To the Editor: Introduction Elevated transaminases are a common complication of many drugs, occurring in up to 27% of patients taking atypical antipsychotics medications (Atasoy et al. 2007). For patients who have no other options than remaining on certain antipsychotics such as olanzapine, physicians must weigh the risks versus benefits of continuing antipsychotic medications. We present a case study that attempted to replicate a previous single case study in which vitamin E therapy successfully reduced damaging effects of olanzapine on liver enzymes (Do¨nmez et al. 2017).
Liver Health
Vitamin E as an Adjuvant Treatment for Non-alcoholic Fatty Liver Disease in Adults: A Systematic Review of Randomized Controlled Trials
Muhammad Usman, Nabiyah Bakhtawar
Cureus . 2020 Jul 6;12(7):e9018. doi: 10.7759/cureus.9018.
Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease. It is characterized by a variety of pathologies, ranging from benign fatty liver to extensive fibrosis and even hepatocellular cancer. Among the several potential risk factors, insulin resistance and increased oxidative stress are the most important. Vitamin E is an antioxidant with a potential to be used as a treatment for NAFLD. Therefore, we carried out a structured systematic review of all RCTs conducted between 2010 and January 2020. After screening, eight RCTs were included. Our systematic review showed that vitamin E has clinical utility in improving biochemical (ALT and AST levels) and histological abnormalities in NAFLD (hepatic steatosis and lobular inflammation). However, vitamin E does not seem to have significant effects on liver fibrosis. Still, vitamin E has the potential to be used as an adjuvant for the treatment of NAFLD, and its use in clinical practice should be advocated.
Inflammatory Diseases and Vitamin E – What Do We Know and Where Do We Go?
Maria Wallert, Lisa Börmel, Stefan Lorkowski
Mol Nutr Food Res . 2020 Jul 21;e2000097. doi: 10.1002/mnfr.202000097. Online ahead of print.
Abstract
Inflammation-driven diseases and related comorbidities, such as the metabolic syndrome, obesity, fatty liver disease and cardiovascular diseases cause significant global burden. There is a growing body of evidence that nutrients alter inflammatory responses and can therefore make a decisive contribution to the treatment of these diseases. Recently, the inflammasome, a cytosolic multiprotein complex, was identified as a key player in inflammation and the development of various inflammation-mediated disorders, with nucleotide-binding domain and leucine-rich repeat pyrin domain (NLRP) 3 being the inflammasome of interest. Here we provide an overview about the cellular signaling pathways underlying nuclear factor ‘kappa-light-chain-enhancer’ of activated B-cells (NF-κB)- and NLRP3-mediated inflammatory processes, the pathogenesis of the inflammatory diseases atherosclerosis and non-alcoholic fatty liver disease (NAFLD); next, we discuss the current state of knowledge for drug-based and dietary-based interventions for treating cardiovascular diseases and NAFLD. To date one of the most important antioxidant in the human diet is vitamin E. Various in vitro and in vivo studies suggest that the different forms of vitamin E and also their derivatives have anti-inflammatory activity. Recent publications suggest that vitamin E – and possibly metabolites of vitamin E – are a promising therapeutic approach for treating inflammatory diseases such as NAFLD.
Effects of Vitamin A and Vitamin E on Attenuation of Amphotericin B-induced Side Effects on Kidney and Liver of Male Wistar Rats
Aref Salehzadeh, Alireza Salehzadeh, Amir-Hossein Maghsood, Shirin Heidarisasan, Masoumeh Taheri-Azandaryan, Abolfazl Ghafourikhosroshahi, Roghayeh Abbasalipourkabir
Environ Sci Pollut Res Int . 2020 Jun 8. doi: 10.1007/s11356-020-09547-w. Online ahead of print.
