Normal Diet Rats Research Articles

Accelerated proliferation of hepatocytes in rats with iron overload after partial hepatectomy

Although iron overload is implicated in hepatocarcinogenesis, the precise mechanism was not known yet. In the present study, we investigated the effect of iron overload upon the induction of hepatocyte proliferation after 70% partial hepatectomy (PH) in rats fed with rat chow with 3% carbonyl iron for 3 months. In normal-diet rats, the increase in Ki-67 labeling index (LI) commenced at 24 h post-PH and the LIs of proliferating cell nuclear antigen (PCNA) incorporated 5-bromo-2'-deoxyuridine (BrdU) and phospho-histone H3 reached maximum values at 36 and 48 h after PH, respectively. In iron-overload rats, the above parameters occurred 12 h earlier compared to that of normal-diet rats, shortening the G0-G1 transition. Interestingly, nuclear staining for metallothionein (MT), which is essential for hepatocyte proliferation, was noted even at 0 h in iron-overload rats, while MT expression occurred at 6 h in the normal rats. Moreover, nuclear factor kappa B (NF-κB) expression, which is an essential early event leading to liver regeneration, was detected in Kupffer cells at 0 h in iron-overload rats. These results may indicate that overloaded iron, maybe through the induction of MT and NF-κB, may keep liver as a state ready to regenerate in response to PH, by bypassing signal transduction cascades involved in the initiation of liver regeneration.

Effects of Vitamin A Deficiency and Opioids on Parvalbumin + Interneurons in the Hippocampus of the HIV-1 Transgenic Rat

Opioid use in HIV infection has been associated with an increased frequency of neurological disease and cognitive impairment and vitamin A deficiency has been linked to progressive HIV disease in drug users. In this report the potential effects of these factors, alone and in combination, on gamma amino butyric acid (GABA)-expression interneurons in hippocampus in the HIV-1 transgenic rat (TG) model were studied. TG and wild-type (WT) F344 Fisher rats deficient in vitamin A from birth were implanted either with a 37.5 mg morphine tablet or with a matching placebo and total numbers of neurons and of parvalbumin+ neurons were quantitated and parvalbumin expression was quantitated in the CA1 hippocampal region of the rats. These studies showed that total neuronal numbers were decreased in the TG versus WT Fisher rats and that this decrease was enhanced by the vitamin A deficient diet and by treatment with morphine. In contrast, there was no significant change noted in numbers of parvalbumin+ neurons. However, levels of parvalbumin expression were decreased for vitamin A deficient and morphine-treated WT rats as compared to WT rats on the normal diet and placebo-treated WT rats. For TG rats, parvalbumin expression was higher for vitamin A deficient TG rats treated with either placebo or morphine than for WT vitamin A deficient rats treated with placebo, and placebo treated vitamin A deficient TG rats showed higher expression than morphine treated vitamin A deficient rats. Expression was also higher for vitamin A deficient morphine-treated rats than for the corresponding WT rat groups and for vitamin A deficient TG rats treated with placebo. For the remaining groups, parvalbumin was similar for the TG and WT rats. These findings suggest that in hippocampus vitamin A deficiency and morphine can increase parvalbumin expression, perhaps as a manifestation of a stress response. Parvalbumin-expressing GABA-ergic interneurons regulate the primary neuronal output from hippocampus that is important for memory and behavior. Therefore, these studies suggest that vitamin A deficiency and morphine might have effects that may impact such outputs and thereby have lasting effects on cognitive status.

