Vitamin E rescues valproic acid-induced testicular injury in rats: Role of autophagy

Amira Ebrahim Alsemeh, Marwa Mahmood Ahmed, Amal Fawzy, Walaa Samy, Marwa Tharwat, Samar Rezq

Life Sci . 2022 May 1;296:120434. doi: 10.1016/j.lfs.2022.120434. Epub 2022 Feb 25.

Abstract

Aims: Valproic acid (VPA), a commonly used antiepileptic drug, can induce testicular oxidative stress and injury. Altered autophagic response usually follows testicular injury. The study aims to evaluate the role of autophagy in the protective effect of the antioxidant vitamin E (Vit E) against VPA-induced testicular injury.

Materials and methods: VPA (100, 300, and 500 mg/kg/day) was administered for 8 days. The protective group received both Vit E (50 mg/kg) and VPA (500 mg/kg). The testicular weight, sperm analysis, and serum testosterone concentration, as well as testicular histopathology, steroidogenic gene expression, and oxidative stress markers were evaluated. The mRNA or protein expression of autophagy-related proteins [adenosine monophosphate-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), microtubule-associated protein light chain 3 (LC3), Beclin1, and p62] were measured using RT-PCR or immunohistochemistry.

Key findings: VPA resulted in lower testes weight and sperm quality with aberrant morphology. VPA dose-dependently induced testicular oxidative stress, which was associated with decreased steroidogenic gene expression and serum testosterone levels, as well as deteriorated histopathology. These biochemical and histological changes were also associated with autophagy induction (higher LC3 and Beclin1, and lower p62) that was lost with the highest toxic dose (500 mg/kg). The attenuated autophagy with the highest dose was accompanied by AMPK downregulation and mTOR upregulation. Vit E protected against VPA-mediated oxidative stress and toxicity while also restoring autophagic response and AMPK/mTOR levels.

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Effect of vitamin E supplementation on cardiometabolic risk factors, inflammatory and oxidative markers and hormonal functions in PCOS (polycystic ovary syndrome): a systematic review and meta-analysis

Ghazale Tefagh, Moloud Payab, Mostafa Qorbani, Farshad Sharifi, Yasaman Sharifi, Mahbubeh Sadat Ebrahimnegad Shirvani, Farzad Pourghazi, Rasha Atlasi, Zhaleh Shadman, Nafiseh Rezaei, Erfan Mohammadi-Vajari, Bagher Larijani, Mahbube Ebrahimpur

Sci Rep . 2022 Apr 6;12(1):5770. doi: 10.1038/s41598-022-09082-3.

Abstract

Polycystic ovary syndrome (PCOS) is a common endocrinopathy among reproductive-age women. Various therapeutical approaches are currently used to manage or control symptoms associated with PCOS. This systematic review intended to assess the effects of Vit E supplementation on cardiometabolic risk factors, inflammatory and oxidative markers, and hormonal functions in PCOS women based on the clinical trial’s results. The databases including PubMed, Scopus, Cochrane, Web of Science, and Embase were used to find all relevant studies. The authors reviewed all relevant clinical trials via systematic evaluation of abstracts and titles. Searches were conducted on August 1, 2020. After the initial search and reading of the article’s title and abstract, 353 articles were reviewed; finally, 12 articles met the inclusion criteria. Vitamin E supplementation improves lipid profile, decreases insulin and HOMA-IR levels. Furthermore, while Vitamin E supplementation decreases LH and testosterone concentrations, it increases FSH and progestrone concentrations. The following meta-analysis showed that vitamin E supplementation made statistically significant improvements in triglyceride (TG) and low-density lipoproteins (LDL) levels, meanwhile, pooled mean difference for waist circumference (WC) and HOMA-IR were also statistically significant. Supplementary regimens containing vitamin E can positively affect metabolic and hormonal parameters in women with PCOS.

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Are Vitamin E Supplementation Beneficial for Female Gynaecology Health and Diseases?

Nur Amira Md Amin, Siti Hamimah Sheikh Abdul Kadir, Akmal Hisyam Arshad, Norhaslinda Abdul Aziz, Nurul Alimah Abdul Nasir, Normala Ab Latip

Molecules . 2022 Mar 15;27(6):1896. doi: 10.3390/molecules27061896.

Abstract

Vitamin E is known as an essential vitamin, and many studies had demonstrated the importance of vitamin E throughout the reproductive process, such as miscarriage, premature birth, preeclampsia, and intrauterine growth restriction, which could be caused by a lack of vitamin E during pregnancy. Its potent antioxidant properties can counteract the oxidative stress induced by oxygen free radicals and imbalance of oxidative-antioxidant levels, hence it may play a role in maintaining the normal function of the female reproductive system. Despite the fact that vitamin E is acknowledged as the substance needed for reproduction, its beneficial effects on female fertility, gynaecological health, and diseases are still poorly understood and lacking. Therefore, the goal of this paper is to provide a summary of the known roles of vitamin E supplementation in women for gynaecological health and reproductive-related diseases, as well as its future perspective.

