Protective effect of vitamin A on ARA-C induced intestinal damage in mice.

BACKGROUND: Cytarabine (ARA-C) has been used for many years in the treatment of patients with leukemia and lymphoma. Gastrointestinal ulceration and mucositis are two of the well-known side effects of ARA-C. We set out to investigate whether vitamin A (VA) can help prevent ARA-C-induced mucosal lesions in mice. MATERIALS AND METHODS: Mice were divided into 5 groups. Group I (control group) received only saline; group II received ARA-C plus saline; group III received ARA-C plus VA; group IV received ARA-C plus a lipid solution, and group V received VA alone. VA (5000 IU/kg) was administered orally to the mice once daily for 7 days. ARA-C (3.6 mg) was administered intraperitoneally for 5 days to groups II, III and IV, starting on the third day of VA treatment. Intestinal segments from the proximal end of the jejunum of treated mice were isolated. RESULTS: There was improved mucosal integrity, less necrosis and increased villus length with advanced mucosal proliferation in crypts in the VA plus ARA-C group when compared to the ARA-C groups without VA. CONCLUSION: We conclude that VA has a protective effect against ARA-C-induced mucosal damage in mice.

Chronic treatment with fluoxetine and sertraline prevents forced swimming test-induced hypercontractility of rat detrusor muscle.

Serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors represent important targets for the development of new treatments for detrusor overactivity and urinary incontinence. The present study was undertaken to investigate the effects of the forced swimming test (FST) on the contractile response of isolated rat detrusor muscle and to examine the effects of in vivo treatments of fluoxetine and sertraline on altered detrusor muscle contractility. Fluoxetine (20 mg/kg ip) and sertraline (10 mg/kg ip) were administered once a day for 14 days. Rats were exposed to the FST on the 15th day. After the test, detrusor muscles were removed and placed in organ baths, and the contraction responses induced by carbachol, potassium chloride (KCl) and electrical field stimulation (EFS) were recorded. The contractile responses of detrusor muscle strips to carbachol and electrical field stimulation were found to be increased at all carbachol doses and frequencies, respectively. FST also increased the contractile responses to KCl, which is used to test the differences in postreceptor-mediated contractions. The hypercontractile responses of detrusor strips to carbachol, EFS and KCl were abolished by treatment with both fluoxetine and sertraline. These treatments also decreased the immobility duration in the FST consistent with an antidepressant-like effect in this test. The results of this study provide the first evidence that FST increases contractility of the rat detrusor muscle, and this hypercontractility was abolished by chronic treatments of fluoxetine and sertraline at antidepressant doses by decreasing the postreceptor-mediated events.

Effect of a Carbohydrate-Rich Diet on Rat Detrusor Smooth Muscle Contractility: An Experimental Study.

OBJECTIVES: We aimed to investigate the effect of a carbohydrate-rich diet on detrusor contractility in rats. MATERIALS AND METHODS: Sprague-Dawley rats were randomized into two groups. The control group received regular food and water. The study group received carbohydrate-rich diet for six weeks. The rats' detrusor muscle was isolated for pharmacological and histopathological examinations. RESULTS: In the control and study groups, mean body weights were 431.5 ± 27.6 g and 528.0 ± 36.2 g, respectively (p < 0.001). Electrical stimulation of the detrusor strips of the control group resulted in gradual contraction. A decreased contractile response was shown in the study group. Acetylcholine in 10-7-10-3 molar concentration produced a decreased contractile response in the study group, compared to the control group (p < 0.01). The study group showed marked subepithelial and intermuscular fibrosis in the bladder. CONCLUSION: Carbohydrate-rich diet causes marked subepithelial and extracellular fibrosis and changes in contractility in the detrusor within a six-week period. Changes have higher costs in therapeutic choices and correction of these changes remains difficult. Putting an end to carbohydrate-rich diet would seem to be more cost-effective than dealing with the effects of consuming it in high proportions which should be the national policy worldwide.

Evaluation of Postoperative Anti-nociceptive Efficacy of Intrathecal Dexketoprofen in Rats.

