Annapurna Akula

Biochemical, histological and echocardiographic changes during experimental cardiomyopathy in STZ-induced diabetic rats

Diabetes mellitus is associated with an increased susceptibility to cardiovascular disease and it has been suggested that alterations in myocardial function may contribute to the development of diabetic cardiovascular complications. The objective of the present study is to examine the left ventricular (LV) function in streptozotocin (STZ)-induced diabetic rats in a definite course of time by non-invasive methods, i.e. M-mode and Doppler echocardiography. From the results, it was found that treatment of animals with STZ resulted in increase in blood glucose, triglycerides, cholesterol, low density lipoproteins (LDL) and decrease in serum total protein levels. Echocardiographic studies revealed that LV internal dimension (mm) during systole was significantly increased after 12 weeks of diabetes when compared to base line data of the same animals and with control animals 6.50+/-0.13 versus 4.25+/-0.17, versus 4.34+/-0.25 (P<0.05), however there was no significant change after 4-8 weeks of diabetes. Also LV internal dimension (mm) during end diastole increased significantly only after 12 weeks of diabetes than to base line data of the same animals and with control animals 7.71+/-0.34 versus 6.18+/-0.25, versus 6.25+/-0.18 (P<0.05). Fractional shortening (%), 15.69+/-5.1 versus 31.22+/-1.7, versus 30.56+/-2.1 (P<0.05), and ejection fraction (%) 37+/-2.31 versus 68.18+/-2.8, versus 60.32+/-3.5 (P<0.05), differ significantly after 12 weeks of diabetes when compared to base line data of the same animals and with control animals. E-wave (cm/s) was significantly decreased after 12 weeks of diabetes 21.11+/-1.5 versus 35.19+/-4.5, versus 32.75+/-3.0 (P<0.05), and A-wave (cm/s) was significantly increased after 12 weeks of diabetes 34.88+/-4.2 versus 19.21+/-2.8, versus 20.59+/-2.1 (P<0.05); thus, diabetic animals after 12 weeks had an inversed E/A ratio. Histological studies revealed that after 8 weeks of diabetes, necrosis was minimal, but after 12 weeks of diabetes extensive focal endomyocardial necrosis was observed. From this study, we conclude that overt LV systolic and diastolic dysfunction was fully visible at 12 weeks of diabetes on echocardiography and this non-invasive technique of echocardiography is useful in diagnosing LV dysfunction in diabetic rats without the need of invasive histopathological procedures.

Synthesis, characterization and biological evaluation of some novel 2,4-thiazolidinediones as potential cytotoxic, antimicrobial and antihyperglycemic agents.

A series of some novel 2,4-thiazolidinediones (TZDs) (2a-x) have been synthesized and characterized by FTIR, (1)H NMR, (13)C NMR and LC mass spectral analysis. All the synthesized compounds were evaluated for their cytotoxicity, antimicrobial and in vivo antihyperglycemic activities. Among the tested compounds for cytotoxicity using Brine Shrimp Lethality assay, compound 2t ((Z)-5-(4-((E)-3-oxo-3-(thiophen-2-yl)prop-1-enyl)benzylidene)-1,3-thiazolidine-2,4-dione) exhibited significant inhibitory activity at ED(50) value 4.00±0.25 μg/mL and this level of activity was comparable to that of the reference drug podophyllotoxin with ED(50) value 3.61±0.17 μg/mL. Antimicrobial activity was screened using agar well diffusion assay method against selected Gram-positive, Gram-negative and fungal strains and the activity expressed as the minimum inhibitory concentration (MIC) in μg/mL. From the results of antimicrobial activity compound 2s ((Z)-5-(4-((E)-3-(3,5-bis(benzyloxy)phenyl)-3-oxoprop-1-enyl)benzylidene)-1,3-thiazolidine-2,4-dione) was found to be the most active against all the tested strains of microorganisms with MIC value 16 μg/mL. In vivo antihyperglycemic effect of twenty four TZDs (2a-x) at different doses 10, 30 and 50mg/kg b.w (oral) were assessed using percentage reduction of plasma glucose (PG) levels in streptozotocin-induced type II diabetic rat models. From the results, the novel compound 2x ((Z)-5-(4-((E)-3-(9H-fluoren-2-yl)-3-oxoprop-1-enyl)benzylidene)-1,3-thiazolidine-2,4-dione) exhibited considerably potent blood glucose lowering activity than that of the standard drug rosiglitazone and it could be a remarkable starting point to evaluate structure-activity relationships and to develop new lead molecules with potential cytotoxicity, antimicrobial and antihyperglycemic activities. In addition molecular docking studies were carried out against PPARγ molecular target using Molegro Virtual Docker v 4.0 to accomplish preliminary confirmation of the observed in vivo antihyperglycemic activity.