Effects of hypercholesterolemia on contrast media-induced nephrotoxicity in rats

To explore the effects of short- and long-term dietary hypercholesterolemia on contrast media-induced nephrotoxicity in rats. The male Wistar rats were fed either a normal rodent diet or a high cholesterol diet. At the end of 2 and 8 weeks, 8 rats from each group received a tail vein injection of either Iohexol injection (groups NC and HC) or vehicle (groups N and H). Blood lipid, renal function, renal hemodynamics, renal and urinary prostaglandin E2 (PGE2) and thromboxane B2 (TXB2), renal nitric oxide and malondialdehyde (MDA) were determined at Day 1 following the administration of contrast media. The dosing of contrast media induced obviously increased serum creatinine compared with normal rats ((185 ± 28) vs (53 ± 3) µmol/L, P < 0.01) and severe renal tubular necrosis in rats with a high cholesterol diet for 8 weeks but did not in normal-diet rats or rats with a high cholesterol diet for 2 weeks. The renal and urinary levels of PGE2 and TXB2 increased significantly in rats of groups H and HC at the end of 8 weeks. The renal production of nitric oxide decreased while the concentration of MDA increased markedly in groups HC and H at the end of 8 weeks. Long-term hypercholesterolemia appears to be a risk factor of contrast media-induced acute renal failure. And it may be associated with the disorder of intrarenal prostaglandins and the abnormality of renal nitric oxide system as induced by lipid peroxidation.

Alterations in peripheral purinergic and muscarinic signaling of rat bladder after long-term fructose-induced metabolic syndrome.

We explored the pathophysiologic mechanisms of long-term fructose-induced lower urinary tract symptoms (LUTS) in rats. Male Wistar rats were fed with fructose for 3 or 6 months. Biochemical and transcystometric parameters were compared between fructose-fed and age-matched normal-diet rats. Pelvic nerve and external urethral sphincter-electromyogram activity recordings were performed to investigate fructose effects on neural control of bladders. Mitochondrial structure, ATP and acetylcholine content and purinergic and muscarinic cholinergic receptors were examined. Cytosolic cytochrome C staining by Western blot and immunocytochemistry for mitochondrial injury and PGP 9.5 stain for nerve density were also determined. The fructose-fed rats with higher plasma triglyceride, LDL and fasting glucose levels displayed LUTS with increased frequency and suppressed voiding contractile amplitude in phase 1 and phase 2 duration versus normal-diet control. Fructose feeding altered the firing types in pelvic afferent and efferent nerves and external urethral sphincter-electromyogram activity. Increased mast cell number, disrupted and swollen mitochondria, increased cytosolic cytochrome C stain and expression and decreased nerve density in bladder smooth muscle layers appeared in the fructose-fed rats. Fructose feeding also significantly reduced ATP and acetylcholine content and enhanced protein expression of postsynaptic P(2)X(1), P(2)X(2) and P(2)X(3) purinergic receptors and M(2) and M(3) muscarinic cholinergic receptors expression in the smooth muscles of urinary bladder. Long-term fructose feeding induced neuropathy and myopathy in the urinary bladders. Impaired mitochondrial integrity, reduced nerve density, ATP and acetylcholine content and upregulation of purinergic and muscarinic cholinergic receptors expression may contribute to the bladder dysfunction of fructose-fed animals.

Comparative hepatic proteome analysis between lean and obese rats fed a high‐fat diet reveals the existence of gender differences

Gender differences in obesity stem from metabolic and hormonal differences between sexes and contribute to differences between women and men in health risks attributable to obesity. We hypothesized that liver may be an ideal target for the evaluation of gender differences in obesity development in response to a high-fat diet (HFD). Therefore, to test this hypothesis, we performed a global proteome analysis in the liver of lean and obese rats of both genders who were fed an HFD through 2-DE combined with MALDI-TOF-MS. When rats were exposed to HFD, male rats gained more body weight with increased values of plasma biochemical parameters than female rats. Image analysis and further statistical analysis of a 2-DE protein map allowed for the detection and identification of 34 proteins that were significantly modulated in a gender-dependent manner. We found 19 proteins showing identical gender-different regulation in both normal diet (ND) and HFD. Five proteins also showed clear gender differences in both ND and HFD; however, their regulation modes in HFD were opposite to those in ND. Of particular interest, 10 proteins showed gender differences only in either ND or HFD rats. Present proteomic insight into gender-dimorphic protein modulation in liver would aid in the improvement of gender awareness in the health-care system and in implementation of evidence-based gender-specific clinical recommendations.

