Arsenic trioxide (AsO) is utilized for treating patients suffering from hematological malignancies particularly acute promyelocytic leukemia. Unfortunately, the extensive application of this chemotherapeutic agent has been limited due to its adverse effects such as cardiotoxicity. Ellagic acid, as a phenolic compound, has shown to exert antioxidant, anti-inflammatory, antifibrotic, and antiatherogenic properties. It is also capable of protecting against drug toxicity. In this study, we evaluated whether ellagic acid can protect against AsO-induced heart injury in rats. Thirty-two male Wistar rats were randomly divided into four treatment groups, that is, control (0.2 mL of normal saline, intraperitoneally (ip)), AsO (5 mg/kg, ip), AsO plus ellagic acid, and ellagic acid (30 mg/kg, orally) groups. The drugs were administered daily for 10 days and pretreatment with ellagic acid was performed 1 h prior to AsO injection. Cardiotoxicity was characterized by electrocardiological, biochemical, and histopathological evaluations. Our results showed that ellagic acid pretreatment significantly ameliorated AsO-induced increase in glutathione peroxidase activity and malondialdehyde concentration ( p < 0.05 and p < 0.001, respectively) and also diminished QTc prolongation ( p < 0.0001) and cardiac tissue damages. Pretreatment with ellagic acid also lowered the increased troponin I ( p < 0.0001) and creatine kinase isoenzyme MB ( p < 0.01) levels in response to AsO. In conclusion, results of this study demonstrated that ellagic acid has beneficial cardioprotective effects against AsO toxicity. It is suggested that the protective effects were mediated by antioxidant properties of ellagic acid.

Background: Royal Jelly (RJ), a food item secreted by worker honeybees, is a mixture that contains protein, glucose, lipid, vitamins, and minerals; it is widely used as a commercial medical product. Previous studies have shown that RJ has a number of physiological effects, such as anti-inflammatory, antitumor, antiallergic and antioxidant activities. Objectives: In the present study, the anti-inflammatory properties of RJ were investigated in formalin-induced rat paw edema. Materials and Methods: In this study, 30 male Wistar albino rats were divided into five equal groups (n = 6) as follows: test groups received different doses (25, 50 and 100 mg/kg, ip) of RJ and a negative control group received normal saline (5 mL/kg) and a positive control group received aspirin (300 mg/kg, i.p). Edema was induced on the right hind paw of the rat by a subplantar injection of 100 µL of formalin (2.5%) after 30 minutes. Paw edema was measured in the rats received the drugs, saline and aspirin before and after the formalin injection during 5 hours, using a plethysmometer. Results:The results showed that RJ has a dose-dependent anti-inflammatory effect and the highest anti-inflammatory effect was observed in the doses of 50 and 100 mg/kg. Conclusions: Royal jelly has potent anti-inflammatory effects compared to aspirin and it could be used in the treatment of inflammation. However, further studies are required to determine the active components in RJ responsible for this effect and its mechanism of action.

The impaired biosynthesis of the β-globin chain in β-thalassemia leads to the accumulation of unpaired alpha globin chains, failure in hemoglobin formation, and iron overload due to frequent blood transfusion. Iron excess causes oxidative stress and massive tissue injuries. Advanced glycation end products (AGEs) are harmful agents, and their production accelerates in oxidative conditions. This study was conducted on 45 patients with major β-thalassemia who received frequent blood transfusions and chelation therapy and were compared to 40 healthy subjects. Metabolic parameters including glycemic and iron indices, hepatic and renal functions tests, oxidative stress markers, and AGEs (carboxymethyl-lysine and pentosidine) levels were measured. All parameters were significantly increased in β-thalassemia compared to the control except for glutathione levels. Blood glucose, iron, serum ferritin, non-transferrin-bound iron (NTBI), MDA, soluble form of low-density lipoprotein receptor, glutathione peroxidase, total reactive oxygen species (ROS), and AGE levels were significantly higher in the β-thalassemia patients. Iron and ferritin showed a significant positive correlation with pentosidine (P < 0.01) but not with carboxymethyl-lysine. The NTBI was markedly increased in the β-thalassemia patients, and its levels correlated significantly with both carboxymethyl-lysine and pentosidine (P < 0.05). Our findings confirm the oxidative status generated by the iron overload in β-thalassemia major patients and highlight the enhanced formation of AGEs, which may play an important role in the pathogenesis of β-thalassemia major.

