Zinc Deficiency and Oxidative Stress Involved in Valproic Acid Induced Hepatotoxicity: Protection by Zinc and Selenium Supplementation

Ahangar, Nematollah; Naderi, Maloos; Noroozi, Abdolali; Ghasemi, Maryam; Zamani, Ehsan; Shaki, Fatemeh

doi:10.1007/s12011-017-0944-z

Cited by 30 publications

(19 citation statements)

References 51 publications

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“…Zn and Se were responsible for the regulation and homeostasis of different cytoprotective proteins against diabetes-induced oxidative stress and DNA damage in testes. 27 The present study findings demonstrated that Zn and Se combination treatment has beneficial effects in diabetes-induced germ cell damage. The present study showed that the Zn and Se combination treatment modulated the plasma Zn level and testicular Zn and Se levels during the diabetic condition.…”

Section: Discussionsupporting

confidence: 66%

“…26 It has been shown that the combination of Zn þ Se showed more protective effects than per se Se in valproic acidinduced hepatotoxicity in Wistar rats. 27 Table 1 summarizes the various reports on the protective effect of Zn and Se in different experimental studies alone as well as in combination. Considering the significance of germ cell damage and the increased incidences of diabetes in humans, the present intervention study was undertaken with the combination treatment of Zn and Se to explore the possible ameliorative effects.…”

Section: Introductionmentioning

confidence: 99%

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Zinc and selenium combination treatment protected diabetes-induced testicular and epididymal damage in rat

2020

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Diabetes increases the possibility of germ cell damage, hypogonadism, and male infertility. Diabetic condition negatively impacts zinc (Zn) and selenium (Se) levels in the body. Zn and Se are among the most important trace elements involved in the regulation of redox reaction, antioxidants enzymes activities, and DNA expression in a germ cell. The present study aimed to elucidate the combined effects of Zn and Se treatment on diabetes-induced germ cell damage in male Sprague Dawley rats. Type 1 diabetes was induced by the single intraperitoneal (i.p.) injection of streptozotocin (55 mg/kg). Zn (3 mg/kg, i.p.) and Se (0.5 mg/kg, i.p.) were administered daily for 8 consecutive weeks. All the animals were provided with normal feed and water throughout the study. The effects on germ cell damage were evaluated by body weight, feed-water intake, organ weight, sperm count, motility, sperm head morphology, biochemical analysis, histology, immunohistochemistry, halo assay, germ cell comet assay, testes terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end-labeling (TUNEL) assay, sperm TUNEL assay, serum protein pattern analysis, and subcellular analysis using transmission electron microscopy. Further, the expressions of nuclear erythroid-derived related factor 2, catalase, glutathione peroxidase 4, and glutathione peroxidase 5 were carried out to ascertain the mechanism of protection. The present results demonstrated that 8 weeks combined treatment of Zn (3 mg/kg, i.p.) and Se (0.5 mg/kg, i.p.) reduced diabetes-induced germ cell damage. This study further highlighted that Zn and Se combination treatment might be a better strategy for the germ cell protection in diabetes and deserve further investigation.

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Section: Discussionsupporting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Zinc and selenium combination treatment protected diabetes-induced testicular and epididymal damage in rat

2020

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“…21 Furthermore, the hepatotoxic effects of VPA have been associated with depressed levels of serum zinc and selenium contributing to oxidative damage, as well as histological and biochemical defects in hepatocytes of rats. 22 In another report, VPA treatment reduced the cell viability of HepG2 hepatic cancer cell line and increased the release of ALT and AST from these cells. 23 On the other hand, the cytotoxic effects of VPA have been modulated by genetic variations in Cytochrome P450 2C9 (CYP2C9) and Acyl-CoA Synthetase Medium Chain Family Member 2A (ACSM2A) genes.…”

Section: Discussionmentioning

confidence: 93%

Protective Effects of Ursodeoxycholic Acid on Valproic Acid Induced Hepatotoxicity in Epileptic Children with Recurrent Seizure; A Double-Blinded Randomized Clinical Trial

