Role of the trace metals, selenium and zinc, in pilocarpine-induced epilepsy in rats

Excitotoxic brain lesions, such as epilepsy, lead to increasing destruction of neurons, in the course of few hours after the insult. The deadly cascade of events possibly involves detrimental actions by free radicals, proinflammatory cytokines and the activation of pro-apoptotic transcription factors, which finally result in neuronal destruction. Several reports suggest that the level of some trace elements play a vital role in seizure conditions to prevail. The aim of the present study was to assess the possible modulatory role of the trace elements, selenium and zinc on pilocarpine-induced epilepsy in rats.The study was carried out on 40 male albino rats, weighing 150-200 grams that were divided into the following groups each of 10 rats: Group I: control rats that received intraperitoneal [i.p.] saline, Group II: pilocarpine induced epilepsy, Group 111: selenium pretreated for 3 weeks before pilocarpine injection and Group IV: zinc pretreated for 3 weeks before pilocarpine injection. The seizure latency and severity for each rat was recorded. Twenty four hours following pilocarpine injection, rats were exsanguinated and the following parameters were determined: cerebral caspase-3 activity [as a marker of apoptosis], interleukin-lbeta [IL-ljB], reduced glutathione [GSH] and malondialdehyde [MDA] concentrations, serum neuron specific enolase[NSE] concentration [as a marker of brain injury].Intraperitoneal injection of pilocarpine in rats resulted in progression to limbic seizures with progressing behavioural scores at various time intervals [recorded every 30 minutes up to 2 hours]. Latency to forelimb clonus was 51.86 +/- 1.89 min. The results of the present study demonstrated significantly increased cerebral MDA concentration together with significant decrease in cerebral GSH concentration in non-treated pilocarpine injected rats compared to normal control rats. A significant increase in cerebral caspase-3 activity, and in cerebral 1L-1/beta as well as in serum NSE concentrations could be observed in non-treated pilocarpine-injected rats compared to normal control rats. Pretreatment with selenium or zinc reduced the severity of pilocarpine- induced seizures. In addition, both trace elements decreased the latency to attain the forelimb clonus [score 4]. A significant decrease in cerebral MDA and IL-1/beta, serum NSE concentrations could be observed in selenium and zinc-treated rats compared to non-treated pilocarpine-injected rats. A significant' increase in cerebral GSH concentration was observed in zinc-treated, but not in selenium-treated ones.The results of the present study confirm the role of the trace elements, selenium and zinc, in mitigating epilepsy. Further human studies to evaluate the role of trace elements in epilepsy are recommended. Furthermore, since antiepileptic drugs [AEDs] are reported to induce zinc and selenium deficiency,thus combining these trace elements with AEDs are worthy to be evaluated

Effect of peroxisome proliferator- activated receptor-gamma [PPAR-Y] ligands on gastric mucosal injury induced by ischemia/reperfusion in rats

Peroxisome proliferator-activated receptor-gamma [PPAR-y] has recently been implicated as regulator of cellular proliferation and inflammatory responses. The aim of the present study was to investigate the effects of two PPAR-y agonists [rosiglitazone and pioglitazone] on ischemia-reperfusion [I/R]- induced gastric mucosal injury in rats, one and 24 h after reperfusion. Methods: Gastric ischemia was induced for 30 min by applying a small vascular clamp to the celiac artery and reperfusion was produced by removal of the clamp in male albino rats. The drugs and vehicle were given orally, 2 h before the vascular clamping. The results showed that I/R elevated the mucosal levels of lipid peroxide [LPX], lactate dehydrogenase [LDH] and tumor necrosis factor-alpha [TNF-alpha] and myeloperoxidase [MPO] activity in the gastric mucosa. On the other hand, I/R decreased the mucosal levels of reduced glutathione [GSH] and superoxide dismutase [SOD]. These biochemical changes were accompanied by an increase in the formation of gastric lesions, which was reduced by either rosiglitazone or pioglitazone. Both drugs tended to normalize the estimated biochemical changes one and 24h after reperfusion. The results indicate that both rosiglitazone and pioglitazone possess a gastroprotective effect against mucosal injury induced by I/R in rats, which could be attributed to their antioxidant effects and their anti-inflammatory properties

