Abstract
Background
Multiple Sclerosis (MS) is a burdensome, chronic and autoimmune disease of the central nervous system. We aimed to report the incidence, prevalence, mortality, and Disability ...Adjusted Life Years (DALYs) of MS in Iran at a national level for different age and sex groups over a period of 28 years (1990–2017).
Methods
Data were extracted from the Global Burden of Disease study (GBD) from 1990 to 2017, published by the Institute for Health Metrics and Evaluation. The incidence of DALYs and prevalence of MS were estimated to report the burden of MS based on sex and age in Iran from 1990 to 2017.
Results
At the national level, the Age-Standardized Incidence Rate (ASIR), Age-Standardized Prevalence Rate (ASPR), Age-Standardized DALYs Rate (ASDR) and the Age-Standardized Mortality Rate (ASMR) in Iran in 2017 were 2.4 (95% Uncertainty Interval UI: 2.1 to 2.7), 69.5 (62.1 to 77.8), 29.1 (23.6 to 34.7), and 0.4 (0.3 to 0.4) per 100,000 population, respectively. During the period of 1990 to 2017, all measures increased, and were higher among females. The incidence rate began upward trend at the age of 20 and attained its highest level at the age of 25.
Conclusion
In Iran, all of the age-standardized MS rates have been increasing during the 28 years from 1990 to 2017. Our findings can help policy makers and health planners to design and communicate their plans and to have a better resource allocation, depending on the incidence and prevalence of the growing numbers of MS patients in Iran.
Drug-induced liver injury (DILI) is a major problem for pharmaceutical industry and drug development. Mechanisms of DILI are many and varied. Elucidating the mechanisms of DILI will allow clinicians ...to prevent liver failure, need for liver transplantation, and death induced by drugs. Methimazole and propylthiouracil (PTU) are two convenient antithyroid agents which their administration is accompanied by hepatotoxicity as a deleterious side effect. Although several cases of antithyroid drugs-induced liver injury are reported, there is no clear idea about the mechanism(s) of hepatotoxicity induced by these medications. Different mechanisms such as reactive metabolites formation, oxidative stress induction, intracellular targets dysfunction, and immune-mediated toxicity are postulated to be involved in antithyroid agents-induced hepatic damage. Due to the idiosyncratic nature of antithyroid drugs-induced hepatotoxicity, it is impossible to draw a specific conclusion about the mechanisms of liver injury. However, it seems that reactive metabolite formation and immune-mediated toxicity have a great role in antithyroids liver toxicity, especially those caused by methimazole. This review attempted to discuss different mechanisms proposed to be involved in the hepatic injury induced by antithyroid drugs.
An important challenge during orthotopic liver transplantation (OLT) is optimal coagulation management. There are diverse studies regarding effect of Mg sulfate on coagulation system. This study ...evaluates the impact of Mg sulfate on the coagulation parameters of the rotational thromboelastometry (ROTEM) in patients about to undergo OLT. In this randomized clinical trial, 60 patients who were going to undergo OLT were randomly allocated into two groups. In the Mg group, the patients received a 1.5 g infusion of Mg 5 min before the surgical incision. In the control group, patients received a physiological saline instead of Mg. Plasma Mg levels before and after the infusions were measured in both groups. Also, three ROTEM tests: EXTEM, INTEM and FIBTEM were performed before and after the infusions. Baseline mean plasma magnesium levels were within normal range in the control and Mg groups: 2.06 and 2.18 mg/dl, respectively. After magnesium therapy, the mean plasma Mg level in the Mg group increased to 2.78 mg/dl in compared to the control group that was 2.01 mg/dl (
P
< 0.000). Mean value of the clotting time (CT) in the magnesium group were significantly decreased from 129.50 ± 7.76, 381.86 ± 8.51 and 114.26 ± 6.80 to 86.13 ± 3.4, 209.33 ± 6.68 and 81.56 ± 5.01 in the EXTEM, INTEM, and FIBTEM respectively after intervention in the Mg group (
P
= 0.001). Among patients with end-stage liver diseases who have ROTEM evidence of hypocoagulability, magnesium could correct CT parameter of the ROTEM tests.
Methimazole is the most convenient drug used in the management of hyperthyroid patients. However, associated with its clinical use is hepatotoxicity as a life threatening adverse effect. The exact ...mechanism of methimazole-induced hepatotoxicity is still far from clear and no protective agent has been developed for this toxicity.
