scholarly journals Pharmacodynamic and pharmacokinetic effects of flumazenil and theophylline application in rats acutely intoxicated by diazepam

2009 ◽  
Vol 66 (2) ◽  
pp. 141-148
Author(s):  
Zoran Segrt ◽  
Snezana Djordjevic ◽  
Vesna Jacevic ◽  
Vesna Kilibarda ◽  
Slavica Vucinic ◽  
...  

Background/Aim. The majority of symptoms and signs of acute diazepam poisoning are the consequence of its sedative effect on the CNS affecting selectively polisynaptic routes by stimulating inhibitory action of GABA. The aim of the present study was to examine the effects of combined application of theophylline and flumazenil on sedation and impaired motor function activity in acute diazepam poisoning in rats. Methods. Male Wistar rats were divided in four main groups and treated as follows: group I - with increasing doses of diazepam in order to produce the highest level of sedation and motor activity impairment; group II - diazepam + different doses of flumazenil; group III - diazepam + different doses of theophylline; group IV - diazepam + combined application of theophylline and flumazenil. Concentrations of diazepam and its metabolites were measured with LC-MS. The experiment was performed on a commercial apparatus for spontaneous motor-activity registration (LKBFarad, Sweden). Assessment of diazepam- induced neurotoxic effects and effects after theophylline and flumazenil application was performed with rotarod test on a commercial apparatus (Automatic treadmill for rats, Ugo Basile, Italy). Results. Diazepam in doses of 10 mg/kg and 15 mg/kg produced long-time and reproducible pharmacodynamic effects. Single application of flumazenil or theophylline antagonized effects of diazepam, but not completely. Combined application of flumazenile and theophylline resulted in best effects on diazepaminduced impairment of motoric activity and sedation. As a result of theopylline application there was better elimination of diazepam and its metabolites. Conclusion. Combined application of flumazenil and theophylline resulted in the best antidotal effects in the treatment of diazepam poisoned rats. These effects are a result of different mechanisms of their action, longer half-life of theophylline in relation to that of flumezenil and presumably the diuretic effect of theophylline.

2021 ◽  
Vol 10 (3) ◽  
pp. 192-195
Author(s):  
Ranganathan V ◽  
◽  
Malik JK ◽  
Rao GS ◽  
◽  
...  

The effect of concurrent exposure of toxic concentrations of lead and endosulfan were evaluated on oxidative stress parameters in male wistar rats. Group I served as untreated control whereas Group II received drinking water containing lead as lead acetate @1000 ppm (Pb1000). Group III was exposed to feed containing technical grade endosulfan @ 100 ppm (E100). Group IV was exposed to Pb (1000) +E (100). All the treatments were given daily for 28 days. Combination of lead and endosulfan modified the indices of oxidative stress in the parameters such as lipid peroxidation, reduced glutathione, superoxide dismutase and catalase in rats as compared to their individual compounds. The results suggest that the combination of these individual compounds may have the potential to modify oxidative stress produced by single compounds in male rats


2007 ◽  
Vol 26 (5) ◽  
pp. 383-388 ◽  
Author(s):  
Betul Gulalp ◽  
Yuksel Gokel ◽  
Derya Gumurdulu ◽  
Gulsah Seydaoglu ◽  
Kenan Daglioglu ◽  
...  

The objective of this study is to investigate the functions of parotid and pancreatic glands in response to intoxication with parathion-methyl (PM) and the effects of treatment in rats. Seventy-five male Wistar rats were divided equally into five groups: Group I, control; group II, received atropine and pralidoxime (2-PAM) for 24 h, but no PM; group III, oral PM but no atropine and 2-PAM; group IV, PM and atropine for 24 h and 2-PAM; group V, PM and atropine for 96 h and 2-PAM. After the administration of the chemicals, blood samples were drawn to test for amylase, lipase, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE), while pancreatic and parotid glands of each rat were removed for light microscopic examination. Amylase levels were found significantly elevated in groups II, III, IV, and V, whereas lipase levels were supranormal in groups III, IV, and V. The blood levels of AChE were decreased in groups III and IV and BChE were decreased in II, III, IV, and V. No evidence of pancreatitis and parotitis was identified in the histopathologic evaluation in any group in 96 h; however, hyperchromasia, irregularity in nuclei, and binuclear cells were observed in all parotid glands in group V. Parotitis and pancreatitis were not evident; however, hyperamylasemia and hyperlipasemia were found, whereas various histologic changes in parotid glands were documented in the groups that were administered organophosphate and treatment.