Effect of selective and non-selective cyclooxygenase inhibitors on survival, platelet function and vein wall inflammation in a rat model of deep vein thrombosis

Worldwide, the withdrawal of rofecoxib and valdecoxib from the United State, Australian and European markets with substantial decline in the number of prescriptions for celecoxib attract attention. Inhibition of vascular synthesis of prostacyclin [PGI[2]] leaving platelet thromboxane A[2][TXA[2] synthesis unopposed is thought to increase risk ofthrombotic events. To decrease this risk, adding low aspirin has been suggested. In the present study, we compared celecoxib alone and with low-dose aspirin to indomethacin and to low-dose aspirin regarding the effects on survival, platelet function and vein wall inflammation in a rat model of deep vein thrombosis [DVT] induced by 3 days inferior vena cava ligation.The results showed significant decline in rate of survival in the celecoxib group and enhanced thrombogenesis compared to aspirin and indomethacin. Co-administration of low dose aspirin significantly reduced wet thrombus weight compared to celecoxib monotherapy. Platelet function was assessed by bleeding time and two platelet proteins released into plasma from a granules during platelet activation namely platelet factor 4 [PF4] and micro 3-thromboglobulin [f]-TG]. In the celecoxib group, bleeding time was not altered while plasma PF4 and /beta-TG were high compared to sham group. The level of these platelet markers in celecoxib group was comparable to the DVT group denoting significant platelet activation. Conversely, indomethacin, aspirin alone or with celecoxib were associated with significant increase in bleeding time and significant low values of plasma PF4 and /3-TG compared to DVT group denoting significant inhibition of platelet activity. All COX inhibitor treatments were associated with significant anti-inflammatory effect demonstrated by the low values of vein wall content of tumor necrosis factor-a [TNF-alpha] and interleukin-1 beta [IL-1beta] compared to DVT group. However, attenuation in the rise of myeloperoxidase activity was significant only with indomethacin possibly due to its greater anti-inflammatory effect.The present study shows that celecoxib shares standard non-steroidal anti-inflammatory [NSAIDs] e.g. indomethacin and aspirin, significant anti-inflammatory effect but seems to lack significant inhibitory effect on platelets. This would raise concerns about increased risk of acute vascular events in patients receiving COX-2 inhibitors. The risk may be increased with underlying inflammatory disorders and platelet activation e.g. venous stasis

Role of histamine in ovariectomy-induced osteoporosis in rats

It has been reported that histamine increases osteoclast activity and number through H1 and H2 receptors, respectively, whereas other studies indicated that the histamine effects on bone resorption were indirect. The present study was designed to assess the possible effect of the H1 receptor antagonist [promethazine] and the H2 receptor antagonist [ranitidine], alone and in combination compared with the bisphosphonate [alendronate], as a standard treatment of osteoporosis, on ovariectomy-induced osteoporosis in rats. The present study was conducted on 60 female albino rats that were divided into 6 groups, each of JO rats. Group I: sham-operated, Group II: non-treated ovariectomized [OVX] rats, while groups III, 1V V and VI were OVX rats treated with alendronate, promethazine, ranitidine and combination ofpromethazine and ranitidine, respectively. The results of the present study demonstrated that urinary deoxypyridinoline [DPY]/creatinine and serum osteocalcin concentration significantly increased in the OVX non-treated group compared to the sham-operated group, indicating an increased bone turnover. In addition, serum alkaline phosphatase [ALP] activity and serum phosphorus [F] concentration were significantly higher in the OVX non-treated group than in the sham-operated group. Meanwhile, no significant dfference among groups I to VI was observed in the mean serum calcium [Ca] concentration. Treatment of OVX rats with alendronate significantly decreased urinary DPY/creatinine as compared to the OVX non-treated group. Moreover, alendronate significantly decreased serum osteocalcin and F concentrations and serum ALP activity as compared to the OVX non-treated group. Similarly, treatment of OVX rats with promethazine, ranitidine or their combination significantly deceased urinary DPY/creatinine as compared to the OVX non-treated group. Furthermore, the combination of both drugs .reased urinary DPY/creatinine at a higher significant level when compared to each drug alone. In addition, e was no significant difference, regarding this parameter, between the combination, alendronate and shamyrerated groups. Moreover, treatment of OVX rats with promethazine, ranitidine or their combination sigi4ficantly serum osteocalcin and F concentrations and serum ALP activity as compared to the OVX non-treated-group. Furthermore, there was no statistically significant difference, regarding these parameters, between the pnethazine, ranitidine, their combination and alendronate-treated groups. However, there were statistically significant differences, regarding these parameters, between all the drug-treated groups and the sham-operated. It may be concluded from the findings of the present study that the use of the H1 and H2 receptor agonists [promethazine and ranitidine] could be effective in decreasing bone resorption, increasing bone formation and diminishing ovariectomy-induced osteoporotic changes. These findings might be of help in developing therapeutic regimens to protect against postmenopausal osteoporosis in women