Infarct size limiting effect of apstatin alone and in combination with enalapril, lisinopril and ramipril in rats with experimental myocardial infarction.

Bradykinin is a potent vasoactive peptide that is known to elicit a number of biological responses. A number of peptidases have been identified to possess kininase activity, the inhibition of which increases the availability and effectiveness of kinins. We wished to determine the cardioprotective actions of an aminopeptidase P inhibitor, apstatin alone and in combination with enalapril/lisinopril/ramipril in an in vivo rat model of acute ischemia (30 min) and reperfusion (4 h). Myocardial infarction was produced by occlusion of the left anterior descending coronary artery for 30 min followed by 4 h of reperfusion. Infarct size was measured by using the staining agent 2,3,5-triphenyl tetrazolium chloride (TTC). Lipid peroxide levels in serum and in heart tissue were estimated spectrophotometrically. A lead II electrocardiogram was monitored at various intervals throughout the experiment. Infarct size was reduced to a greater extent with apstatin and with combined inhibition it was further reduced. Infarct size reduction obtained with the combined inhibition came to normal with the prior administration of B2 bradykinin antagonist HOE140 suggests the involvement of bradykinin in the cardioprotective actions of apstatin.

Prediabetes and alzheimer's disease

Aging patients with diabetes are at higher risk of developing Alzheimers disease. Emerging evidences demonstrate the role of brain insulin resistance, which is a key mediator in prediabetes and diabetes mellitus that may lead to Alzheimers disease. Insulin and insulin-like growth factors regulate many biological processes such as axonal growth, protein synthesis, cell growth, gene expression, proliferation, differentiation, and development. Among these, the energy metabolism and synaptic plasticity are the major transduction processes regulated by insulin, which are the core objectives for learning and memory. It was also proposed that hyper insulinemia induced insulin resistance results in injury to the central nervous system by the activation of glycogen synthase kinase 3β which is the key ailment in the cognitive decline. Hence, the endogenous brain specific insulin impairments and signaling account for the majority of Alzheimers abnormalities.

Calcium regulation and Alzheimer's disease

Abstract Activation of the neuron induces transient fluctuations in [Ca2+]i. This transient rise in [Ca2+]i is dependent on calcium entry via calcium channels and release of calcium from intracellular stores, finally resulting in increase in calcium levels, which activates calcium regulatory proteins to restore the resting calcium levels by binding to the calcium-binding proteins, sequestration into the endoplasmic reticulum and the mitochondria, and finally extrusion of calcium spike potential from the cell by adenosine triphosphate-driven Ca2+ pumps and the Na+/Ca2+ exchanger. Improper regulation of calcium signaling, sequentially, likely contributes to synaptic dysfunction and excitotoxic and/or apoptotic death of the vulnerable neuronal populations. The cognitive decline associated with normal aging is not only due to neuronal loss, but is fairly the result of synaptic connectivity. Many evidences support that Ca2+ dyshomeostasis is implicated in normal brain aging. Thus the chief factor associated with Alzheimers disease was found to be increase in the levels of free intracellular calcium, demonstrating that the excessive levels might lead to cell death, which provides a key target for the calcium channel blockers might be used as the neuroprotective agents in Alzheimers disease.

Proteomic Analysis in Diabetic Cardiomyopathy using Bioinformatics Approach

Diabetic cardiomyopathy is a distinct clinical entity that produces asymptomatic heart failure in diabetic patients without evidence of coronary artery disease and hypertension. Abnormalities in diabetic cardiomyopathy include: myocardial hypertrophy, impairment of contractile proteins, accumulation of extracellular matrix proteins, formation of advanced glycation end products, and decreased left ventricular compliance. These abnormalities lead to the most common clinical presentation of diabetic cardiomyopathy in the form of diastolic dysfunction. We evaluated the role of various proteins that are likely to be involved in diabetic cardiomyopathy by employing multiple sequence alignment using ClustalW tool and constructed a Phylogenetic tree using functional protein sequences extracted from NCBI. Phylogenetic tree was constructed using Neighbour—Joining Algorithm in bioinformatics approach. These results suggest a causal relationship between altered calcium homeostasis and diabetic cardiomyopathy that implies that efforts directed to normalize calcium homeostasis could form a novel therapeutic approach.

Effect of wheat grass powder on aluminum induced Alzheimer's disease in Wistar rats.

