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In this study, we evaluated the hypothesis that long term dietary restriction would have beneficial effects on the oxidative stress and antioxidant enzyme systems in liver, heart and kidney in adult mate rats undergoing different intensities of swimming exercise. Sixty male, Sprague-Dawley rats were assigned as either dietary restricted on every other week day (DR) or fed ad libitum (AL) groups, and each group was further subdivided into sedentary, endurance swimming exercise training (submaximal exercise) and exhaustive swimming exercise (maximal exercise) groups. Animals in the submaximal exercise group swam 5 days/week for 8 weeks, while maximal exercise was performed as an acute bout of exercise. In parallel with the increase in the intensity of the exercise, the degree of lipid peroxidation and protein oxidation were increased in both the DR and AL groups; however the rate of increase was lower in the DR group. Reduced glutathione (GSH), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) enzyme activities were lower in the DR group than in the AL group. In parallel with the increase in exercise intensity, GSH and GR enzyme activities decreased, whereas an increase was observed in GSH-Px enzyme activity. In conclusion, the comparison between the DR and AL groups with the three swimming exercise conditions shows that the DR group is greatly protected against different swimming exercise-induced oxidative stress compared with the AL group.

Developmental exposure to endocrine disrupting drugs and environmental toxicants has been shown to alter a variety of physiological processes in mature offspring. Body (core) temperature (T-c) is a tightly regulated homeostatic system but is susceptible to disruptors of the hypothalamic pituitary thyroid (HPT) axis. We hypothesized that thermoregulation would be disrupted in adult offspring exposed perinatally to an HPT disruptor. Propylythiouracil (PTU) was used as a prototypical compound because of its well known antithyroidal properties. FLU was added to the drinking water of pregnant rats in concentrations of 0, 1, 2, 3, and 10 ppm from gestational day (GD) 6 through postnatal day (PND) 21. Adult male offspring were implanted with radiotransmitters to monitor T-c and motor activity (MA) and were observed undisturbed at an ambient temperature of 22 degrees C for 12 consecutive days. Data were averaged into a single 24 hour period to minimize impact of ultradian changes in T-c and MA. All treatment groups showed a distinct circadian temperature rhythm. Rats exposed to 10 ppm FLU exhibited a marked deviation in their regulated T-c with a reduction of approximately 0.4 degrees C below that of controls throughout the daytime period and a smaller reduction at night. Rats exposed to 1 or 2 ppm also had smaller but significant reductions in T-c. MA was unaffected by PTU. Overall, developmental exposure to moderate doses of an antithyroidal drug led to an apparent permanent reduction in T-c of adult offspring that was independent of changes in MA Published by Elsevier Inc.

Melittin is a polypeptide component of bee venom that leads to an increase in arachidonic acid release and subsequently in prostaglandin synthesis by activating phospholipase A 2 . Recently we demonstrated that centrally or peripherally administrated melittin caused pressor effect and central thromboxane A 2 (TXA 2 ) and cholinergic system mediated these effects of melittin. Also centrally injected histamine leads to pressor and bradycardic response by activating central histamine receptors in normotensive rats and central cholinergic system involved the effects of histamine. The present study demonstrates an involvement of the central histaminergic system in melittin-induced cardiovascular effect in normotensive rats. Experiments were carried out in male Sprague Dawley rats. Intracerebroventricularly (i.c.v.) injected melittin (0.5, 1 and 2nmol) caused dose- and time-dependent increases in mean arterial pressure (MAP) and decrease in heart rate (HR) as we reported previously. Moreover, H 2 receptor antagonist ranitidine (50nmol; i.c.v.) almost completely and H 3 /H 4 receptor antagonist thioperamide (50nmol; i.c.v.) partly blocked melittin-evoked cardiovascular effects, whereas H 1 receptor blocker chlorpheniramine (50nmol; i.c.v.) had no effect. Also centrally injected melittin was accompanied by 28% increase in extracellular histamine concentration in the posterior hypothalamus, as shown in microdialysis studies. In conclusion, results show that centrally administered melittin causes pressor and bradycardic response in conscious rats. Moreover, according to our findings, there is an involvement of the central histaminergic system in melittin-induced cardiovascular effects.

