Maternal endotoxemia induces renal collagen deposition in adult offspring: Role of NADPH oxidase/TGF-β1/MMP-2 signaling pathway

Farias JS, Santos KM, Lima NKS, Cabral EV, Aires RS, Veras AC, Paixão AD, Vieira LD

Arch Biochem Biophys. 2020 May 15;684:108306. doi: 10.1016/ Epub 2020 Feb 17.


Maternal endotoxemia has been shown to increase renal collagen deposition in the offspring. Renal fibrosis is a hallmark of progressive chronic kidney disease. It was investigated whether maternal reactive oxygen species (ROS) leads to renal fibrosis or exacerbates unilateral ureteral obstruction (UUO)-induced renal fibrosis in the offspring of dams treated with lipopolysaccharide (LPS). Furthermore, it was studied the role of matrix metalloproteinases (MMPs) in these changes. Adults Wistar rats were obtained from dams submitted to LPS administration through the third part of gestation. To evaluate the role of maternal ROS, part of the dams received α-tocopherol simultaneously with LPS. Part of the offspring in each group was submitted to UUO at adulthood when sub-groups were treated with NADPH oxidase inhibitor, apocynin. Maternal LPS administration increased proteinuria, systolic arterial pressure and renal collagen deposition in adult offspring. LPS offspring rats also presented higher MMP-2 activity in parallel to a decreased renal cortical TIMP-2 content. These changes were correlated to increased amounts of TGF-β1 and NOX2. Maternal α-tocopherol treatment prevented collagen deposition and reduced arterial pressure in adult offspring. α-Tocopherol also inhibited maternal endotoxemia-induced changes in TGF-β1/NOX2/MMP-2 signaling. UUO led to increased collagen deposition in the contralateral kidneys of LPS offspring, which was correlated to increased NADPH oxidase activity and prevented by NADPH oxidase inhibition. In summary, maternal endotoxemia led to alterations in the TGF-β1/NOX2/MMP-2 signaling pathway in renal tissue concomitant with collagen deposition, therefore contributing to hypertension in adult offspring.

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Metabolism and Biological Activity of α-Tocopherol Derived From Vitamin E-enriched Transgenic Maize in Broilers

Zhan Tengfei, Han Yunsheng, Tang Chaohua, Zhao Qingyu, Sun Dandan, Li Ying, Jia Xueting, Zhou Lingyun, Zhang Junmin

J Sci Food Agric . 2020 May 9. doi: 10.1002/jsfa.10480


Background: The aim of this study was to investigate the metabolism of α-tocopherol derived from vitamin E-enriched transgenic maize (VER) and its effects on antioxidant and immune functions in broilers aged 1 to 42 days. A total of 360 1-day-old male broilers were randomly divided into three groups containing six replicates with 20 broilers per replicate. The negative control (NC) group and the positive control (PC) group were given non-GM maize and non-GM maize plus exogenous vitamin E (VE), respectively, and the VER group was given VER replacing the non-GM maize given to the NC group. Between days 1 and 21 and days 22 and 42, VE levels were 4.38 and 4.63 mg kg-1 in the NC group, and 14.11 and 14.91 mg kg-1 in the PC and VER group, respectively.

Results: The results showed that α-tocopherol from both VER and additives increased α-tocopherol transfer protein and cytochrome P450 concentrations. Additionally, serum α-tocopherol and α-tocopherylquinone levels of broilers in the PC and VER groups were significantly higher than those in the NC group (P < 0.05). Compared with the NC group, broilers in both groups that received α-tocopherol had reduced NF-κB p65 concentrations, significantly decreased serum prostaglandin E2 , IL-6, malondialdehyde, and hydrogen peroxide levels (P < 0.05), and significantly increased glutathione, glutathione peroxidase, and total antioxidant capacity (P < 0.05).

Conclusion: In summary, both VER and non-GM maize fortified with exogenous VE showed similar effects on broilers, indicating that the α-tocopherol in VER has sufficient biological activity.

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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.


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).

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Microemulsion co-delivering vitamin A and vitamin E as a new platform for topical treatment of acute skin inflammation

Praça FG, Viegas JSR, Peh HY, Garbin TN, Medina WSG, Bentley MVLB

Mater Sci Eng C Mater Biol Appl. 2020 May;110:110639. doi: 10.1016/j.msec.2020.110639. Epub 2020 Jan 7.


