantly higher in the sera of all patients with breast cancer as compared with the controls. However, the levels of GSH and vitamins A, C, and E, as well as the activities of copper and zinc GPx and CAT were decreased in patients with breast cancer when compared with the controls. CONCLUSION: The study provides further evidence for the presence of oxidative stress in the serum of patients with breast carcinoma. Patients with higher levels of MDA showed deficiencies of antioxidants and trace elements in the serum. A poor dietary antioxidant status and high oxidant levels are associated with the risk of breast cancer, thus suggesting that patients with breast cancer should take nutritive supplements to balance the antioxidant and oxidant levels for better outcomes.

Intranasal delivery of quercetin-loaded mucoadhesive nanoemulsion for treatment of cerebral ischaemia.

BACKGROUND: Quercetin (QUR), as an antioxidant flavonoid, exhibits potential role in the amelioration of cerebral ischaemia; however, poor solubility as well as oral absorption results low serum and tissue levels for this drug. PURPOSE OF THE STUDY: To enhance bioavailability, this study aims to prepare QUR nanoemulsions and administer via non-invasive nasal route in order to evaluate the drug targeting in brain. METHODS: Quercetin mucoadhesive nanoemulsion (QMNE) was prepared (ionic gelation method) and optimized using various parameters, that is, particle size, entrapment efficiency, zeta potential and ex vivo permeation study. RESULTS: The results observed for optimized QMNE were as follows: mean globule size (91.63 ± 4.36 nm), zeta potential (-17.26 ± 1.04 mV), drug content (99.84 ± 0.34%) and viscosity (121 ± 13 cp). To evaluate the extent of bioavailability for QMNE via post-intranasal (i.n.) administration, Ultra performance liquid chromatography-mass spectroscopy (UPLC-ESI-Q-TOF-MS/MS)-based bioanalytical method was developed and validated for pharmacokinetics, biodistribution, brain-targeting efficiency (9333.33 ± 39.39%) and brain drug-targeting potential (2181.83 ± 5.69%) which revealed enhanced QUR brain bioavailability as compared to intravenous administration (i.v.). Furthermore, improved neurobehavioral activity (locomotor and grip strength), histopathology and reduced infarction volume effects were observed in middle cerebral artery occlusion (MCAO)-induced cerebral ischemic rats model after i.n. administration of QMNE. CONCLUSION: This study supports a significant role for QMNE in terms of high brain-targeting potential and formulation efficiency due to ease of access and effective targeting in brain.

Role of melatonin in mitigating nonylphenol-induced toxicity in frontal cortex and hippocampus of rat brain.

Nonylphenol (NP), an environmental endocrine disruptor mimics estrogen and is a potential toxicant both under in vitro and in vivo conditions. In this study, the effect of melatonin on NP- induced neurotoxicity and cognitive alteration was investigated in adult male Wistar rats. Melatonin supplementation has been known to protect cells from neurotoxic injury. The animals were divided into three groups namely, control (vehicle) which received olive oil orally and treated rats received NP (25 mg/kg, per os) thrice a week for 45 days while the third group i.e., NP + melatonin, animals were co-administered melatonin (10 mg/kg, i.p.) along with NP. On the 46th day, rats were assessed for anxiety, motor co-ordination, grip strength and cognitive performance using Morris water maze test and then sacrificed for biochemical and histopathological assays in brain tissues. Melatonin improved the behavioral performance in NP exposed group. The results showed that NP significantly decreased the activity of acetylcholine esterase (AchE), monoamine oxidase (MAO) and Na+/K+-ATPase, in rat brain tissue along with other enzymes of antioxidant milieu. The outcome of the study shows that NP, like other persistent endocrine disrupting pollutants, creates a potential risk of cognitive, neurochemical and histopathological perturbations as a result of environmental exposure. Taken together, our study demonstrates that melatonin is protective against NP-induced neurotoxicity.

Modulation of Behavioral Deficits and Neurodegeneration by Tannic Acid in Experimental Stroke Challenged Wistar Rats.

