Evacuation the Effect of Single- and Multi-dose Administration of Ethanolic Extract of Pinus eldarica Pollen Against Acetaminophen-induced Rat Liver Injury

Introduction: Acetaminophen (APAP)-induced liver injury is one of the main causes of acute liver failure in the world. Pinus eldarica is specially distributed in the north of Iran and has been used for decades to treat wounds, pain, infection, fever, bronchitis and inflammation in many countries. This study was undertaken to evaluate the role of pine pollen extract (PE) on APAP-induced hepatotoxicity. Methods: This study was conducted in two separate parts: single- and multi- dose administration of PE. In a multiple dosing regimen, different doses of extract (10, 20, 30, 40 and 50 mg/kg) were orally administrated for 2 weeks and then on the 15th day, the animals received a single dose of APAP (600 mg/kg). In the second part, the highest dose of PE (50 mg/kg) was orally administrated half an hour after receiving the APAP at dose of 600 mg/kg. The negative and positive control groups were treated with normal saline and N-acetylcysteine (NAC), respectively. At the end of procedure, the biochemical parameters including alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) as well as pathological findings were evaluated. Results: A single and multiple oral dose of APAP increased the serum level of ALT, AST and ALP that were significantly attenuated by PE administration in both model. Indeed, exposure to APAP caused extensive necrosis and lymphocytic inflammation that were completely prevented by single- and multi-dose administration of PE, specially at a high dose. Conclusion: Finally, the present results indicate that PE could reverse the reduction of aminotransferases and improve histological changes of APAP-induced liver toxicity. Further research is needed to confirm this finding and reveal the exact mechanisms

Counteracting arsenic toxicity: Curcumin to the rescue?

Arsenicosis leads to various irreversible damages in several organs and is considered to be a carcinogen. The effects of chronic arsenic poisoning are a result of an imbalance between pro- and antioxidant homeostasis, oxidative stress, as well as DNA and protein damage. Curcumin, the polyphenolic pigment extracted from the rhizome of Curcuma longa, is well-known for its pleiotropic medicinal effects. Curcumin has been shown to have ameliorative effects in arsenic-induced genotoxicity, nephrotoxicity, hepatotoxicity, angiogenesis, skin diseases, reproductive toxicity, neurotoxicity, and immunotoxicity. This review aims to summarize the scientific evidence on arsenic toxicity in various organs and the ameliorative effects of curcumin on the arsenic toxicity

Deoxyribonucleic acid damage in Iranian veterans 25 years after wartime exposure to sulfur mustard

• Background: More than 100,000 Iranian veterans and civilians still suffer from various long-term complications due to their exposure to sulfur mustard (SM) during the Iran–Iraq war in 1983–88. The aim of the study was to investigate DNA damage of SM in veterans who were exposed to SM, 23–27 years prior to this study. • Materials and Methods: Blood samples were obtained from the veterans and healthy volunteers as negative controls. Lymphocytes were isolated from blood samples and DNA breaks were measured using single-cell microgel electrophoresis technique under alkaline conditions (comet assay). Single cells were analyzed with “Tri Tek Comet Score version 1.5” software and DNA break was measured based on the percentage of tail DNA alone, or in the presence of H2O2 (25 μM) as a positive control. • Results: A total of 25 SM exposed male veterans and 25 male healthy volunteers with similar ages (44.66 ± 6.2 and 42.12 ± 5.75 years, respectively) were studied. Percentage of the lymphocyte DNA damage was significantly (p < 0.01) higher in the SM-exposed individuals than in the controls (6.47 ± 0.52 and 1.31 ± 0.35, respectively). Percentages of DNA damage in the different age groups of 35–39, 40–44, 45–49, and 50–54 years in SM-exposed veterans (5.48 ± 0.17, 6.7 3 ± 1.58, 6.42 ± 0.22, and 7.27 ± 0.38, respectively) were all significantly (p < 0.05) higher than the controls (1.18 ± 0.25, 1.53 ± 0.22, 1.27 ± 0.20, and 1.42 ± 0.10, respectively). The lymphocytes incubated with H2O2 had much higher DNA damage as expected. The average of tail DNA is 42.12 ± 2.75% for control cells + H2O2 and 18.48 ± 2.14% for patients cells + H2O2; P < 0.001. • Conclusion: SM exposure of the veterans revealed DNA damage as judged by the comet assay

Telomere shortening associated with increased levels of oxidative stress in sulfur mustard-exposed Iranian veterans

Sulfur Mustard (SM) is the most widely used chemical weapon. It was used in World War 1 and in the more recent Iran-Iraq conflict. Genetic toxicity and DNA alkylation effects of SM in molecular and animal experiments are well documented. In this study, lymphocytic telomere lengths and serum levels of isoprostane F2α were measured using q-PCR and enzyme immunoassay-based methods in 40 Iranian veterans who had been exposed to SM between 1983-88 and 40 non-exposed healthy volunteers. The relative telomere length in SM-exposed individuals was found to be significantly shorter than the non-exposed individuals. In addition, the level of 8-isoprostane F2α was significantly higher in the SM-exposed group compared to controls. Oxidative stress can be caused by defective antioxidant responses following gene mutations or altered activities of antioxidant enzymes. Chronic respiratory diseases and infections may also increaseoxidative stress. The novel finding of this study was a the identification of ‘premature ageing phenotype’. More specifically, telomere shortening which occurs naturally with aging is accelerated in SM-exposed individuals. Oxidative stress, mutations in DNA repair genes and epimutaions may be among the major mechanisms of telomere attrition. These findings may help for a novel therapeutic strategy by telomere elongation or for validation of an exposure biomarker for SM toxicity

