Pyrethroid-Induced Organ Toxicity and Anti-Oxidant-Supplemented Amelioration of Toxicity and Organ Damage: The Protective Roles of Ascorbic Acid and α-Tocopherol

Mohsen S Al-Omar, Mamuna Naz, Salman A A Mohammed, Momina Mansha, Mohd N Ansari, Najeeb U Rehman, Mehnaz Kamal, Hamdoon A Mohammed, Mohammad Yusuf, Abubaker M Hamad, Naseem Akhtar, Riaz A Khan

Int J Environ Res Public Health . 2020 Aug 25;17(17):E6177. doi: 10.3390/ijerph17176177.

Abstract

The pyrethroid toxicants, fatal at high doses, are found as remnants of crop pesticides and ingredients of commercially available insecticides. The toxic effects of high-content insecticidal pyrethroid formulations are available in 0.05 g, 1.17 g, and 0.04 g pyrethroid-instilled products, namely burning coils, pyrethroid-soaked mats, and liquid formulations of pyrethroids that release pyrethroid vapor/smoke upon heating. They provided 5.46 g/kg, 21.15 g/kg, and 4.24 g/kg of toxicants to the experimental animals over a total of 3 weeks/5 h per os (p.o.) administration, producing necrosis, hyperemia, and fatty changes in the liver; fiber separation in cardiac muscles; atrophy, lymphatic infiltration, blood vessel congestion, and hyperemia in the heart tissues of the experimental animals. The glomerular tuft necrosis, cytoplasmic degeneration of renal tubular cells, necrotic tubules, congestion, and dilatation of blood vessels were observed in the kidney tissue of intoxicated animals. Air-space enlargement, interstitial inflammation, lymphocyte infiltration aggregates, connective tissue infiltration by inflammatory cells, and hyperemia were found in the lung tissues. The pyrethroid toxicants also produced nervous tissue degeneration and decreased neurons in the brain, which were observed through histopathological examinations of the brain, lungs, heart, kidneys, and liver. The protective effects of ascorbic acid (AA/vitamin C) and α-tocopherol (E307/vitamin E) at 100 mg/kg oral doses administered daily for the entire period of the toxicant exposure of three weeks to the experimental mice, aged between 3-4 months and weighing ≈30 g, ameliorated the tissue damage, as observed through the histopathological examinations. The ascorbic acid caused recovery of the liver, kidney, brain, and heart tissue damage, while α-tocopherol was effective at ameliorating the damage in the kidneys and lung tissue compared with the control groups. The high levels of tissue damage recovery suggested a prophylactic effect of the concurrent use of ascorbic acid and α-tocopherol for the subjects under the exposure of pyrethroids.

Shabnum Aamir, Zia Ud Din, Zahid Sarfaraz Khan, Humaira Imtiaz, Faheem Ul Haq, Hajira Ishaq

J Ayub Med Coll Abbottabad . Jul-Sep 2020;32(3):295-298.

Abstract

Background: Chemical induced nephrotoxicity is one of the main causes of acute kidney injury. The objective of this study was to determine the antioxidant effect of vitamin E against carbon tetrachloride induced tubulointerstitial and glomerular damage in the kidney of albino mice.

Methods: The study had been conducted on albino mice. The duration of study was for five weeks. A total of 35 animals were randomly divided into five groups A, B, C, D and E .The group A served as control group, group B was administered only with carbon tetrachloride (no vitamin E) and groups C, D and E received test drug (vitamin E) in doses of 1, 10 and 50mg/kg body weight respectively along with CCl4. The animals were dissected and kidneys were excised for microscopic study for possible histo-morphological effects.

Results: It was observed that carbon tetrachloride treated experimental groups developed tubulo-interstitial and glomerular changes as compared to control group A. The results suggested that these changes were significantly reduced in vitamin E treated groups especially in dose of 50 mg/kg body weight.

Conclusions: This study reveals that tubulointerstitial and glomerular damage caused by carbon tetrachloride can be reduced by vitamin E in dose of 50 mg/kg body weight.

Francisca A de Leeuw, Julie A Schneider, Sonal Agrawal, Sue E Leurgans, Martha Clare Morris

Alzheimers Dement (N Y) . 2020 Aug 24;6(1):e12021. doi: 10.1002/trc2.12021. eCollection 2020.

Abstract

Introduction: Higher brain tocopherol levels have been associated with lower levels of Alzheimer’s disease (AD) neuropathology; however, the underlying mechanisms are unclear.

