Activity In Male Wistar Rats Research Articles

Effects of co-treatment with pioglitazone and methotrexate on experimentally induced rheumatoid arthritis in Wistar albino rats.

OBJECTIVES:Rheumatoid arthritis (RA) is a chronic inflammatory disease primarily affecting the synovial joints of the body. Methotrexate (MTX) is considered as a mainstay in the management of RA. However, monotherapy with MTX in RA is often limited by potential long-term toxicity. The present study was conducted to evaluate if MTX-pioglitazone combination therapy has an add-on benefit over monotherapy with MTX or pioglitazone on disease activity in male Wistar rats in adjuvant-induced arthritis model.MATERIALS AND METHODS:Arthritis was induced by single subcutaneous injection of complete Freund's adjuvant (CFA) in thirty male Wistar albino rats. They were then divided into five equal groups, which included two control groups (arthritic and nonarthritic), pioglitazone-treated (1.35 mg/kg daily), MTX-treated (0.225 mg/kg daily), and MTX + pioglitazone-treated. The disease-modifying action of the drugs was assessed by various physiological, hematological, and biochemical parameters along with histopathological and radiological analysis of affected joints. The experimental data were statistically assessed by one-way ANOVA.RESULTS:There was a significant reduction of disease activity in the MTX monotherapy group when compared with disease control. However, pioglitazone monotherapy group failed to demonstrate any significant effect on disease activity. The MTX-pioglitazone combination group demonstrated greater suppression of disease activity as compared to MTX and pioglitazone monotherapy and disease control group (P < 0.05).CONCLUSION:The present study demonstrates that the combination therapy of MTX with pioglitazone offers better control of disease activities in RA as compared to MTX or pioglitazone monotherapy.

Design, synthesis and biological evaluation of novel pyrazolo-pyrimidinones as DPP-IV inhibitors in diabetes.

We report the design, synthesis, biological activity and docking studies of series of novel pyrazolo[3,4-d]pyrimidinones as DPP-IV inhibitors in diabetes. Molecules were synthesized and evaluated for their DPP-IV inhibition activity. Compounds 5e, 5k, 5o and 6a were found to be potent inhibitors of DPP-IV enzyme. Amongst all the synthesized compounds, 6-methyl-5-(4-methylpyridin-2-yl)-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one (5k) was found to be the most active based on in vitro DPP-IV studies and also exhibited promising in vivo blood glucose lowering activity in male Wistar rats.

Effects of gallic acid on exploratory behavior and locomotor activity in rats

PURPOSE: The present study investigated the effects of GA on exploratory behavior and locomotor activity in male Wistar rats. METHODS: GA (20 mg/kg) or saline were administrated orally to different groups of rats for 7, 14, 21 and 30 days. At the end of each experimental period, the changes in rat behavior were recorded in an Opto Varimex apparatus. The number of horizontal and vertical movements recorded every minute served as a measure of exploratory activity and habituation. The total number of movements was used as a measure of locomotor activity. RESULTS: It was found that after 7 days of treatment, GA did not significantly affect exploratory behavior and locomotor activity of rats compared to the saline-treated controls. After the 14 day treatment period, GA did not significantly affect horizontal activity but reduced the number of vertical movements. After 21 and 30 days, GA significantly reduced both horizontal and vertical movements of rats compared to the controls. At all testing periods, GA did not disturb habituation which is considered as an elementary form of learning. CONCLUSION: The present study suggested that GA applied subchronically to rats has a sedative effect and does not disturb the memory and learning processes.