Background: Tetracyclines are antimicrobial agents that possess anti-inflammatory and matrix metalloproteinase (MMP) inhibitory effects. Tetracycline, doxycycline, and minocycline have shown different potencies in inhibiting various MMPs. MMPs are a conserved family of zinc-dependent endopeptidases, which are involved in various physiologic and pathologic conditions. MMP-9 is among the most important proteases involved in the development of cardiovascular disease, cancer, and inflammatory disease Objectives: Considering the central role of MMP-9 in the above-mentioned diseases and the variable inhibitory potentials of routine tetracyclines, including tetracycline, doxycycline, and minocycline, this study measured the inhibitory effect of these routine tetracycline agents on MMP-9 activity obtained from U-937 cell cultures using the zymography method. Materials and Methods: An MMP-9-rich culture medium of U-937 cells was used as the source of the enzyme. Serial dilutions of 5, 20,

Objective:Carvedilol is a nonselective third generation β-blocker that does not display the negative effects of traditional β-blockers. Regarding the antioxidant, anti-inflammatory and distinct metabolic properties of carvedilol which are similar to that of high-density lipoprotein (HDL) and paraoxonase 1 (PON1), the present study intends to investigate the effects of carvedilol treatment on malondialdehyde (MDA) and soluble lectin-like ox-low-density lipoprotein (LDL) receptor (sLOX-1) as markers of oxidative stress in association to lipid profiles, apolipoproteins (apo), and PON1 activity in hypertensive patients.Patients and Methods:This clinical trial study was performed on forty patients with mild to moderate essential hypertension. Subjects were studied before and after 2 months treatment with carvedilol, 25 mg daily. Lipids and lipoproteins were measured using a biochemistry analyzer. PON and arylesterase activity were assayed using paraoxon and phenyl acetate as substrates, respectively. MDA was quantified using a chemical colorimetric assay. ELISA was used to measure sLOX-1.Results:Our results showed that carvedilol treatment decreased systolic and diastolic blood pressure as much as forty and 16 mmHg, respectively (P < 0.001). It also increased HDL, total cholesterol, and serum PON1 activity (P < 0.05), but the levels of triglyceride, LDL, apo A-I, and apo B did not significantly change. There was an inverse correlation between serum PON1 activity and serum MDA.Conclusion:This study confirmed the antihypertensive effect of the drug and its beneficial metabolic effects through augmenting HDL and PON1 activity. We propose that the antioxidant effects of carvedilol can be partially attributed to increased PON-1 activity.

Background: Advanced glycation end-products (AGEs) cause proinflammatory responses and macromolecular damages. Advanced oxidation protein products (AOPPs) are protein biomarkers for oxidative stress. Levels of AGEs and AOPPs increase with the progression of chronic renal dysfunction. Objectives: In this study, we aimed to measure these species in patients with renal transplantation and to analyze their correlation with the measured glomerular filtration rate (GFR) and renal function parameters. Patients and Methods: Eighty renal transplant patients and normal subjects were recruited. GFR was measured by the two-sample plasma method with technetium-99m-labeled diethylenetriaminepentaacetic acid (TC99m-DTPA) clearance. Biochemical measurements included creatinine, cystatin C, urea, total protein, and pentosidine. Serum AGEs were determined using a fluorometric assay and AOPPs were estimated spectrophotometrically. Results: The measured GFR found to be significantly decreased in renal transplant patients compared to the control subjects (P< 0.001). Levels of AGEs, AOPPs, serum creatinine, and cystatin C were increased in renal transplant patients with lower values of measured GFR (mGFR). A significant association between the levels of AGEs species (serum fluorescence and pentosidine) and mGFR when adjusted for creatinine and other risk factors in multiple linear regression model analysis was found (P=0.05 and P=0.001, respectively). Conclusions: This study demonstrated increased levels of pentosidine and AGEs in transplant recipients were associated with decreased mGFR. Their accumulation can be predictive for the progression of chronic allograft loss of function.

Background: Arsenic trioxide (As2O3) is used for treating patients with acute promyelocytic leukemia (APL). The extensive application of this drug has been limited due to its severe cardiotoxicity. Montelukast is a selective leukotriene receptor antagonist with antioxidant and anti-inflammatory properties. Objectives: This study evaluated whether montelukast could protect against As2O3-induced cardiotoxicity in vivo. Methods: Thirty-two male Wistar rats (150 to 200 g) were divided to 4 treatment groups: control (0.2 mL of saline, ip), As2O3 (5 mg/kg, ip), As2O3 plus MONT, and MONT (20 mg/kg, po). All drugs were administered daily for 10 days and pretreatment with MONT was performed 1 hour prior to As2O3 administration. Cardiotoxicity was estimated by electrocardiological, biochemical, and histopathological evaluations. Results:The results indicated that the combination treatment of montelukast and As2O3 markedly (P < 0.05) inhibited As2O3-induced lipid peroxidation and attenuated QT interval (QT) prolongation and histopathological alterations. Pretreatment with montelukast also suppressed increased troponin I and creatinine kinase-muscle brain (CK-MB) isoenzyme levels in response to As2O3 (P < 0.01). Conclusions:In conclusion, the current results demonstrated that montelukast possesses beneficial cardio-protective properties against As2O3 toxicity. It was also proposed that these protective effects were mediated by antioxidant modifications of montelukast.