Response In Wistar Rats Research Articles

Early Enhanced Beta Cell Replication in Normoglycaemic Wistar Rats in Response to a Subdiabetogenic Dose of Streptozotocin

The effect of a single subdiabetogenic dose of streptozotocin (30 mg/kg body weight) on pancreatic insulin content and relative beta cell volume has been studied in normoglycaemic Wistar rats treated with streptozotocin either 2, 3 or 14 days after STZ was given. A single intravenous injection of streptozotocin caused a significant reduction of pancreatic insulin content, islet and beta cell volume, accompanied by a significantly diminished islet insulin content. The glucose- and 3-isobutyl-1-methylxanthine-stimulated insulin secretion was significantly lower in islets obtained 2 or 3 days after streptozotocin injection compared with those of vehicle-treated controls. 14 days after streptozotocin injection, beta cell volume and pancreatic insulin content partially recovered. At this time islet insulin content and secretory responsiveness were enhanced compared to the early phase following streptozotocin administration. The incorporation of [3H] thymidine into islet DNA was significantly enhanced at day 2 or 3 after streptozotocin application, whereas at day 14 the DNA synthesis corresponded to values from control rats. Despite persisting normoglycaemia, the beta cell volume of streptozotocin-treated rats was only 52% vs. control values, thus indicating the unresponsiveness of residual beta cells to compensate spontaneously for the beta cell loss.

Environmental enrichment improves cognitive deficits in Spontaneously Hypertensive Rats (SHR): Relevance for Attention Deficit/Hyperactivity Disorder (ADHD)

The interaction between genes and environment seems to be relevant for the development of Attention Deficit/Hyperactivity Disorder (ADHD), one of the most prevalent childhood psychiatric diseases. The occurrence of ADHD is typically associated with poor academic performance, probably reflecting learning difficulties and/or cognitive impulsiveness. The inbred Spontaneously Hypertensive Rats (SHR) strain has often been considered as an animal model of ADHD, since they ‘naturally’ display the main ADHD symptomatology. Although pharmacological agents improve SHR's cognitive deficits, little is known about the involvement of environmental factors in SHR disabilities and to what extent ‘protective’ non-pharmacological factors may be considered as strategy for ADHD prevention. Here we investigated whether the rearing environment during neurodevelopment may counteract later cognitive deficits presented by adult SHR. Wistar (WIS) rats were also used to investigate whether the putative effects of environmental enrichment depend on a specific genetic background. The animals were reared in enriched environment (EE) or standard environment (SE) from the post-natal day 21 until 3 months of age (adulthood) and tested for cognitive and non-cognitive phenotypes. EE improved SHR's performance in open field habituation, water maze spatial reference, social and object recognition tasks, while non-cognitive traits, such as nociception and hypertension, were not affected by EE. Response of WIS rats was generally not affected by the present EE. These results show that the general low cognitive performance presented by SHR rats strongly depends on the rearing environment and they may suggest modifications of the familial environment as a putative preventive strategy to cope with ADHD.

Suppressive effect of quercetin on acute stress-induced hypothalamic-pituitary-adrenal axis response in Wistar rats

The flavonoid quercetin is considered to have beneficial effects on human health. We recently have shown that quercetin-enriched foods reduced the duration of immobility time in a rat forced swimming test, indicating that dietary quercetin is promising as an antidepressant-like factor, whereas its mechanism of action is poorly understood. The aim of this study is to investigate the effects of quercetin on water immersion-restraint (WIR), stress-induced hypothalamic-pituitary-adrenal (HPA) axis activation, which is a major component of stress response and plays an important role in the pathology of depression. Quercetin administration to rats significantly suppressed WIR stress-induced increase of plasma corticosterone and adrenocorticotropic hormone levels as well as the mRNA expression of corticotropin-releasing factor ( CRF) in the hypothalamic region. In addition, quercetin modulated the DNA binding activities of glucocorticoid receptor and phosphorylated cyclic adenosine 3′,5′-monophosphate (cAMP) response element binding protein as well as the phosphorylation of extracellular signal-regulated kinase 1/2 in the hypothalamic region, all of which are known to regulate the expression of CRF mRNA. Taken together, these results suggest that dietary quercetin attenuates the HPA axis activation by the suppression of the CRF mRNA expression.

