Anuradha Majumdar

Phytochemicals and their potential usefulness in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract with unclear etiology, namely ulcerative colitis and Crohns disease. Various drug therapies including aminosalicylates and immunomodulators have been approved for use; they have shown to produce diverse side effects. To overcome these limitations of the current therapeutics for IBD, extensive research is underway to identify drugs that are effective and free of undesirable side effects. Recently, various naturally occurring phytochemicals that cover a wide range of chemical entities such as polyphenols, terpeniods, flavonoids, and alkaloids have received attention as alternative candidates for IBD therapy. These phytochemicals act by modulating the immune response, various transcription factors, or reduce cytokine secretion. This review summarizes the findings of recent studies on phytochemicals as therapeutic agents in the management of IBD. Copyright

Neurobehavioural Changes and Brain Oxidative Stress Induced by Acute Exposure to GSM900 Mobile Phone Radiations in Zebrafish ( Danio rerio )

The impact of mobile phone (MP) radiation on the brain is of specific interest to the scientific community and warrants investigations, as MP is held close to the head. Studies on humans and rodents revealed hazards MP radiation associated such as brain tumors, impairment in cognition, hearing etc. Melatonin (MT) is an important modulator of CNS functioning and is a neural antioxidant hormone. Zebrafish has emerged as a popular model organism for CNS studies. Herein, we evaluated the impact of GSM900MP (GSM900MP) radiation exposure daily for 1 hr for 14 days with the SAR of 1.34W/Kg on neurobehavioral and oxidative stress parameters in zebrafish. Our study revealed that, GSM900MP radiation exposure, significantly decreased time spent near social stimulus zone and increased total distance travelled, in social interaction test. In the novel tank dive test, the GSM900MP radiation exposure elicited anxiety as revealed by significantly increased time spent in bottom half; freezing bouts and duration and decreased distance travelled, average velocity, and number of entries to upper half of the tank. Exposed zebrafish spent less time in the novel arm of the Y-Maze, corroborating significant impairment in learning as compared to the control group. Exposure decreased superoxide dismutase (SOD), catalase (CAT) activities whereas, increased levels of reduced glutathione (GSH) and lipid peroxidation (LPO) was encountered showing compromised antioxidant defense. Treatment with MT significantly reversed the above neurobehavioral and oxidative derangements induced by GSM900MP radiation exposure. This study traced GSM900MP radiation exposure induced neurobehavioral aberrations and alterations in brain oxidative status. Furthermore, MT proved to be a promising therapeutic candidate in ameliorating such outcomes in zebrafish.

Coenzyme Q10 abrogated the 28 days aluminium chloride induced oxidative changes in rat cerebral cortex

Objective: The present study was designed to elucidate the impact of oral administration of aluminium chloride for 28 days with respect to oxidative stress in the cerebral cortex of female rats. Further, to investigate the potentials of Coenzyme (Co) Q10 (4, 8, and 12 mg/kg, i.p.) in mitigating the detrimental changes. Materials and Methods: Biochemical estimations of cerebral lipid peroxidation (LPO), reduced glutathione (GSH), vitamin E and activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were carried out after 28 days of aluminium chloride (AlCl 3 ) and Co Q10 exposures along with histopathological examination of cerebral cortex of the rats. Results: Subacute exposure to AlCl 3 ( 5 mg/kg) led to significant decrease in levels of GSH, vitamin E and activities of SOD, CAT, GPx, and an increase in LPO of cerebral cortex. These aberrations were restored by Co Q10 (12 mg/kg, i.p.). This protection offered was comparable to that of L-deprenyl (1 mg/kg, i.p.) which served as a reference standard. Histopathological evaluations confirmed that the normal cerebral morphology was maintained by Co Q10. Conclusion: Thus, AlCl 3 exposure hampers the activities of various antioxidant enzymes and induces oxidative stress in cerebral cortex of female Wistar rats. Supplementation with intraperitoneal Co Q10 abrogated these deleterious effects of AlCl 3 .

Resveratrol potentiates the effect of dexamethasone in rat model of acute lung inflammation.

Cigarette smoking is considered to be the main etiological factor in Chronic Obstructive Pulmonary Disease (COPD). In this study, we explored the potential of resveratrol, to reinstate the effectiveness of dexamethasone when administered as an adjunct in acute lung inflammation induced by cigarette smoke (CS) and lipopolysaccharide (LPS). CS and LPS instillation produced acute inflammatory response exhibited by increased leukocyte count, particularly neutrophils, total protein, MMP-9 activity, cytokines like TNF-α, IL-8 in bronchoalveolar lavage fluid (BALF) as well as elevated myeloperoxidase activity, and lipid peroxidation in lung. These alterations were not abated by dexamethasone (2.5mg/kg & 10mg/kg) and resveratrol (50mg/kg) alone. Combination of resveratrol (50mg/kg) and dexamethasone (2.5mg/kg) significantly reduced all inflammatory parameters. The protective effect of the combination was abolished when co-administered with sirtinol, a SIRT1 inhibitor. The results indicate that the combination therapy may serve as a potential approach for treating lung inflammatory conditions like COPD.