Methods: We studied the relations of α- and γ-tocopherol brain levels to microglia density in 113 deceased participants from the Memory and Aging Project. We used linear regression analyses to examine associations between tocopherol levels and microglia densities in a basic model adjusted for age, sex, education, apolipoprotein E (APOE)ε4 genotype (any ε4 allele vs. none) , and post-mortem time interval, and a second model additionally adjusted for total amyloid load and neurofibrillary tangle severity.

Results: Higher α- and γ-tocopherol levels were associated with lower total and activated microglia density in cortical but not in subcortical brain regions. The association between cortical α-tocopherol and total microglia density remained statistically significant after adjusting for AD neuropathology.

Discussion: These results suggest that the relation between tocopherols and AD might be partly explained by the alleviating effects of tocopherols on microglia activation.

Nora Sovira, Munar Lubis, Pustika Amalia Wahidiyat, Franciscus D Suyatna, Djajadiman Gatot, Saptawati Bardosono, Mohammad Sadikin

Clin Exp Pediatr . 2020 Aug;63(8):314-320. doi: 10.3345/cep.2019.00542. Epub 2020 Aug 15.

Abstract

Background: The accumulation of unpaired α-globin chains in patients with β-thalassemia major may clinically create ineffective erythropoiesis, hemolysis, and chronic anemia. Multiple blood transfusions and iron overload cause cellular oxidative damage. However, α-tocopherol, an antioxidant, is a potent scavenger of lipid radicals in the membranes of red blood cells (RBCs) of patients with β-thalassemia major.

Purpose: To evaluate the effects of α-tocopherol on hemolysis and oxidative stress markers on the RBC membranes of patients with β-thalassemia major.

Methods: Forty subjects included in this randomized controlled trial were allocated to the placebo and α-tocopherol groups. Doses of α-tocopherol were based on Institute of Medicine recommendations: 4-8 years old, 200 mg/day; 9-13 years old, 400 mg/day; 14-18 years old, 600 mg/day. Hemolysis, oxidative stress, and antioxidant variables were evaluated before and after 4-week α-tocopherol or placebo treatment, performed before blood transfusions.

Results: Significant enhancements in plasma haptoglobin were noted in the α-tocopherol group (3.01 mg/dL; range, 0.60-42.42 mg/dL; P=0.021). However, there was no significant intergroup difference in osmotic fragility test results; hemopexin, malondialdehyde, reduced glutathione (GSH), or oxidized glutathione (GSSG) levels; or GSH/GSSG ratio.

Conclusion: Use of α-tocopherol could indirectly improve hemolysis and haptoglobin levels. However, it played no significant role in oxidative stress or as an endogen antioxidant marker in β-thalassemia major.

Jun Yang, Xuemei Ding, Shiping Bai, Jianping Wang, Qiufeng Zeng, Huanwei Peng, Yue Xuan, Zuowei Su, Keying Zhang

Animals (Basel) . 2020 Aug 13;10(8):E1409. doi: 10.3390/ani10081409.

Abstract

This study was conducted to investigate the effects of broiler breeder dietary vitamin E and egg storage time on the egg characteristics, hatchability, and antioxidant status of the egg yolks and newly hatched chicks. A total of 512 71-week-old Ross 308 breeder hens were fed the same basic diets containing 6 or 100 mg/kg vitamin E for 12 weeks. During this time, a total of 1532, 1464, and 1316 eggs were independently collected at weeks 8, 10, and 12, respectively, and subsequently stored for 0 or 14 d before hatching. The outcomes from three trials showed that prolonged egg storage time (14 vs. 0 d) negatively affected (p < 0.05) the egg characteristics, hatchability traits, and the yolk total antioxidant capacity (T-AOC) (p < 0.05). Chicks derived from the stored eggs exhibited higher malonaldehyde (MDA) and T-AOC in the serum and yolk sac (p < 0.05). Broiler breeder dietary vitamin E (100 vs. 6 mg/kg) increased (p < 0.05) the hatchability and the antioxidant status of the yolks as indicated by a higher α-tocopherol content and T-AOC and lower MDA level (p < 0.05). The supplementation of vitamin E also remarkably increased (p < 0.05) the total superoxide dismutase (T-SOD) activity (yolk sac, weeks 8 and 12) and T-AOC (serum, weeks 8, 10, and 12; yolk sac, weeks 8 and 12) and decreased (p < 0.05) the MDA content of chicks (yolk sac, week 10; serum, week 12). Interactions (p < 0.05) were found between the broiler breeder dietary vitamin E and egg storage time on the hatchability and antioxidant status of chick tissues. Broiler breeder dietary vitamin E (100 vs. 6 mg/kg) increased (p < 0.05) the hatchability and the T-AOC in the serum and liver of chicks, and decreased (p < 0.05) the early embryonic mortality and the MDA content in the yolk sacs of chicks derived from eggs stored for 14 d but not for 0 d. In conclusion, prolonged egg storage time (14 vs. 0 d) increased the embryonic mortality, decreased the hatchability, and impaired the antioxidant status of egg yolks and newly hatched chicks, while the addition of broiler breeder dietary vitamin E (100 vs. 6 mg/kg) could partly relieve these adverse impacts induced by long-term egg storage.