This study attempts to evaluate the hepatotoxicity induced by methimazole at different experimental conditions in a mice model. Methimazole-induced hepatotoxicity was investigated in different situations such as enzyme induced and/or glutathione depleted animals.
Methimazole (100 mg/kg, i.p) administration caused hepatotoxicity as revealed by increase in serum alanine aminotransferase (ALT) activity as well as pathological changes of the liver. Furthermore, a significant reduction in hepatic glutathione content and an elevation in lipid peroxidation were observed in methimazole-treated mice. Combined administration of L-buthionine sulfoximine (BSO), as a glutathione depletory agent, caused a dramatic change in methimazole-induced hepatotoxicity characterized by hepatic necrosis and a severe elevation of serum ALT activity. Enzyme induction using phenobarbital and/or β-naphtoflavone beforehand, deteriorated methimazole-induced hepatotoxicity in mice. N-acetyl cysteine (300 mg/kg, i.p) administration effectively alleviated hepatotoxic effects of methimazole in both glutathione-depleted and/or enzyme induced animals.
The severe hepatotoxic effects of methimazole in glutathione-depleted animals, reveals the crucial role of glutathione as a cellular defense mechanism against methimazole-induced hepatotoxicity. Furthermore, the more hepatotoxic properties of methimazole in enzyme-induced mice, indicates the role of reactive intermediates in the hepatotoxicity induced by this drug. The protective effects of N-acetylcysteine could be attributed to its radical/reactive metabolite scavenging, and/or antioxidant properties as well as glutathione replenishment activities.
Background: Drug-induced liver injury is a critical clinical complication. Hence, finding new and safe protective agents with potential clinical application is of value. Isoniazid (INH) is an ...antituberculosis agent widely used against Mycobacterium tuberculosis infection in human. On the other hand, hepatotoxicity is a clinical complication associated with isoniazid therapy. Oxidative stress and its associated events are major mechanisms identified for INH-induced liver injury. Carnosine is an endogenously found peptide widely investigated for its hepatoprotective effects. On the other hand, robust antioxidant and cytoprotective effects have been attributed to this peptide. Methods: The current study designed to evaluate the potential cytoprotective properties of carnosine against INH-induced cytotoxicity in drug-exposed primary cultured rat hepatocytes. Primary cultured rat hepatocytes were incubated with INH (1.2 mM). Results: INH treatment caused significant increase in cell death and lactate dehydrogenase (LDH) release. On the other hand, it was found that markers of oxidative stress including reactive oxygen species were significantly increased in INH-treated cells. Cellular glutathione reservoirs were also depleted in INH-treated group. Carnosine treatment (50 and 100 µM) significantly diminished INH-induced oxidative stress and cytotoxicity. Conclusion: These data mention carnosine as a potential protective agent with therapeutic capability against INH hepatotoxicity.
Objective
Post‐tonsillectomy pain is a common morbidity in children. The aim of this study was to compare the efficacy of celecoxib with acetaminophen on pain relief in pediatric day‐case ...tonsillectomy.
Methods
We compared the analgesic effect of celecoxib (99 patients) with acetaminophen (100 patients) for the management of post‐tonsillectomy pain. Post‐tonsillectomy pain score was evaluated three times a day for 7 days. In addition, the incidence of post‐tonsillectomy bleeding and the rate of patients who returned to regular diet were evaluated.
Results
In the first day, we observed lower mean pain score in the celecoxib group, than the acetaminophen group (P = 0.013). The overall pain score in other days was not significantly different between the two groups. In the celecoxib group, more patients resumed regular amount of oral intake within the first 3 days. Also, the rate of post‐tonsillectomy bleeding in the two groups was not statistically different.
Conclusion
We recommend celecoxib as a more suitable choice than acetaminophen for post‐tonsillectomy pain management in the first day and resuming regular diet within 3 days.
Level of Evidence: 1b.