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Drug release, stability and efficiency of vitamin e loaded in liposomes for bovine sperm protection in cryopreservation medium

L Taouzinet, S Fatmi, A Khellouf, M Lahianl-Skiba, M Skiba, M Iguer-Ouada

Cryo Letters . Jan-Feb 2022;43(1):50-57.

Abstract

Background: It is known that a considerable number of drugs in clinical use or under development are water-insoluble drugs with poor bioavailability. The liposomal delivery system has drawn attention as one of the noteworthy approaches to increase both dissolution and absorption because of its biocompatibility and ability to encapsulate hydrophobic molecules in the lipid domain. However, several drawbacks have been reported, the most common is liposome structural instability.

Objective: To encapsulate alpha tocopherol into liposomes, to determine the new formulation stability and to study the drug-release of alpha tocopherol into the sperm cryopreservation medium.

Materials and methods: The liposomes prepared by an ethanol injection method were characterized for size stability, alpha tocopherol release and sperm motility tests.

Results: The prepared unilamellar vesicles had both narrow size distribution (around 99 nm) and a good physical and chemical stability at 4°C during 12 months. The liposomes did not release the vitamin E immediately, but retained the protectant for 24 hours, probably due to the rigidity of the liposomal fence which was reinforced by adding cholesterol. Then, all vitamin E molecules were released by 48 hours. Release was potentially by Fickian diffusion probably by the creation of mini-ducts due to both agitation and fence hydration. Moreover, semen motility treated with vitamin E liposome preparations was significantly improved compared to all other treatments (including commonly used sperm conservation media).

Conclusion: The stable vitamin E liposomes formulated in this work are a promising alternative for semen cryopreservation protection.

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α-Tocopherol Prevents Sperm Apoptosis and Necrosis in Rats Exposed to 2,3,7,8-Tetrachlorodibenzo-p-dioxin

Dewa Ketut Meles, Kadek Rachmawati, Iwan Sahrial Hamid, Imam Mustofa, Wurlina Wurlina, Niluh Suwasanti, Desak Ketut Sekar Cempaka Putri, Suzanita Utama

Vet Med Int . 2022 Feb 21;2022:3685686. doi: 10.1155/2022/3685686. eCollection 2022.

Abstract

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a persistent organic pollutant that induces overproduction of reactive oxygen species (ROS). Studies on avoiding the adverse effects of dioxin pollution exposure are needed in all aspects, including reproductive health. This study aimed to determine the effect of α-tocopherol on superoxide dismutase (SOD) and malondialdehyde (MDA) levels, live spermatozoa, apoptosis, and necrosis in male rats exposed to dioxin as a model. Thirty healthy 12-week-old male rats were randomly divided into five groups. Rats in the control group were given corn oil twice daily at 4-hour intervals. The remaining rats were given TCDD 700 mg/kg BW daily, followed by administration of corn oil and α-tocopherol at doses of 77, 140, and 259 mg/kg BW/d for T0, T1, T2, and T3 groups, respectively. The treatments were conducted for 45 days; all rats were euthanized to collect blood and testicular samples on day 46. The results showed that exposure of TCDD resulted in a decrease in SOD activity and live spermatozoa and increased MDA level and death, apoptosis, and necrosis of spermatozoa (T0) compared to the control (C) group (p < 0.05). The administration of α-tocopherol, starting from the doses of 77 (T1), 149 (T2), and 259 mg (T3) per kg BW, was sequentially followed by returning MDA levels, recovering SOD activities, and restoration in the percentage of living, dead, apoptotic, and necrotic spermatozoa, similar (p > 0.05) to those of the control group. It could be concluded that the administration of α-tocopherol resolves the harmful effects of TCDD on the viability of spermatozoa in rats as a model.

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The Effect of Oral Vitamin E on Semen Parameters and IVF Outcome: A Double-Blinded Randomized Placebo-Controlled Clinical Trial

Soudabeh Sabetian, Bahia Namavar Jahromi, Sina Vakili, Sedighe Forouhari, Shohreh Alipour

Biomed Res Int . 2021 Oct 11;2021:5588275. doi: 10.1155/2021/5588275. eCollection 2021.