Effects Of Ferulic Acid On Exploratory Behavior And Locomotor Activity In Rats

Summary Ferulic acid (FA), called also hydroxycinnamic acid, is a polyphenol compound found in many foods such as coffee, apples, rice, oats and wheat. It acts as an antioxidant but its other activities in vivo have not been well studied as a whole. The aim of the present study was to investigate the effects of FA on exploratory behavior and locomotor activity in male Wistar rats. FA was administrated orally (20 mg/kg) to different groups of rats for 7, 14, 21 and 30 days. These groups were compared respectively with saline-treated controls. At the end of each experimental period, the changes in exploratory behavior and locomotor activity were recorded in an Opto Varimex apparatus (Columbus Instruments, USA). The number of horizontal and vertical movements recorded every minute for the first 5 min served as a measure of exploratory activity and habituation to the new environment. The total number of movements during the first 5 min and during the whole 10-min period of observation was used as a measure of locomotor activity. It was found that FA at all doses for all treatment periods did not significantly affect exploratory behavior and locomotor activity of rats, when compared with the saline-treated controls. At all testing periods, FA did not disturb habituation. As habituation is considered an elementary form of learning, the present study suggested that FA did not disturb the memory and learning processes in rats.

The effects of intermittent training and age on blood lactate (La) Level and lactate dehydrogenase enzyme (LDH) activity in male wistar rats.

Introduction: Physical activity and age are among the factors affecting lactate levels and lactate dehydrogenase activity. Physical activity appears to be able to counterbalance the morphological and metabolic changes associated with aging that decrease physical ability and performance. Objectives: The purpose of the present study was to assess the effects of interval training on blood lactate levels and lactate dehydrogenase activity in young and old rats. Materials and Methods: A total of 40 male rats were selected and then divided into two age groups -the old group (20 rats aged 27 months and weighing 389±31 g) and the young group (20 rats aged 3 months and weighing 224±13 g). Each group was itself randomly divided into an experimental group (n=10) and a control group (n=10). The training protocol involved 4 minutes of running on the treadmill with intervals of 2 minutes active resting in 10 training bouts of 60 minutes, for 6 sessions per week and for 8 weeks and gradually increasing in intensity. Twenty-four hours after the last training session, the rats were anesthetized with a mixture of ketamine and xylazine in order for their blood sample to be collected from their cardiac puncture. Their lactate levels and LDH activity were then measured by an enzymatic method. Data were analyzed using the one-way ANOVA and Tukey's post-hoc test. Results: The results showed no significant differences in blood lactate levels between the four groups; however, LDH activity was significantly higher in the young experimental group than in the young control group (p<0/05). Conclusion: The results indicate that lactate is increasingly cleared by interval training. It also appears that the effect of training on lactate clearance is similar in both young age and old age. Monitoring blood lactate levels benefits muscle glycogen replenishment and intracellular pH (pHi) regulation.

Effects ofAronia melanocarpafruit juice on exploratory behaviour and locomotor activity in rats

The main bioactive substances in Aronia melanocarpa fruit juice (AMFJ) are polyphenols (flavonoids, procyanidins, and phenolic acids). A great number of polyphenols are able to traverse the blood-brain barrier. In recent years more attention is drawn to the ability of these substances to influence central nervous system functions. The aim of the present study was to investigate the effects of AMFJ on exploratory behaviour and locomotor activity in male Wistar rats. AMFJ was administered orally for 7, 14, 21, and 30 days at three increasing doses (2.5, 5, and 10 ml kg−1). The changes in exploratory behaviour and locomotor activity were recorded in an Opto Varimex apparatus. It was found that the low doses of AMFJ (2.5 and 5 ml kg−1) for all treatment periods did not significantly affect exploratory behaviour and locomotor activity of rats compared to the saline-treated controls. AMFJ at the highest dose of 10 ml kg−1 had no significant effect on exploration and locomotion for the treatment periods of 7 and 14 days, while for the periods of 21 and 30 days it significantly decreased the number of horizontal and vertical movements, which might be the result of a sedative effect. At all the doses and testing periods, AMFJ did not disturb the progressive decrease in motor behaviour, suggesting habituation.