Abnormal intestinal function related to hypocupremia in a rodent model

Copper deficiency affects the peripheral (PNS) and central (CNS) nervous systems and can lead to neurological deficits in humans. No studies have addressed whether copper deficiency affects the enteric nervous system (ENS). We hypothesized that ENS abnormalities impair intestinal function in copper deficiency. We induced copper deficiency in rats by nutritional deprivation. Once hypocupremia was achieved, we euthanized the animals and harvested the small and large intestine. The longitudinal smooth muscle from the jejunum and colon was suspended in organ baths and contractility in response to electrical field stimulation (EFS) was assessed. Mucosa was also isolated from each region and placed into modified Ussing chambers to determine whether the copper deficiency leads to alterations in epithelial transport measured as a change in short circuit current across the mucosa in response to EFS. A copper deficient diet (CDD) in normal rats for 9 weeks was sufficient to produce hypocupremia. Colonic smooth muscle contractility was significantly decreased in response to EFS in rats fed a CDD compared with controls, however, jejunal smooth muscle contractility in response to EFS in rats fed a CDD rats resembled that observed in controls. No significant changes in secretory function were observed in either region in response to CDD. Dietary copper deficiency produces significant changes in the neural regulation of colonic smooth muscle contractility in a rodent model. Thus, along with CNS and PNS effects in humans, copper deficiency results in abnormal ENS regulation of intestinal function in rats.

Impaired vascular responses to relaxin in diet-induced overweight female rats

Relaxin mediates renal and mesenteric vascular adaptations to pregnancy by increasing endothelium-dependent vasodilation and compliance and decreasing myogenic reactivity. Diet-induced overweight and obesity are associated with impaired endothelial dysfunction and vascular remodeling leading to a reduction in arterial diameter. In this study, we tested the hypothesis that local vascular responses to relaxin are impaired in diet-induced overweight female rats on a high-fat cafeteria-style diet for 9 wk. Rats were chronically infused with either relaxin or placebo for 5 days, and vascular responses were measured in isolated mesenteric arteries and the perfused kidney. Diet-induced overweight significantly increased sensitivity to phenylephrine (by 17%) and vessel wall thickness, and reduced renal perfusion flow (RPFF; by 16%), but did not affect flow-mediated vasodilation, myogenic reactivity, and vascular compliance. In the normal weight rats, relaxin treatment significantly enhanced flow-mediated vasodilation (2.67-fold), decreased myogenic reactivity, and reduced sensitivity to phenylephrine (by 28%), but had no effect on compliance or RPFF. NO blockade by l-NAME diminished most relaxin-mediated effects. In diet-induced overweight rats, the vasodilator effects of relaxin were markedly reduced for flow-mediated vasodilation, sensitivity to phenylephrine, and myogenic response compared with the normal diet rats, mostly persistent under l-NAME. Our data demonstrate that some of the vasodilator responses to in vivo relaxin administration are impaired in isolated mesenteric arteries and the perfused kidney in diet-induced overweight female rats. This does not result from a decrease in Rxfp1 (relaxin family peptide receptor) expression but is likely to result from downstream disruption to endothelial-dependent mechanisms in diet-induced overweight animals.

High-fat diet induces emergence of brown-like adipocytes in white adipose tissue of spontaneously hypertensive rats

Obesity has a profound adverse impact on health. In this study, we present evidence for high-fat diet (HFD)-induced emergence of brown-like adipocytes in white adipose tissue (WAT) of the spontaneously hypertensive rat (SHR). We studied adult males fed a HFD or normal diet (ND) for 12 weeks. At the end of the 12-week dietary intervention, HFD compared with ND rats showed significantly higher whole-body energy expenditure. HFD vs. ND rats also showed higher expression of genes involved in fatty acid oxidation, mitochondrial biogenesis and brown fat adipogenesis, as well as augmented mitochondrial mass in WAT but not in the liver or skeletal muscle. Consistent with the molecular changes, in HFD but not in ND rats, histological and immunohistochemistry-based analyses of WAT demonstrated the presence of small multilocular cells staining positively for uncoupling protein 1, indicating the emergence of brown-like adipocytes in WAT. Our results suggest that SHR may have the capacity to increase energy expenditure in response to a chronic HFD that may be linked to the emergence of brown-like adipocytes in WAT. Thus, the SHR may be an important genetic model to uncover novel mechanisms of resistance to dietary obesity.

