Tehran University Medical Journal

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The purpose of this study was investigation of effect of cholestasis on bromocriptine-induced yawning in male rats. Bromocriptine, the agonist of dopamine receptors (especially "D2"), causes yawning in male intact rats. In the present study, cholestasis was produced in male rats by surgery and ligation of common bile duct. The number of yawning induced by intraperitoneal injection of bromocriptine (11 mg/kg) was compared in cholestatic rats with sham operated and control groups. Immediately after injection of the drug and putting animals on the frame of behavioral study, the number of yawning was determined in a period of one hour. Obtained results, indicated significant difference in the number of bromocriptine-induced yawning between cholestatic rats and the other two groups. There wasn't significant difference between sham and control rats. These results indicate that some changes occur in cholestatic rats which increase sensitivity and response of dopamine receptors. Since it is proved that dopamine agonist-induced yawning is mediated via nitric oxide, and also level of nitric oxide is increased in cholestasis, it can be supposed that the mentioned response may be due to elevated level of nitric oxide. On the other hand, increased number of yawning in cholestatic rats may be due to increased level of endogenous opioids in these animals.

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One of the useful function of melatonin is its protective effect against endogenous oxidants. The object of this investigation was to study the protective effect of melatonin on stress-induced gastric lesions.
Results: Our results show that pretreatment of animals with melatonin decrease the stress-induced gastric lesions dose dependently.
L-NAME, a nitric oxide synthesis inhibitor, potentiat the stress-induce gastric lesions and melatonin produced gastro-protective effect against concurrent stress and L-NAME-induced gastric lesions.
Conclusion: Our results indicate that melatonin may produce its gastro-protective effect Via increasing level of nitric oxide.

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Obstructive cholestasis is associated with overproduction of endogenous opioids (EOP), nitric oxide (NO), and cytokins in the blood streams. Therefore we investigated the relationship between obstructive cholestasis and function of germ cells in adult male rats.
Material and Methods: To study this, we used three groups of animals: No-surgery, Sham-surgery, and surgical ligation of the bile duct. After 3 weeks all animal were killed by ether, serum concentrations of FSH, LH and testosterone were determined by Radioimmunoassay, apoptosis was evaluated by DNA fragmentation detected by in situ terminal deoxynucloetidyl Transfrase-mediated dUTP nike end labeling (TUNEL).
Results: The mean of FSH level in cholestatic, control and sham groups were 13.22+ 1.038, 18.14+ 1.276, and 16.92+ 1.072 ng/ml, respectively. The mean of LH level in cholestatic, control and sham groups were 0.83 + 0.21, 2.058 ± 0.26, and 1.84 + 0.17 ng/ml, respectively. In addition, the mean of testosterone level in cholestatic, control and sham groups were 1.52 ± 0.16, 2.41 ± 0.18, and 2.31 + 0.14 ng/ml, respectively. The results of this study were indicated that serum FSH, LH and testosterone were significantly lower in cholestatic than control and sham groups (p=0.0195, P= 0.0029, and P=0.0023, respectively). However there was no significant difference in apoptotic index between all of groups (P=0.195). The apoptotic index in cholestatic, control and sham rats were 9.897± 1.374, 7.086 + 0.91, and 7.729 + 1.101, respectively.
Conclusion: These findings have been shown which as obstructive cholestasis was decreased the levels of serum gonadotropins and testosterone but it has no significant effector testicular germinal cells apoptosis.

 

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Background: Relaxation of the corpus cavernosum plays a major role in penile erection. Nitric oxide (NO) is known to be the most important factor mediating relaxation of corpus cavernosum, which is mainly derived from nonadrenergic noncholinergic (NANC) nerves. The aim of the present study was to investigate the effect of biliary cirrhosis on nonadrenergic noncholinergic (NANC)-mediated relaxation of rat corpus cavernosum as well as the possible relevant roles of endocannabinoid and nitric oxide systems.

Methods: Corporal strips from sham-operated and biliary cirrhotic rats were mounted under tension in a standard oxygenated organ bath with guanethidine sulfate (5 µM) and atropine (1 µM) to induce adrenergic and cholinergic blockade. The strips were precontracted with phenylephrine hydrochloride (7.5 µM) and electrical field stimulation was applied at different frequencies (2, 5, 10, 15 Hz) to obtain NANC-mediated relaxation. In separate precontracted strips of the sham and cirrhotic groups, the concentration-dependent relaxant responses to sodium nitroprusside (10 nM-1mM), as an NO donor, were assessed.  

Results: The NANC-mediated relaxation was significantly enhanced in cirrhotic animals (P<0.01). Anandamide potentiated the relaxations in both groups (P<0.05). The cannabinoid CB1 receptor antagonist AM251 (10 µM) and the vanilloid receptor antagonist capsazepine (10 µM) each significantly prevented the enhanced relaxations in cirrhotic rats (P<0.01). The CB2 receptor antagonist AM630 had no effect on relaxations in the cirrhotic group. In a concentration-dependent manner, L-NAME (30-1000 nM) inhibited relaxations in both the sham and cirrhotic groups, although cirrhotic groups were more resistant to the inhibitory effects of L-NAME. The degree of relaxation induced by sodium nitroprusside (10 nM-1 mM) was similar in the two groups.