In this study, we developed a water-in-oil microemulsion containing vitamin A (retinol) and vitamin E (α-tocopherol), which serves as a multifunctional nanosystem that co-delivers antioxidants and displayed additive effect against acute skin inflammation. Microemulsion (ME) was prepared by mixing a surfactant blend (Tween 80 and propylene glycol, 5:1) with isopropyl myristate and water (ratio of 50:40:10, respectively). Vitamin A (0.05% w/w concentration) and/or vitamin E (0.1% w/w concentration) were incorporated into the surfactant mixture of ME by stirring with a magnetic stirrer for 30 min. This multifunctional ME displayed physical stability, with low cytotoxicity in 3T3 cell line, as well as cellular internalization into the cytosol. In vivo treatments using ME delivering α-tocopherol reduced dermal expression of TNF-α by 1.3-fold (p < 0.01), when compared to unloaded ME treatment group. When retinol was added into the ME containing α-tocopherol, it further reduced TNF-α expression by 2-fold (p < 0.001), suggesting the additive effect of vitamin E and vitamin A in the treatment against skin inflammation. In conclusion, we successfully developed the use of water-in-oil ME to pack both vitamin E and vitamin A, and demonstrated for the first time its anti-inflammatory potential when applied topically to TPA-induced inflamed skin.

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Do Antioxidant Vitamins Prevent Exercise-Induced Muscle Damage? A Systematic Review

María Martinez-Ferran, Fabian Sanchis-Gomar, Carl J Lavie, Giuseppe Lippi, Helios Pareja-Galeano

Antioxidants (Basel) . 2020 Apr 29;9(5):E372. doi: 10.3390/antiox9050372.


Free radicals produced during exercise play a role in modulating cell signaling pathways. High doses of antioxidants may hamper adaptations to exercise training. However, their benefits are unclear. This review aims to examine whether vitamin C (VitC) and/or vitamin E (VitE) supplementation (SUP) prevents exercise-induced muscle damage. The PubMed, Web of Science, Medline, CINAHL, and SPORTDiscus databases were searched, and 21 articles were included. Four studies examined the effects of acute VitC SUP given pre-exercise: in one study, lower CK levels post-exercise was observed; in three, no difference was recorded. In one study, acute VitE SUP reduced CK activity 1 h post-exercise in conditions of hypoxia. In three studies, chronic VitE SUP did not reduce CK activity after an exercise session. Chronic VitE SUP did not reduce creatine kinase (CK) concentrations after three strength training sessions, but it was effective after 6 days of endurance training in another study. Chronic SUP with VitC + E reduced CK activity post-exercise in two studies, but there was no such effect in four studies. Finally, three studies described the effects of chronic VitC + E SUP and long-term exercise, reporting dissimilar results. To conclude, although there is some evidence of a protective effect of VitC and/or VitE against exercise-induced muscle damage, the available data are not conclusive.

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Application of Vitamin E Acetate on Staple Lines and Anastomoses of Roux-en-Y Gastric Bypass: Impact on Postoperative Pain and Acute Phase Reactants

Jaime Ruiz-Tovar, Alejandro Garcia, Carlos Ferrigni, Manuel Duran

Obes Surg . 2020 Apr 27. doi: 10.1007/s11695-020-04635-9.


Purpose: Postoperative pain after laparoscopic surgery has 3 components: parietal, visceral, and associated with pneumoperitoneum. Visceral pain accounts for around 30% of the total pain and is less amenable to be controlled by multimodal analgesia. The topical application of vitamin E ointment has demonstrated an anti-inflammatory effect in the local inflammatory response against surgical aggression. Vitamin E has been also associated with a reduction in postoperative pain of skin wounds. The aim of this study was to evaluate the effect of the topical application of vitamin E acetate on staple lines and anastomoses of Roux-en-Y gastric bypass, as part of a multimodal analgesia scheme within an Enhanced Recovery After Surgery (ERAS) program.