OBJECTIVE To find out the effect of wheat grass on aluminum induced Alzheimers disease in Wistar rats. METHODS Memory impairment was induced by aluminum chloride (4.2 mg/kg, i.p.) for 28 d. Memory function was assessed by Morris water maze test. To study the activity of wheat grass (100 mg/kg, p.o.), Wistar rats were administered it for 28 d along with aluminum chloride. Biochemical parameters of oxidative stress were estimated in brain after the treatment. RESULTS The major finding of this study is that aluminum enhanced oxidative stress. Wheat grass showed a significant improvement in reduction of this oxidative stress by reduction of malondialdehyde levels and enhancement of superoxide dismutase and catalase levels. CONCLUSIONS The present study clearly demonstrated the beneficial effects of wheat grass that shows good antioxidant properties, and this remarkable effect of wheat grass may act as a key to treat Alzheimers disease.

Protective effect of naringin on pentylenetetrazole (PTZ)-induced kindling; possible mechanisms of antikindling, memory improvement, and neuroprotection

The present study investigated the effects of Naringin on seizure severity, progress of kindling, memory impairment, oxidative stress, neurochemicals, and neural damage in Pentylenetetrazole (PTZ)-induced kindling. Alternate intra-peritoneal injections of PTZ induced kindling at 22 injections of PTZ. In comparison with the PTZ group, pretreatment with Naringin 30 min prior to PTZ administration and on a PTZ-free day was found to lead to a decreased seizure score, a mitigated progress of kindling, decreased transfer latency, and increased total number of arm entries, % alternation behavior in Y maze, and % conditioned avoidance response in a pole climbing apparatus. Biochemical analysis of the frontal and temporal cortexes and the hippocampus of the brain showed that Naringin attenuated the level of lipid peroxidation (MDA) and augmented the reduced glutathione, superoxide dismutase, catalase, and total thiol results in decreased oxidative stress compared with the PTZ group and control group. Investigation of neurochemicals revealed a minute change in gamma amino butyric acid (GABA), glutamate and dopamine, and decreased AChE in the three regions. Increased CA1 neuronal density in the hippocampus and increased cell density in the frontal and temporal regions indicate the potential of naringin to act against PTZ-induced kindling, memory impairment, oxidative stress, neurochemical changes, and histological aberrations.

Vitis vinifera acts as anti-Alzheimer's agent by modulating biochemical parameters implicated in cognition and memory

Background Aluminum a known neuro and cholinotoxin has been implicated in the pathogenesis of Alzheimer’s disease. Its exposure is associated with impairment of the memory and cognition. Objective The present study was undertaken to evaluate the anti-Alzheimer’s activity of Vitis vinifera in aluminum induced Alzheimer’s disease. Materials and methods In this study, we investigated the behavioral and biochemical effects of aluminum in Sprague-Dawley rats. Animals were exposed to aluminum chloride (100 mg/kg/day) orally for a period of 8 weeks. Vitis was given in doses of 250 mg/kg and 500 mg/kg for 16 weeks and the possible effects of Vitis vinifera on the expression of Tau and amyloid precursor protein were evaluated by PCR analysis and the possible activities of lipid peroxidation, inflammation and anti-cholinesterase activity were evaluated. Results Aluminum intoxication was associated with significant impairment in learning and memory in Morris water maze test. A significant improvement was observed with Vitis vinifera in a dose dependent manner. Conclusion The findings of the present study revealed the significant neuroprotective actions of Vitis vinifera by modifying the biochemical parameters and inhibited the mRNA expression of Amyloid Precursor Protein and Tau, which are the key pathological hallmarks of Alzheimer’s disease, which was further confirmed by histopathological observations.

Bioinformatics Analysis of Functional Protein Sequences Reveals a Role for Tumor Necrosis Factor-α and Nitric Oxide in Insulin Resistance Syndrome

Using bioinformatics techniques and sequence analyses algorithms, we identified that tumor necrosis factor-α (TNF-α) and nitric oxide (NO) have a significant role in the pathobiology of insulin resistance syndrome, a condition that is common in subjects with abdominal obesity, hypertension, dyslipidemia, atherosclerosis, and coronary heart disease and are accompanied by endothelial dysfunction due to reduced endothelial nitric oxide generation. TNF-α has neurotoxic actions, stimulates inducible NO synthase activity, and modulates the expression of neurotransmitters involved in the control of feeding and thermogenesis. NO is a neurotransmitter and influences secretion and actions of various hypothalamic peptides and neuropeptides. Insulin suppresses the production of TNF-α but stimulates that of endothelial NO. This close interaction between TNF-α, NO, hypothalamic peptides, and insulin suggests that regulation of TNF-α and NO production and action could be critical in the management of insulin resistance syndrome and its associated conditions.