Effect of PUFA-rich plant oil on risk factors of STZ-induced diabetes in Wistar rats

ObjectiveThis study has been focused on the effect of an n-6 polyunsaturated fatty acid (PUFA) rich plant oil on oxidation and glycooxidation stress markers as well as on antioxidant enzyme activities in male Wistar rats with streptozotocin-induced diabetes.MethodsThe non-diabetic and diabetic groups of Wistar rats were administered plant oil at concentrations of 100 and 500 mg/kg body weight and controls without plant oil. The parameters of glycaemic control, lipid profile, total antioxidant status, antioxidant enzyme activities, together with oxidative and glycooxidative stress markers were measured in the blood.ResultsThe intake of the plant oil did not significantly influence the parameters of glycaemic control and significantly increased the levels of all lipid profile parameters in the diabetic rats. Plant oil administration significantly decreased the total antioxidant status and glutathione peroxidase activity and the activity of Cu/Zn superoxide dismutase was significantly increased. The plant oil also increased the levels of lipoperoxides and advanced the glycation end products.DiscussionThese results suggest that the plant oil with high concentrations of n-6 PUFA – linoleic acid, acts prooxidatively when administered to the rats.

Effect of 5Hz electromagnetic waves on movement behavior in male wistar rats (in vitro)

Various stresses during life can affect metabolism and brain activities, immune and endocrine systems directly and indirectly, and ultimately, causes animal behavior change. The cellular and molecular level change in neurotransmitter and hormone concentrations led to the functional changes of operating systems in the intracellular organelles. These events cause of course oxidative stress. All these reactions cause general or limited inflammation that is characterized by increased phenomena of inflammatory cytokines. Electromagnetic waves are the most important stimulus of ions and biomolecules therefore they change ions movement in a living organism. This process can lead to neuronal and behavioral changes. Yet, certainly, radiation pattern, intensity and magnetic field strength will be highly effective in response (reaction). In the present study, short-term (one day) and medium-term (3 days and 7days) and long-term (19 days and 21 days) effects of extremely low-frequency waves (ELF) on behavioral and metabolic activities in male wistar rats with an average weight 180-250g have been investigated.

P.1.h.026 Effects of obestatin and its fragment (1–4) on algesthesia and behavioural activity in male wistar rats

P.1.h.026 Effects of obestatin and its fragment (1–4) on algesthesia and behavioural activity in male wistar rats

Synthesis, Hypoglycaemic, Hypolipidemic and PPARγ Agonist Activities of 5‐(2‐Alkyl/aryl‐6‐Arylimidazo[2,1‐b][1,3,4]thiadiazol‐5‐yl)methylene‐1,3‐Thiazolidinediones

A novel series of 5-(2-alkyl/aryl-6-arylimidazo[2,1-b][1,3,4]thiadiazol-5-yl)methylene-1,3-thiazolidinediones were synthesized as possible PPARγ agonists. The structures of these target molecules were established by spectral and analytical data. All the newly synthesized compounds were screened for their in vivo hypoglycaemic and hypolipidemic activity in male Wistar rats. Further, compounds with good activity were screened for PPARγ agonist activity. Among the screened compounds, 5-{[2-Cyclohexyl-6-(4-methoxyphenyl)imidazo[2,1-b] [1,3,4]thiadiazol-5-yl]methylene}-1,3-thiazolidine-2,4-dione (3i) exhibits promising hypoglycaemic and hypolipidemic activity via potential PPARγ agonist activity.

Melatonin reduces body weight gain and increases nocturnal activity in male Wistar rats

AimThis study evaluated the effect of the administration of melatonin, the chief secretory product of the pineal gland, on the body weight in male Wistar rats. Main methodsThe animals were housed for 4months in cages equipped to log horizontal activity within a thermostatically-controlled chamber, under a 12h/12h light/dark photoperiod (lights on at 08:00h). After acclimatization, the animals were divided into two groups: (1) control animals, and (2) melatonin-treated animals. Melatonin was administered in tap water (20μg/ml), and fresh drinking fluid was changed twice weekly. Rats were fed a standard diet ad libitum. Key findingsFood and water intake, body weight, the amplitude of the activity/rest rhythm (motor activity), and blood melatonin and glucose concentrations were measured. The administration of melatonin did not influence either food or water intake or glucose levels relative to those found in the control animals. However, melatonin administration reduced body weight gain and increased nocturnal locomotor activity. The peak concentration of melatonin was found at night coinciding with the increase in nocturnal activity. SignificanceThe results show that exogenous melatonin reduces body weight gain without having marked effects on metabolism. This may be due in part to the increased nocturnal activity shown by the animals treated with the indoleamine.