The transplantation of tissues raises many yet unsolved problems of fundamental interest, and is of potentially great clinical importance, especially in endocrinology. The present investigation is concerned with three main problems: the immunological reactions associated with the growth of homografts in the anterior chamber of the eye and subcutaneously; the role of the reticulo-endothelial system in the resistance to homografts; and the applicability of Halsted’s principle to auto- and homografts of endocrine tissue, and the mechanism involved. Four groups of experiments are described. In group I, a preliminary study of auto- and homografts of thyroid in the guinea-pig, it is shown that, if a total thyroid deficiency is produced in the host, autografts are uniformly successful both in the anterior chamber and subcutaneously, whereas homografts are usually successful in the anterior chamber but rarely so when made subcutaneously. Halsted’s principle holds good for anterior chamber grafts whether auto- or homografts, i.e. the proportion of successful grafts increases pari passu with the degree of thyroid deficiency produced in the host, but appears to be less applicable to subcutaneous autografts. Some light is thrown on the mechanism of Halsted’s principle by the observation that successful anterior chamber grafts can be obtained in non-thyroidectomized hosts if injections of pituitary thyrotrophic hormone are given. The experiments of group II are concerned with the immunological phenomena relating to thyroid homografts. It is shown that a subcutaneous homograft of thyroid in the guinea-pig is demonstrably antigenic and the same is true of a homograft in the anterior chamber provided this is undergoing destruction. The state of immunity induced is general and extends to the anterior chamber. The existence of a state of immunity induced by a homograft is shown by the diminished chance of a subsequent homograft ‘taking’, but ‘immunization’ (by means of a subcutaneous graft) of an animal which already has a homograft established in the anterior chamber does not appear to modify the behaviour of the latter. In group III it is shown that a homograft transferred after some months from the anterior chamber to a subcutaneous site is more likely to survive than a primary subcutaneous homograft. It thus appears that when a homograft is established in the anterior chamber for a sufficiently long time a process of adaptation occurs as between graft and host. The experiments of group IV relate to the behaviour of auto- and homografts of spleen in the anterior chamber, and of simultaneous thyroid and splenic grafts. It is shown that the chances of success of a thyroid homograft in the anterior chamber are greatly reduced if the latter is provided with reticulo-endothelial tissue in the shape of a simultaneous autograft of spleen, but that a simultaneous homograft of spleen from the same donor has little or no deleterious effect. The mechanism of this phenomenon has not been fully elucidated but would appear to be either cellular, humoral or a combination of the two.


Author(s):  
Фаргат Вагапов ◽  
Fargat Vagapov ◽  
Наталья Гизатова ◽  
Natal'y Gizatova

The purpose of research is increase of beef productivity and beef quality of Simmental calves at introduc-tion in a diet of feeding different doses of the drug Vetosporin suspension. Of the half-yearly animals, 40 males were selected and formed into group IV for the experiment. The differences were only in feeding. The young were fed the studied additive Vetosporin suspension. In this case, the supplement was an addi-tion to the basic diet of animals of the experimental II-IV groups. The volume of the additive added was 0.1; 1.0; and 2 ml per 10 kg of live weight, respectively. Control group I, consumed exclusively a diet that does not contain an additive. Based on the results of the experiment at the age of 18 months. The prevalence of bulls of the experimental live weight over peers was observed, which was 4.4-25.3 kg (0.78-4.67%). The study of the studied indicators after control slaughter in the context of groups showed the superiority of bulls of experimental groups in all the periods studied. It is established that at the age of 15 months. The size of the removable live weight of the youngest of the control group was less by 8.0-19.7 kg (1.75-4.29%) than in the animals of the test groups. In this case, the leading position was occupied by the youngest of group III, the prevalence of which was 0.7-11.7 (0.14 -2.51%). It should be noted that after 3 months a simi-lar picture of the distribution of the studied quantities was observed. As for the output of carcass, we can note the following. Outsider among the animals of the experimental groups was the control group. So the bulls of group I were inferior to those who received the additive by 0.7-1.3%. At 18 months, as well as at 15 months, the dominant position was occupied by gobies of experimental groups. It should be noted that among the animals of the experimental groups the leading place was occupied by the bulls receiving the feed additive in a dose of 1.0 ml per 10 kg of live weight, that is, the youngest of the III group.