Effect of silymarin, melatonin, and N-acetylcysteine on bleomycin-induced lung injury in rats

Pulmonary fibrosis is the end stage of a heterogeneous group of disorders of known and unknown etiology. One of the clinically important causative agents in pulmonary fibrosis is bleomycin [BLM]. Silymarin is an old herbal remedy known to protect a cell membrane against xenobiotic injury principally due to its antioxidant potential. Melatonin, which is the chief secretory product of the pineal gland, was recently found to be a potent free radical scavenger and antioxidant. The antioxidant, N-acetylcysteine [NAC], has shown beneficial effects in diseases in which reactive oxygen species appear to be involved. The aim of the present study was to assess and compare the protective effect of orally administered silymarin, melatonin, or N-acetylcysteine on lung injury induced in rat model by endotracheal instillation of BLM. Fifty six animals were divided into: group I [control group] [n=24] which were equally subdivided into IA [vehicle and intratracheal saline]; IB [silymarin and intratracheal saline]; IC [melatonin and intratracheal saline]; ID [NAC and intratracheal saline]. Group II [treatment group] [n=32]: which were equally subdivided into IIA [vehicle and intratracheal BLM]; IIB [silymarin and intratracheal BLM]; IIC [melatonin and intratracheal BLM]; IID [NAC and intratracheal BLM]. silymarin was taken in a dose of 50 mg/kg/day suspended in 2% gum acacia mucilage. Melatonin was administered in a dose of 10 mg/kg/day. NAC was given in a dose of 486.6 mg/kg/ day. Treatments were administered orally for 14 days after the day of BLM or saline instillation. Animals received endotracheally a single dose of BLM hydrochloride [5 mg/kg body weight] to produce pulmonary fibrosis. Bronchoalveolar lavage fluid [BALF] was used to measure total protein concentration, lactate dehydrogenase [LDH] activity, and total glutathione levels. Lung tissue homogenates were used to measure myeloperoxidase [MPO] activity, lipid peroxide [LPO] content, and total lung collagen. The body weight of rats not exposed to BLM increased with time. Rats in group IIA failed to gain weight during the first week; thereafter weight gain paralleled that observed in rats not exposed to BLM. A similar but less marked trend was noticed for treated rats. Bleomycin produced a significant increase in lung weight. Treatment with silymarin, melatonin, or NAC decreased lung weight but statistical significance was not reached. The lung hydroxyproline levels were increased in BLM-instilled rats [group IIA] but significantly deceased on treatment with silymarin, melatonin, or NAC. The total cell count and neutrophil cell count in BALF were significantly increased in BLM-exposed rat group. On the contrary of melatonin and NAC, treatment with silymarin significantly decreased these elevated cell counts. The elevated protein concentration in BALF due to the effect of BLM instillation was not reduced by treatment with any of the drugs used. Treatment with silymarin, melatonin, or NAC significantly attenuated the increased LDH activity following BLM instillation. Bleomycin was shown to reduce glutathione levels in the lung. Treatment with silymarin, melatonin, or NAC resulted in a significant increase of glutathione in BALF. Silymarin, but not melatonin or NAC significantly attenuated the increase in lung MPO activity following BLM instillation. The lipid peroxide content in the lung was significantly increased in BLM instilled rats. Treatment with silymarin, melatonin, or NAC attenuated this elevated peroxidation. We conclude that treatment with silymarin inhibit lung fibrotic progression induced by BLM. The decreased neutrophil recruitment to the lung, attenuation of cell damage and the antioxidant properties of silymarin may be involved in its protective mechanism against pulmonary fibrosis. Melatonin also exerts protection against BLM- induced pulmonary fibrosis, probably by suppressing oxidative stress. Treatment with oral NAC is partially effective against lung fibrosis which may be due to replenishment of lung glutathione or reduction of damage to lung structure in the early stage of the disease