Synthesis, hypoglycemic and hypolipidemic activities of novel thiazolidinedione derivatives containing thiazole/triazole/oxadiazole ring

Novel thiazolidinedione derivatives were synthesized by incorporating pharmacologically significant heterocycles viz, substituted thiazole, triazole, and oxadiazole moieties linked to the central phenyl ring via heteroatomlinkage with one/two carbon spacer as the structural analogs of Pioglitazone by employing multistep synthetic protocols. Structures of all the newly synthesized intermediates and target molecules were established by analytical and spectral data. These newly synthesized compounds were screened for their invivo hypoglycemic and hypolipidemic activities in male wistar rats. Some of the synthesized compounds demonstrated good activity.

Alternative complement pathway and factor B activities in rats with altered blood levels of thyroid hormone

Evaluating the activity of the complement system under conditions of altered thyroid hormone levels might help elucidate the role of complement in triggering autoimmune processes. Here, we investigated alternative pathway (AP) activity in male Wistar rats (180 ± 10 g) after altering their thyroid hormone levels by treatment with triiodothyronine (T3), propylthiouracil (PTU) or thyroidectomy. T3 and thyroxine (T4) levels were determined by chemiluminescence assays. Hemolytic assays were performed to evaluate the lytic activity of the AP. Factor B activity was evaluated using factor B-deficient serum. An anti-human factor B antibody was used to measure factor B levels in serum by radial immunodiffusion. T3 measurements in thyroidectomized animals or animals treated with PTU demonstrated a significant reduction in hormone levels compared to control. The results showed a reduction in AP lytic activity in rats treated with increasing amounts of T3 (1, 10, or 50 µg). Factor B activity was also decreased in the sera of hyperthyroid rats treated with 1 to 50 µg T3. Additionally, treating rats with 25 µg T3 significantly increased factor B levels in their sera (P < 0.01). In contrast, increased factor B concentration and activity (32%) were observed in hypothyroid rats. We conclude that alterations in thyroid hormone levels affect the activity of the AP and factor B, which may in turn affect the roles of AP and factor B in antibody production.

Antidiarrhoeal activity of ethanol and aqueous extracts of Carum copticum seeds in experimental rats

ObjectiveTo investigate the antidiarrhoeal activity of 95% total alcoholic extract (TAE) and total aqueous extract (TAQ) of Carum copticum (C. copticum) seeds. MethodsAntidiarrhoeal activity of C. copticum seed extracts at a dose of 100 mg/kg BW was evaluated using experimentally induced castor oil diarrhoea, gastrointestinal transit of charcoal meal and enteropooling activity in male wistar rats and compared to standard drugs. ResultsAt a dose of 100 mg/Kg BW (TAQ and TAE) significantly decreased the diarrhoeal droppings in castor oil induced diarrhoea, the mean distance travelled by charcoal meal showed a significant reduction in the secretion of gastrointestinal fluid accumulation by 39.90% to 50.70%. C. copticum extracts on castor oil induced fluid accumulation showed a greater inhibitory effect on Na+ levels than on K+ concentrations. ConclusionsThese results suggest that C. copticum seed extracts could be used for the treatment of diarrhoea.