BACKGROUND: Some studies have suggested that the intrathecal use of cyclooxygenase enzyme inhibitors provides an anti-nociceptive effect. Therefore, the occurrence of side effects seen in systemic usage can be eliminated. AIMS: The primary objective of this experimental, randomized, controlled trial was to test the hypothesis asserting that intrathecal dexketoprofen trometamol would demonstrate an analgesic effect during postoperative period. STUDY DESIGN: Animal experimentation. METHODS: Forty rats were randomized into 4 groups 7 days after intrathecal catheterization; the following drugs were given through catheter lumens: Group Lidocaine (Group L): Lidocaine 20 µg; Group Lidocaine-Morphine (Group LM): Lidocaine 20 µg and morphine 0.5 µgr; Group Lidocaine-Dexketoprofen (Group LD): Lidocaine 20 µg and dexketoprofen trometamol 100 µg; and Group Dexketoprofen (Group D): Dexketoprofen trometamol 100 µg. Paw incision was achieved under ether inhalation. To measure analgesic potential, hot plate and tail immersion tests were used as nociceptive tests during the postoperative period. RESULTS: The mean reaction times detected in groups during hot plate and tail immersion tests were shortest in Group L at 15, 30, 45, 60, 75, 90, 105, and 120 minutes after start of surgery (p<0.01, all others). In the groups using dexketoprofen, as in the morphine group, longer reaction times were detected than in the lidocaine group at all measurement times except 120 minutes (p<0.01). CONCLUSION: Intrathecal dexketoprofen in the optimal perioperative pain management is effective, and can be administered as an adjuvant in clinics after neurotoxicity studies in animals, and effective dose studies in volunteers.

Evaluation of antinociceptive and neurotoxic effects of intrathecal dexmedetomidine in rats.

OBJECTIVE: Dexmedetomidine has been reported to produce analgesia after intrathecal administration. In the present study the α2-adrenoceptor agonist dexmedetomidine was evaluated for its potential spinal neurotoxic effects. MATERIAL AND METHODS: Three days after intrathecal cannulation, rats were administered either dexmedetomidine (3 µg/30 µL, i.t.) or saline (30 µL, i.t.). Antinociceptive, sedative and motor effects of intrathecal administrations of dexmedetomidine or saline were evaluated during 90 min. The tail-flick and hot plate tests were used to assess the thermal nociceptive threshold. Seven days after drug administration, animals were sacrified and spinal cords were evaluated for histopathological changes by light microscopy. RESULTS: Dexmedetomidine administered intrathecally produced antinociception. Antinociception was accompanied by immediate sedation and loss of placing-stepping reflexes that lasted over 40 min in all dexmedetomidine administered rats. In all rats, microscopic examination revealed mild gliosis and minimal infiltration of inflamatory r cells in posterior white matter. Mild (total score 4-6) histopathologic lesions were seen in four animals in dexmedetomidine adminisered rats, but there was no statistically significant difference when compared with the saline administered rats. CONCLUSION: We observed that intrathecal injections of dexmedetomidine at the dose of 3 µg/30 µL produce antinociception but did not cause any histopathological sign of injury in the spinal cord.

The role of heart-type fatty acid-binding protein in the evaluation of carbon monoxide poisoning in rats.

Acute carbon monoxide (CO) poisoning can cause early and persistent damages in tissues sensitive to hypoxia. This study investigated serum heart-type fatty acid-binding protein (H-FABP) levels as a biomarker of acute CO poisoning in rats. The rats were exposed to a mixture of either 3000 (group A) or 5000 (group B) parts per million (ppm) CO in air, or to ambient air (group C, control group). Blood samples were taken just before, immediately after and 6 hours after the exposure, and serum H-FABP and troponin-I levels were measured. The consciousness level was evaluated just after the exposure. The survival rate was monitored for 7 days. Serum H-FABP levels increased just after the CO exposure in both groups A and B. Additionally, H-FABP level was higher in group B than in group A, immediately after the exposure. However, serum troponin-I levels only increased at 6 hours after the CO exposure in groups A and B. Consciousness and survival rates in group B were lower than that in group A. Our results suggest that H-FABP might have potential to be an early and quantitative parameter of clinical severity and prognosis in CO poisoning.

Subsequent alterations in the contractile property of the vas deferens according to duration of spermatic cord torsion.

OBJECTIVE: To determine whether twisting of the ipsilateral vas deferens results in alteration of its contractility. DESIGN: Experimental study. SETTING: University animal lab. ANIMAL(S): 24 male Wistar rats. INTERVENTION(S): All the rats in the experimental groups underwent spermatic cord torsion. Durations of torsion were 45 minutes, 3 hours, and 24 hours in groups 2, 3, and 4, respectively. In groups 2 and 3, subgroups b were created to evaluate late effects using in vitro pharmacological techniques. MAIN OUTCOME MEASURE(S): The contractility of the vas deferens was evaluated in groups 1, 2a, 3a, and 4 right after and in groups 2b and 3b 48 hours after the initial operation. RESULT(S): Group 4 and subgroups 2b and 3a had significantly diminished responses compared with the control group, whereas in subgroups 2a and 3b, the responses to noradrenaline and to single-pulse field stimulation were not significantly different. CONCLUSION(S): The impairment of contractility with the twisting of the vas deferens might be another factor responsible for subfertility, particularly that related to sperm transport. The unfavorable late change in short duration of torsion may be the result of either ischemia and reperfusion injury or sympathetic overactivation in the acute period of torsion.