Hepatic benefits of sodium-glucose cotransporter 2 inhibitors in liver disorders

Diabetic patients are at higher risk of liver dysfunction compared with the normal population. Thus, using hypoglycemic agents to improve liver efficiency is important in these patients. Sodium-glucose cotransporters-2 inhibitors (SGLT2i) are newly developed antidiabetic drugs with potent glucose-lowering effects. However, recent limited evidence suggests that they have extra-glycemic benefits and may be able to exert protective effects on the liver. Hence, these drugs could serve as promising pharmacological agents with multiple benefits against different hepatic disorders. In this review, the current knowledge about the possible effects of SGLT2 inhibitors on different forms of liver complications and possible underlying mechanisms are discussed

The Predictive Role of Parathyroid Hormone for Nonalcoholic Fatty Liver Disease following Bariatric Surgery

Background. Morbid obesity is frequently complicated by chronic liver diseases, including nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and fibrosis. Parathyroid hormone (PTH) is found to be elevated in morbid obesity due to the defective hepatic metabolism of vitamin D. Bariatric surgery is performed to help patients with BMI>40 kg/m2 to effectively lose weight, particularly in patients with obesity who are afflicted with complications such as NAFLD/NASH. Objective. This study aimed to evaluate the PTH level as a predictor of hepatic function in individuals with morbid obesity who have undergone bariatric surgery. Methods. Ninety subjects with morbid obesity referred for Roux en-Y gastric bypass surgery were recruited. After IRB approval, demographic profiles, anthropometric factors, liver biopsy, and laboratory tests were obtained. The two-dimensional shear wave elastography (2D-SWE) technique was applied to assess hepatic stiffness. Results. A significant reduction occurred six months after bariatric surgery in the anthropometric indices p<0.001, hepatic elasticity p=0.002, alanine aminotransferase p<0.001, serum alkaline phosphatase p<0.001, gamma-glutamyl transpeptidase (GGT) p<0.001, and nonalcoholic fatty liver disease fibrosis score (NFS) p<0.001. Serum PTH concentration was not predictive of postsurgical liver fibrosis and steatosis at six months but could predict weight loss success rate. No significant alteration in serum PTH levels was observed between presurgical vs. postsurgical time points. Conclusion. A significant reduction was observed in the anthropometric parameters, liver enzymes, and hepatic elasticity after bariatric surgery. No significant effect was found on PTH levels

Exploring the effect of intravenous lipid emulsion in acute methamphetamine toxicity

Objective(s): The increasing use of methamphetamine (METH) in the last decades has made it the second most abused drug. Advancs in the area of intravenous lipid emulsion (ILE) have led to its potential application in the treatment of poisoning. The present study aims to investigate the potential role of ILE as an antidote for acute METH poisoning. Materials and Methods: Two groups of six male rats were treated by METH (45 mg/kg), intraperitoneally. Five to seven min later, they received an infusion of 18.6 ml/kg ILE 20% through the tail vein or normal saline (NS). Locomotor and behavioral activity was assessed at different time after METH administration. Body temperature and survival rates were also evaluated. Brain and internal organs were then removed for histological examination and TUNEL assay. Results: ILE therapy for METH poisoning in rats could prevent rats mortalities and returned the METH-induced hyperthermia to normal rates (

Disruption of murine limb development in vitro by a teratogen : role of P53 dependent and independent cell death

In this thesis, the effects of an active analog of cyclophosphamide (4-hydroperoxycyclophosphamide, 4OOH-CPA), an alkylating agent and teratogen, on mouse limb development, cell death and the role of the p53 gene in this process were studied. A mouse limb bud culture system was used for this purpose. Limbs developed normally in this system and showed physiological apoptosis in a spatio-temporal-controlled manner. Drug treatment caused limb reduction malformations, increased the amount of apoptosis and triggered its occurrence prematurely, primarily in areas with physiological apoptosis. This indicated that drug-treatment might have engaged the already available program of apoptosis in the developing limb, and suggested this might be the cause of limb malformations. Next we examined the induction pattern of three proteins, cathepsin D, transglutaminase and clusterin, known to be involved in the molecular mechanism of apoptosis. The pattern of their induction suggested that cathepsin D was involved in the digestion of apoptotic debris, transglutaminase was active in preserving the cellular integrity during apoptosis, and clusterin played a role in later phases of apoptosis. Since 4OOH-CPA causes DNA damage, we studied the role of the p53 gene, a DNA-damage response gene involved in regulating cell cycle and apoptosis, in a p53-transgenic mouse model. Absence of p53 led to more severe limb malformations in the treated limbs. To investigate the reason(s) for this higher sensitivity to drug insult, cell death and cell cycle patterns were studied. While wild-type limbs showed an induction of apoptosis by drug treatment, which might be crucial in eliminating damaged cells, the null limbs were resistant to this effect. Furthermore, in response to 4OOH-CPA-treatment, the cell cycle was not arrested in p53 -/- limbs, in contrast to wild-type limbs; this arrest is necessary for DNA repair. Further investigation revealed the occurrence of necrosis in p53 -/- limbs. Thus, w