Antioxidant and hepatoprotective potential of Aegle marmelos Correa. against CCl4-induced oxidative stress and early tumor events

The antioxidant properties and inhibitory effect on early tumor promoter markers of A. marmelos (25 and 50 mg/Kg b. wt. orally) have been evaluated. Male Wistar rats were pre-treated for seven consecutive days with A. marmelos prior to CCl4 (1 mL Kg− 1 body weight p. o., in corn oil [1:1 v/v]) treatment. Pre-treatment with A. marmelos suppressed lipid peroxidation (LPO), xanthine oxidase (XO) and release of serum toxicity marker enzymes viz, SGOT, LDH, SGPT dose-dependently and significantly (p < 0.001). Hepatic antioxidant status viz, reduced glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), quinone reductase (QR), catalase (CAT) were concomitantly restored in A. marmelos-treated groups (p < 0.001). In addition, A. marmelos pretreatment also prevented the CCl4-enhanced ornithine decarboxylase (ODC) and hepatic DNA synthesis significantly (p < 0.001). In conclusion, carbon tetrachloride-induced liver toxicity was strikingly attenuated by A. marmelos treatment and the study gives some insight into the mechanisms involved in diminution of free radical generating toxicants and enhancement of the antioxidant armory, hence preventing further tissue damage, injury and hyperproliferation.Thus, these findings indicate that A. marmelos attenuates CCl4-mediated hepatic oxidative stress, toxicity, tumor promotion and subsequent cell proliferation response in Wistar rats.

Spatial Memory Perfomance of Wistar Rats Exposed to Mobile Phone

INTRODUCTIONWith the tremendous increase in number of mobile phone users world wide, the possible risks of this technology have become a serious concern.OBJECTIVEWe tested the effects of mobile phone exposure on spatial memory performance.MATERIALS AND METHODSMale Wistar rats (10–12 weeks old) were exposed to 50 missed calls/day for 4 weeks from a GSM (900/1800MHz) mobile phone in vibratory mode (no ring tone). After the experimental period, the animals were tested for spatial memory performance using the Morris water maze test.RESULTSBoth phone exposed and control animals showed a significant decrease in escape time with training. Phone exposed animals had significantly (~3 times) higher mean latency to reach the target quadrant and spent significantly (~2 times) less time in the target quadrant than age- and sex-matched controls.CONCLUSIONMobile phone exposure affected the acquisition of learned responses in Wistar rats. This in turn points to the poor spatial navigation and the object place configurations of the phone-exposed animals.

Rat Strain Differences in Pulmonary Artery Smooth Muscle Ca2+Entry Following Chronic Hypoxia

Effects of chronic hypoxia (CH) on store- and receptor-operated Ca(2+) entry (SOCE, ROCE) in pulmonary vascular smooth muscle (VSM) are controversial, although whether genetic variation explains such discrepancies in commonly studied rat strains is unclear. Since protein kinase C (PKC) can inhibit Ca(2+) permeable nonselective cation channels, we hypothesized that CH differentially alters PKC-dependent inhibition of SOCE and ROCE in pulmonary VSM from Sprague-Dawley and Wistar rats. To test this hypothesis, we examined SOCE and endothelin-1 (ET-1)-induced ROCE in endothelium-disrupted, pressurized pulmonary arteries from control and CH Sprague-Dawley and Wistar rats. Basal VSM Ca(2+) was elevated in CH Wistar, but not Sprague-Dawley, rats. Further, CH attenuated SOCE in VSM from Sprague-Dawley rats, while augmenting this response in Wistar rats. CH reduced ROCE in arteries from both strains. PKC inhibition restored SOCE in CH Sprague-Dawley arteries to control levels, while having no effect on SOCE in Wistar arteries or on ROCE in either strain. We conclude that effects of CH on pulmonary VSM SOCE are strain dependent, whereas inhibitory effects of CH on ROCE are strain independent. Further, PKC inhibits SOCE following CH in Sprague-Dawley, but not Wistar, rats but does not contribute to ET-1-induced ROCE in either strain.