Oxidative stress and inflammatory responses play a critical contributing factor in cerebral ischemia and reperfusion, which lead to lipid peroxidation and neuronal dysfunction that may represent a target for therapeutic intervention. The present study was aimed to elucidate the neuroprotective effect of tannic acid (TA), a natural polyphenol with potential antioxidant and antiinflammatory properties on middle cerebral artery occlusion (MCAO) model in rats. To test this hypothesis, male Wistar rats were pretreated with TA (50 mg/kg b.wt.) and then subjected to 2-h MCAO followed by 22 h of reperfusion. After 2-h MCAO/22-h reperfusion, neurological deficit, infarct sizes, activities of antioxidant enzymes, cytokine level, histology, and immunohistochemistry were used to analyze the expression of glial fibrillary acidic protein (GFAP) in ischemic brain. The pretreatment of TA showed a marked reduction in infarct size, improved neurological function, suppressed neuronal loss, and downregulated the GFAP expression in MCAO rats. A significantly depleted activity of antioxidant enzymes and content of glutathione in MCAO group were protected significantly in MCAO group pretreated with TA. Conversely, the elevated level of thiobarbituric acid reactive species and cytokines in MCAO group was attenuated significantly in TA-pretreated group when compared with MCAO group. The results indicated that TA protected the brain from damage caused by MCAO, and this effect may thorough diminish the oxidative stress and inflammatory responses.

The effect of safranal loaded mucoadhesive nanoemulsion on oxidative stress markers in cerebral ischemia.

Antioxidants, with reported neuroprotective activity, encounter free radical induced neural damage leading to reduced risk of cerebral ischemia-reperfusion (IR) injury. Safranal, an antioxidant drug with potential role in the amelioration of cerebral ischemia, endures low solubility and poor absorption property thus resulting a low serum and tissue bioavailability. This research aims to prepare nanoemulsion with the concept; to increase the bioavailability in order to reduce oxidative stress-induced brain injury as well as to evaluate the brain-drug targeting following non-invasive nasal route administration in middle cerebral artery occlusion (MCAO) animal model. Titration method was used to prepare safranal mucoadhesive nanoemulsion (SMNE) followed by further characterization, i.e. entrapment efficiency, particles size, and zeta potential study. Optimized SMNE showed; mean globule size of 89.64 nm (±9.12), zeta potential -11.39 mV (±1.32), drug content 98.47% (±1.01), and viscosity of 124 cp (±14). Rats were subjected to 2 h of MCAO, successively followed by a 22 h reperfusion, after which the grip strength, locomotor activity, and biochemical studies, i.e. glutathione reductase (GR), glutathione peroxidase, lipid peroxidation, catalase, and superoxide dismutase were studied as assessment tool for effective treatment in brain. SMNE administered i.n. (intranasal) in MCAO induced cerebral ischemia rats exhibited significant improvement in neurobehavioral (locomotor and grip strength) and antioxidant activity as well as histopathological studies. The toxicity studies performed at the end revealed safe nature of developed SMNE.

Heavy Metal-Induced Systemic Dysfunction Attenuated by Tannic Acid.

Lead toxicity is a major public health concern. This study was designed to investigate the effects of oral administration of tannic acid (TA) on lead acetate (LA)-induced oxidative stress in rat liver and kidney. Rats were treated with 50 mg/kg body weight of TA against LA-induced oxidative stress 3 times/week for 2 weeks. At a rate of 50 mg/kg of body weight, LA was given intraperitoneally 3 times/week for 2 weeks. Results show significantly elevated levels of oxidative stress markers observed in LA-treated rats, whereas significant depletion in the activity of nonenzymatic and enzymatic antioxidants as well as histological changes were observed in LA-treated rat liver and kidney. TA treatment significantly attenuated the altered levels of oxidative stress biomarkers for nonenzymatic and enzymatic antioxidants. We demonstrated that TA exhibits potent antioxidant and protected against oxidative damage in rat liver and kidney induced by LA treatment. These findings were further supported by histopathological findings in liver and kidney showing that TA protected tissue from the deleterious effects of LA treatment. These outcomes suggest that the consumption of TA may confer a protective effect against lead intoxication through its antioxidative effect.

Rutin-encapsulated chitosan nanoparticles targeted to the brain in the treatment of Cerebral Ischemia.