Organophosphates (OP) are potent pesticide commonly utilized in agricultural and domestic use. However, plentitude of data represent their side effects in different body tissues. We attempted to ...study whether betanin (a natural pigment) is able to mitigate some OPs-induced hepatotoxicity in primary rat hepatocytes. Cell viability, lactate dehydrogenase (LDH) leakage, reactive oxygen species (ROS) formation, lipid peroxidation (LPO), glutathione (GSH) depletion and mitochondrial depolarization were tested as toxicity markers. The outcomes revealed that betanin (25μM) significantly increased cell viability, plummeted ROS formation and LPO, restored cellular GSH reservoirs and protected mitochondria after chlorpyrifos (CPF) (300μM), diazinon (DZN) (600μM) and dichlrovos (DDVP) (400μM) treatment. Taken together, all data suggests the potential protective role of betanin in OPs-induced hepatotoxicity in which the mechanism appears to be inhibition of ROS formation and mitochondrial protection.
Display omitted
•Betanin boosts cells viability against organophosphates-induced hepatotoxicity.•Organophosphates-mediated mitochondrial toxicity has been inhibited by betanin.•Betanin has a profound role in mitigation of OP-medaited oxidative damage.
1. Olanzapine (OLZ) is a widely used atypical antipsychotic agent for the treatment of schizophrenia and other disorders. Serious hepatotoxicity and elevated liver enzymes have been reported in ...patients receiving OLZ. However, the cellular and molecular mechanisms of the OLZ hepatotoxicity are unknown.
2. In this study, the cytotoxic effect of OLZ on freshly isolated rat hepatocytes was assessed. Our results showed that the cytotoxicity of OLZ in hepatocytes is mediated by overproduction of reactive oxygen species (ROS), mitochondrial potential collapse, lysosomal membrane leakiness, GSH depletion and lipid peroxidation preceding cell lysis. All the aforementioned OLZ-induced cellular events were significantly (p < 0.05) prevented by ROS scavengers, antioxidants, endocytosis inhibitors and adenosine triphosphate generators. Also, the present results demonstrated that CYP450 is involved in OLZ-induced oxidative stress and cytotoxicity mechanism.
3. It is concluded that OLZ hepatotoxicity is associated with both mitochondrial/lysosomal involvement following the initiation of oxidative stress in hepatocytes.
Overexpression of renin angiotensin system (RAS) components and nuclear factor-kappa B (NF-kB) has a key role in various cancers. Blockade of RAS and NF-kB pathway has been suggested to reduce cancer ...cell proliferation. This study aimed to investigate the role of angiotensin II and NF-kB pathway in liver hepatocellular carcinoma cell line (HepG2) proliferation by using azilsartan (as a novel Ag II antagonist) and Bay 11-7082 (as NF-kB inhibitor). HepG2 cells were treated with different concentrations of azilsartan and Bay 11-7082. Cytotoxicity was determined after 24, 48, and 72 h by MTT assay. Reactive oxygen spices (ROS) generation and cytochrome c release were measured following azilsartan and Bay11- 7082 treatment. Apoptosis was analyzed qualitatively by DAPI staining and quantitatively through flow cytometry methodologies and Bax and Bcl-2 mRNA and protein levels were assessed by real time PCR and ELISA methods, respectively. The cytotoxic effects of different concentration of azilsartan and Bay11- 7082 on HepG2 cells were observed as a reduction in cell viability, increased ROS formation, cytochrome c release and apoptosis induction. These effects were found to correlate with a shift in Bax level and a downward trend in the expression of Bcl-2. These findings suggest that azilsartan and Bay11- 7082 in combination or alone have strong potential as an agent for prevention or treatment of liver cancer after further studies.
Amitriptyline, one of the commonly used tricyclic antidepressants, caused rare but severe hepatotoxicity in patients who received it continuously. Previous findings showed that the intermediate ...metabolites of amitriptyline produced by CYP450 are involved in hepatic injury. Melatonin is an antiaging and antioxidant hormone synthesized from pineal gland. The aim of present study was to evaluate the protective role of melatonin in an in vitro model of isolated rat hepatocytes.
Markers such as cell viability, reactive oxygen species formation, lipid peroxidation, mitochondrial membrane potential, and hepatocytes glutathione content were evaluated every 60 minutes for 180 minutes.
Present results indicated that administration of 1mM of melatonin effectively reduced the cell death, ROS formation and lipid peroxidation, mitochondrial membrane potential collapse, and reduced cellular glutathione content caused by amitriptyline.
Our results indicated that melatonin is an effective antioxidant in preventing amitriptyline-induced hepatotoxicity. We recommend further in vivo animal and clinical trial studies on the hepatoprotective effects of melatonin in patients receiving amitriptyline.
PDF