Exacerbation of alcohol-induced oxidative stress in rats by polyunsaturated Fatty acids and iron load.

The hypothesis that excessive intake of vegetable oil containing polyunsaturated fatty acids and iron load precipitate alcohol-induced liver damage was investigated in a rat model. In order to elucidate the mechanism underlying this synergism, the serum levels of iron, total protein, serum glutamate pyruvate transaminase, liver thiobarbituric acid reactive substances, and activities of antioxidant enzymes superoxide dismutase, catalase in liver of rats treated with alcohol, polyunsaturated fatty acids and iron per se and in combination were examined. Alcohol was fed to the rats at a level of 10-30% (blood alcohol was maintained between 150-350 mg/dl by using head space gas chromatography), polyunsaturated fatty acids at a level of 15% of diet and carbonyl iron 1.5-2% of diet per se and in combination to different groups for 30 days. Hepatotoxicity was assessed by measuring serum glutamate pyruvate transaminase, which was elevated and serum total protein, which was decreased significantly in rats fed with a combination of alcohol, polyunsaturated fatty acids and iron. It was also associated with increased lipid peroxidation and disruption of antioxidant defense in combination fed rats as compared to rats fed with alcohol or polyunsaturated fatty acids or iron. The present study revealed significant exacerbation of the alcohol-induced oxidative stress in presence of polyunsaturated fatty acids and iron.

Understanding mitochondrial biogenesis through energy sensing pathways and its translation in cardio-metabolic health

Abstract Mitochondria play a pivotal role in physiological energy governance. Mitochondrial biogenesis comprises growth and division of pre-existing mitochondria, triggered by environmental stressors such as endurance exercise, caloric restriction, cold exposure and oxidative stress. For normal physiology, balance between energy intake, storage and expenditure is of utmost important for the coordinated regulation of energy homeostasis. In contrast, abnormalities in these regulations render the individual susceptible to cardiometabolic disorders. This review provides a comprehensive coverage and understanding on mitochondrial biogenesis achieved through energy-sensing pathways. This includes the complex coordination of nuclear, cytosolic and mitochondrial events involving energy sensors, transcription factors, coactivators and regulators. It focuses on the importance of mitochondrial biogenesis in cardiometabolic health. Lastly, converging on the benefits of caloric restriction and endurance exercise in achieving cardiometabolic health.

Therapeutic interventions using a combination of Telmisartan and omega 3-fatty acids in sodium arsenite-induced vascular endothelial dysfunction in rats: modulation through ATP-sensitive K+ channels and eNOS.

Abstract Background: Effective diet/drug combinations may show additive or synergistic effects in reducing endothelial risk factors vis-à-vis monotherapies. The study evaluated the effect of combined therapy of Telmisartan and omega 3-fatty acids in sodium arsenite-induced vascular endothelial dysfunction (VED) in rats. Methods: Forty-eight male Wistar rats (180–220 g) were randomized into eight groups; control, sodium arsenite (1.5 mg/kg/day) exposed, sodium arsenite exposure followed by treatment with Telmisartan, omega 3-fatty acids, the combination and/or endothelial modulators for 2 weeks depending on the allocated group. VED was assessed by estimating vascular reactivity. Serum thiobarbituric acid-reactive substances (TBARS), nitrite/nitrate levels, reduced glutathione (GSH) levels, superoxide dismutase (SOD) activity, serum cholesterol and triglyceride levels were also determined. Results: Sodium arsenite produced VED by attenuating acetylcholine-induced endothelial relaxation (% Rmax= 45.36), decreasing levels of serum nitrite/nitrate (9.28 μM/mg protein), GSH (16.06 μg/mg of protein), SOD activity (30.69 units/mg protein) and increasing TBARS (0.19 µM/mg protein) compared with control group. The combined therapy with Telmisartan (10 mg/kg/day) and omega 3-fatty acids (180 mg/kg/day) (% Rmax=80.93, 13.09 µM/mg protein, 25.93 μg/mg of protein, 57.84 units/mg protein and 0.08 µM/mg protein, respectively) significantly abolished the respective derangements induced by sodium arsenite. Further, this combination significantly prevented rise in serum cholesterol and triglyceride levels that was induced by sodium arsenite. However, the ameliorative effects of this combination were abated by N-omega-nitro-L-arginine methyl ester (L-NAME) and glibenclamide. Conclusions: Combined therapy of Telmisartan and omega 3-fatty acids attenuated VED, by activating enzyme nitric oxide synthase (eNOS) through opening of ATP-sensitive K+ channels.