Abstract

Background: Male infertility is a main clinical problem that affects about 7% of all men worldwide. Many patients with male infertility are caused by a reduced antioxidant capacity of semen. Several antioxidant supplements, especially vitamin E, are proposed to help male infertility treatment. This project was goaled to study the effects of oral synthetic vitamin E (400 IU/day) for eight weeks on betterment of semen parameters and pregnancy rate.

Methods: After dropping the cases, 124 infertile couples with a male factor who were admitted to the IVF program were included. The male patients with idiopathic abnormal motility and/or morphology were randomized into two groups: 61 receiving vitamin E and 63 as the control group receiving placebo for eight weeks. The pretreatment semen parameters of both groups were compared with those of posttreatment. The pregnancy outcomes were considered between the two groups.

Results: There were no significant differences statistically between before and after treatment in the term of sperm volume, count, motility, and morphology. Furthermore, the IVF outcomes of the two groups were not different significantly, either. Interestingly, the percent of normal sperm in the placebo group was significantly decreased after eight weeks.

Conclusion: Vitamin E supplementation might neutralize free radical activity to keep sperm from more oxidative damages. Further studies regarding the influence of higher acceptable doses of vitamin E on semen characteristics and fertility rates are needed. This study was registered as a two-arm, blinded, randomized, placebo-controlled clinical trial (IRCTID: IRCT2014020616506N1, 2014-03-18).

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Protective effect of vitamin E on sperm parameters, chromatin quality, and DNA fragmentation in mice treated with different doses of ethanol: An experimental study

Mohamad Reza Doostabadi, Mohammadmehdi Hassanzadeh-Taheri, Mahmoud Asgharzadeh, Masoomeh Mohammadzadeh

Int J Reprod Biomed . 2021 Jul 27;19(6):525-536. doi: 10.18502/ijrm.v19i6.9374. eCollection 2021 Jun.

Abstract

Background: Excessive consumption of alcohol induces an increase in oxidative stress production and can lead to detrimental effects on the male reproductive system.

Objective: To evaluate the possible protective effects of coadministration of vitamin (vit) E on the detrimental changes in the sperm quality of mice administered ethanol.

Materials and methods: Fifty-four BALB/c mice were categorized into nine groups (n = 6/each). The control group received a basal diet while the eight experimental groups received ethanol 10%; ethanol 20%; vit. E 100 mg; vit. E 200 mg; ethanol 10% + vit. E 100 mg; ethanol 10% + vit. E 200 mg; ethanol 20% + vit. E 100 mg; ethanol 20% + vit. E 200 mg. After 35 days, the sperm parameters and sperm chromatin were assessed.

Results: The results demonstrated a significant reduction in the motility rate, normal morphology rate, viability rate, increase in abnormal DNA structure and packaging (TB staining), and DNA damage (TUNEL) in ethanol consumer groups. In addition, the findings showed a significant increase in the aforementioned parameters in ethanol- and vit. E-consumer groups compared to the ethanol-only consumer groups. The ethanol group received 20% of the most damage among the groups. The group receiving vit. E 100 mg and those receiving ethanol 10% + vit. E 200 mg gained the highest benefit among the groups.

Conclusion: Sperm forward progressive motility, normal morphology rate, and viability decreased in the ethanol groups. Also, the rates of spermatozoa with abnormal DNA structure and DNA fragmentation increased in the ethanol groups. Our findings revealed that the coadministration of vit. E and ethanol can protect destructive changes in DNA structure and damage.

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Activated Nrf-2 Pathway by Vitamin E to Attenuate Testicular Injuries of Rats with Sub-chronic Cadmium Exposure

Zhuo Chen, Zhicai Zuo, Kejie Chen, Zhuangzhi Yang, Fengyuan Wang, Jing Fang, Hengmin Cui, Hongrui Guo, Ping Ouyang, Zhengli Chen, Chao Huang, Yi Geng, Wentao Liu, Huidan Deng

Biol Trace Elem Res . 2021 Jun 25. doi: 10.1007/s12011-021-02784-1. Online ahead of print.