OBJECTIVE: Rutin, a potent antioxidant, has been reported to reduce the risk of ischemic disease. Our study aims to prepare rutin-encapsulated-chitosan nanoparticles (RUT-CS-NPs) via ionic gelation method and determine its results, based on different parameters i.e. surface morphology characterization, in-vitro or ex-vivo release, dynamic light scattering and differential scanning calorimetry (DSC), for treating cerebral ischemia. METHODS: UPLC-ESI-Q-TOF-MS/MS was used to evaluate the optimized RT-CS-NPs1 for brain-drug uptake as well as to follow-up the pharmacokinetics, bio-distrbution, brain-targeting efficiency and potential after intranasal administration (i.n.). KEY FINDINGS: A particle size of <100nm for the formulation, significantly affected by drug:CS ratio, and entrapment efficiency and loading capacity of 84.98%±4.18% and 39.48%±3.16%, respectively were observed for RUT. Pharmacokinetics, bio-distribution, brain-targeting efficiency (1443.48±39.39%) and brain drug-targeting potential (93.00±5.69%) showed enhanced bioavailability for RUT in brain as compared to intravenous administration. In addition; improved neurobehavioral activity, histopathology and reduced infarction volume effects were observed in middle cerebral artery occlusion (MCAO) induced cerebral ischemic rats model after i.n. administration of RUT-CS-NPs. CONCLUSION: A significant role of mucoadhesive-RT-CS-NPs1 as observed after high targeting potential and efficiency of the formulation prove; RUT-CS-NPs are more effectively accessed and target easily the brain.

Tannic acid alleviates lead acetate-induced neurochemical perturbations in rat brain.

Oxidative stress has been projected as a promising mechanism involved in lead exposure. The lead predisposition catalyzes oxidative reactions and generates reactive oxygen species. The present study was carried out to investigate the effect of oral administration of tannic acid (TA) on behavioral deficit, antioxidative deterioration induced by lead acetate (LA) exposure on experimental rat brain. Male Wistar rats were treated with 50mg/kg body weight of LA and TA for three times a week for two weeks. Our data showed LA-induced profound elevation of ROS production and oxidative stress, as evidenced by increased levels of oxidative stress markers such as lipid peroxidation and protein carbonyl observed in LA treated rats, whereas significant depletion in the activity of non-enzymatic antioxidants, enzymatic antioxidants, neurotoxicity biomarker and histological changes were observed in LA treated rat brain. However, TA administration restored antioxidant status of brain significantly when compared to control. Our results demonstrate that TA exhibits potent antioxidant properties and suppresses oxidative damages in rat brain induced by LA treatment. These findings were further supported by the neurotoxicity biomarker and histopathological findings in the brain tissue showed that TA protected tissue from deleterious effects of LA exposure. It is concluded, these data suggest that LA induces oxidative stress and supplementation of TA has a powerful antioxidant effect, and it protected rat brain from poisonous effect of LA exposure in experimental rat.

Perillyl alcohol improves functional and histological outcomes against ischemia-reperfusion injury by attenuation of oxidative stress and repression of COX-2, NOS-2 and NF-κB in middle cerebral artery occlusion rats.

Perillyl alcohol (PA) is a monoterpene found in essential oils of mints, cherries, citreous fruits and lemon grass, reported to have antioxidant and anti-inflammatory properties. However, the role of PA in stroke is still illusive. Since oxidative stress and inflammation play a pivotal role in ischemia-reperfusion (I-R) injury, this study was designed to elucidate the potential effects of PA against I-R induced pathology in rat׳s brain. Middle cerebral artery occlusion (MCAO) for 2h followed by 22h reperfusion in Wistar male rats (250-280g, 14-16 weeks old) induced the behavioral and histological alterations along with exhausted antioxidant status and enhanced inflammatory mediators. However, PA administration (25, 50 and 100mg/kg b.wt orally once daily for 7 days) prior to MCAO significantly attenuated neurological deficits related to flexion test and spontaneous motor activity, improved grip strength and motor coordination in a dose dependent manner. PA treatment also inhibited oxidative stress in MCAO rats as evident from decreased lipid peroxidation and augmented level of reduced glutathione and restored activities of catalase, glutathione peroxidase, and glutathione reductase and thus, reduced infarct volume and protected the brain histology after I-R injury. Furthermore, PA markedly suppressed the level of proinflammatory cytokines (IL-1ß, TNF α and IL-6) and down regulated expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (NOS-2) and nuclear factor κB (NF-κB) in MCAO group. In conclusion, PA mediates neuroprotection against I-R injury via mitigation of oxidative stress and inflammation and thus, may be a good therapeutic approach in stroke prone patient.