Playback of 22-kHz and 50-kHz ultrasonic vocalizations induces differential c-fos expression in rat brain

Rodent ultrasonic vocalizations, which serve as sensitive measures in a number of relevant individual and social behaviours, have become increasingly interesting for biopsychological studies on emotion and motivation. Of these, high frequency (50-kHz) ultrasonic vocalizations can index a positive emotional state, and induce approach, whereas low frequency (22-kHz) ultrasonic vocalizations can induce avoidance and may index anxiety, since they are emitted during various unconditioned and conditioned aversive situations. While cholinergic and dopaminergic systems have been implicated, specific neural substrates that sub-serve these vocalization-dependent states remain to be elucidated. Using c-fos immunocytochemistry, we revealed neural activity in brain areas of naïve male Wistar rats in response to playback of 22-kHz and flat and frequency-modulated 50-kHz ultrasonic vocalizations. Presentation of background noise or no acoustic stimulus at all constituted the controls. Playback of 50-kHz ultrasonic vocalizations led to approach behaviour. Acoustically stimulated animals demonstrated differential activation in auditory areas, with a frequency-dependent activation in the auditory cortex. Specific forebrain, thalamic, hypothalamic and brainstem areas were also activated differentially. While 50-kHz playback induced sparse fos-like immunoreactivity in frontal association cortex, nucleus accumbens, thalamic parafascicular and paraventricular nuclei, 22-kHz playback elicited c-fos expression in the perirhinal cortex, amygdalar nuclei and the periaqueductal gray. This study unveils neural substrates that are activated during ultrasonic playback perception, which could sub-serve the affective states elicited by these vocalizations.

Biocompatibility of different intracanal medications in rat bucal submucosa tissue

The aim of this study was to analyze the buccal tissue responses of Wistar rats to 2% chlorhexidine solution, calcium hydroxide and the association of both products. For this purpose, 30 specimens were randomly implanted in the filtrum of the four upper and lower hemiarches with a polyethylene tube containing one of the following substances: 2% chlorhexidine solution, calcium hydroxide and 2% chlorhexidine solution (test groups); calcium hydroxide and distilled water and distilled water (control groups). Ten rats each were distributed according to time interval of evaluation at 7, 15 and 30 days. The histological sections were stained with Harris hematoxylin and eosin. Analysis was performed with an optical microscope at x100, x200 and x400 magnifications by an expert examiner blinded to the materials. The sections were classified by scores attributed to inflammatory events and by a ranking determined according to the severity of the inflammation. The results of the inflammatory events and severity ranking were submitted to the Kruskal-Wallis test at a 0.05 level of significance. No statistically significant difference occurred among the tested materials; however, all materials showed a decreased of severity with respect to longer time intervals.

Analysis of the anxiolytic-like effect of TRH and the response of amygdalar TRHergic neurons in anxiety

Thyrotropin-releasing hormone (TRH) was first described for its neuroendocrine role in controlling the hypothalamus-pituitary-thyroid axis (HPT). Anatomical and pharmacological data evidence its participation as a neuromodulator in the central nervous system. Administration of TRH induces various behavioural effects including arousal, locomotion, analepsy, and in certain paradigms, it reduces fear behaviours. In this work we studied the possible involvement of TRHergic neurons in anxiety tests. We first tested whether an ICV injection of TRH had behavioural effects on anxiety in the defensive burying test (DBT). Corticosterone serum levels were quantified to evaluate the stress response and, the activity of the HPT axis to distinguish the endocrine response of TRH injection. Compared to a saline injection, TRH reduced cumulative burying, and decreased serum corticosterone levels, supporting anxiolytic-like effects of TRH administration. The response of TRH neurons was evaluated in brain regions involved in the stress circuitry of animals submitted to the DBT and to the elevated plus maze (EPM), tests that allow to correlate biochemical parameters with anxiety-like behaviour. In the DBT, the response of Wistar rats was compared with that of the stress-hypersensitive Wistar Kyoto (WKY) strain. Behavioural parameters were analysed in recorded videos. Animals were sacrificed 30 or 60min after test completion. In various limbic areas, the relative mRNA levels of TRH, its receptors TRH-R1 and -R2, and its inactivating ectoenzyme pyroglutamyl peptidase II (PPII), were determined by RT-PCR, TRH tissue content by radioimmunoassay (RIA). The extent of the stress response was evaluated by measuring the expression profile of CRH, CRH-R1 and GR mRNA in the paraventricular nucleus (PVN) of the hypothalamus and in amygdala, corticosterone levels in serum. As these tests demand increased physical activity, the response of the HPT axis was also evaluated. Both tasks increased the levels of serum corticosterone. WKY rats showed higher anxiety-like behaviour in the DBT than Wistar, as well as increased PVN mRNA levels of CRH and GR. TRH mRNA levels increased in the PVN and TSH values remained unchanged in both strains although TRH content decreased in the medial basal hypothalamus of Wistar rats only. TRH content was measured in several limbic regions but only amygdala showed specific task-related changes after DBT exposure of both strains: increased TRH content. Expression of TRH mRNA decreased in the amygdala of Wistar, suggesting inhibition of TRHergic neuronal activity in this region. The participation of amygdalar TRH neurons in anxiety was confirmed in the EPM where TRH expression and release correlated with the number of entries, and the % of time spent in open arms, supporting an anxiolytic role of these TRH-neurons. These results contribute to the understanding of the involvement of TRH during emotionally charged situations and shed light on the participation of particular circuits in related behaviours.