Madison M Fagan, Patricia Harris, Amanda Adams, Robert Pazdro, Amber Krotky, Jarrod Call, Kylee J Duberstein

J Equine Vet Sci . 2020 Aug;91:103103. doi: 10.1016/j.jevs.2020.103103. Epub 2020 Apr 29.

Abstract

Vitamin E is an essential antioxidant that may benefit athletes by reducing oxidative stress and influencing cytokine expression. Supplements can be derived from natural or manufactured synthetic sources. This study aimed to determine (1) if supplemental vitamin E is beneficial to exercising horses and (2) if there is a benefit of natural versus synthetic vitamin E. After 2 weeks on the control diet (vitamin E-deficient grain and hay), 18 horses were divided into three groups and fed the control diet plus (1) 1000 IU/d synthetic α-tocopherol (SYN-L), (2) 4000 IU/d synthetic α-tocopherol (SYN-H), or (3) 4000 IU/d RRR-α-tocopherol (natural source [NAT]). On day 7, horses began a 6-week training protocol, with standard exercise tests (SETs) performed before and after the 6-week protocol. Venous blood samples were collected on days 0, 7, 29, and 49. Horses fed NAT had higher α-tocopherol (P < .05) at post-SET1 through post-SET2. Plasma thiobarbituric acid-reactive substance levels were lower in NAT versus SYN-L horses after SET2 (P = .02). Serum aspartate aminotransferase was lower after exercise in NAT horses versus SYN-L and SYN-H (P = .02), and less reduction in stride duration was seen after exercise in NAT as compared with SYN-L and SYN-H (P = .02). Gene expression of tumor necrosis factor α was lower in NAT compared with SYN-H (P = .01) but not SYN-L. In conclusion, feeding higher levels of natural vitamin E source resulted in higher serum α-tocopherol levels as well as some improvement in oxidative and inflammatory response and improved functional outcomes in response to an exercise test.

Panagiotis Theodosis-Nobelos, Georgios Papagiouvannis, Eleni A Rekka

Mini Rev Med Chem . 2020 Aug 7. doi: 10.2174/1389557520666200807132617. Online ahead of print.

Abstract

Vitamin E, essential for human health, is widely used worldwide for therapeutic or dietary reasons. The differences in the metabolism and excretion of the multiple vitamin E forms are presented in this review. The important steps that influence the kinetics of each form and the distribution and processing of vitamin E forms by the liver are considered. The antioxidant as well as non-antioxidant properties of vitamin E forms are discussed. Finally, synthetic tocopherol and trolox derivatives, based on the design of multitarget directed compounds, are reviewed. It is demonstrated that selected derivatization of vitamin E or trolox structures can produce improved antioxidants, agents against cancer, cardiovascular and neurodegenerative disorders.

F Sánchez-Rubio, P J Soria-Meneses, A Jurado-Campos, J Bartolomé-García, V Gómez-Rubio, A J Soler, M M Arroyo-Jimenez, M J Santander-Ortega, M Plaza-Oliver, M V Lozano, J J Garde, M R Fernández-Santos

Free Radic Biol Med . 2020 Aug 5;160:47-56. doi: 10.1016/j.freeradbiomed.2020.07.024. Online ahead of print.