Role of silymarin and melatonin in freund's adjuvant arthritis and mixed-type hypersensitivity in rats

Silymarin is reported to be hepatoprotective against a number of experimentally studied hepatotoxins. Besides its known antioxidative properties and its ability to act as a free radical [FR] scavenger, silymarin exerts an important anti-inflammatory action. Similarly, melatonin has antioxidative properties both at physiological concentrations or when administered at pharmacological doses. The present study was conducted to investigate the effect of silymarin and melatonin on immunologically mediated chronic inflammation. Two models were chosen, namely, Freund's adjuvant arthritis [FA] and mixed-type hypersensitivity [MH] in rats. The effect of both drugs was assessed on the basis of biochemical markers in blood and inflammatory exudate. The investigated drugs were given orally during the course of inflammation development. The results demonstrated that, in either model, silymarin reduced the elevated serum and exudate [local] leukotriene B[4] [LTB[4]] and interleukin-6 [IL-6] levels. The anti-inflammatory effect of silymarin was also accompanied by reduction or normalization of elevated systemic and/or local levels of lipid peroxide [LP], superoxide dismutase [SOD], and reduced glutathione [GSH]. On the other hand, treatment with melatonin resulted in insignificant effects in serum level of LTB[4] in FA as well as in sera and exudates of animals subjected to MH. Meanwhile, melatonin significantly increased the level of IL-6 in sera of both models as well as in exudates of MH model. In contrast, the antioxidant effect of melatonin was similar to that of silymarin in both models of inflammation. It could be concluded that silymarin confers a good anti-inflammatory activity against arthritis in rat, leading to improvement of the oxidative stress induced by the arthritic insult. The reparative effect of silymarin could be mediated via reduction of LTB[4] and IL-6. Due to its peculiar ability to enhance proinflammatory cytokine production, melatonin might thus play a pathogenic role in rheumatoid arthritis [RA] in despite of its antioxidant effect

Role of rosiglitazone and pravastalin in freund's adjuvant arthritis and mixed-type hypersensitivity in rats

Recent studies have shown that peroxisome proliferator- activated receptor- gamma [PPAR gamma] may participate in control of inflammation, especially in modulating the production of inflammatory mediators. Similarly, the cholesterol lowering drugs, statins, have been found to exhibit anti-inflammatory properties that are beyond their lipid lowering effects. The present study was conducted to investigate the effect of a PPAR gamma agonist [rosiglitazone] and a statin [pravastatin] on immunologically mediated chronic inflammation. Two models were chosen, namely, Freund's adjuvant arthritis [FA] and mixed- type hypersensitivity [MH] in rats. The effect of these drugs was assessed on the basis of biochemical markers in blood and / or inflammatory exudate. The investigated drugs were given orally daily during the course of inflammation development. The results of the present study demonstrated that, in either model, rosiglitazone and pravastatin reduced the elevated serum and exudate [local] leukotriene B[4] [LTB[4]] and interleukine-6 [IL-6] levels. The anti-inflammatory effect of these drugs was also accompanied by reduction or normalization of elevated systemic and or local levels of lipid peroxide [LP], superoxide dismutase [SOD], and reduced glutathione [GSH]. It could be concluded that long-term treatment with rosiglitazone or pravastatin confers a good anti-inflammatory activity against arthritis in rat, leading to improvement of the oxidative stress induced by the arthritic insult. The reparative effect of these drugs could be mediated via reduction of LTB[4] and IL-6

possible reno- and vascufoprotective of drugs that inhibit the renin angiotensin system in diabetic rats

