Possible Potentiation by Certain Antioxidants of the Anti-Inflammatory Effects of Diclofenac in Rats

In the present study, we investigated the potential beneficial impact of the addition of antioxidant supplements to diclofenac regimen in a model of carrageenan-induced paw. Rats were treated daily with antioxidants, that is, a-lipoic acid (50 mg/kg), selenium (2.5 mg/kg), vitamin C (1 g/kg), vitamin E (300 mg/kg), or zinc (25 mg/kg) on seven successive days and then received a single treatment with diclofenac or saline before carrageenan was injected to induce paw inflammation. The results indicated that these combinations did not significantly affect the percentage inhibition of paw edema caused by diclofenac alone; however, some combination treatments ameliorated signs of concomitant oxidative stress (such as alterations in plasma malondialdehyde (MDA) levels, hemolysate reduced glutathione levels, and erythrocytic superoxide dismutase enzyme activities) imparted by diclofenac alone. In some cases, few tested antioxidants in combination with diclofenac resulted in increased plasma levels of interleukin- (IL-) 6 and C-reactive protein (CRP). In conclusion, the results of these studies suggested to us that the added presence of natural antioxidants could be beneficial as standard anti-inflammatory therapeutics for a patient under diclofenac treatment, albeit that these effects do not appear to significantly build upon those that could be obtained from this common anti-inflammatory agent per se

Resveratrol and fenofibrate ameliorate fructose-induced nonalcoholic steatohepatitis by modulation of genes expression

AIM: To evaluate the effect of resveratrol, alone and in combination with fenofibrate, on fructose-induced metabolic genes abnormalities in rats. METHODS: Giving a fructose-enriched diet (FED) to rats for 12 wk was used as a model for inducing hepatic dyslipidemia and insulin resistance. Adult male albino rats (150-200 g) were divided into a control group and a FED group which was subdivided into 4 groups, a control FED, fenofibrate (FENO) (100 mg/kg), resveratrol (RES) (70 mg/kg) and combined treatment (FENO + RES) (half the doses). All treatments were given orally from the 9(th) week till the end of experimental period. Body weight, oral glucose tolerance test (OGTT), liver index, glucose, insulin, insulin resistance (HOMA), serum and liver triglycerides (TGs), oxidative stress (liver MDA, GSH and SOD), serum AST, ALT, AST/ALT ratio and tumor necrosis factor-α (TNF-α) were measured. Additionally, hepatic gene expression of suppressor of cytokine signaling-3 (SOCS-3), sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), malonyl CoA decarboxylase (MCD), transforming growth factor-β1 (TGF-β1) and adipose tissue genes expression of leptin and adiponectin were investigated. Liver sections were taken for histopathological examination and steatosis area were determined. RESULTS: Rats fed FED showed damaged liver, impairment of glucose tolerance, insulin resistance, oxidative stress and dyslipidemia. As for gene expression, there was a change in favor of dyslipidemia and nonalcoholic steatohepatitis (NASH) development. All treatment regimens showed some benefit in reversing the described deviations. Fructose caused deterioration in hepatic gene expression of SOCS-3, SREBP-1c, FAS, MDA and TGF-β1 and in adipose tissue gene expression of leptin and adiponectin. Fructose showed also an increase in body weight, insulin resistance (OGTT, HOMA), serum and liver TGs, hepatic MDA, serum AST, AST/ALT ratio and TNF-α compared to control. All treatments improved SOCS-3, FAS, MCD, TGF-β1 and leptin genes expression while only RES and FENO + RES groups showed an improvement in SREBP-1c expression. Adiponectin gene expression was improved only by RES. A decrease in body weight, HOMA, liver TGs, AST/ALT ratio and TNF-α were observed in all treatment groups. Liver index was increased in FENO and FENO + RES groups. Serum TGs was improved only by FENO treatment. Liver MDA was improved by RES and FENO + RES treatments. FENO + RES group showed an increase in liver GSH content

Angiotensin antagonists and renal ischemia/reperfusion: Possible modulation by l-carnitine

Introduction: Ischemia/reperfusion (I/R) injury and therapy with angiotensin antagonists were shown to exert significant effects on the kidney. The study aimed to investigate the protective effect, if any, of l-carnitine on the initial nephrotoxic effects of ramipril or losartan on I/R insult in rats. Methods: I/R was induced through bilateral renal ischemia for 60 min followed by 60 min of reperfusion. Groups I and II received both 1% Tween 80 p.o. and saline i.p. and served as sham-operated and I/R control groups, respectively. Groups III–VII received 2 weeks pretreatment with ramipril (1 mg/kg; p.o.), losartan (10 mg/kg; i.p.), l-carnitine (200 mg/kg; i.p.) and l-carnitine plus either ramipril or losartan, respectively. Chosen markers included kidney function tests, oxidative stress and inflammatory biomarkers as well as histological assessment of kidney sections. Results: I/R increased plasma creatinine and urea levels but decreased albumin level; meanwhile, it increased the kidney tumor necrosis factor-alpha (TNF-α) content, myeloperoxidase (MPO) and plasma lactate dehydrogenase (LDH) activities. Moreover, I/R decreased kidney carnitine, glutathione, and total nitrate/nitrite contents as well as superoxide dismutase activity. Both ramipril and losartan elevated creatinine and urea levels; meanwhile, they lowered raised LDH, TNF-α and MPO as compared to I/R-control group. l-carnitine alone or combined with either agent decreased creatinine and urea levels, LDH and MPO activities as well as TNF-α content as compared to ramipril or losartan monotherapy. Conclusions: l-carnitine can protect the kidney from the initial deleterious effects of either ramipril or losartan in rats subjected to I/R most probably by virtue of its antioxidant and anti-inflammatory effects