Abstract

Cadmium (Cd), a heavy metal element, cumulates in the testis and can cause male reproductive toxicity. Although vitamin E (VE) as one of potential antioxidants protects the testis against toxicity of Cd, the underlying mechanism remained uncompleted clear. The aim of this study was to investigate whether the Nrf-2 pathway is involved with the protective effect of VE on testicular damages caused by sub-chronic Cd exposure. Thirty-two SD rats were divided into four groups and orally administrated with VE and/or Cd for 28 consecutive days: control group, VE group (100 mg VE/kg), Cd group (5 mg CdCl2/kg), and VE + Cd group (100 mg VE/kg + 5 mg CdCl2/kg). The results showed that 28-day exposure of Cd caused accumulation of Cd, histopathological lesions, and alternations of sperm parameters (elevated rate of abnormal sperm, decreased count of sperm, declined motility, and viability of sperm). Moreover, the rats exposed to Cd showed significant oxidative stress (increased contents of MDA and decreased levels or activities of T-AOC, GSH, CAT, SOD and GSH-Px) and inhibition of Nrf-2 signaling pathway (downregulation of Nrf-2, HO-1, NQO-1, GCLC, GCLM and GST) of the testes. In contrast, VE treatment significantly reduced the Cd accumulation, alleviated histopathological lesions and dysfunctions, activated Nrf-2 pathway, and attenuated the oxidative stress caused by Cd in the testes of rats. In conclusion, VE, through upregulating Nrf-2 pathway, could protect testis against oxidative damages induced by sub-chronic Cd exposure.

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Protective role of vitamin E in testicular development of mice exposed to valproic acid

Daniel Conei, Mariana Rojas, Luis Santamaría, Jennie Risopatrón

Andrologia . 2021 Jun 21;e14140. doi: 10.1111/and.14140. Online ahead of print.

Abstract

Valproic acid (VPA) is a teratogenic antiepileptic, causing alterations in oxidative stress in prenatal development, being altered the development of the male reproductive system. The purpose of this study was to determine the protective effect of vitamin E (VE) on the testicular development in embryos, foetuses and pubertal mice exposed to VPA, VPA+VE and only VE. Sixty pregnant adult female mice were used, to which they were administered 600 mg/kg of VPA (VPA groups), 600 mg/kg of VPA and 200 IU of VE (VPA+VE groups), 200 IU VE (VE groups) and 0.3 ml of 0.9% physiological solution (control groups), showing at 12.5 days post-coital (dpc), 17.5 dpc and 6 weeks postnatal testicular development, and proliferative and apoptotic indices. The groups treated with VPA presented a smaller testicular volume, with greater interstitial space and a delay in the conformation of the testicular cords, shorter lengths and diameters of the germinal epithelium, a smaller number of germline and somatic cells, an increase in cells apoptotic and less proliferation, with significant differences. VE-treated groups behaved similarly to controls. In conclusion, VE reduces the effects caused by VPA throughout testicular development, from embryonic stages, continuing until pubertal stages.

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α-Tocopherol Stereoisomer Profiles in Matched Human Maternal and Umbilical Cord Plasma

Matthew J Kuchan, Stephen J DeMichele, Karen J Schimpf, Xinhua Chen

Curr Dev Nutr . 2021 May 3;5(6):nzab073. doi: 10.1093/cdn/nzab073. eCollection 2021 Jun.

Abstract

Background: α-Tocopherol (αT) is essential for fetal development. One study has shown that the human placenta preferentially transfers the natural stereoisomer, RRR-αT. But prenatal supplements generally contain synthetic αT (S-αT).

Objectives: We aimed to determine if umbilical cord plasma is enriched for RRR-αT in racially diverse neonates from both uncomplicated and complicated pregnancies and if cord RRR-αT enrichment is impacted by maternal αT stereoisomer profile.

Methods: We measured αT and αT stereoisomers in plasma from a randomly selected subset of 66 predominantly black and Hispanic maternal-fetal pairs from the Camden Study involving control (= 28) and complicated pregnancies (= 38). We collected maternal plasma at study entry (week 16 gestation; w16) and week 28 gestation (w28) and cord plasma at birth.

Results: RRR-αT was the predominant stereoisomer in all maternal and cord plasma samples, but S-αT stereoisomers were found in most samples and comprised a high percentage of αT in some maternal-neonate pairs. Cord plasma had a higher percentage RRR-αT (< 0.05) and lower percentage S-αT (< 0.0001) than w28 plasma. Pregnancy status did not impact maternal or cord plasma concentrations of αT, RRR-αT, or S-αT; except plasma from complicated pregnancies was higher in S-αT at w28 than at w16 (< 0.05). Maternal w28 αT did not correlate with cord αT. However, both maternal w28 αT and S-αT positively correlated with both cord S-αT (r = 0.340, = 0.0049; r = 0.538, < 0.00001) and percentage S-αT (r = 0.399, = 0.001; r = 0.786, < 0.00001) but negatively correlated with cord percentage RRR-αT (r = -0.399, = 0.0009; r = -0.786, < 0.00001).

Conclusions: The proportion of RRR-αT was higher in cord compared with maternal plasma in both uncomplicated and complicated pregnancies. Our data suggest that maternal S-αT raises cord S-αT and decreases the proportion of RRR-αT in the neonatal circulation. Because the bioactivities of RRR-αT and S-αT differ, this warrants future research to determine the importance of our observations to neonatal αT status.

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