Aim: The renin angiotensin system [RAS] plays an important role in the development of diabetic renovascular pathology characteristic of diabetic nephropathy [DN]. Through inhibition of RAS by different mechanisms, angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin II type 1 receptor blockers [ARBs] could slow the progression of diabetic renovascular disease. Thus, the present study was undertaken to test the hypothesis that a combination of an ACEI [fosinopril] and an ARB [candesartan] could exert additive reno- and vasculoprotective effects in uninephrectomized [UNE], streptozotocin [STZ] -induced diabetic rats. Material and Fifty male albino rats weighing 150-200 g were used in the present study. Rats were divided into five groups [each of ten rats]; ten rats of them were taken as normal sham-operated group. The remaining forty rats were subjected to left unilateral nephrectomy and then three weeks later, diabetes was induced by a single intravenous injection of STZ. The UNE STZ - diabetic rats were further subdivided into: control rats that were given no additional treatment but insulin s.c., UNE STZ -diabetic rats treated with fosinopril in addition to insulin for 16 weeks, UNE STZ - diabetic rats treated with candesartan in addition to insulin for 16 weeks and the fifth group was UNE STZ -diabetic rats treated with a combination of fosinopril and candesartan in addition to insulin for 16 weeks. UNE STZ - diabetic rats exhibited the characteristic features of diabetic renal disease including increased BP, plasma creatinine [PCr], urinary albumin excretion [UAE], kidney weight [KW], BG and glycosylated hemoglobin [HbAIc] together with decreased urinary creatinine [UCr] and creatinine clearance [CrCI]. Furthermore, control rats showed significant elevations in plasma transforming growth factor-beta 1 [TGF-D 1] and in renal malondialdehyde [MDA] associated with significant reduction in renal reduced glutathione [GSH]. Edothalial dysfunction [ED] of renal arteries isolated from STZ-diabetic rats, evidenced by a significant decrease in percentage of maximal relaxation in response to acetylcholine [ACH], has been also demonstrated. Oral administration of fosinopril or candesartan for 16 weeks in UNE STZ diabetic rats produced significant decreases in KW,BP, PCr,UAE, plasma TGED1 and renal MDA concentration together with significant increase in UCr, CrC 1 and renal GSH concentration. Vasculoprotective effect of fosinopril and candesartan has been also found, evidenced by a significant increase in the percentage of maximal relaxation in response to Ach in renal arteries isolated from UNR STZ-diabetic rats treated with fosinopril or candesartan Treatment of UNE diabetic rats with a combination of an ACEI [Fosinopril] and an ARB [candesartan] improved most of the estimated biochemical parameters as well as BP more significantly than either drug alone, but the combination of both drugs did not result in a significant difference in the percentage of maximal relaxation in response to Ach in renal arteries compared to either drug given alone. Conclusions: the results of the present study demonstrated that ACEIs and ARBs have a comparable degree of reno- and vasculoprotection in UNE STZ- induced diabetic rats Moreover, the present study demonstrated an additive renoprotective effect of combination therapy with ACEIs and ARBs over monotherapy with either class alone

Effect of some hypolipidemic drugs on glycemic control, lipid profile and some oxidative indiced in experimental hyperlpidemic diabetic rats