Study to Evaluate Hepatotoxic Characterizations Induced Through Ethanol in Albino Rats Mus Musculus

Abstract Objective: To determine structural and functional hepatic characterizations induced through the ethanol in albino rats mus musculus. Study Design: This study was an experimental Ran-domized Control Trial (RCT). Place and Duration: The study was conducted at the experimental research laboratory of Government Col-lege University Lahore with collaboration of College of Medicine Al-Kharj University and Obeid Speciali-zed Hospital,Riyadh,Saudi Arabia from January 2010 to December 2010. Material and Methods: Hundred male albino rats of 6 - 8 weeks old, weighing 150 - 200 gm each were divided into two groups of fifty each. Group A served as control and was given normal rat diet; Group B was given ethanol at a dose of 0.6 ml (0.5 gm) / 100 gm / day for 8 weeks. At the end of the experiment, blood was drawn from each animal by cardiac puncture for liver function tests. Each animal was then sacrificed under chloroform anaesthesia and its liver was remo-ved. Results: The mean values of Serum alanin-amino-transferase (ALT) and gamma glutamyl transferase (GGT) in group A were 28.17 ± 7.13 and 28.33 ± 3.05 respectively; where as in group B, the mean values of these enzymes were 84.33 ± 10.89 and 80.33 ± 4.37 U/L respectively, Students test showed statistically significant increase in the mean values of ALT and GGT in group B as compared with those in group A, p value being < 0.05. Liver was normal in appearance in all animals. The mean weight and volume of the liver in group A were 10.90 ± 0.39 gm and 10.33 ±0.42 ml respectively; where as, in group B, these were 13.25 ± 0.50 gm and 13.23 ± 0.38 ml respectively. Students t test showed statistically significant difference (p value being < 0.05) for weight and volume of the liver of group B when compared with those in group A. Liver preparations for histological study were examined under the light microscope. Group A showed normal liver histology, the mean size of hepatocytes and their nuclei was 21.25 ± 0.38 and 7.52 ± 0.12 µm respec-tively. In - group B, the mean size of hepatocytes and their nuclei was 26.24 ± 0.54 and 7.53 ± 0.12 µm res-pectively; the hepatocytes contained large number of cytoplasmic vacuoles, pyknotic nuclei were also obser-ved and portal areas showed lymphocytes infiltration;. Students t test showed statistically significant differ-rence in the mean value of the size of hepatocytes; Chi-square test also showed statistically significant difference in the percentage of hepatocytes containing cytoplasmic vacuoles, pyknotic nuclei and percentage of portal areas showing lymphocytic infiltration in the of the liver of the animals in group B, when compared with those in group A (p value being< 0.05). Conclusion: Ethanol is hepatotoxic in albino rats as evident from the functional disorder and structural changes in the live. Key Words: Ethanol, hepatotoxicity Pyknotic nuclei, Hepatocytes.

The Effects of Chromium Complex and Level on Glucose Metabolism and Memory Acquisition in Rats Fed High-Fat Diet

Conditions in which glucose metabolism is impaired due to insulin resistance are associated with memory impairment. It was hypothesized that supplemental chromium (Cr) may alleviate insulin resistance in type 2 diabetes and consequently improve memory acquisition, depending upon its source and level. In a complete randomized design experiment, male Wistar rats (n=60; weighing 200-220 g) were fed either normal (8%, normal diet (ND)) or high-fat (40%, high-fat diet (HFD)) diet and supplemented with Cr as either chromium-glycinate (CrGly) or chromium-acetate (CrAc) at doses of 0, 40, or 80 μg/kg body weight (BW) via drinking water from 8 to 20 weeks of age. Feeding HFD induced type 2 diabetes, as reflected by greater glucose/insulin ratio (2.98 vs. 2.74) comparing to feeding ND. Moreover, HFD rats had greater BW (314 vs. 279 g) and less serum (53 vs. 68 μg/L) and brain (14 vs. 24 ng/g) Cr concentrations than ND rats. High-fat diet caused a 32% reduction in expressions of glucose transporters 1 and 3 (GLUTs) in brain tissue and a 27% reduction in mean percentage time spent in the target quadrant and a 38% increase in spatial memory acquisition phase (SMAP) compared with ND. Compared with supplemental Cr as CrAc, CrGly was more effective to ameliorate response variables (i.e., restoration of tissue Cr concentration, enhancement of cerebral GLUTs expressions, and reduction of the glucose/insulin ratio and SMAP) in a dose-response manner, especially in rats fed HFD. Supplemental Cr as CrGly may have therapeutic potential to enhance insulin action and alleviate memory acquisition in a dose-dependent manner, through restoring tissue Cr reserve and enhancing cerebral GLUTs expressions.

