Effect of telmisartan in collagen induced arthritis in rats

Rheumatoid arthritis [RA] is a chronic, systemic inflammatory disease affecting approximately 1% of people worldwide irrespective of race. Regarding the pathobiology of RA, oxidative stress is an important mechanism that underlies destructive and proliferative synovitis. Telmisartan, ahighly selective ARB is receiving attention because of its properties unrelated to ATIR antagonism including partial agonism for proliferator-activated receptor [PPAR]-gamma nuclear receptor system and modulation of oxidative stress and inhibition of pro-inflammatory stimuli. Thus, the aim of this work is to study the effect of Telmisartan on the progression of rheumatoid arthritis. The standard non-steroidal anti-inflammatory drug, Celecoxib, was used as a reference drug for purposes of comparison. Fourty rat were randomly divided into 2 main groups. Group I: 10 rats; considered as control group and received saline. Group II: 30 rats were subdivided into 3 equal subgroups [10 rats/subgroup] as the following: Subgroup II A: considered as collagen-induced Arthritis group in which an intradermal injection at 5 to 6 sites at the base of the tail with 300 micro1 of emulsified CII. Subgroup II B: Rats were treated with Celecoxib in a dose of 10 mg/kg daily intragastrically by gavage at the onset of clinical arthritis for 4 weeks. Subgroup II C: Rats were treated with telmisartan in a dose of 10 mg/kg daily intragastrically by gavage at the onset of clinical arthritis for 4 weeks. Arthritis was monitored every 4 days by using a macroscopic scoring system. Rats were sacrificed at day 44 of clinical onset of arthritis [day 0], and then blood samples were collected for analysis. CIA rats showed a significant increase in ESR and MDA levels. Also, a significant decrease in antioxidant enzymes. Both Telmisartan and celecoxcibe improve oxidative stress parameters and clinical arthritis score. The present study suggests that Telmisartan treatment at the dosage of 10 mg /kg possesses anti-inflammatory effects. Thus, Telmisartan can be as a design of novel therapeutic strategies for RA

potential renoprotective effect of selective cyclooxygenase inhibitors in experimental diabetic nephropathy

Diabetic nephropathy is a major microvascular complication of diabetes and eventually leads to end-stage renal disease. The present study designed to evaluate the renal effects of selective COX-2 inhibitors on the progression of renal injury in experimental model of diabetic nephropathy. Fifty rats were randomly divided into five equal groups: normal control rats, streptozotocin [STZ]-induced diabetic rats without treatment, STZ-induced diabetic rats treated with celecoxib, STZ-induced diabetic rats treated with enalapril, and STZ-induced diabetic rats treated with combination. Sixteen weeks later, serum glucose, renal functions, and oxidative stress parameters were evaluated. Periodic acid-Schiff [PAS] staining was used to examine the morphological changes by light microscopy. STZ-induced diabetes led to development of diabetic nephropathy associated with increased oxidative stress. Both celecoxib and enalapril produced comparable level of renoprotection manifested by significant decrease of serum creatinine and microalbuminuria, which was accompanied by significant decrease of renal malondialdyehyde content, significant increase of renal reduced glutathione content and superoxide dismutase activity. Glomerulosclerosis seen in untreated-diabetic group were prevented by both celecoxib and enalapril. Combination treatment was superior in renoprotective effects. In conclusion, the selective COX-2 inhibitor celecoxib may prevent or retard the development of diabetic nephropathy

Possible beneficial effect of trimetazidine on experimentally-induced peptic ulcer in rats

Background: Peptic ulcers mainly are etiologically related to infection' with Helicobacter pylori or use of nonsteroidal anti-inflammatory drugs [NSAIDs]. The cytoprotective role of antioxidants in the prevention and healing of gastric lesions has been widely investigated. Trimetazidine [TMZ], a metabolic agent with a cytoprotective properties through many actions. The aim of this work is to investigate the beneficial effect of trimetazidine in preventing indomethacin-induced gastric damage and compare it with traditionally used lansoprazol regarding its role in controlling oxidative damage

Methods: The present study was done on 40 rats. They were divided into 2 main groups. Group I: 10 rats as control group, received distilled water. Group II: consists of 30 animals; subdivided into 3 equal subgroups as the following: Subgroup II A: Indomethacin-induced ulceration group. Rats were treated with indomethacin in a single of 45mg/kg intragastrically. Subgroup II B: Rats were treated with lansoprazole in a dose of 4mg/kg for 7 days before induction of ulceration by indomethacin. Subgroup II C: Rats were treated with trimetazidine in a dose of 20mg/ kg for 7 days before induction of ulceration by indomethacin. Blood and stomach were obtained for biochemical analysis and macroscopic examination respectively

Results: Indomethacin-treated rats showed a significant increase in MDA and a significant decrease in GSH and SOD. Tnimetazidine and lansoprazole restored tissue GSH and SOD with a fall in tissues TBARS. Also, both drugs decreased macroscopic gross lesion score of gastric mucosa

Conclusion: The present work demonstrated that tnimetazidine has a protective effect in preventing indomethacin-induced peptic ulcer. It is as effective as lansoprazole, however, it is safe without side effects

hepato protective effect of pioglitazone ischemic reperfusion injury

Hepatic ischemia/reperfusion [I/R] injury is the main cause of hepatic damage and is inevitable after hepatic surgery, liver transplantation, shock, trauma. Despite the recent improvements in liver preservation and surgical techniques, hepatic I/R injury remains an important clinical complication. To control this complicated physiological as well as pathological process, further studies are required to find out the key pathway and a novel therapeutic approach. PPAR gamma may be a protective regulator against ischemic damage. The aim of this study is to study the effect of pioglitazone on hepatic ischemic-reperfusion injury and compare its effect with ischemic preconditioning

Method: The present study was done on 40 rats. They were randomly subdivided into 4 equal groups [10 rats each]: Group I: Consisted of 10 rats considered as sham- operated group. Group II: Consisted of 10 rats served as ischemia-reperfusion group 90 minutes of ischemia followed by 6 hours of reperfusion. Group III: Consisted of 10 rats; As group 2 but with previous preconditioning induced by 10 minutes of ischemia followed by 15 minutes of reperfusion. This preconditioning period has been demonstrated to be the most effective against the hepatic injury in the same experimental model shown in the present study. Group IV: Consisted of 10 rats; As group 2 but with previous administration of Pioglitazone for 7 days before ischemia. Mice were sacrificed at 6 h after reperfusion, and then blood and liver samples were collected for analysis

Results: Ischemia-reperfusion produced a significant increase in SGPT and MDA levels. It also prodced, a significant decrease in GSH and SOD levels. Preconditioning and pioglitazone produced a significant decrease in SGPT and MDA. It also prodced, a significant increase in GSH and SOD levels

Conclusion: The therapeutic effects of PPAR-gamma ligands reach far beyond their use as insulin sensitizers. PPAR-gamma has been implicated as a regulator of cellular inflammatory and ischemic responses