Diabetic patients, especially those with type-2 diabetes, are at a higher risk of developing cardiovascular disease. The specific pattern of diabetic dyslipidaemia, hyperglycemia, hyperinsulinemia, increased oxidative stress and inflammatory cytokines are co-operative factors for increasing cardiovascular morbidity and mortality in these patients. The present study was conducted to investigate the impact of different antidyslipidemic agents on these risk factors in a rat model of diabetic dyslipidaemia with hyperinsulinemia. A total of 70 rats were involved in the study; 10 of which served as a normal control group. The remaining rats were lipid-fed and streptozotocin [STZ]-injected, and were randomly assigned to no treatment [control group] or to 2-month treatment with pravastatin, fenofibrate, cholestyramine, nicotinic acid or fish oil. The lipid-fed STZ-injected rats developed high fasting serum glucose and glycated hemoglobin [HbAlc] levels together with hyperinsulinemia. They also acquired the characteristic pattern of diabetic dyslipidemia, i.e. increased levels of low density lipoprotein-cholesterol [LDL-C] and triglycerides [TG], and decreased high density lipoprotein-cholesterol [HDL-C] level. This was associated with increased markers of oxidative stress and inflammation "increased serum levels of malondialdehyde [MDA] and tumor necrosis factor-alpha [TNF-c_ together with decreased concentration of reduced glutathione and superoxide dismutase [SOD] activity in liver and kidney' Both pravastatin and fenofibrate significantly decreased serum cholesterol, LDL-C and TG, and increased serum HDL-C. However, only fenofibrate could normalize serum levels of HDL-C and TG. Cholestyramine significantly decreased serum levels of total cholesterol and LDL-C but increased the serum level of TG. Nicotinic acid produced significant decreases in serum TG and LDL-C levels and a significant increase in serum HDL-C level. Fish oil only significantly decreased the serum TG level. Fenofibrate and fish oil produced significant decreases in serum glucose, HbAJc and serum insulin levels. Pravastatin only decreased serum insulin level significantly. Cholestyramine did not affect the glycemic control, Nicotinic acid, on the other hand, produced significant increases in serum glucose, HbAlc and serum insulin levels. .Pravastatin, fenofibrate and fish oil decreased the oxidative stress and serum level of TNF-a. On the other hand, cholestyramine and nicotinic acid did not significantly change any of the studied oxidative and inflammatory parameters. Major outcome clinical studies are required to compare the effect of the most promising agents, pravastatin, fenofibrte, fish oil and/or their possible combinations on the overall mortality and morbidity in diabetic dyslipidemic patients

Role of peroxisome proliferator activated receptor [PPAR] agonists in experimental liver fibrosis in rats

The ligand-dependent transcription factors, peroxisome proliferator-activated receptors [PPARs] are expressed in hepatic stellate cells [HSCs], which are the cells reported to play a central role in liver fibrosis. It has been reported that the transcriptional activity of PPAR gamma and alpha is reduced during activation of HSCs. The aim of the present study was to evaluate whether oral administration of pioglitazone [alpha PPAR gamma ligand], and bezafibrate [alpha PPAR alpha ligand], might retard liver fibrosis in rats. Fifty male albino rats weighing 150-200 g were used in the present study. Rats were divided into five groups, each often rats. Group I, injected intraperitonealy [i.p.] by thioacetamide [TAA]. Group II, injected i.p. by saline. Groups III and IV, treated with bezafibrate and pioglitazone respectively, orally starting from the first day of TAA administration. Group V, served as a control group for groups III and IV. The duration of the study was six weeks. Administration of TAA to rats for six weeks resulted in significant increases in portal pressure, serum cytokines [tumor necrosis factor-alpha TNF-alpha and transforming growth factor-beta 1 TGF-beta 1], hepatic hydroxyproline [HPO], and serum aspartate aminotransferase [AST] and alanine aminotransferase [ALT] associated with a significant decrease in hepatic glycogen concentration. On the other hand, the two PPAR ligands, pioglitazone and bezafibrate, produced a significant decrease in portal pressure, a significant decrease in serum TNF-alpha and TGF-beta 1, a significant improvement in all the estimated parameters of liver function, as well as a significant decrease in hepatic HPO concentration in rats that received the drugs for six weeks compared to the control untreated rats. The results of the present study demonstrated that the PPAR agonists, pioglitazone and bezafibrate were effective in preventing the fibrogenic process via modulating the action of the cytokines TNF-alpha and TGF- beta1. Further studies on humans are needed in order to assess the clinical use of PPAR agonists in patients with liver fibrosis

comparative study of the effect of peroxisome proliferator - activated receptor gamma [PPAR - gamma] ligands and angiotensin converting enzyme [ACE] inhibitors on experimental colitis in rats