Sitagliptin prevents the development of metabolic and hormonal disturbances, increased β-cell apoptosis and liver steatosis induced by a fructose-rich diet in normal rats

The aim of the present study was to test the effect of sitagliptin and exendin-4 upon metabolic alterations, β-cell mass decrease and hepatic steatosis induced by F (fructose) in rats. Normal adult male Wistar rats received a standard commercial diet without (C) or with 10% (w/v) F in the drinking water (F) for 3weeks; animals from each group were randomly divided into three subgroups: untreated (C and F) and simultaneously receiving either sitagliptin (CS and FS; 115.2mg/day per rat) or exendin-4 (CE and FE; 0.35 nmol/kg of body weight, intraperitoneally). Water and food intake, oral glucose tolerance, plasma glucose, triacylglycerol (triglyceride), insulin and fructosamine concentration, HOMA-IR [HOMA (homoeostasis model assessment) for insulin resistance], HOMA-β (HOMA for β-cell function) and liver triacylglycerol content were measured. Pancreas immunomorphometric analyses were also performed. IGT (impaired glucose tolerance), plasma triacylglycerol, fructosamine and insulin levels, HOMA-IR and HOMA-β indexes, and liver triacylglycerol content were significantly higher in F rats. Islet β-cell mass was significantly lower in these rats, due to an increase in the percentage of apoptosis. The administration of exendin-4 and sitagliptin to F animals prevented the development of all the metabolic disturbances and the changes in β-cell mass and fatty liver. Thus these compounds, useful in treating Type2 diabetes, would also prevent/delay the progression of early metabolic and tissue markers of this disease.

E0078 The effect of acute atorvastatin on cardioprotection of ischaemic postconditioning in diabetes mellitus

ObjectiveThis study was to investigate if the low dose of acute atorvastatin treatment could affect the cardioprotection of ischaemic post-conditioning (Ipost) in type 2 diabetes mellitus (T2DM) during ischaemia and...

Parametrial Adipose Tissue and Metabolic Dysfunctions Induced by Fructose‐rich Diet in Normal and Neonatal‐androgenized Adult Female Rats

Hyperandrogenemia predisposes an organism toward developing impaired insulin sensitivity. The aim of our study was to evaluate endocrine and metabolic effects during early allostasis induced by a fructose-rich diet (FRD) in normal (control; CT) and neonatal-androgenized (testosterone propionate; TP) female adult rats. CT and TP rats were fed either a normal diet (ND) or an FRD for 3 weeks immediately before the day of study, which was at age 100 days. Energy intake, body weight (BW), parametrial (PM) fat characteristics, and endocrine/metabolic biomarkers were then evaluated. Daily energy intake was similar in CT and TP rats regardless of the differences in diet. When compared with CT-ND rats, the TP-ND rats were heavier, had larger PM fat, and were characterized by basal hypoadiponectinemia and enhanced plasma levels of non-esterified fatty acid (NEFA), plasminogen activator inhibitor-1 (PAI-1), and leptin. FRD-fed CT rats, when compared with CT-ND rats, had high plasma levels of NEFA, triglyceride (TG), PAI-1, leptin, and adiponectin. The TP-FRD rats, when compared with TP-ND rats, displayed enhanced leptinemia and triglyceridemia, and were hyperinsulinemic, with glucose intolerance. The PM fat taken from TP rats displayed increase in the size of adipocytes, decrease in adiponectin (protein/gene), and a greater abundance of the leptin gene. PM adipocyte response to insulin was impaired in CT-FRD, TP-ND, and TP-FRD rats. A very short duration of isocaloric FRD intake in TP rats induced severe metabolic dysfunction at the reproductive age. Our study supports the hypothesis that the early-androgenized female rat phenotype is highly susceptible to developing endocrine/metabolic dysfunction. In turn, these abnormalities enhance the risk of metabolic syndrome, obesity, type 2 diabetes, and cardiovascular disease.