Colon targeted beads loaded with pterostilbene: Formulation, optimization, characterization and in vivo evaluation

Background Pterostilbene has a proven chemopreventive effect for colon carcinogenesis but suffers low bioavailability limitations and therefore unable to reach the colonic tissue. Objective and methodology To overcome the issue of low bioavailability, pterostilbene was formulated into an oral colon targeted beads by ionic gelation method using pectin and zinc acetate. Optimization was carried out by 23 factorial design whereby the effect of pectin concentration (X1), zinc acetate concentration (X2) and pterostilbene:pectin ratio (X3) were studied on entrapment efficiency (Y1) and in vitro drug release till 24 h (Y2). The optimized beads were characterized for shape and size, swelling and surface morphology. The optimized beads were uniformly coated with Eudragit S-100 using fluidized bed coater. Optimized coated beads were characterized for in vitro drug release till 24 h and surface morphology. Pharmacokinetic and organ distribution study were performed in rats to ascertain the release of pterostilbene in colon. Results The optimized formulation comprised of 2% w/v of pectin concentration (X1), 2% w/v of zinc acetate concentration (X2) and 1:4 of pterostilbene:pectin ratio (X3), which showed a satisfactory entrapment efficiency (64.80%) and in vitro release (37.88%) till 24 h. The zinc pectinate beads exhibited sphericity, uniform size distribution, adequate swelling and rough surface. The optimized coated beads achieved 15% weight gain, displayed smooth surface and optimum drug release. Pterostilbene from optimized coated beads appeared in the plasma at 14 h and reached the Cmax at 22 h (Tmax), whereas plain pterostilbene exhibited Tmax of 3 h. Discussion and conclusion Thus, larger distribution of pterostilbene was obtained in the colonic tissue compared to stomach and small intestinal tissues. Thus, delayed Tmax and larger distribution of pterostilbene in colonic tissue confirmed the targeting of beads to colon.

Lipid Architectonics for Superior Oral Bioavailability of Nelfinavir Mesylate: Comparative in vitro and in vivo Assessment

AbstractNelfinavir mesylate (NFV), a human immunodeficiency virus (HIV) protease inhibitor, is an integral component of highly active anti retro viral therapy (HAART) for management of AIDS. NFV possesses pH-dependent solubility and has low and variable bioavailability hampering its use in therapeutics. Lipid-based particulates have shown to improve solubility of poorly water soluble drugs and oral absorption, thereby aiding in improved bioavailability. The current study compares potential of vesicular and solid lipid nanocarriers of NFV with drug nanocrystallites and microvesicular systems like cochleates in improving bioavailability of NFV. The paper outlines investigation of systems using in vitro models like in vitro lipolysis, in vitro release, and permeation through cell lines to predict the in vivo potential of nanocarriers. Finally, in vivo pharmacokinetic study is reported which provided proof of concept in sync with results from in vitro studies. Graphical Abstractᅟ

Rats exposed to 2.45 GHz of non-ionizing radiation exhibit behavioral changes with increased brain expression of apoptotic caspase 3

In recent years there has been a tremendous increase in use of Wi-Fi devices along with mobile phones, globally. Wi-Fi devices make use of 2.4GHz frequency. The present study evaluated the impact of 2.45GHz radiation exposure for 4h/day for 45days on behavioral and oxidative stress parameters in female Sprague Dawley rats. Behavioral tests of anxiety, learning and memory were started from day 38. Oxidative stress parameters were estimated in brain homogenates after sacrificing the rats on day 45. In morris water maze, elevated plus maze and light dark box test, the 2.45GHz radiation exposed rats elicited memory decline and anxiety behavior. Exposure decreased activities of super oxide dismutase, catalase and reduced glutathione levels whereas increased levels of brain lipid peroxidation was encountered in the radiation exposed rats, showing compromised anti-oxidant defense. Expression of caspase 3 gene in brain samples were quantified which unraveled notable increase in the apoptotic marker caspase 3 in 2.45GHz radiation exposed group as compared to sham exposed group. No significant changes were observed in histopathological examinations and brain levels of TNF-α. Analysis of dendritic arborization of neurons showcased reduction in number of dendritic branching and intersections which corresponds to alteration in dendritic structure of neurons, affecting neuronal signaling. The study clearly indicates that exposure of rats to microwave radiation of 2.45GHz leads to detrimental changes in brain leading to lowering of learning and memory and expression of anxiety behavior in rats along with fall in brain antioxidant enzyme systems.