Immune response in Wistar rats with high and low level of situational anxiety

A large sample of Wistar rats was divided into 2 groups of high-anxiety and low-anxiety animals by the time spent in the open arms of the elevated plus-maze. This selection was based on the criterion of time (low-anxiety animals, not less than 10 sec; high-anxiety animals, not more than 2 sec). Immunization with T-dependent antigen was performed on the day of behavioral testing. The number of rosette-forming cells in high-anxiety rats significantly decreased on day 5 after immunization. A genetically determined relationship probably exists between low activity of the immune response and high level of reactive anxiety.

Continuous infusion of the cannabinoid WIN 55,212-2 to the site of a peripheral nerve injury reduces mechanical and cold hypersensitivity.

Cannabinoids have analgesic and anti-inflammatory properties but their use is limited by psychotropic activity at CNS receptors. Restricting cannabinoid delivery to peripheral tissues at systemically inactive doses offers a potential solution to this problem. WIN 55,212-2 was continuously delivered to the site of a partial ligation injury to the sciatic nerve via a perineural catheter connected to a mini-osmotic pump implanted at the time of injury. Bilateral reflex limb withdrawal behaviour was measured in adult male Wistar rats in response to mechanical and cooling stimulation of the hind paw. Compared with vehicle treatment, WIN 55,212-2 (1.4 microg microl(-1) hr(-1)) reduced hypersensitivity to stimuli applied to the injured limb at 2, 4 and 6 days after injury. The effects of WIN 55,212-2 (0.6-2.8 microg microl(-1) hr(-1)) were dose-dependent. Estimated EC(50) values for reduction in mean responses to mechanical and cooling stimulation (day 4 post-surgery) were 1.55 (95% C.I, [1.11-2.16]) microg microl(-1) hr(-1) and 1.52 (95% C.I, [1.07-2.18]) microg microl(-1) hr(-1), respectively. When delivered to the contralateral side to injury, WIN 55,212-2 (1.4 or 2.8 microg microl(-1) hr(-1)) did not significantly affect nerve injury-associated hypersensitivity. Co-perineural application of a CB(1) receptor antagonist SR141716a and WIN 55,212-2 prevented the effects of WIN 55,212-2 on hypersensitivity. Co-application of CB(2) receptor antagonist SR144528 reversed WIN 55,212-2's effect on mechanical hypersensitivity on day 2 only. These data support a peripheral antihyperalgesic effect of WIN 55,212-2 when delivered directly to the site of a nerve injury at systemically inactive doses.

Effect of gallic acid on renal biochemical alterations in male Wistar rats induced by ferric nitriloacetic acid