Physical restraint of rodents is needed for nose-only exposure to airborne toxicants and is also used as a means of psychological stress. Hyperthermia is often observed in restrained rats, presumably as a result of impairments in heat dissipation. However, such a hyperthermic response should be dependent on the prevailing ambient conditions. To understand how ambient temperature (T(a)) affects the thermoregulatory response to restraint, core temperature (T(c)) and heart rate (HR) were monitored by telemetry in rats subjected to 1 h of physical restraint while T(a) was maintained at 14-30 °C in 2 °C increments. The T(c) of unrestrained rats was unaffected by T(a). During restraint, T(c) was elevated at ambient temperatures with the exception of 14 °C, at which the rats became mildly hypothermic. There was an inverse relationship between T(a) and HR in both unrestrained and restrained rats; however, HR was significantly elevated in restrained rats at all ambient temperatures except 22 and 24 °C. Heat loss from the tail, estimated from T(c) and tail skin temperature, was markedly reduced at all but the highest ambient temperatures in restrained rats. The data suggest that the T(a) limits of normothermia are narrowed in the restrained rat. That is, between 16 and 20 °C, the rat maintains a relatively stable T(c) that is slightly elevated above that of the unrestrained rat. At ambient temperatures above or below this range, the rat shows signs of hyperthermia and hypothermia, respectively. In contrast, the limits of normothermia for unrestrained rats range from 14 (or lower) to 30 °C. Overall, the ideal T(a) for restrained rats appears to be 20 °C and no higher than 22 °C for the thermoregulatory system to maintain a regulated T(c) in rats well adapted to physical restraint.

The aim of the current study was to elucidate the underlying central mechanism(s) of the cardiovascular effects evoked by centrally injected melittin and arachidonic acid (AA) in hemorrhaged hypotensive condition, specifically, from central AA release from the cell membrane under the influence of phospholipase A(2) (PLA(2)) to central thromboxane A(2) (TXA(2)) signaling via the cyclooxygenase (COX) pathway. As the main control of the study, melittin (3 mu g) or AA (150 mu g) was injected intracerebroventricularly (i.c.v.) after the hemorrhage procedure, which was performed by withdrawing a total volume of 2.2 ml of blood/100 g body weight over a period of 10 min. Both treatments generated a pressor response and abolished the hypotension-induced hemorrhage. Pretreatment with the PLA(2) inhibitor mepacrine (500 mu g; i.c.v.) completely blocked the pressor response to melittin in the hemorrhagic hypotensive state. Pretreatments with the nonselective COX inhibitor indomethacin (200 mu g; i.c.v.) or the TXA(2) synthesis inhibitor furegrelate (250 or 500 mu g; i.c.v.) were made to test the role of central COX activity and, subsequently, the TXA(2) signaling pathway in the melittin- or AA-mediated reversal of hemorrhagic hypotension. Indomethacin completely prevented the pressor response to melittin and AA in the hemorrhaged, hypotensive state, but furegrelate did so only partially. In conclusion, these findings suggest that central COX activity and, subsequently, the central TXA(2) signaling pathway, are, at least in part, involved in the melittin- or AA-induced reversal effect during hemorrhagic shock.

1. The aims of the present study were to determine the cardiovascular effects of arachidonic acid (AA) and to investigate the peripheral mechanisms mediating these effects in haemorrhage-induced hypotensive rats. 2. Acute haemorrhage was induced by withdrawing a total volume of 2.2 mL blood/100 g bodyweight over a period of 10 min. Rats were then injected with 75-300 microg, i.c.v., AA and cardiovascular changes were monitored over the next 60 min. Plasma catecholamine and vasopressin levels, as well as plasma renin activity (PRA), were measured 10 min after injection of 150 microg AA in haemorrhage-induced hypotensive awake rats. In addition, rats were pretreated with saline (1 mL/kg, i.v.), the vasopressin V(1) receptor antagonist [beta-mercapto-beta,beta-cyclopentamethylenepropionyl(1),O-Me-Tyr(2),Arg(8)]-vasopressin (10 microg/kg, i.v.), the alpha(1)-adrenoceptor antagonist prazosin (500 microg/kg, i.v.), the non-specific angiotensin II receptor antagonist saralasin (250 microg/kg, i.v.) or a combination of these three antagonists 5 min before injection of AA (150 microg, i.c.v.). The effects of these antagonists on responses to AA were determined. 3. Arachidonic acid caused dose- and time-dependent increases in mean arterial pressure and heart rate and reversed hypotension in haemorrhaged rats. Haemorrhage itself produced an increase in plasma catecholamine and vasopressin levels, as well as PRA; injection of AA produced further increases in these parameters, ranging from 39-123%, under hypotensive conditions. Under hypotensive conditions, pretreatment of rats with all three receptor antagonists produced similar partial blockade of the pressor response to AA, but not the increase in heart rate. Moreover, combined administration of all three receptor antagonists prior to the i.c.v. injection of 150 microg AA completely abolished the pressor response to AA in haemorrhage-induced hypotensive rats. 4. These results indicate that centrally administered AA reverses hypotension by increasing blood pressure and heart rate in the hypotensive setting. The observed increases in plasma catecholamine and vasopressin levels, as well as PRA, mediate the pressor response to AA in haemorrhage-induced hypotensive rats.