Light and Electron Microscopic Study of Thoracic Aorta in Premature Menopause-Induced Rats and the Possible Protective Role of Ginger

Introduction: Premature menopausal age increases the risk of atherosclerosis, hypertension, coronary heart disease and mortality. On the other hand, estrogen replacement therapy in menopausal women may increase the risk of breast cancer. Aim of the Work: To study the histological changes in thoracic aorta in premature menopause-induced rats and the possible protective role of Ginger. Materials and Methods: Thirty six adult female rats aged three months were used in this study. Rats were divided into two groups: group A (control group, n=12 rats) and group B (experimental group, n=24 rats). Bilateral ovariectomy was performed to the experimental group, which was then divided into two equal groups: group B1 rats fed normal diet and group B2 rats fed ginger (500 mg/kg/body weight) enriched diet. Six-months after ovariectomy, specimens from the thoracic aorta were taken, processed and examined by light microscope and scanning and transmission electron microscope. Results: Light microscopic study of thoracic aorta of group B1 showed a sub-endothelial mass of aggregated foamy cells was seen projecting into the lumen with focal degeneration in the elastic laminae below this mass. The tunica media showed large number of smooth muscles (SMCs) with vacuolated cytoplasm. Moreover, aortic aneurysm was also noticed. The mean intima-media thickness was significantly increased (103.84±7.5 μm) (*P<0.001). Scanning electron microscopic study showed irregular luminal surface of the aorta with multiple elevated streaks, endothelial projections, erosions and a large thrombus attached to the endothelium. The ultrastructure study showed Lipid-loaded monocyts attached to the endothelium and Lipid-loaded SMCs in the media. Moreover the Lipid-loaded endothelial cells showed small condensed nucleus and discontinuous cell membrane with absence of the electron dense bodies. The internal elastic lamina appeared thin and electron dense. Meanwhile light and electron microscopic study of group B2 aorta showed attenuated histopathological changes and the mean intima-media thickness was significantly decreased (83.6 ± 7.4μm μm) (*P<0.001). Conclusion: Ginger significantly attenuated the premature menopause-induced morphological changes in the rat thoracic aorta. Therefore Ginger enriched diet could be recommended for early menopausal women as well as individuals with high risk of atherosclerosis, hypertension and coronary heart disease.

Nutritional status alters saccharin intake and sweet receptor mRNA expression in rat taste buds

Sweet taste usually signifies the presence of caloric food. It is commonly accepted that a close association exists among sweet taste perception, preference, and nutritional status. However, the mechanisms involved remain unknown. To investigate whether nutritional status affects the preference for palatable solutions and alters sweet taste receptor gene expression in rats, we measured saccharin intake and preference using a two-bottle preference test, and changes in body weight, plasma leptin levels, and gene expression for the sweet taste receptor in taste buds in high-fat diet-induced obese rats and chronically diet-restricted rats. We found that the consumption and preference ratios for 0.01 and 0.04 M saccharin were significantly lower in the high-fat diet-induced obese rats than in the normal diet rats, while the serum leptin levels were markedly increased in obese rats. Consistent with the changes in saccharin intake, the gene expression level of the sweet taste receptor T1R3 was significantly decreased in the high-fat diet-induced obese rats compared with the control rats. By contrast, the chronically diet-restricted rats showed remarkably enhanced consumption and preference for 0.04 M saccharin. The serum leptin concentration was decreased, and the gene expression of the leptin receptor was markedly increased in the taste buds. In conclusion, our results suggest that nutritional status alters saccharin preference and the expression of T1R3 in taste buds. These processes may be involved in the mechanisms underlying the modulation of peripheral sweet taste sensitivity, in which leptin plays a role.