The present study is an effort to identify a potent chemopreventive agent against various diseases (including cancer) in which oxidative stress and cell proliferation plays an important causative role. This study was designed to investigate the effect of gallic acid against ferric nitrilotriacetic acid (Fe-NTA)-induced carcinogen/ drug metabolizing phase I and phase II enzymes, antioxidative parameters, kidney markers, tumour promotion markers and lipid peroxidation (LPO) in kidney of male Wistar rats. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) caused significant depletion in the detoxification and antioxidant enzyme armoury with concomitant elevation in renal LPO, serum creatinine, blood urea nitrogen, hydrogen peroxide generation, ornithine decarboxylase activity and [3H]thymidine incorporation into renal DNA. However, pretreatment of animals with gallic acid (10 and 20 mg/kg body weight) resulted in a significant decrease in the levels of the parameters measured (P <0.001). Renal glutathione content (P <0.001), glutathione metabolizing enzyme (P <0.001) and antioxidant enzyme levels were also recovered to a significant level (P <0.001). The enhanced reduced glutathione level and enzyme activities involved in xenobiotic metabolism and maintaining antioxidant status of cells are suggestive of a chemopreventive efficacy of gallic acid against Fe-NTA-mediated oxidative stress, toxicity and cell proliferative response in Wistar rats.

Tamarix gallica ameliorates thioacetamide–induced hepatic oxidative stress and hyperproliferative response in Wistar rats

Tamarix gallica, a hepatic stimulant and tonic, was examined for its ability to inhibit thioacetamide (TAA)-induced hepatic oxidative stress, toxicity and early tumor promotion response in male Wistar rats. TAA (6.6 mmol/kg body wt. i.p) enhanced lipid peroxidation, hydrogen peroxide content, glutathione S-transferase and xanthine oxidase with reduction in the activities of hepatic antioxidant enzymes viz., glutathione peroxidase, superoxide dismutase and caused depletion in the level of hepatic glutathione content. A marked increase in liver damage markers was also observed. TAA treatment also enhanced tumor promotion markers, ornithine decarboxylase (ODC) activity and [3H] thymidine incorporation into hepatic DNA. Pretreatment of rats orally with Tamarix gallica extract (25 and 50 mg/kg body weight) prevented TAA-promoted oxidative stress and toxicity. Prophylaxis with Tamarix gallica significantly reduced the susceptibility of the hepatic microsomal membrane for iron-ascorbate induced lipid peroxidation, H2O2 content, glutathione S-transferase and xanthine oxidase activities. There was also reversal of the elevated levels of liver marker parameters and tumor promotion markers. Our data suggests that Tamarix gallica is a potent chemopreventive agent and may suppress TAA-mediated hepatic oxidative stress, toxicity, and tumor promotion response in rats.

Inhibition of potassium bromate-induced renal oxidative stress and hyperproliferative response by Nymphaea alba in Wistar rats

KBrO3-mediated renal injury and hyperproliferative response in Wistar rats. In this communication, we report the efficacy of Nymphaea alba on KBrO3 (125 mg/kg body weight, intraperitoneally) caused reduction in renal glutathione content, renal antioxidant enzymes and phase-II metabolising enzymes with enhancement in xanthine oxidase, lipid peroxidation, γ-glutamyl transpeptidase and hydrogen peroxide (H2O2). It also induced blood urea nitrogen, serum creatinine and tumor promotion markers, viz., ornithine decarboxylase (ODC) activity and DNA synthesis. Treatment of rats with Nymphaea alba (100 and 200 mg/kg body weight) one hour before KBrO3 (125 mg/kg body weight, i.p.) resulted in significant decreases in xanthine oxidase lipid peroxidation, γ-glutamyl transpeptidase, H2O2 generation, blood urea nitrogen, serum creatinine, renal ODC activity and DNA synthesis Renal glutathione content, glutathione metabolizing enzymes and antioxidant enzymes were also recovered to significant levels These results show that Nymphaea alba acts as chemopreventive agent against KBrO3-mediated renal injury and hyperproliferative response.

Chemomodulatory effect of Ficus racemosa extract against chemically induced renal carcinogenesis and oxidative damage response in Wistar rats