Exhaustive exercise may generate oxidative stress in brain and reported findings are conflicting. Long term dietary restriction (DR) may be useful in the inhibiting of free oxygen radicals generated during exhaustive exercise in the brain of rat. Hence, in this study we evaluated beneficial effects of long term DR on the oxidative stress and antioxidant enzyme systems in brain cortex and lung in rats after different intensities of swimming exercise. Sprague-Dawley rats (60) were assigned as DR and ad libitum (AL) groups, and each group was further subdivided into three groups namely control (sedentery), submaximal exercise (endurance exercise) and maximal exercise (exhaustive swimming exercise) groups. Animals in the endurance exercise group swam 5 days/week for 8 weeks while exhaustive swimming group was subjected to an acute bout of exercise. With the increase in intensity of exercise, degree of lipid peroxidation (LP) and protein oxidation (PO) were also increased in DR and AL groups; however rate of increase was lower in DR group than AL group. Glutathione (GSH) and glutathione peroxidase (GSH-Px) activity were lower but glutathione reductase (GR) activity was higher in DR group compared to AL group in endurance and exhaustive swimming exercise. With increase in exercise intensity, GSH and GR enzyme activity decreased, whereas an increase was observed in GSH-Px enzyme activity. There was no difference in LP, PO, GSH and GR activity between DR and AL groups. GSH-Px activity in brain cortex was significantly lower in DR group than in AL group and sedentary rats. Results indicate that long term dietary restriction may protect against endurance and exhaustive swimming exercise-induced oxidative stress in rats by inhibiting oxidative stress.

Recently we demonstrated that centrally administrated melittin, a phospholipase A(2) (PLA(2)) activator, caused the pressor effect in normotensive, conscious rats. In the present study, we aimed to determine the cardiovascular effect of peripherally injected melittin and the involvement of the central cholinergic system on these effects in the normotensive conscious rats. For this reason, 250, 500 or 1000microg/kg doses of melittin were injected intraperitoneally to normotensive male Sprague Dawley rats. Melittin produced dose- and time-dependent increases in mean arterial pressure (MAP) and heart rate (HR). Both peripheral (5mg/kg; i.p.) and central (500microg; i.c.v.) pretreatment with indomethacin, nonselective inhibitor of cyclooxygenase (COX) 1 and 2, totally abolished cardiovascular effect of melittin. Intraperitoneal (i.p.) pretreatment with propranolol, a nonselective beta-adrenergic receptor blocker, completely abolished the tachycardic response to melittin. Also, the pressor effect of melittin was partially attenuated in these rats. In order to test the mediation of the central cholinergic system on the pressor and tachycardic effects of melittin, the rats were pretreated with atropine sulfate (10microg; i.c.v.), a cholinergic nonselective muscarinic receptor antagonist, mecamylamine (50microg; i.c.v.), a cholinergic nonselective nicotinic receptor antagonist, methyllycaconitine (10microg; i.c.v.) or alpha-bungarotoxin (10microg; i.c.v.), selective antagonists of alpha7 subtype nicotinic acetylcholine receptors (alpha7nAChRs) 15min prior to melittin (500microg/kg; i.p.) injection. Pretreatment with mecamylamine, methyllycaconitine or alpha-bungarotoxin partially diminished the pressor and tachycardic response to melittin in the normotensive conscious rats whereas pretreatment with atropine sulfate had no effect. In conclusion, our data demonstrate that peripherally administered melittin exerts a clear pressor and tachycardic effect by activating COX pathway. The activation of central cholinergic nicotinic receptors, predominantly alpha7nAChRs, appears to be involved in the pressor and tachycardic effects of the drug.