Time course of serum S100B protein and neuron-specific enolase levels of a single dose of chlorpyrifos in rats.

Organophosphate (OP) compounds are a large class of chemicals, many of which are used as pesticides. It is suggested that OPs specifically affect glia and neurons. Effects of acute exposure to chlorpyrifos (CPF), which is a common organophosphorus pesticide used worldwide, on neuron-specific enolase (NSE) and S100B levels in rat blood during 7 days were assessed. Rats were evaluated either before (0 hr) or 2, 12, 24, 48 and 168 hr (7 days) after injection of CPF (279 mg/kg, s.c.) or vehicle (peanut oil, 2 ml/kg, s.c.) for clinical signs of toxicity. Immediately after the evaluation of toxicity, blood samples were taken for biochemical assays. CPF administration produced decreases in body-weight and temperature, which were observed for first time at 12 hr after CPF administration and continued for 168 hr (p < 0.05-0.001). Serum S100B and NSE levels were acutely increased 2 hr after CPF administration and remained high at 12 hr (p < 0.01-0.001). NSE and S100B levels were not different in either CPF or vehicle groups at following time points. Serum butyrylcholinesterase (EC 3.1.1.8; BuChE) activity was dramatically reduced at 2 hr after CPF and remained low at each time points during 7 days (p < 0.01-0.001). Our results suggest that the usefulness of serum levels of these glia- and neuron-specific marker proteins in assessing OP toxicity, specifically CPF-induced toxicity.

Effect of prenatal levetiracetam exposure on motor and cognitive functions of rat offspring.

PURPOSE: We aimed to establish the physical, motor, and cognitive teratogenic effect of levetiracetam exposure throughout pregnancy in rats. METHODS: Thirty-two Sprague-Dawley pregnant female rats were divided into four groups. Groups 1-3 were treated with different doses of levetiracetam (25, 50, 100 mg/kg/d) from gestational days 1 to 18. Group 4 (control group) was treated with the same volume of saline. The day of occurrence for pinna detachment, incisor eruption, eye opening, ear opening, and fur development were also monitored. Righting reflex, negative geotaxis, and grip response were evaluated as measures of the development of reflexes. The cognitive and motor developments were established with T-maze, holeboard, Y-maze, locomotor activity, and passive avoidance test. RESULTS: Levetiracetam exposure at 25, 50 and 100 mg/kg/d doses did not affect the timing of physical landmark developments. The dose of 100 mg/kg/d resulted in a significant delay in reaction time of the surface righting reflex compared to the control group. Two higher dose groups (50 and 100 mg/kg/d) had delay in the appearance of negative geotaxis reflex compared to the control group. Both groups maternally exposed to 50 and 100 mg/kg/d had a lower percentage of grip strength response comparing to control group on the first day of testing. On the second test day, only pups prenatally exposed to 100 mg/kg/d levetiracetam persistently had a significantly lower percentage of response. We could not find a significant difference between groups in tests for the locomotor activity, memory, and learning (T- and Y-maze, passive avoidance test), and explorative behavior (holeboard tests). CONCLUSION: We showed that levetiracetam had only a transient impact on reflex maturation and no impact on physical and cognitive function in offspring of rats exposed to the drug during pregnancy. Levetiracetam may become a promising candidate for the treatment of epileptic women in pregnancy.

Effect of sildenafil on anxiety in the plus-maze test in mice.

Several studies have shown a role of nitric oxide/cyclic guanosine monophosphate signaling pathway in the regulation of anxiety. The effects of the phosphodiesterase (PDE) 5 inhibitors on anxiety are not fully understood. The aim of present study was to investigate the possible role of sildenafil, an inhibitor of cyclic GMP-specific phosphodiesterase, on anxiety in the plus-maze test in mice. Sildenafil at a dose of 0.5 mg/kg had no significant effect on the behavior in the plus-maze test but at doses of 1 and 3 mg/kg induced an anxiogenic effect. The combination of sildenafil (1 mg/kg, i.p.) and methylene blue (1 mg/kg, i.p.) abolished the anxiogenic-like effect of sildenafil. The combination of sildenafil (1 mg/kg, i.p.) and L-arginine (50 mg/kg, i.p.) decreased the percentage of time spent in open arms compared to saline-treated group. Diazepam at a dose of 2 mg/kg significantly increased the percentage of time spent in open arms (p < 0.05). Sildenafil at a dose of 3 mg/kg and the combination of L-arginine (50 mg/kg, i.p.) and sildenafil (1 mg/kg, i.p.) significantly decreased the locomotor activity (p < 0.05). These results suggest that a nitric oxide-cGMP pathway seems to play an important role in sildenafil-induced anxiogenic-like effect.