Quantitation of parvalbumin+ neurons and human immunodeficiency virus type 1 (HIV-1) regulatory gene expression in the HIV-1 transgenic rat: effects of vitamin A deficiency and morphine

Vitamin A (VA) deficiency in human immunodeficiency virus (HIV) infection has been associated with more progressive HIV disease, which may be enhanced by opioid use. In these studies, we examined the effects of VA deficiency and morphine on frontal cortex neuronal numbers in the HIV-1 transgenic (Tg) rat. These studies showed that total numbers of neurons were similar for rats on the VA-deficient diet as for rats on the normal diet and these numbers were not affected by treatment with morphine. In contrast, numbers of neurons that expressed the calcium-binding protein parvalbumin, which is a marker interneurons that express the inhibitory neurotransmitter gamma-aminobutyric acid (GABAergic neurons) were decreased for wild-type (Wt) rats on the VA-deficient diet and for Wt rats treated with morphine. In addition, parvalbumin+ neurons were also decreased for Tg rats on a normal diet but increased to normal levels when these animals were placed on the VA-deficient diet and treated with morphine. Analysis of expression of the genes that code for the HIV regulatory proteins vif, vpr, nef, and tat in frontal cortex and adjacent subcortical white matter showed that tat expression was increased in the morphine-treated Tg rat on the VA-deficient diet as compared to untreated Tg rats on the normal diet and untreated VA-deficient rats. These studies therefore suggest that VA deficiency, opioid exposure, and HIV infection alone and in combination may potentially alter neuronal metabolic activity and induce cellular stress, resulting in the observed changes in levels of parvalbumin expression. The specific mechanisms that underlie these effects require further study.

Dealcoholized red wine reverse vascular remodeling in an experimental model of metabolic syndrome: role of NAD(P)H oxidase and eNOS activity

The present study examines the effect of chronic administration of dealcoholized red wine Malbec (DRW) on vascular remodeling and NAD(P)H oxidase and endothelial nitric oxide synthase activity (eNOS) in an experimental model of metabolic syndrome induced by fructose administration. Thirty-day old male Wistar rats were fed a normal rat diet (control) or the same diet plus 10% fructose in drinking water (FFR). During the last 4 weeks of a 10-week period of the corresponding diet, a subgroup of control and FFR (n=8 each) received DRW in their drinking water. Systolic blood pressure (SBP), a homeostasis model assessment of insulin resistance (HOMA-IR), aortic NAD(P)H oxidase and eNOS activity in the heart and vascular tissue were evaluated. Vascular remodeling was evaluated in the left carotid artery (CA) and interlobar, arcuate and interlobular renal arteries (RA) through lumen to media (L/M) ratio determination. At the end of the study FFR increased the SBP (p < 0.001), HOMA-IR (p < 0.001), and aortic NAD(P)H oxidase activity (p < 0,05) but reduced cardiac and vascular eNOS activity (p < 0.01), L/M ratio in CA (p < 0.001) and RA (p < 0.01) compared with the C group. DRW reduced SBP (p < 0.05), aortic NAD(P)H oxidase (p < 0.05), and recovered eNOS activity (p < 0.001) and L/M in CA (p < 0.001) and RA (p < 0.001) compared with FFR. This study provides new data about the beneficial effect of DRW on oxidative stress and vascular remodeling in the experimental model of metabolic syndrome. Data suggest the participation of mechanisms involving oxidative stress in FFR alterations and the usefulness of natural antioxidant substances present in red wine in the reversion of these changes.

The neuroprotective effect of fish n-3 fatty acids in the hippocampus of diabetic rats