Abstract
Despite the fact that amphotericin B (AmB) is currently considered as the first choice for treatment of visceral leishmaniasis, it is associated with some side effects. This study was designed to investigate the protective effects of vitamins A and E against amphotericin B-induced adverse effects in the kidney and liver of rat. Thirty male Wistar rats aged 7-8 weeks and weighing around 200 g were randomly divided into five groups, each one containing six rats. The first to fifth groups received olive oil as the control groups, AmB, AmB + vitamin A, AmB + vitamin E, and AmB + vitamins A + E, respectively. Rats received vitamins by gavage (vitamin A, 1000 IU/kg and vitamin E, 100 IU/kg) and amphotericin B by injections (5.5 mg/kg body weight). The treatment was constantly continued for 5 days and days 7 and 21. At the end of the study, serum level of TAC, TOS, MDA, liver enzyme activity (ALT, AST, ALP, LDH), renal factors (urea, uric acid, and creatinine), lipid profile as well as histopathological changes of the liver and kidney were investigated. AmB significantly increased serum level of creatinine, urea, uric acid, ALP, TOS, MDA, and kidney and renal tissue damage (p < 0.05). Supplementation AmB with vitamins A and E alone or combination improved oxidative stress status, liver and renal tissue structure, and functional parameters and serum lipid profile. This study highlighted the effects of vitamin A and vitamin E on attenuation of amphotericin B-induced side effects on the kidney and liver of male Wistar rats. Combination of the two vitamins is more effective than either alone improving the oxidative stress status, serum lipid profile, or liver and renal tissue structure and functional parameters.
Effect of Anoectochilus roxburghii flavonoids extract on H2O2 – Induced oxidative stress in LO2 cells and D-gal induced aging mice model
Wang L, Chen Q, Zhuang S, Wen Y, Cheng W, Zeng Z, Jiang T, Tang C
J Ethnopharmacol. 2020 May 23;254:112670. doi: 10.1016/j.jep.2020.112670. Epub 2020 Mar 3.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE:
Anoectochilus roxburghii (A. roxburghii) is a popular folk medicine in many Asian countries, which has been used traditionally for treatment of some diseases such as diabetes, tumors, hyperlipemia, and hepatitis. The ethanol extract from A. roxburghii was recently shown to exert better ability to scavenge free radicals in vitro and possess antioxidant on natural aging mice in vivo.
AIM OF THE STUDY:
This study is to characterize the chemical composition, and investigate the protective effect of the A. roxburghii flavonoids extract (ARF) against hydrogen peroxide (H2O2)-induced oxidative stress in LO2 cells in vitro and D-galactose (D-gal)-induced aging mice model in vivo, and explore the underlying mechanisms.
MATERIALS AND METHODS:
The chemical components of the flavonoids extract fromA. roxburghii were detected by ultraperformance lipid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). H2O2 was used to establish an oxidative stress model in LO2 cells. Cytotoxic and protective effects of ARF on the LO2 cells were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Moreover, the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and malondialdehyde (MDA) in cell supernatants were measured by commercial reagent kits. Kun-Ming mice were induced to aging with D-gal (400 mg/kg, BW) by subcutaneous injection for 58 days. From the 28th day to the 58th day of D-gal treatment, ARF (122.5, 245 and 490 mg/kg, BW) and vitamin E (100 mg/kg, BW) were orally administrated to aging mice once a day for consecutive 30 days. After 25 days of the treatment with ARF, learning and memory were assessed using Morris Water Maze (MWM). At the end of the test period, the animals were euthanized by cervical dislocation, and the levels of SOD, GSH-PX, and MDA in serum, liver homogenates and brain homogenates were measured. The levels of monoamine oxidase (MAO) and acetylcholinesterase (AchE) were determined in brain homogenates. Skin and liver histopathological morphology were observed by H&E staining. Furthermore, antioxidant-related gene expression levels in the liver were carried out by quantitative real-time polymerase chain reaction (qRT-PCR).
RESULTS:
Nine flavonoids were identified in the extracts of A. roxburghii. In vitro assay, a high concentration of ARF (>612.5 μg/ml) reduced the survival rate and had toxic effects on LO2 cells. In addition, ARF (245 μg/ml, 490 μg/ml) and Vitamin C (200 μg/ml) markedly inhibited generations of MDA and increased activities of SOD, GSH-PX in H2O2-induced LO2 cells supernatants. In vivo assay, ARF (122.5 mg/kg, 245 mg/kg and 490 mg/kg) and Vitamin E (100 mg/kg) not only ameliorated learning and memory ability but also improved skin and liver pathological alterations. Strikingly, ARF significantly decreased MDA and MAO levels, markedly enhanced antioxidant enzyme (SOD and GSH-PX) activities. Further, compared to the D-gal group, ARF could obviously up-regulate glutathione peroxidase-1 (GPx-1) and glutathione peroxidase-4 (GPx-4) mRNA levels.
CONCLUSIONS:
These findings suggested that ARF protects LO2 cells against H2O2-induced oxidative stress and exerts the potent anti-aging effects in D-gal aging mice model, which may be related to the inhibition of oxidative stress. Flavonoid compounds may contribute to the anti-oxidative capability and modulating aging.