et al. 2020

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Background : There are controversies regarding the protective role of ursodeoxycholic acid (UDCA) against valproic acid (VPA)-induced hepatotoxicity in children. In the present clinical trial, we assessed the potential role of UDCA in preventing VPA-induced fluctuations of hepatic enzymes in epileptic children with recurrent seizures. Methods: Two-hundred children with epileptic seizures were randomly allocated into either intervention (VPA+UDCA) or control (VPA+ placebo) group. Fluctuations of liver enzymes were recorded at baseline, as well as 48 hours, 1 month, and 3 months following the interventions. Results: The mean age of the patients was 7.33±2.96 years (the range of 4-16). Males and females constituted 43 (43%) and 57 (57%) subjects in each group respectively. There were no significant differences in the baseline levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) between the intervention and control groups. At 48 hours post-intervention, AST and ALT increased 1.7% and 11.05% (23.18±7.91 and 30.75±4.20 IU/l) in the intervention group and 21.3% and 35% (28.46±3.71 and 35.62±7.72 IU/l) in the control group respectively (P<0.0001). Both AST (P<0.001) and ALT (P=0.03) levels were significantly lower in the intervention than placebo group at 1-month post-intervention. At 3-month post-intervention; however, while AST level still was significantly higher in the control (29.87±5.41 IU/l) than intervention (21.63±6.87 IU/l, P<0.0001), ALT level was not significantly different between the two groups (32.72±5.59 IU/l and 32.01±7.89 IU/l respectively, P=0.5). Conclusion: UDCA can be an effective drug to manage VPA-induced fluctuations of hepatic enzymes in children with recurrent epileptic seizures.

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“…VPA-induced hepatotoxicity promotes oxidative stress and elevate the production of ROS (Karaca et al, 2014). Ahangar et al (2017) showed that as a result of VPA application of 200 mg/kg/day for 4 weeks, the level of MDA increased compared to the control group, and lipid peroxidation decreased with Zn and Se supplementation. In this study, MDA level increased in VPA group compared to control, although GLP-2 supplementation partially decreased MDA level, but it was not statistically significant.…”

Section: Discussionmentioning

confidence: 95%

Glukagon benzeri peptit-2 Sıçanlarda Valproik Asite Bağlı Hepatik Yaralanmaya Karşı Korunmaya Yardımcı Olabilir

Öztopuz¹,

Aylanç²,

Şehitoğlu³

et al. 2020

European Journal of Science and Technology

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VPA is widely used in epilepsy and other psychological disorders, increasing the probability of developing non-alcoholic liver disease in long-term treatments. GLP-2 is a proglucagon belonging to the peptide family expressed in the intestine, pancreas and brain to date. Although there are many studies on the use of GLP-2 for therapeutic purposes on the gastrointestinal system, its effect on liver toxicity is unknown. We aimed to investigate the effect of GLP-2 administration on hepatic function in a rat model with VPA-induced hepatotoxicity. Rats were injected intraperitoneally at 500 mg/kg and GLP-2 5µg/kg a day. The rats (200-250g) were separated into four groups (n=7). Group C was administrated 1 mL of 0.9% SF, Group GLP treated with GLP-2 (5µg/kg/day), Group GLP+VPA were received GLP-2 (5µg/kg) 1 h prior to VPA (500 mg/kg), Group VPA received VPA (500 mg/kg), 1 h prior to 1 mL of 0.9% SF ip (n=7). Liver tissues were used to investigate effects of VPA and GLP-2 in the liver 15 days after application. While VPA caused moderate but significant liver damage according to biochemical results, mRNA expression of cytokines were found to significantly increase after the day 15. VPA administration significantly induced expression of Interleukin 1 beta (IL-1β), Tumor necrosis factor alpha (TNF-α), Interleukin 10 (IL-10). In contrast, GLP-2 treatment reduced expression of IL-1β, TNF-α and IL-10. Also malondialdehyde (MDA), glutathione s-transferase (α-GST), superoxide dismutase activities (SOD), total antioxidant status (TAS) and total oxidant status (TOS) levels were estimated. GLP-2 had positive effects on both liver enzymes and oxidative stress markers in VPA-induced hepatotoxicity. These results suggest that endogenous GLP-2 administration is associated with a mechanism that moderately protects liver tissue.

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Zinc Deficiency and Oxidative Stress Involved in Valproic Acid Induced Hepatotoxicity: Protection by Zinc and Selenium Supplementation

Cited by 30 publications

References 51 publications

Zinc and selenium combination treatment protected diabetes-induced testicular and epididymal damage in rat

Zinc and selenium combination treatment protected diabetes-induced testicular and epididymal damage in rat

Protective Effects of Ursodeoxycholic Acid on Valproic Acid Induced Hepatotoxicity in Epileptic Children with Recurrent Seizure; A Double-Blinded Randomized Clinical Trial

Glukagon benzeri peptit-2 Sıçanlarda Valproik Asite Bağlı Hepatik Yaralanmaya Karşı Korunmaya Yardımcı Olabilir

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