Red wine polyphenols correct vascular function injured by chronic carbon tetrachloride intoxication

The aim of the study was to evaluate the effect of red wine polyphenols extract Provinols™ on the development of cardiovascular injury in the model of carbon tetrachloride (CCl4) intoxication. We followed the thoracic aorta vasoactivity and left ventricle nitric oxide (NO) synthase activity in male Wistar rats. In the preventive experiment lasting for 12 weeks the control group, the group receiving CCl4 (0.5 ml/kg) two times a week subcutaneously, the group receiving Provinols™ (30 mg/kg/day) in drinking water and the group receiving CCl4+Provinols™ was used. In the recovery experiment, the initial 12 weeks of CCl4 treatment were followed by 3 weeks of spontaneous recovery or recovery with Provinols™. CCl4-intoxication resulted in the injury of vasoactivity which was demonstrated by the inhibition of acetylcholine-induced relaxation as well as noradrenaline-induced contraction. In the preventive as well as recovery experiment administration of polyphenols refreshed endothelium-dependent relaxant response and normalized inhibited contraction to adrenergic stimuli. Provinols™ treatment significantly increased NO-synthase activity in all groups. The results revealed beneficial effects of red wine polyphenols on vascular function injured by chronic CCl4 intoxication. The correction of endothelial function seems to be attributed to the activation of NO pathway by polyphenols.

Investigation of Anti-Inflammatory, Analgesic and Antipyretic Properties of Madhuca Indica Gmel

The crude methanolic extract of Madhuca indica (Sapotaceae) at 50,100 and 200 mg/kg body weight was evaluated for anti-inflammatory, analgesic and antipyretic activities in male wistar rats. Anti-inflammatory activity was studied by using carrageenan-induced oedema right hind paw volume while the analgesic effect was evaluated using acetic acid-induced abdominal pains, i.e. nociception response and the brewer's yeast-induced pyrexia model was used for antipyretic investigation. Phytochemical screening of the alcoholic extract revealed the presence of cardiac glycosides, flavonoids, saponins, steroids, tannins and terpenes. All the doses of the plant methanolic extract and the indomethacin significantly inhibited carrageenan-induced inflammation that was not dose-dependent. The plant extract reduced the acetic acid-induced pain licking. The plant extract reduced the brewer's yeast-provoked elevated body temperature in rats after 60 mins for 50 and 100 mg/kg dose range and 30 mins for 200 mg/kg dose range. The results suggest a potential benefit of M indica methanolic extract in treating conditions associated with fever, inflammation and pain. These properties might be adduced to the presence of the phytoconstituents.

Subacute toxicity of p,p′-DDT on rat thyroid: Hormonal and histopathological changes

The purpose of this study is to assess the effect of p,p′-DDT on thyroid activity of male Wistar rats. Pesticide was administered intraperitoneally (i.p.) for 10 consecutive days at doses of 50 and 100 mg/kg/day. At the end of the treatment, the endpoints examined included serum total levels of triiodothyronine (T 3), total thyroxine (T 4), and thyroid stimulating hormone (TSH). Thyroid gland histopathology and tissue metabolism of thyroid hormone (T 4 UDP-glucuronyltransferase UDP-GT and 5′-deiodinases) were determined. DDT treatment altered thyroid function namely by increasing hepatic excretion of T 4 glucuronide. At the dose of 50 mg/kg it decreased T 4 circulating levels and increased thyroid 5′-deiodinase type I (5′-D-I) and brown adipose tissue (BAT) 5′-deiodinase type II (5′-D-II) activities but it did not affect liver 5′-D-I activity which might contribute to the maintenance of the serum T 3 level. Treatment with 100 mg DDT/kg decreased serum thyroid hormone concentration and tissue 5′-D-I activity without affecting BAT 5′-D-II activity. Gland histomorphological analysis showed hyperplasia and squamous metaplasia with abundant colloid. These observations associated to the elevated serum TSH levels and gland hypertrophy suggest that DDT exposure induced an hypothyroidism state with a colloid goiter in rats.