Author(s):  
SALEH NUHU ◽  
HAUWA IDRIS AHMAD ◽  
AISHA MUHAMMAD GARBA ◽  
TASIU ABDULLAHI SULAIMAN

Objectives: The objective of this study was to find the histologic and motor activity effect of lead on prenatally and postnatally exposed Wistar rats. Methods: In this study, twelve Wistar Rats were used and grouped into four groups of two females and one male. Group I rats served as the control and allowed feed and water freely. The rats in Group II were administered 500ppm of Pb through drinking water from gestation day 8 (GD8) to parturition (GD21). While Group III rats were given 500ppm of Pb in drinking water from postnatal day 1 (PND1) to PND21. The rats in the fourth group (Group IV) were given 500ppm of Pb from GD8 to PND21. Palmer grasp reflex was conducted to assess the motor activity of the rat pups. The animals were then humanely sacrificed and the frontal cortices were isolated for routine histological processing. Results: The histological study has shown normal neurons in the control group while degenerating cells exhibiting karyolysis, pyknosis, karyorrhexis, vacuolation were seen in the lead-treated groups. Group II and Group IV showed considerate deficit in their motor activity while Group III showed mild effect. Conclusion: From this study, lead exposure of Wistar rats at both prenatal and postnatal period of development has effect on the histology of the frontal cortex as well as on their motor activity.


2014 ◽  
Vol 41 (3) ◽  
pp. 193-197 ◽  
Author(s):  
Austry Ferreira de Lima ◽  
Laercio Gomes Lourenço ◽  
Délcio Matos ◽  
Célio Fernando de Sousa Rodrigues

OBJECTIVE: To evaluate the protective effect of celecoxib in the esophageal mucosa in rats undergoing esofagojejunostomy. METHODS: Sixty male Wistar rats from the vivarium of the University of Health Sciences of Alagoas were used for the experiment. The animals were divided into four groups: Group I, 15 rats undergoing esofagojejunostomy with the use of celecoxib postoperatively; Group II, 15 rats undergoing esofagojejunostomy without the use of celecoxib; Group III, 15 rats undergoing celiotomy with bowel manipulation; and Group IV, 15 rats without surgery and using celecoxib. The observation period was 90 days. After the death of the animals, the distal segment of the esophagus was resected and sent for microscopic analysis. RESULTS: esofagojejunostomy caused macroscopic and microscopic esophagitis. Esophagitis was equal in both groups I and II. In groups III and IV esophageal lesions were not developed. CONCLUSIONS: celecoxib had neither protective nor inducing effect on esophagitis, but had a protective effect on dysplasia of the animals of group I.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Dinesh Babu Jestadi ◽  
Alugoju Phaniendra ◽  
Undru Babji ◽  
Bhavatharini Shanmuganathan ◽  
Latha Periyasamy

The aim of the present study was to investigate the effects of low dose of atrazine on reproductive system of male Wistar rats. 16 rats were divided into four groups of four animals each. Group I (nondiabetic) and group III (diabetic) animals served as controls that received safflower oil (300 μL/kg bw/day), respectively. Group II (nondiabetic) and group IV (diabetic) animals received atrazine (300 μg/kg bw/day). Nonsignificant decrease in the activities of antioxidant and steroidogenic enzymes and sperm parameters suggests that atrazine did not produce any effect on reproductive system of rats. Histological findings also revealed that atrazine at a dose of 300 μg/kg bw did not produce any testicular toxic effects in nondiabetic and diabetic atrazine treated rats. Low dose of atrazine did not show reproductive toxicity in rats. To know the effects of atrazine in diabetic rats further studies have to be carried out with increased concentration of atrazine.