Ferric nitrilotriacetate (Fe-NTA) is a well-known renal carcinogen. In this communication, we show the chemopreventive effect of Ficus racemosa extract against Fe-NTA-induced renal oxidative stress, hyperproliferative response and renal carcinogenesis in rats. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) enhances renal lipid peroxidation, xanthine oxidase, γ-glutamyl transpeptidase and hydrogen peroxide (H 2O 2) generation with reduction in renal glutathione content, antioxidant enzymes, viz., glutathione peroxidase, glutathione reductase, catalase, glucose-6-phosphate dehydrogenase and phase-II metabolising enzymes such as glutathione- S-transferase and quinone reductase. It also enhances blood urea nitrogen, serum creatinine, ornithine decarboxylase (ODC) activity and thymidine [ 3H] incorporation into renal DNA. It also enhances DEN ( N-diethylnitrosamine) initiated renal carcinogenesis by increasing the percentage incidence of tumors. Treatment of rats orally with F. racemosa extract (200 and 400 mg/kg body weight) resulted in significant decrease in γ-glutamyl transpeptidase, lipid peroxidation, xanthine oxidase, H 2O 2 generation, blood urea nitrogen, serum creatinine, renal ODC activity, DNA synthesis ( P < 0.001) and incidence of tumors. Renal glutathione content ( P < 0.01), glutathione metabolizing enzymes ( P < 0.001) and antioxidant enzymes were also recovered to significant level ( P < 0.001). Thus, our data suggests that F. racemosa extract is a potent chemopreventive agent and suppresses Fe-NTA-induced renal carcinogenesis and oxidative damage response in Wistar rats.

Induction of renal oxidative stress and cell proliferation response by ferric nitrilotriacetate (Fe-NTA): diminution by soy isoflavones

Ferric nitrilotriacetate (Fe-NTA) is a known potent nephrotoxic agent. In this communication, we report the chemopreventive effect of soy isoflavones on renal oxidative stress, toxicity and cell proliferation response in Wistar rats. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) enhances γ-glutamyl transpeptidase, renal lipid peroxidation, xanthine oxidase and hydrogen peroxide (H 2O 2) generation with reduction in renal glutathione content, antioxidant enzymes, viz., glutathione peroxidase, glutathione reductase, catalase, glucose-6-phosphate dehydrogenase and phase-II metabolising enzymes such as glutathione-S-transferase and quinone reductase. Fe-NTA treatment also induced tumor promotion markers, viz., ornithine decarboxylase (ODC) activity and thymidine [ 3 H ] incorporation into renal DNA. A sharp elevation in the levels of blood urea nitrogen and serum creatinine has also been observed. Treatment of rats orally with soy isoflavones (5 mg/kg body weight and 10 mg/kg body weight) resulted in significant decreases in γ-glutamyl transpeptidase, lipid peroxidation, xanthine oxidase, H 2O 2 generation, blood urea nitrogen, serum creatinine, renal ODC activity and DNA synthesis ( P < 0.001). Renal glutathione content ( P < 0.01), glutathione metabolizing enzymes ( P < 0.001) and antioxidant enzymes were also returned to normal levels ( P < 0.001). Thus, our data suggest that soy isoflavones may be used as an effective chemopreventive agent against Fe-NTA-mediated renal oxidative stress, toxicity and cell proliferation response in Wistar rats.

Abrogation of potassium bromate-induced renal oxidative stress and subsequent cell proliferation response by soy isoflavones in Wistar rats.

Potassium bromate (KBrO3) is a potent nephrotoxic agent. In this study, we show the modulatory effect of soy isoflavones on KBrO3-mediated renal oxidative stress and subsequent cell proliferation response in Wistar rats. KBrO3 (125 mg/kg body weight, intraperitoneally) caused reduction in renal glutathione content, activities of renal anti-oxidant enzymes, viz., glutathione peroxidase, glutathione reductase, catalase, glucose-6-phosphate dehydrogenase and phase-II metabolising enzymes such as glutathione-S-transferase and quinone reductase with enhancement in xanthine oxidase, lipid peroxidation, gamma-glutamyl transpeptidase and hydrogen peroxide (H2O2). KBrO3 treatment also induced blood urea nitrogen, serum creatinine and tumor promotion markers, viz., ornithine decarboxylase (ODC) activity and thymidine [3H] incorporation into renal DNA. Treatment of rats orally with soy isoflavones (5 mg/kg body weight and 10 mg/kg body weight) resulted in a significant decrease in xanthine oxidase (P < 0.05), lipid peroxidation, gamma-glutamyl transpeptidase, H2O2 generation, blood urea nitrogen, serum creatinine, renal ODC activity and DNA synthesis (P < 0.001). There was also significant recovery of renal glutathione content (P < 0.01), anti-oxidant enzymes and phase-II metabolising enzymes (P < 0.001). Thus, our results show that soy isoflavones acts as potent chemopreventive agent against KBrO3-mediated renal oxidative stress, toxicity and subsequent cell proliferation response in Wistar rats.