Non-alcoholic Fatty Liver Disease and Diabetes Mellitus
Gebran Khneizer, Syed Rizvi, Samer Gawrieh
Adv Exp Med Biol . 2020 May 19. doi: 10.1007/5584_2020_532.
Abstract
Nonalcoholic fatty liver disease (NAFLD) has emerged as the leading liver disease globally. NAFLD patients can have a progressive phenotype, non-alcoholic steatohepatitis (NASH) that could lead to cirrhosis, liver failure and cancer. There is a close bi-directional relationship between NAFLD and type 2 diabetes mellitus (T2DM); NAFLD increases the risk for T2DM and its complications whereas T2DM increases the severity of NAFLD and its complications. The large global impact of NAFLD and T2DM on healthcare systems requires a paradigm shift from specialty care to early identification and risk stratification of NAFLD in primary care and diabetes clinics. Approach to diagnosis, risk stratification and management of NAFLD is discussed. In addition to optimizing the control of coexisting cardiometabolic comorbidities, early referral of NAFLD patients at high risk of having NASH or significant fibrosis to hepatology specialist care may improve management and allow access for clinical trials. Lifestyle modifications, vitamin E, pioglitazone and metformin are currently available options that may benefit patients with T2DM and NAFLD. The burst of clinical trials investigating newer therapeutic agents for NAFLD and NASH offer hope for new, effective and safe therapies in the near future.
Efficacy of Vitamin E in Methotrexate-Induced Hepatotoxicity in Rheumatoid Arthritis: An Open-Label Case-Control Study
Binit Vaidya, Manisha Bhochhibhoya, Shweta Nakarmi
Int J Rheumatol . 2020 May 1;2020:5723485. doi: 10.1155/2020/5723485.
Abstract
Objective: To examine the efficacy of vitamin E in methotrexate- (MTX-) induced transaminitis in patients with rheumatoid arthritis (RA).
Methods: A case-control study was conducted at a tertiary rheumatology center for 12 months. Patients with RA on MTX and deranged aminotransferases were included. Patients with previous liver diseases, baseline transaminitis before methotrexate initiation, alcohol intake, muscle diseases, under hepatotoxic drugs, and aminotransferases > 3 times the upper normal limit were excluded. The patients were divided into treatment (vitamin E 400 mg bid for 3 months) and control groups (no vitamin E) using a random number table. The dose of MTX was unaltered. Follow-up was done after 3 and 6 months. Independent t-test was done to compare means of two groups. Paired t-test was done to compare differences in mean.
Results: Among 230 patients, 86.5% were female with a mean BMI of 25.9 ± 4.5 kg/m2. In the treatment group, SGPT and SGOT at baseline were 73.1 ± 20.4 and 60.2 ± 24.5 IU/L, respectively; at 3-month follow-up 44.6 ± 34.2 and 38.3 ± 20.8 IU/L, respectively; and at 6-month follow-up 40.4 ± 35.7 and 34.2 ± 21.9 IU/L, respectively. In the control group, SGPT and SGOT at baseline were 63.4 ± 15.1 and 46.8 ± 13.7 IU/L, respectively, and at 3-month follow-up 55.8 ± 45.9 and 45.5 ± 30.9 IU/L, respectively. Significant decrease in the level of aminotransferases was seen in the treatment group (p value < 0.001) and not in the control group (p values 0.161 and 0.728, respectively). The change in levels of SGPT and SGOT from baseline to 3 months of follow-up was statistically significant in between two study groups (p values 0.007 and <0.001, respectively). From the control group, 29 patients were crossed over to vitamin E for the next 3 months. SGPT and SGOT decreased from 97.6 ± 44.1 to 46.1 ± 40.9 and 69.3 ± 34.9 to 29.1 ± 11.6 IU/L, respectively (p values 0.031 and 0.017, respectively).
Role of Magnetic Resonance Imaging in the Monitoring of Patients with Nonalcoholic Fatty Liver Disease: Comparison with Ultrasonography, Lipid Profile, and Body Mass Index
Makhija N, Vikram NK, Kaur G, Sharma R, Srivastava DN, Madhusudhan KS
J Clin Exp Hepatol. 2020 Mar-Apr;10(2):139-149. doi: 10.1016/j.jceh.2019.09.002. Epub 2019 Sep 20.
Abstract
AIM:
The aim of this study was to study the role of magnetic resonance imaging (MRI) in monitoring hepatic fat content in cases of nonalcoholic fatty liver disease (NAFLD).