Introduction: Diabetes mellitus may lead to functional and structural changes in the brain. Fish oil is a rich source of n-3 essential fatty acids (EFA) such as eicosapentaenoic and docosahexoenoic acids. We examined the neuroprotective effects of fish n-3 EFA in the hippocampus of diabetic rats.Materials and methods: Nineteen adult male rats were divided into three groups. Group I (control; n = 6) was fed a normal rat diet. Group II (diabetic; n = 6) was fed a normal rat diet and streptozotocin (STZ) was administered to induce diabetes mellitus. Group III (n-3 + diabetic; n = 7) was fed a normal rat diet and fish n-3 EFA (Marincap®, 0.4 g/kg/day) for 8 weeks and STZ was administered to induce diabetes mellitus. The levels of malondialdehyde (MDA) and activities of superoxide dismutase (SOD) and catalase (CAT) were measured in the left hippocampus after the animals were sacrificed. The right hemisphere was completely blocked. The sections were stained with Cresyl Violet and apoptotic neurons were counted in the hippocampus.Results: The levels of MDA and activities of SOD and CAT increased in diabetic rats compared to control rats. However, the levels of MDA and activities of SOD and CAT decreased in n-3 + diabetic rats compared to diabetic rats. Also, the number of apoptotic neurons increased in diabetic rats compared to control rats and decreased in n-3 + diabetic rats compared to diabetic rats.Conclusions: Fish n-3 EFA reduces oxidative stress and induces apoptotic changes in the hippocampus of STZ-diabetic rats. The addition of fish n-3 EFA to diets may be useful to prevent functional and structural changes to cerebral centers due to diabetes mellitus.

High‐fat Diet Alters PP2A, TC10, and CIP4 Expression in Visceral Adipose Tissue of Rats

The aim of this study was to investigate a possible link between high-fat diet (HFD)-induced obesity and the expression of protein phosphatase 2A (PP2A) and Cdc42-interacting protein 4 (CIP4) proteins, potential downstream components of the IRS/PI3K/AKT and CAP/Cbl/TC10 pathway, respectively, in the visceral adipose tissue. Twenty male Sprague-Dawley rats were randomly divided into two groups and were given either HFD or the normal diet (ND) for 8 weeks. The HFD-induced changes in the expression of the epididymal adipose tissue genes involved in the insulin-signaling pathways were evaluated using real-time reverse-transcription PCR and western blot analysis. The exposure of rats to HFD for 8 weeks resulted in a significant increase in the expression of PP2A at both the transcriptional and translational levels, along with a marked reduction in the levels of phosphorylated AKT and insulin receptor substrate-1 (IRS-1) in the cytosol of visceral adipocytes, compared with the ND rats. Besides, there were significant HFD-induced decreases in the mRNA and protein levels of CIP4 and TC10 in the adipose tissue of rats. These data suggest that HFD might have a relevance to insulin resistance by increasing the expression of PP2A, an inhibitor of AKT activity in the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, and also by suppressing the expression of TC10 and CIP4, downstream effectors of the Cbl/CAP/TC10 insulin-signaling cascade in the visceral adipose tissue.

Genes are differentially expressed in the epididymal fat of rats rendered obese by a high-fat diet

The aim of present study was to identify the visceral adipose tissue genes differentially expressed in a well-characterized rat model of high-fat diet (HFD)-induced obesity. Male Sprague-Dawley rats were fed either the HFD (17 g lard + 3 g corn oil/100 g) or the normal diet (5 g corn oil/100 g) for 9 weeks. The HFD rats weighed 55% more and accumulated 85% to 133% greater visceral fats than did the normal-diet rats (P < .05). Animals given the HFD for 9 weeks acquired dyslipidemia, fatty liver, insulin resistance, and hyperleptinemia along with the overexpression of several obesity-related genes, such as leptin, tumor necrosis factor alpha, resistin, peroxisome proliferator-activated receptor gamma2, CCAAT/enhancer-binding protein alpha, and sterol regulatory element-binding protein-1c, in the epididymal adipose tissue. The differential gene expression profile obtained from the cDNA microarray analysis followed by the real-time polymerase chain reaction confirmation led to a recruitment of several uncharacterized adipose tissue genes responding to the HFD. We report herein, for the first time, that a series of genes which might be implicated in the insulin-stimulated glucose transporter 4 translocation, such as protein phosphatase 2 (formerly 2A), cell division cycle 42-interacting protein 4, syntaxin 6, linker of T-cell receptor pathways 10, as well as the genes which might be involved in cancer development, such as heat shock 10-kd protein 1, and ras-related C3 botulinum toxin substrate 1, were differentially expressed in the epididymal adipose tissue of rats rendered obese by an HFD.