In the current study, we aimed to determine the cardiovascular effects of arachidonic acid and peripheral mechanisms mediated these effects in normotensive conscious rats. Studies were performed in male Sprague Dawley rats. Arachidonic acid was injected intracerebroventricularly (i.c.v.) at the doses of 75, 150 or 300 microg and it caused dose- and time-dependent increase in mean arterial pressure and decrease in heart rate in normal conditions. Maximal effects were observed 10 min after 150 and 300 microg dose of arachidonic acid and lasted within 30 min. In order to evaluate the role of main peripheral hormonal mechanisms in those cardiovascular effects, plasma adrenaline, noradrenaline, vasopressin levels and renin activity were measured after arachidonic acid (150 microg; i.c.v.) injection. Centrally injected arachidonic acid increased plasma levels of all these hormones and renin activity. Intravenous pretreatments with prazosin (0.5 mg/kg), an alpha1 adrenoceptor antagonist, [beta-mercapto-beta,beta-cyclopentamethylenepropionyl1, O-Me-Tyr2-Arg8]-vasopressin (10 microg/kg), a vasopressin V1 receptor antagonist, or saralasin (250 microg/kg), an angiotensin II receptor antagonist, partially blocked the pressor response to arachidonic acid (150 microg; i.c.v.) while combined administration of these three antagonists completely abolished the effect. Moreover, both individual and combined antagonist pretreatments fully blocked the bradycardic effect of arachidonic acid. In conclusion, our findings show that centrally administered arachidonic acid increases mean arterial pressure and decreases heart rate in normotensive conscious rats and the increases in plasma adrenaline, noradrenaline, vasopressin levels and renin activity appear to mediate the cardiovascular effects of the drug.

To investigate the appropriate surgical method that should be selected in the localized fecal peritonitis due to colonic injuries with 24 hours delay.Colonic injuries were performed in 35 rats and the repairs were carried out after 24 hours. Seven rats (%20) died of generalized peritonitis in this period. The remaining 28 rats in which fecal peritonitis were localized by surrounding organs, were randomized in two groups: colostomy (n=14) and primary anastomosis (n=14). Intraabdominal complications and 15 days mortality were assessed.The groups had similar results according to intraabdominal complications. The 15 days survival was 71.4 % for the colostomy group and 78.5 % for the anastomosis group (p=0.31)If the injured or perforated colon is surrounded by the organs and so the generalized peritonitis is avoided, primary anastomosis would have similar results with colostomy despite fecal contamination and prolonged intervention time.

The objective of this study was to determine the scolicidal effects of saline in different concentrations using different exposure times and to examine whether hypertonic saline can be used to irrigate the abdomen when there is a free intraperitoneal perforation of hydatid disease. Various concentrations of saline solutions (0.09%, 3.0%, 6.5%, 10%, 15%, 20%, 25%, 30%) were added to concentrated echinococcus granulosus sediments for the following times: 1, 2, 3, 4, 5, 10, 15, 30, 45, and 60 minutes. Normal (0.09%), 3.0%, and 6.5% saline resulted in high viability ratios after 60 minutes' exposure. Complete lethality for 10%, 15%, 20%, 25%, and 30% saline occurred at the end of 75, 10, 6, 3, and 3 minutes, respectively. During the second part of the study, 20 Sprague-Dawley rats were used for abdominal saline irrigation in four groups: 30% NaCl for 3 minutes; 20% NaCl for 6 minutes; intravenous isotonic dextrose water and furosemide plus 30% NaCl irrigation for 3 minutes; the same prophylactic therapy plus 20% NaCl irrigation for 6 minutes. Sodium and chloride values rose significantly (20–30%) shortly after hypertonic saline irrigation in each group (p < 0.01). Support with isotonic dextrose and furosemide before irrigation did not have any beneficial effect on biochemical values or mortality. The 24- and 48-hour mortality rates were 70% and 90%, respectively. These studies illustrate that the scolicidal effect of hypertonic saline is limited in low concentrations, but an increase in the concentration can augment its adverse effects. Peritoneal irrigation with hypertonic saline should be avoided for intraabdominal perforated hydatid disease. Therefore, we concluded that hypertonic saline is not a good scolicidal agent to prevent recurrence of hydatid disease.