Peroxisome proliferator - activated receplor-gamma [PPAR- gamma], a member of the nuclear hormone receptor superfamily originally shown to play a critical role in adipocyte differentiation and glucose homeostasis, has recently been implicated as a regulator of cellular proliferation and inflammatory responses. In addition, increasing evidence supports an association between inflammation and angiotensin converting enzyme [ACE]. The aim of this study was to investigate the efficacy of ACE inhibitors [captopril and enalapril] and a PPAR- gamma ligand [rosiglitazone] on acetic acid-induced colitis in rats. Colitis was induced by intracolonic injection of 2 ml of 3% acetic acid. One hundred adult male albino rats were studied in this work. The animals were divided into two main groups, each of fifty rats: group I, of long duration of inflammation and treatment [Three weeks] and group II, of short duration of inflammation and treatment [two days]. Each group was subdivided into five subgroups, each of ten rats namely; control, acetic acid untreated, captopril, enalapril and rosiglitazone-treated rats. The investigated drugs were given two days after induction of colitis and continued daily for three weeks in group I, and for two days before and two days after induction of colitis in group II. Intracolonic injection of acetic acid in rats produced significant inflammation, assessed by the ulcer index score, weight of the colon and the colonic tissue level of myeloperoxidase enzyme in acetic acid untreated rats of both groups. These parameters were significantly improved by administration of captopril, enalapril and rosiglitazone. The effect of rosiglitazone was more potent than captopril and enalapril in both groups. Furthermore, the colonic tissue level of glutathione reductase enzyme was significantly reduced in acetic acid untreated rats of both groups. This reduction was significantly inhibited by the three investigated drugs in both groups, with better results with rosiglitazone than captopril and enalapril - treated rats in both groups. Rosiglitazone, captopril and enalapril also significantly improved the tissue level of lipid peroxides which was significantly elevated in acetic acid - untreated rats of both groups. However, the efficacy of rosiglitazone in reducing the lipid peroxides level was more significant than captopril and enalapril in both groups. this study provides an evidence that the PPAR- gamma ligand, rosiglitazone and the two ACE inhibitors, captopril and enalapril confer a good anti-inflammatory activity against acetic acid-induced colitis in rats. This leads to improvement of oxidative stress induced by the inflammatory insult, with the better results being with rosiglitazone than with captopril and enalapril

study on some pharmacologic manipulations of diet-induced obesity in rats

Aim: Obesity is a major health problem that represents an energy imbalance associated with complications, including cardiovascular disease, diabetes, and an increased mortality rate. The aim of the present work was to study some pharmacological manipulations of diet-induced obesity [DIO] in rats. Subjects and The study was conducted on 60 adult male albino rats that were divided into two groups; the DIO group fed high-calorie diet [HCD] [n=48] and the normal control group [n=12] fed normal laboratory diet. After 8 weeks, DIO rats were subdivided into four subgroups [each of 12 rats] that received the lipase inhibitor [orlistat], or the PPAR-gamma agonist [rosiglitazone], or the beta3-agonist [trecadrine] or a vehicle orally for 3 weeks. After the specified period, the following obesity variables were recorded: body weight, obesity index, food intake and rectal temperature. Blood samples were withdrawn for determination of serum metabolic parameters: glucose, triglycerides [TG], free fatty acids [FFA], leptin and insulin levels. Rats were sacrificed; and the remaining obesity variables were measured: retroperitoneal and interscapular fat as well as liver weight. The use of a HCD for 8 weeks resulted in a significant increase in all the measured obesity variables [except for rectal temperature] together with a significant increase in all the measured serum parameters as compared to rats that received normal laboratory diet. Orlistat administration for 3 weeks caused a significant decrease in all obesity variables with no significant change in food intake. A significant decrease in serum TG, FFA, insulin and leptin levels was also evident. Rosiglitazone-treated rats exhibited a significant decrease in liver weight together with a significant increase in fat pads weight and rectal temperature. Trecadrine produced significant reduction in obesity variables except for interscapular fat weight and rectal temperature that were significantly increased. Significant improvements in all serum metabolic parameters were noted with rosiglitazone and trecadrine treatment. Conclusions: From the current study, it can be concluded that lipase inhibitors and beta 3 agonists are effective in reducing body weight, while PPAR-gamma agonists are effective in improving insulin sensitivity and lipid abnormalities and so are rather effective as an adjuvant therapy to control the subsequent metabolic derangements relevant to obesity. Extrapolating these findings, especially the role of beta3-agonists, awaits further human trials before recommending it as a standard antiobesity drug