possible role for gastroprotectives on aspirin-induced gastric ulcer in rats

Gastric ulcer is a discontinuity in the gastric mucosa that occurs due to imbalance between gastric mucosal protective factors and aggressive factors. The Aim of the present work was to test and compare the protective effects of an antisecretory H2 receptor blocker; ranitidine and other recently suggested gastroprotective drugs: L-arginine; a precursor of NO, zinc sulfate; an anti-inflammatory antioxidant agent and pioglitazone; a PPAR-gamma agonist, on a rat model of aspirin induced gastric ulcer. Acute gastric lesion was induced in rats by a single oral dose of aspirin 300mg/ kg body weight. L-arginine 200mg / kg b. wt, zinc sulfate 80 mg/ kg b. wt, and pioglitazone 10 mg / kg b. wt. were given alone and in combination with ranitidine 50 mg / kg b. wt for 3 days before induction of gastric lesion. Aspirin induced a significant increase in gastric mucosal lesion score and free and total gastric hydrochloric acid with a significant decrease in gastric nitric oxide and mucin levels as compared to normal group. A significant increase in gastric malondialdhyde and decrease in reduced glutathione as compared to normal group. L-arginine, zinc sulfate, and pioglitazone produced improvement of most of the measured parameters as compared to non-treated group. Combination of L-arginine and ranitidine was superior in prophylaxis against aspirin-induced gastric ulcer when compared to the effects of each drug used individually, and the other studied combinations. The role of HCl and NO seems more important in the pathogenesis of aspirin induced gastric ulcer, as evidenced by the better protective effects of combination of ranitidine and L-arginine in comparison to the ranitidine with either zinc sulfate or pioglitazone

possible cytoprotectiye effect of vitamins C and E and L-carnitine on monosodium glutamate induced oxidative stress in the rat

Monosodium glutamate [MSG] consumption has increased throughout the world as flavoring agent in cooking. However, consumption of a highly palatable diet has been shown to cause endothelial dysfunction, cardiovascular disease and various age-related degenerative disease processes long before development of any significant obesity. The major purpose of the present study was to investigate the effects of MSG on glucose metabolism, lipid profile and oxidative stress. A secondary purpose was to determine the possible protective effect of vitamin C, vitamin E and L-carnitine [LC], separately or in combination in MSG inducing oxidative stress in the rat. Sixty male albino rats weighing from 100-150 g were included in this study. Rats were divided into two main groups. Group 1, [10 rats] served as a control group for group II, and were received 1 ml of physiological saline [0.9%], daily subcutaneously [s.c.] for eight weeks. Group II: MSG -induced oxidative stress [50 rats] injected s.c. MSG in a dose of 200 mg/kg.b.wt. daily for eight weeks. Rats were further subdivided into A, B, C, D and E, each of ten rats. Group- A, received 1 ml of 2% gum acacia daily orally for eight weeks starting from the first day of MSG administration. Groups B, C, D treated with orally daily vitamin C in a dose of 100 mg/kg.b.wt. or vitamin E in a dose of 10 mg/kg.b.wt. or L-carnitine in a dose of 200 mg/kg.b.wt for the same previous duration. Group-E, received vitamins C, E and LC in the same previous doses and durations. S.C. injections of MSG produced significant increases in body weight, serum levels of glucose, insulin, leptin, total cholesterol, LDL-cholesterol and triglycerides, while HDL- cholesterol and Apo A 1 were significantly decreased. There were insignificant changes in serum iron, ferrritin and total iron binding capacity [TIBC] The levels of glutathione and the activities of both catalase and superoxide dismutase [SOD] in heart, liver and kidney were significantly decreased. In addition, there were significant decreases in both basal arid insulin stimulated glucose uptake by the soleus muscle and fatty tissue of the rat. Intake of vit. C or vit. E or LC, reduced the abnormalities in body weight, glucose metabolism, lipid profile and antioxidant enzymes. Also, they procducd a significant increase in both basal and insulin stimulated glucose uptake by the soleus muscle and fatty tissue of the rat. Still vit. C revealed better effects as compared to the corresponding groups. The combination of vit. C and E and LC was found to be the best as shown by the correction of glucose metabolism, lipid profile and highest levels of antioxidant enzymes as compared to the corresponding groups. MSG enhanced food intake. Overfeeding induced metabolic disorders associated with oxidative stress. The present study provides evidence that combination of antioxidant vitamins C and E with LC combat metabolic disorders and oxidative stress induced by MSG. Thus, sufficient dietary intake of these vitamins with LC is beneficial in combating MSG adverse effects