Conclusions: Biliary cirrhosis enhances the neurogenic relaxation in rat corpus cavernosum probably via the NO pathway and cannabinoid CB1 and vanilloid VR1 receptors.

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Background: Relaxation of the corpus cavernosum plays an important role in penile erection. Previous studies have suggested that nitric oxide (NO) appears to be the most important relaxant involved in the erection process. The aim of the present study was to evaluate the effect of cholestasis in nNOS and eNOS activity of corpus cavernosum.
Methods: forty-two adult male Sprague-Dawley rats were divided equally into seven groups: control, sham operated, 2-, 7-, and 14-day bile duct-ligated animals, 7-day bile duct-ligated chronically treated with L-NAME (3mg/kg/day, i.p.) and 7-day bile duct-ligated animals chronically treated with Naltrexone (20 mg/kg/day, i.p.). The animals in each group were killed and the cavernosal tissues analyzed histologically by light and transmission electron microscopy, with NOS activity detected on NANC nerves and endothelium using an NADPH-diaphorase staining technique.
Results: our results showed that NADPH diaphorase staining in corporal NANC nerves and endothelium of sham-operated and control group had equal intensity. The staining was more intense in 2-day cholestatic rats than in control group, the staining intensity increased in 7-, and 14-day groups too. There were no significant differences between control group and 7-day cholestatic rats that had been treated chronically with L-NAME or Naltrexone.
Conclusions: These results state that in corpus cavernosum of cholestatic rats there is a time-dependent increase in NOS activity of the corporal NANC nerves and endothelium. inhibition of nitric oxide and endogenous opioids by L-NAME or Naltrexone during cholestasis may play a key role in preventing the adverse effects of cholestasis.

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Background: It is well known that erectile dysfunction is most commonly associated with diabetes, affecting 35% to 75% of men with diabetes mellitus. Several studies have been carried out to find appropriate strategies for treatment of diabetes-induced erectile dysfunction. The aim of the present study was to investigate the ability of acute administration of the endogenous cannabinoid anandamide in vitro to alter the NANC-mediated relaxation of corpus cavernosum from diabetic rats and the possible role of nitric oxide in this manner.

Methods: Diabetes was induced by the administration of streptozotocin for eight weeks. Corpora cavernosa were isolated in organ baths for measurement of agonist-evoked or electrical field stimulation (EFS)-evoked smooth muscle tensions.

Results: The neurogenic relaxation of phenylephrine (7.5 µM) precontracted isolated corporal strips was impaired in diabetic animals. Anandamide (0.3, 1 and 3 µM) enhanced the relaxant responses to EFS in diabetic strips in a dose-dependent manner. This effect was antagonized by either the selective cannabinoid CB1 receptor antagonist AM251 (1 µM) or the selective vanilloid receptor antagonist capsazepine (3 µM). Concurrent administration of partially effective doses of L-arginine (10 µM) and anandamide (0.3 µM) exerted a synergistic improvement in EFS-induced relaxation of diabetic strips (p<0.001). The relaxant responses to the nitric oxide donor sodium nitroprusside of the subjects in the diabetic and control groups were similar.

Conclusion: For the first time, we demonstrated that acute administration of an endogenous cannabinoid, alone or in combination with L-arginine could improve the NO-mediated relaxation of cavernosal smooth muscle in diabetic rats and this effect was mediated by cannabinoid CB1 and vanilloid VR1 receptors within the tissue.
 

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Background: Biliary cirrhosis is a chronic disease marked by the progressive destruct-tion of liver. There is no known cure for this disease however, medications may slow its progression. The present study was designed to investigate the effect of quercetin as a plant derived flavonoid on the hepatic injury reduction of biliary cirrhotic rats.
Methods: Thirty male Sprague-Dawley rats aged 6-7 months were randomized into three groups of ten each. One group served as control (sham operated), while the other two groups underwent a complete bile-duct ligation (BDL). Four weeks after the opera-tion, serum bilirubin, alkaline phosphatase (ALP), alanine amino-transferase (ALT), and aspartate amino-transferase (AST) were measured in two BDL groups to confirm the occurrence of cirrhosis. Then one of the BDL groups received placebo and the other one injected intraperitoneally with 50mg/kg of quercetin once a day for a period of four weeks. At the end of the study, hepatic enzymes and serum bilirubin were measured again. Liver species were tested for histological characteristics.
Results: Quercetin could decrease serum level of bilirubin (7.4±0.9 vs. 8.9±1.6 mg/dL P<0.05), ALP (1387±76.9 vs. 2273±65.3 IU/L P<0.001) and ALT (601.9±38.1 vs. 644.8±37.4 IU/L P<0.05) compared to cirrhotic group. AST was higher in cirrhotic groups compared to control both in the 4th and 8th week. However, the difference between BDL and BDL+Q groups was not statistically significant. Quercetin decreased ALT/AST ratio, as an indicator of liver damage. No significant histological changes were observed in quercetin group.
Conclusion: These data suggest that although quercetin did not change histological characteristics of liver, it could significantly decrease bilirubin, alkaline phosphatase and alanine amino-transferase, indicating less liver injury.