Gui Mi Ko

Transplantation of bone marrow mesenchymal stem cells decreases oxidative stress, apoptosis, and hippocampal damage in brain of a spontaneous stroke model

Stroke is the most common cause of motor disabilities and is a major cause of mortality worldwide. Adult stem cells have been shown to be effective against neuronal degeneration through mechanisms that include both the recovery of neurotransmitter activity and a decrease in apoptosis and oxidative stress. We chose the lineage stroke-prone spontaneously hypertensive rat (SHRSP) as a model for stem cell therapy. SHRSP rats can develop such severe hypertension that they generally suffer a stroke at approximately 1 year of age. The aim of this study was to evaluate whether mesenchymal stem cells (MSCs) decrease apoptotic death and oxidative stress in existing SHRSP brain tissue. The results of qRT-PCR assays showed higher levels of the antiapoptotic Bcl-2 gene in the MSC-treated animals, compared with untreated. Our study also showed that superoxide, apoptotic cells, and by-products of lipid peroxidation decreased in MSC-treated SHRSP to levels similar those found in the animal controls, Wistar Kyoto rats. In addition, we saw a repair of morphological damage at the hippocampal region after MSC transplantation. These data suggest that MSCs have neuroprotective and antioxidant potential in stroke-prone spontaneously hypertensive rats.

Central administration of a nitric oxide precursor abolishes both the hypothalamic serotonin release and the hypophagia induced by interleukin-1β in obese Zucker rats

Serotonin-induced anorexia has long been recognized as an important part of the CNS mechanisms controlling energy balance. More recently, interleukin-1beta and nitric oxide have been suggested to influence this control, possibly through modulation of hypothalamic serotonin. The present work aimed at investigating the interaction of these systems. We addressed whether 5-HT is affected during IL-1beta-induced anorexia in obese Zucker rats and the influence of the central NO system on this IL-1beta/5-HT interaction. Using microdialysis, we observed that an intracerebroventricular injection of 10 ng IL-1beta significantly stimulated 5-HT extracellular levels in the VMH, with a peak variation of 102+/-41% above baseline. IL-1beta also significantly reduced the 4-h feeding by 33% and the 24-h feeding by 42%. Contrarily, these effects were absent when IL-1beta was injected 2 h after the i.c.v. administration of 20 microg of the NO precursor L-arginine. The results suggest that, in obese Zucker rats, activation of the serotonergic system in the medial hypothalamus participates in IL-1beta-induced anorexia. Since L-arginine, probably through NO stimulation, abolished both the anorexia and the serotonergic activation, it can be proposed that the NO system, either directly or indirectly, counteracts IL-1beta anorexia. The hypothalamic serotonergic system is likely to mediate this NO effect.

Evaluation of the isoflavones and estrogen effects on the rat adrenal

Abstract The aim of this study was to evaluate the morphometry and the gene expression of Ki-67, VEGF and caspase 3 and the stress oxidative in the adrenal gland of ovariectomized rats treated with estrogen or isoflavones. We used 15 Wistar rats ovariectomized treated with isoflavones or estrogen during 30 days. At the end of the treatment, the left adrenal gland was removed for subsequent histological studies and the right was used to evaluate gene expression of angiogenesis (VEGF-A), cell proliferation (Ki-67), apoptose (caspase 3 clivated) and oxidative stress. Treatment with estrogen showed a largest increase in the layers of the adrenal cortex than with isoflavones. These hypertrofic effects agree with higher expression elevation of Ki67 and VEGF, which did not occur with the caspase 3, indicating that isoflavones have great proliferative effect on the adrenal gland. Similar results were also observed on superoxide quantification show that isoflavone has a protective effect against oxidative stress. Our results indicate positively the trophic therapeutic potential of isoflavones has a protective effect and can contribute to the development of effective therapies to decrease the symptoms of menopause.

Methods of acute biological assays in guinea-pigs for the study of toxicity and innocuity of drugs and chemicals

In this study, 602 samples were tested by the following assays performed at the animal facilities (Cedeme) of the Federal University of Sao Paulo (UNIFESP): 385 for dermal irritability, 90 for ocular irritability (discontinued in 1995), 31 for systemic toxicity by injection, 26 for oral acute toxicity, 15 for toxicity by intracutaneous injection, 15 for skin sensitization, 15 for toxicity of serum and vaccines for human use, 14 for toxicity by intramuscular implantation, 7 for pyrogens, 2 for acute dermal toxicity, and 2 for irritation of mucous membrane. The following agents were tested: cosmetics and related substances (42.0%), chemicals used in industry (32.9%), plastics, rubber, and other polymers (15.9%), agrotoxics (4.0%), medicines (2.7%), and vaccines (2.5%). In the present description, emphasis was given to tests of dermal irritability and sensitization. This work was conducted entirely in animal facilities, according to our general belief that animal facilities at universities, while considering ethic principles and sanitary, genetic, nutritional, and pathophysiological controls, also require laboratories specialized in areas such as transgenics, cryopreservation, ambiental physiology, functional genomics, alternative models, and mainly activities and research on methods in toxicology, as focused in this study.