Fructose induced metabolic syndrome in rats, a role for Glitazones, fibrates and statins

The metabolic syndrome is a constellation of symptoms and signs that include central obesity, insulin resistance, dysglycemia. dyslipidemia and hypertension. .The present work aimed to study the effect of a Peroxisome Proliferator Activated Receptor-alpha [PPAR-alpha] agonist [fenofibrate], two PPAR-gamma agonists [rosiglitazone and pioglitazone] and a statin [simvastatin] on glycemic control and lipid profile in fructose-induced metabolic syndrome in rats. The study also aimed to assess the benefits gained from the combination of these agents. The present study was carried out on one hundred and ten white male albino rats. Ten rats received normal laboratory chow. The remaining rats were fed a high fructose diet for induction of metabolic syndrome X. The current study showed that treatment of fructose induced metabolic syndrome [FMS] rats with fenofibrate, rosiglitazone or pioglitazone was associated with significant improvement in glycemic control Fenofibrate treatment was associated with significant decrease in body weight in comparison to rosiglitazone or pioglitazone-treated rats that showed a significant body weight gain. Fenofibrate and simvastatin treatment of FMS rats caused a significant decrease in serum triglycerides [TGs,], cholesterol as well as significant increase in serum high density lipoproteins [HDL]. Only simvastatin resulted in a significant decrease in serum low density lipoproteins [LDL]. The combination of fenofibrate with rosiglitazone or pioglitazone was associated with less body weight gain and a more marked improvement in glycemic control The addition of simvastatin to fenofibrate and rosiglitazone or pioglitazone was associated with a significant improvement in lipid profile when compared to the combination offenofibrate with rosiglitazone or pioglitazone. No further significant improvement in glycemic was control achieved by the addition of simvastatin to nfenofibrate and rosiglitazone or pioglitazone. Given the close relationship between PPAR activity and the metabolic syndrome, PPAR agonists are promising therapeutic agents for diseases including type 2 diabetes mellitus [DM2]. obesity, hypertension, hyperlipidemia and atherosclerosis. Combination drug therapy, which utilizes complementary mechanisms, can be advantageous in patients with significant combined or mixed dyslipidemias. The combination of glitazones and statins was associated with the utmost glycemic control and improvement in lipid profile

Study of possible effects of hormonal therapy on experimentally induced colitis in rats

Both beneficial and detrimental effects have been ascribed to sex steroids. In relation to gut inflammation, data is relatively limited. This study was designed to examine the influence of hormonal environment on severity of mucosal injury, level of interleukin 10 and oxidative stress in experimental colitis in ovariectomized rats. Sixty female albino rats were used in this work; 40 rats were bilaterally ovariectomized [Ovx] and 2 weeks thereafter; colitis was induced by intra-colonic administration of 2ml 3% acetic acid. Ten rats were sham-operated and served as a control normal group. The remaining 10 rats underwent colitis only and served as acetic acid-induced [AAI] colitis control untreated group. The Ovx rats were randomly divided into 4 groups [n=10 each] as follows: Ovx-AAI colitis, estrogen-, progesterone- and tamoxifen- treated Ovx-AAI colitis. The colitis, Ovx-AAI colitis and tamoxifen groups showed grossly and microscopically evident colon mucosal injury [significantly increased ulcer score index], oedema [increased weight of distal colon], inflammatory cell infiltration, increased activity of myeloperoxidase enzyme [MPO], increased tissue malondialdehyde [MDA] and reduced glutathione [GSH] depletion compared to sham group. The Ovx-AAI colitis group showed more significant impairment in all the fore mentioned parameters as compared to the colitis group. The estrogen and progesterone treated Ovx-AAI colitis groups showed less impairment of all parameters used to assess colon mucosal injury, inflammatory response and oxidative stress compared to the non-treated counterpart. A significant decrease in the level of IL-10 was found in the colitis, Ovx-AAI colitis and Tamoxifen groups compared to sham operated group. The level of this cytokine in the estrogen and progesterone groups was comparable to that of the sham-operated group. Decline of IL-10 level may underlie the currently observed enhancement of colon inflammation and oxidative stress in female rats deprived from endogenous and exogenous female sex steroids. Estrogen and progesterone replacement therapy has been associated with restored level of this cytokine and decreased susceptibility to colon inflammation while the anti-estrogen analog tamoxifen lacks such effects

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

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

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