Author(s):  
Jumasni Adnan

Antituberculosis is the most liver damage causes. Rifampicin and Isoniazide, in combination, are toxic compounds. Isoniazide and rifampicin metabolits causes lipid peroxidation. The hepatoprotective effect of rosella calyx water extract on liver damage induced with Isoniazide-rifampicin evaluated by examination of malondialdehid levels in the liver organ. 25 male wistar rats divided into 5 groups, ie group I (INH-rifampicin + rosella water extract 250 mg/kgBW), group II (INH-rifampicin + rosella water extract 125 mg/kgBW), group III (INH-rifampicin + rosella water extract 62.5 mg/kgBW),  group IV (healthy control) and group V (Isoniazide-rifampicin). MDA liver levels were analyzed after 35 days of treatments. The test results of each group are, group I has mean MDA levels 0.023912 + 0.011 mg/ml, group II 0.023526 + 0.009 mg/ml, group III 0.027168 + 0.007 mg/ml group IV 0.03437 + 0.009 mg/ml and group V 0.236846 + 0.118 mg/ml. The kruskal-wallis test showed significantly value 0.008 (p 0.05) and Post hoc Mann U whitney test showed that group V was significantly different to group I, II, III, and IV (p = 0.008) respectively, roselle extract can be used as a hepatoprotector antioxidant to improve the tuberculosis drug consumer quality of life through improved health by lowering lipid peroxidation that causes liver damage.


2021 ◽  
pp. 1901-1907
Author(s):  
Sara T. Elazab ◽  
Omar Samir ◽  
Marwa E. Abass

Background and Aim: Fipronil (FPN) is a potent pesticide that is heavily used around the world in agriculture. However, its irrational use could potentially have deleterious effects on animals and humans. The present study aimed to investigate the ability of sitagliptin (Sit) and losartan (LOS), when used both individually or concurrently, to guard rat liver against the acute hepatotoxicity caused by FPN. Materials and Methods: Forty-two adult male Wistar rats were equally divided into seven groups (6/group). Group I (control) received normal saline (0.5 mL/rat, vehicle for all treatments) by gavage once daily for 10 days. Group II received oral Sit (10 mg/kg body weight [BW]) daily for 10 days and Group III received oral LOS (5 mg/kg BW) daily for 10 days. Group IV received oral FPN (19.4 mg/kg BW; 1/5 of the oral LD50) for the past 5 days of the study. Groups V and VI received oral Sit (10 mg/kg BW) and LOS (5 mg/kg BW) daily, respectively, 5 days prior and 5 days during FPN administration (19.4 mg/kg BW). Group VII received oral Sit (10 mg/kg BW) and LOS (5 mg/kg BW) for 10 days with daily FPN during the past 5 days. After the end of the treatment period, the rats were humanely sacrificed and blood and liver tissue samples were collected for biochemical analysis and histopathological and immunohistochemical investigations. Results: FPN administration resulted in elevated alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase serum concentrations as well as increased malondialdehyde levels and reduced catalase, superoxide dismutase, glutathione peroxidase, and glutathione activity. The histopathological investigation showed disorganization of the hepatic cords and focal necrosis of the hepatocytes in FPN-intoxicated rats. Furthermore, the immunohistochemical examination showed that hepatic caspase-3 was overexpressed in the FPN-treated rats. The administration of Sit and LOS before and alongside FPN markedly mitigated the alterations caused by FPN and the hepatoprotective effects were more prominent in the combination group. Conclusion: Sit and LOS, both individually or in combination, confers considerable hepatoprotection against FPN-induced hepatotoxicity.


Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1998
Author(s):  
Abdullah F. AlAsmari ◽  
Metab Alharbi ◽  
Faleh Alqahtani ◽  
Fawaz Alasmari ◽  
Mohammed AlSwayyed ◽  
...  

Hepatotoxicity caused by chemotherapeutic drugs (e.g., doxorubicin) is of critical concern in cancer therapy. This study focused on investigating the modulatory effects of diosmin against doxorubicin-induced hepatotoxicity in Male Wistar rats. Male Wistar rats were randomly divided into four groups: Group I was served as control, Group II was treated with doxorubicin (20 mg/kg, intraperitoneal, i.p.), Group III was treated with a combination of doxorubicin and low-dose diosmin (100 mg/kg orally), and Group IV was treated with a combination of doxorubicin and high-dose diosmin (200 mg/kg orally) supplementation. A single dose of doxorubicin (i.p.) caused hepatic impairment, as shown by increases in the concentrations of serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. Doxorubicin produced histological abnormalities in the liver. In addition, a single injection of doxorubicin increased lipid peroxidation and reduced glutathione, catalase, and superoxide dismutase (SOD) levels. Importantly, pre-treatment with diosmin restored hepatic antioxidant factors and serum enzymatic activities and reduced the inflammatory and apoptotic-mediated proteins and genes. These findings demonstrate that diosmin has a protective effect against doxorubicin-induced hepatotoxicity.


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