Antispermatogenic Activity Of Morinda Morindoides Root Bark Extract In Male Wistar Rats

To investigate the effect of the aqueous extract of the root bark of Morinda morindoides (Rubiaceae) on the reproductive activity of male Wistar rats, three groups (A, B and C) of six rats each were treated with 400,800 and 1600 mg/kg/day of Morinda morindoides root bark extract respectively for 28 days while 5mls/kg of distilled water was given to the control group D. At the end of the experimental period, animals were sacrificed and sperm characteristics, histology of the testes and epididymis were assessed. Morinda morindoides root bark extract caused a significant reduction (p<0.05) in sperm motility, a significant dose dependent reduction in the sperm count and a significant (p<0.05) dose dependent increase in morphological abnormalities of the spermatozoa of the treated rats. Histopathological evaluation of the testis and epididymis revealed varying degrees of degeneration and necrosis of the germinal epithelia cell of the seminiferous tubules and spermiostasis. Morinda morindoides root bark extract has significant anti-spermatogenic effects on adult male Wistar rats which could impair reproductive activities in these male Wistar rats.

Hepatoprotective effects of Calotropis gigantea extract against carbon tetrachloride induced liver injury in rats

Ethanolic extract (50 %) of stems of Calotropis gigantea R. Br. (Asclepiadaceae) at doses of 250 and 500 mg kg-1 were studied for hepatoprotective activity in male Wistar rats with liver damage induced using carbon tetrachloride, 2 mL kg-1 twice a week. The protective effect of C. gigantea extract was compared with the standard drug silymarin. Various biochemical parameters such as aspartate amino transferase (AST), alanine amino transferase (ALT), glutathione (GSH), lipid peroxide (LPO), superoxidedismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were evaluated. The results revealed that the C. gigantea extract significantly decreased AST, ALT (p < 0.001) and lipid peroxide (p < 0.01) levels. The antioxidant parameters GSH, GPx, SOD and catalase levels were increased considerably compared to their levels in groups not treated with C. gigantea extract.

INCREASED AEROBIC GLYCOLYSIS THROUGH β2 STIMULATION IS A COMMON MECHANISM INVOLVED IN LACTATE FORMATION DURING SHOCK STATES

During septic shock, muscle produces lactate by way of an exaggerated NaK-adenosine triphosphatase (ATPase)-stimulated aerobic glycolysis associated with epinephrine stimulation possibly through beta2 adrenoreceptor involvement. It therefore seems logical that a proportion of hyperlactatemia in low cardiac output states would be also related to this mechanism. Thus, in low-flow and normal-to-high-flow models of shock, we investigate (1) whether muscle produces lactate and (2) whether muscle lactate production is linked to beta2 adrenergic stimulation and Na+K+-ATPase. We locally modulated the adrenergic pathway and Na+K+-ATPase activity in male Wistar rats' skeletal muscle using microdialysis with nonselective and selective beta blockers and ouabain in different models of rodent shock (endotoxin, peritonitis, and hemorrhage). Blood flow at the probe site was evaluated by ethanol clearance. We measured the difference between muscle lactate and blood lactate concentration, with a positive gradient indicating muscle lactate or pyruvate production. Epinephrine levels were elevated in all shock groups. All models were associated with hypotension and marked hyperlactatemia. Muscle lactate concentrations were consistently higher than arterial levels, with a mean gradient of 2.5+/-0.3 in endotoxic shock, 2.1+/-0.2 mM in peritonitis group, and 0.9+/-0.2 mM in hemorrhagic shock (P<0.05 for all groups). Muscle pyruvate concentrations were also always higher than arterial levels, with a mean gradient of 260+/-40 microM in endotoxic shock, 210+/-30 microM in peritonitis group, and 90+/-10 microM in hemorrhagic shock (P<0.05 for all groups). Despite a decrease in blood flow, lactate formation was decreased by all the pharmacological agents studied irrespective of shock mechanism. This demonstrates that lactate production during shock states is related, at least in part, to increased NaK-ATPase activity under beta2 stimulation. In shock state associated with a reduced or maintained blood flow, an important proportion of muscle lactate release is regulated by a beta2 receptor stimulation and not secondary to a reduced oxygen availability.