No abstract

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 Vitamin D deficiency is prevalent in patients with non-alcoholic fatty liver disease (NAFLD), but there are debates on the usefulness of vitamin D treatment. The interindividual variations in response may be due to different genetic backgrounds. The present study evaluated the efficacy of calcitriol treatment in NAFLD patients with regard to the vitamin D receptor (VDR) genotypes of FokI polymorphism. Methods The study was conducted on 128 NAFLD patients randomly divided into two groups and were subjected to intervention with 0.25 mcg calcitriol/day or placebo for 4 months, while anthropometric parameters, glycemic status, lipid profiles, inflammatory markers, liver enzymes, and fatty liver indices were measured. The ARMS-PCR method was used to genotype the VDR FokI polymorphism. Results Calcitriol treatments along with weight loss and diet recommendations decreased the liver enzymes (AST, ALT, and ALP, p < 0.001 for all) and fatty liver indices (HSI, p < 0.01 and APRI, p < 0.001), compared to the baseline. But when the calcitriol effects were compared to the placebo group, only ALP decrease remained significant (17.5 IU. P = 0.02). The prevalent FokI variants in our population were FF (53.1%) and Ff genotype (45.3%). No significant interaction of FokI variants to the calcitriol effects was found except for ALP. The decrease in the ALP activity was higher in calcitriol-received patients with the Ff genotype (p = 0.05). Conclusions The FF and Ff variants of VDR FokI polymorphism did not interact with the effects of calcitriol on fatty liver, but the ALP was more responsive in subjects with the Ff variant. IRCT registration number IRCT2017053034222N1 Registration date: 2017-06-28 - Retrospectively registered, https://en.irct.ir/trial/26203

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.

Background Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have become significant global health concerns. In the present study, we aimed to investigate the effects of saroglitazar, a dual PPARα/γ agonist, fenofibrate, a PPAR-α agonist, and pioglitazone, a PPAR-γ agonist on an animal model of NASH. Methods Male Wistar rats were fed a high-fat (HF) emulsion via gavage for 7 weeks to induce NASH. The HF-treated rats were grouped into four groups to receive saroglitazar, pioglitazone, fenofibrate, or vehicle. We measured body and liver weight, liver enzymes, serum levels of adiponectin and leptin. We also performed histopathological examinations and gene expression analysis of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF- α), transforming growth factor-beta (TGF-β), and monocyte chemoattractant protein 1 (MCP-1). Results Body weight was markedly normalized by both saroglitazar and fenofibrate, while the liver index only decreased significantly with saroglitazar. Saroglitazar corrected ALT, AST, leptin, and adiponectin levels better than pioglitazone and fenofibrate. All PPAR agonists significantly attenuated the upregulation of the proinflammatory and TGF-β genes, which correlated with the improved steatosis, inflammation of liver tissue, and fibrotic lesions. Conclusions As documented by our results, the dual activation of PPARα/γ by saroglitazar could effectively improve steatosis, fibrosis, and aspects of necro-inflammation in the HF-induced NASH model more than fenofibrate and pioglitazone, and it can be more beneficial in the management of NASH.