Methods: A prospective randomized clinical trial was performed. Patients were divided into 2 groups: patients receiving a topical application of vitamin E on staple lines and anastomoses (G1) and patients not receiving it (G2). The primary endpoint was postoperative pain, as measured by VAS 24 h after surgery. Secondary outcomes include morphine rescue needs, acute phase reactants 24 h after surgery, and hospital stay.

Results: One hundred forty patients were included, 70 in each group. Postoperative pain was 10 mm in G1 and 21.8 mm in G2 (p < 0.001). Morphine needs within the first 24 h were 2.9% in G1 and 13.2% in G2 (p = 0.026). C-reactive protein levels were significantly lower in G1 (8.7 mg/dL vs 11.9; p = 0.016). Mean hospital stay was 2.1 days in G1 and 2.9 in G2 (p = 0.019).

Conclusion: Topical application of vitamin E reduces postoperative pain and acute phase reactants, allowing an earlier discharge.

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Anti-allergic Function of α-Tocopherol Is Mediated by Suppression of PI3K-PKB Activity in Mast Cells in Mouse Model of Allergic Rhinitis

Geping Wu, Hongyan Zhu, Xinyang Wu, Lili Liu, Xingkai Ma, Yifang Yuan, Xingli Fu, Ling Zhang, Yan Lv, Di Li, Jianyong Liu, Jianbin Lu, Yan Yu, Menglin Li

Allergol Immunopathol (Madr) . 2020 Apr 22;S0301-0546(20)30036-7. doi: 10.1016/j.aller.2019.11.005.


Background: Alpha-Tocopherol (α-TCP), one major form of vitamin E, has been known as a treatment for airway allergic inflammation. However, the role and mechanism of α-TCP in treating allergic rhinitis remains unclear.

Objective: In this study we examined the inhibitory function of α-TCP in a mouse model of allergic rhinitis.

Methods: Allergic phenotype was examined by hematoxylin and eosin staining. Total IgE, OVA-specific IgE, OVA-specific IgG1 and OVA-specific IgG2a levels were examined by ELISA. mRNA expression was measured by qPCR, protein levels were examined by Western Blot.

Results: Histological analysis of the nasal membranes revealed that there was a significant reduction in inflammatory cells appearance in cross-sections in alpha-TCP treatment of Ovalbumin (OVA)-sensitized mice compared to OVA sensitized animals. In addition, eosinophils were significantly reduced in nasal mucosa of alpha-TCP treatment of OVA-sensitized mice compared to the OVA group. Lower total IgE, OVA-specific IgE, OVA-specific IgG1 and OVA-specific IgG2a levels were found in alpha-TCP treatment of OVA-sensitized mice compared to the OVA group. Furthermore, we found that the subepithelial distribution of tryptase positive mast cells was reduced in the alpha-TCP treatment of OVA-sensitized mice. More importantly, the PI3K-PKB pathway was suppressed by α-TCP in mast cells.

Conclusions: Our results demonstrated that α-TCP-mediated suppression of PI3K-PKB activity in mast cells is a potential mechanism of anti-allergic function of α-TCP.

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Alpha-tocopherol Attenuates the Severity of Pseudomonas aeruginosa-induced Pneumonia

Wagener BM, Anjum N, Evans C, Brandon A, Honavar J, Creighton J, Traber MG, Stuart RL, Stevens T, Pittet JF

Am J Respir Cell Mol Biol. 2020 Apr 3. doi: 10.1165/rcmb.2019-0185OC. [Epub ahead of print]


Pseudomonas aeruginosa is a lethal pathogen that causes high mortality and morbidity in immunocompromised and critically ill patients. The Type III secretion system (T3SS) of P. aeruginosa mediates many of the adverse effects of infection with this pathogen including increased lung permeability in a toll-like receptor 4/Rho A/plasminogen activator inhibitor (PAI)-1-dependent manner. Alpha-tocopherol has anti-inflammatory properties that may make it a useful adjunct in treatment of this moribund infection. We measured transendothelial and transepithelial resistance, Rho A and PAI-1 activation, stress fiber formation, P. aeruginosa T3SS exoenzyme (Exo Y) intoxication into host cells, and survival in a murine model of pneumonia in the presence of P. aeruginosa and pretreatment with α-tocopherol. We found that α-tocopherol alleviated P. aeruginosa-mediated alveolar endothelial and epithelial paracellular permeability by inhibiting RhoA, in part, via PAI-1 activation and increased survival in a mouse model of P. aeruginosa pneumonia. Furthermore, we found that α-tocopherol decreased the activation of RhoA and PAI-1 by blocking the injection of T3SS exoenzymes into alveolar epithelial cells. P. aeruginosa is becoming increasingly antibiotic-resistant. We provide evidence that α-tocopherol could be a useful therapeutic agent for individuals that are susceptible to infection with P. aeruginosa such as those who are immunocompromised or critically ill.