MATERIALS AND METHODS:
41 adults (mean age: 39 years, 22 males; 19 females) with NAFLD were included after obtaining approval from the institutional ethics committee. The baseline clinical (weight, body mass index [BMI]) and biochemical parameters, fatty liver grade on ultrasonography (USG), and hepatic fat signal fraction (FSF) using dual-echo chemical shift imaging and proton density fat fraction on magnetic resonance spectroscopy (MRS-PDFF) were assessed, before and after intervention (dietary and lifestyle changes and oral vitamin E for six months). They were categorized into Group A (good compliance to intervention) and Group B (poor compliance), and the clinical and imaging parameters were compared between them.
RESULTS:
After intervention, Group A (n = 30) showed significant reduction in BMI (28.35 ± 3.25 to 27.14 ± 3.24 kg/m2; P < 0.001), hepatic FSF (19.30 ± 9.09% to 11.18 ± 7.61%; P < 0.05), and MRS-PDFF (18.79 ± 8.53% to 10.64 ± 6.66%). In Group B (n = 11), there was significant increase in BMI (28.85 ± 2.41 to 29.31 ± 2.57 kg/m2; P < 0.001), hepatic FSF (18.96 ± 9.79% to 21.48 ± 11.80%; P < 0.05), and reduction in high-density lipoproteins (P < 0.05). Although there was good correlation between USG and MRS in quantifying liver fat (r = 0.84-0.87; P < 0.001), USG was unable to detect <5.3% change in hepatic fat. There was poor correlation between lipid profile and MRS-PDFF. Change in body weight significantly correlated with change in hepatic fat content (r = 0.76; P < 0.001).
CONCLUSION:
MRI is useful in accurately quantifying and in monitoring hepatic fat content and is better than clinical and biochemical parameters and USG.
Pharmacokinetics and Pharmacodynamics of Ursodeoxycholic Acid in an Overweight Population With Abnormal Liver Function
Yoon S, Lee H, Ji SC, Yoon SH, Cho JY, Chung JY
Clin Pharmacol Drug Dev. 2020 Mar 19. doi: 10.1002/cpdd.790. [Epub ahead of print]
Abstract
Ursodeoxycholic acid (UDCA) is a secondary bile acid that is used to treat primary biliary cholangitis. Although UDCA has a hepatoprotective effect in some diseases, its benefit in nonalcoholic fatty liver disease (NAFLD) remains controversial. We aimed to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of UDCA in overweight subjects with elevated liver enzymes after multiple administrations of UDCA and compare these changes with vitamin E treatment. Overweight subjects (body mass index, 25-30 kg/m2 ) with elevated alanine aminotransferase (ALT) level (40-200 IU/L) were enrolled. Subjects received one of the following three 8-week treatments: UDCA 300 mg twice daily UDCA 300 mg twice daily for 4 weeks followed by UDCA 300 mg twice daily and metformin 500 mg twice daily for 4 weeks, and vitamin E 400 IU twice daily. PK and PD (liver function, lipid profiles, insulin sensitivity, and miR-122) analyses were performed. Thirty subjects were enrolled; 1 subject withdrew his consent during the study. The PK characteristics were similar to those of healthy volunteers. The ALT and miR-122 levels decreased in the UDCA groups, whereas the ALT and aspartate aminotransferase levels decreased in the vitamin E group. The lipid profiles and insulin sensitivity did not show significant changes among the groups. There was no serious adverse event, and the safety profiles were similar among the treatment groups. The liver enzyme and miR-122 levels were decreased by UDCA. Considering UDCA and vitamin E have a hepatoprotective effect and different mechanisms of action, combination therapy could be an option for NAFLD.
Synthesis and Liver Microsomal Metabolic Stability Studies of a Fluorine-Substituted δ-Tocotrienol Derivative
Liu X1,, Poddar S, Song L, Hendrickson H, Zhang X, Yuan Y, Zhou D, Zheng G
ChemMedChem. 2020 Jan 19. doi: 10.1002/cmdc.201900676.
Abstract
A fluoro-substituted δ-tocotrienol derivative, DT3-F2, was synthesized. This compound was designed to stabilize the metabolically labile terminal methyl groups of δ-tocotrienol by replacing one C-H bond on each of the two methyl groups with a C-F bond. However, in vitro metabolic stability studies using mouse liver microsomes revealed an unexpected rapid enzymatic C-F bond hydrolysis of DT3-F2. To the best of our knowledge, this is the first report of an unusual metabolic hydrolysis of allylic C-F bonds.