Abstract

Vitamin E is considered a powerful biological antioxidant; however, its characteristics such as high hydrophobicity and low stability limit its application. We propose to use nanotechnology as an innovative tool in spermatology, formulating nanoemulsions (NE) that accommodate vitamin E, protecting it from oxidation and promoting its release into the medium. The protective effect of the NE against oxidative stress was assessed in red deer epididymal sperm incubated at 37 °C. Cryopreserved sperm from eleven stags were thawed and extended to 400 × 10⁶ sperm/ml in Bovine Gamete Medium (BGM). Once aliquoted, the samples were supplemented with the NE at different concentrations (0, 6 and 12 mM), with or without induced oxidative stress (100 μM Fe²⁺/ascorbate). The samples were evaluated after 0, 2 and 4 h of incubation at 37 °C. Motility (CASA), viability, mitochondrial membrane potential, acrosomal status, lipoperoxidation (C11 BODIPY 581/591), intracellular reactive oxygen species (ROS) production and DNA status (SCSA®) were assessed. After 2 and 4 h of incubation, the NE were able to prevent the deleterious effects of oxidative stress, thus improving total and progression motility (P ˂0.05). Moreover, the highest concentration tested (12 mM) improved almost every sperm kinematic variable (P ˂0.05) and preserved sperm viability in samples subjected to oxidative stress. In addition, 12 mM of NE protected the acrosomes integrity, maintained and protected mitochondrial activity, prevented sperm lipoperoxidation and reduced ROS production (P ˂0.05) in samples subjected to oxidative stress. This work indicates for the first time that vitamin E formulated in NE could be a new approach against sperm oxidative damage. This could be highly relevant for sperm physiology preservation in the context of assisted reproduction techniques.

Flavia Kazue Ibuki, Cassia T Bergamaschi, Marlus da Silva Pedrosa, Fernando Neves Nogueira

Arch Oral Biol . 2020 Aug;116:104765. doi: 10.1016/j.archoralbio.2020.104765. Epub 2020 May 16.

Abstract

Objective: We examined the effects of vitamin C and E supplementation in the prevention of oxidative stress in the salivary glands of STZ-induced diabetic rats.

Design: Forty-eight male Wistar rats were divided into six groups (n = 8 in each): control (C), control supplemented with vitamin C (Cvc) and E (Cve), diabetic (D), and diabetic supplemented with vitamin C (Dvc) and E (Dve). Vitamin C (150 mg/kg) and E (300 mg/kg) were daily administered for 21 days. Serum ascorbic acid and α-tocopherol levels were quantified. Glandular levels of hydrogen peroxide (H₂O₂), superoxide anion (O₂^–), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), malondialdehyde (MDA) and the total antioxidant status (TAS) were estimated.

Results: Vitamin C and E levels were reduced in D group. Vitamin C decreased the levels of O₂^– in the salivary gland of diabetic rats. Vitamin E increased the concentration of O₂^– in PA gland of diabetic animals. In the SM gland of the diabetic group, MDA, SOD, GPx and TAS increased. Dve presented reduced SOD activity and increased GR, GPx, and MDA. Dve increased GPx, Gr and TAS levels. In the PA gland, MDA, SOD, CAT, GPx, GR, and TAS were similar in C and D. TAS, SOD, CAT, GPx, and GR increased in Dvc. Vitamin E supplementation resulted in increased MDA and CAT levels and reduced SOD activity.

Conclusion: In the SM glands of the diabetic rats, vitamin C supplementation improved the antioxidant system, while vitamin E acted as pro-oxidant.

Marisa Palazzo, Francesco Vizzarri, Lubomir Ondruška, Michele Rinaldi, Luigi Pacente, Germano Guerra, Francesco Merolla, Ciro Caruso, Ciro Costagliola

Int J Mol Sci . 2020 Jul 30;21(15):E5426. doi: 10.3390/ijms21155426.

Abstract

This study aimed to evaluate the protective effect of a topical antioxidant and ultraviolet (UV) shielding action formulation containing riboflavin and D-α-tocopherol polyethylene glycol succinate (TPGS) vitamin E against corneal UV-induced damage in vivo rabbit eyes. In vivo experiments were performed using male albino rabbits, which were divided into four groups. The control group (CG) did not receive any UV irradiation; the first group (IG) was irradiated with a UV-B-UV-A lamp for 30 min; the second (G30) and third (G60) groups received UV irradiation for 30 and 60 min, respectively, and were topically treated with one drop of the antioxidant and shielding formulation every 15 min, starting one hour before irradiation, until the end of UV exposure. The cornea of the IG group showed irregular thickening, detachment of residual fragments of the Descemet membrane, stromal fluid swelling with consequent collagen fiber disorganization and disruption, and inflammation. The cornea of the G30 group showed edema, a mild thickening of the Descemet membrane without fibrillar collagen disruption and focal discoloration, or inflammation. In the G60 group, the cornea showed a more severe thickening, a more abundant fluid accumulation underneath the Descemet membrane with focal detachment, and no signs of severe tissue alterations, as were recorded in the IG group. Our results demonstrate that topical application of eye drops containing riboflavin and TPGS vitamin E counteracts UV corneal injury in exposed rabbits.