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Antioxidants Reduce Muscular Dystrophy in the dy2J/dy2J Mouse Model of Laminin α2 Chain-Deficient Muscular Dystrophy

Harandi VM, Oliveira BMS, Allamand V, Friberg A, Fontes-Oliveira CC, Durbeej M

Antioxidants (Basel). 2020 Mar 18;9(3). pii: E244. doi: 10.3390/antiox9030244.


Congenital muscular dystrophy with laminin α2 chain-deficiency (LAMA2-CMD) is a severe neuromuscular disorder without a cure. Using transcriptome and proteome profiling as well as functional assays, we previously demonstrated significant metabolic impairment in skeletal muscle from LAMA2-CMD patients and mouse models. Reactive oxygen species (ROS) increase when oxygen homeostasis is not maintained and, here, we investigate whether oxidative stress indeed is involved in the pathogenesis of LAMA2-CMD. We also analyze the effects of two antioxidant molecules, N-acetyl-L-cysteine (NAC) and vitamin E, on disease progression in the dy2J/dy2J mouse model of LAMA2-CMD. We demonstrate increased ROS levels in LAMA2-CMD mouse and patient skeletal muscle. Furthermore, NAC treatment (150 mg/kg IP for 6 days/week for 3 weeks) led to muscle force loss prevention, reduced central nucleation and decreased the occurrence of apoptosis, inflammation, fibrosis and oxidative stress in LAMA2-CMD muscle. In addition, vitamin E (40 mg/kg oral gavage for 6 days/week for 2 weeks) improved morphological features and reduced inflammation and ROS levels in dy2J/dy2J skeletal muscle. We suggest that NAC and to some extent vitamin E might be potential future supportive treatments for LAMA2-CMD as they improve numerous pathological hallmarks of LAMA2-CMD.

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The use of herbal supplement Renotinex based on terpenes for the complex treatment of patients with urinary stone disease

Medvedev VL, Mihailov IV, Rozenkranc AM, Efremov ME, Muratov KU, Budanov AA

Urologiia. 2020 Mar;(1):32-38.



to evaluate the efficiency of dietary supplements Renotinex for the complex treatment of patients with urinary stone disease who undergone to extracorporeal shock wave lithotripsy (ESWL).


a total of 60 patients with uncomplicated form of the urinary stone disease with the first stone episode (of size up to 1 cm) were evaluated. Patients were divided into two groups of 30 people and treated by ESWL. In the first group, patients additionally received Renotinex. In the second group, standard complex therapy (antispasmodics, analgesics, non-steroidal anti-inflammatory drugs) was prescribed. The urinary level of 2-microglobulin and serum level of tocopherol were considered as markers of damage and inflammation. Pain intensity was assessed using visual analogue scale. Follow-up studies were carried out on the 1st, 7th and 14th day of therapy. Duration of treatment and follow-up was 1 month. The average number of ESWL sessions was 2.6 in both groups.


according to the study, it was established that components of Renotinex had antiseptic, antispasmodic, anti-inflammatory effects on the genitourinary system, enhancing renal blood flow and decreasing the permeability of the kidney capillaries. In addition, Renotinex has diuretic effect and nephroprotective effect, and improves renal function, alleviating aggressive therapeutic influence of ESWL. Antioxidant and nephroprotective effect are among the main mechanisms of action of Renotinex.


In patients who received Renotinex as dietary supplements fragments after ESWL pass twice as fast, while in patients who did not receive Renotinex, there was more pronounced damage to the kidney parenchyma diagnosed by urine level of 2-microglobulin. The serum concentration of vitamin E increases, while taking Renotinex, which may prevent the peroxidation of polyunsaturated lipids in cell membranes and enhances the nephroprotective effect of Renotinex.

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