Attenuation of potassium bromate-induced nephrotoxicity by coumarin (1,2-benzopyrone) in Wistar rats: chemoprevention against free radical-mediated renal oxidative stress and tumor promotion response

We report the modulatory effect of coumarin (1,2-benzopyrone) on potassium bromate (KBrO3) mediated nephrotoxicity in Wistar rats. KBrO3 (125 mg/kg body weight, i.p.) enhances γ-glutamyl transpeptidase, renal lipid peroxidation, xanthine oxidase and hydrogen peroxide (H2O2) generation with reduction in renal glutathione content and antioxidant enzymes. It also enhances blood urea nitrogen, serum creatinine, ornithine decarboxylase (ODC) activity and [3H]-thymidine incorporation into renal DNA. Treatment of rats orally with coumarin (10 mg/kg body weight and 20 mg/kg body weight) resulted in a significant decrease in γ-glutamyl transpeptidase, lipid peroxidation, xanthine oxidase, H2O2 generation, blood urea nitrogen, serum creatinine, renal ODC activity and DNA synthesis (P < 0.001). Renal glutathione content (P < 0.01) and antioxidant enzymes were also recovered to significant level (P < 0.001). These results show that coumarin may be used as an effective chemopreventive agent against KBrO3-mediated renal oxidative stress, toxicity and tumor promotion response in Wistar rats.

Ephedrae herba in Mao-Bushi-Saishin-To Inhibits IgE-Mediated Histamine Release and Increases cAMP Content in RBL-2H3 Cells

Acute effect of Mao-Bushi-Saishin-To (Ma-Huang-Fu-Zi-Xi-Xin-Tang in Chinese: MBS) on histamine release was investigated. The IgE-mediated anaphylaxic response in Wistar rats was significantly suppressed by MBS and Mao. However, Saishin and Bushi had no or little effect on the antigen-mediated anaphylaxic reaction. Mao as well as MBS but not Saishin nor Bushi inhibited IgE-mediated histamine release from rat basophilic leukemia (RBL-2H3) cells. Consistently, MBS and Mao but not Bushi nor Saishin increased cAMP levels in RBL-2H3 cells. However, ephedrine, methylephedrine, and pseudoephedrine, the main components in Mao, did not affect histamine release. From these results, increase of cAMP levels may account for the inhibitory effect of Mao on histamine release. Furthermore, these inhibitory actions of MBS were mainly due to Mao with an ingredient(s) different from ephedrines.

Temporal effects of left versus right middle cerebral artery occlusion on spleen lymphocyte subsets and mitogenic response in Wistar rats

The left and right neocortex of the brain has been shown to exert asymmetrical effects on the immune system. In the present study, we used a middle cerebral artery (MCA) occlusion model in Wistar rats to analyze the influence of unilateral CNS ischemia on spleen cell number and function. The occlusion time was 1 h, followed by reperfusion with survival for 0, 2, 7, 14, and 28 days. Changes in plasma norepinephrine levels were used as an index of peripheral sympathetic activity. Results showed that the total number of spleen cells significantly decreased after 2–28 days of survival in animals with cerebral ischemia compared to sham-operated controls. There was no change in the percentage of CD5 +-CD4 + T cells, MHC class II + cells, or ED1 + macrophages. However, the percentage of CD5 +-CD8 + T cells decreased at 2 days, resulting in an increased CD4/CD8 ratio, and both parameters returned to control levels after 7 days. Mitogen-induced T and B lymphocyte proliferation increased after 0–28 days post-ischemia independently of the mitogen used. There was no difference in immune response or norepinephrine levels between left and right MCA occlusions. These results are consistent with the notion that cerebral ischemia induces mobilization of certain immune cells from the periphery to the brain, where they may contribute to the local inflammatory response. Additionally, the data indicate that cerebral ischemia is followed by a systemic activation of T and B lymphocytes. Absence of asymmetric effects of left versus right stroke, and failure to demonstrate any suppressive effects of left-sided lesions on lymphocyte proliferation, probably reflects the fact that these large cerebral ischemic lesions affect both cortical and subcortical areas.