Curcumin affords protection against valproic acid induced teratogenicity by curtailing oxidative stress and inhibiting CYP2C9 activity

RSC Advances ◽  
2015 ◽  
Vol 5 (101) ◽  
pp. 82756-82764 ◽  
Author(s):  
Akhilesh Kumar ◽  
Hardik Chandasana ◽  
Rabi Sankar Bhatta ◽  
Nikunj Sethi ◽  
Sudhaker Yadav ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Valproic Acid ◽  
Toxic Metabolite ◽  
Dose Dependent ◽  
Cyp2c9 Activity

The toxic metabolite (E)-2,4-diene-VPA is involved in generation of oxidative stress subsequently contributing in induction of malformations and anomalies and that curcumin affords dose dependent amelioration of the anomalies exerted by VPA.

scholarly journals Cardiac Remodeling Induced by All-Trans Retinoic Acid is Detrimental in Normal Rats

2017 ◽  
Vol 43 (4) ◽  
pp. 1449-1459 ◽  
Author(s):  
Renata A. C. Silva ◽  
Andréa F. Gonçalves ◽  
Priscila P. dos Santos ◽  
Bruna Rafacho ◽  
Renan F. T. Claro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Retinoic Acid ◽  
Energy Metabolism ◽  
Cardiac Remodeling ◽  
Citrate Synthase ◽  
Isolated Heart ◽  
Lipid Hydroperoxide ◽  
Dependent Manner ◽  
Heart Study ◽  
Dose Dependent

Background/Aims: This study aimed to discern whether the cardiac alterations caused by retinoic acid (RA) in normal adult rats are physiologic or pathologic. Methods and Results: Wistar rats were assigned into four groups: control animals (C, n = 20) received a standard rat chow; animals fed a diet supplemented with 0.3 mg/kg/day all-trans-RA (AR1, n = 20); animals fed a diet supplemented with 5 mg/kg/day all-trans-RA (AR2, n = 20); and animals fed a diet supplemented with 10 mg/kg/day all-trans-RA (AR3, n = 20). After 2 months, the animals were submitted to echocardiogram, isolated heart study, histology, energy metabolism status, oxidative stress condition, and the signaling pathway involved in the cardiac remodeling induced by RA. RA increased myocyte cross-sectional area in a dose-dependent manner. The treatment did not change the morphological and functional variables, assessed by echocardiogram and isolated heart study. In contrast, RA changed catalases, superoxide dismutase, and glutathione peroxidases and was associated with increased values of lipid hydroperoxide, suggesting oxidative stress. RA also reduced citrate synthase, enzymatic mitochondrial complex II, ATP synthase, and enzymes of fatty acid metabolism and was associated with increased enzymes involved in glucose use. In addition, RA increased JNK 1/2 expression, without changes in TGF-β, PI3K, AKT, NFκB, S6K, and ERK. Conclusion: In normal rats, RA induces cardiac hypertrophy in a dose-dependent manner. The non-participation of the PI3K/Akt pathway, associated with the participation of the JNK pathway, oxidative stress, and changes in energy metabolism, suggests that cardiac remodeling induced by RA supplementation is deleterious.

scholarly journals Autistic-Like Behaviors, Oxidative Stress Status, and Histopathological Changes in Cerebellum of Valproic Acid Rat Model of Autism Are Improved by the Combined Extract of Purple Rice and Silkworm Pupae

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Nartnutda Morakotsriwan ◽  
Jintanaporn Wattanathorn ◽  
Woranan Kirisattayakul ◽  
Kowit Chaisiwamongkol
Keyword(s):  
Oxidative Stress ◽  
Valproic Acid ◽  
Purkinje Cell ◽  
Rat Model ◽  
Cell Loss ◽  
Hot Plate ◽  
Hot Plate Test ◽  
Silkworm Pupae ◽  
Oxidative Stress Status ◽  
Purkinje Cell Loss

Due to the crucial role of oxidative stress on the pathophysiology of autism and the concept of synergistic effect, the benefit of the combined extract of purple rice and silkworm pupae (AP1) for autism disorder was the focus. Therefore, we aimed to determine the effect of AP1 on autistic-like behaviors, oxidative stress status, and histopathological change of cerebellum in valproic acid (VPA) rat model of autism. VPA was injected on postnatal day (PND) 14 and the animals were orally given AP1 at doses of 50, 100, and 200 mg·kg−1BW between PND 14 and PND 40. The autism-like behaviors were analyzed via hot-plate, rotarod, elevated plus-maze, learning, memory, and social behavior tests. Oxidative stress and the histological change in the cerebellum were assessed at the end of study. AP1 treated rats improved behaviors in all tests except that in hot-plate test. The improvement of oxidative stress and Purkinje cell loss was also observed in the cerebellum of VPA-treated rats. Our data suggest that AP1 partially reduced autism-like behaviors by improving oxidative stress and Purkinje cell loss. Further research is required to identify the active ingredients in AP1 and gender difference effect.

Intranasal Toxicity of BMS-181885, A Novel 5-HT1 Agonist

1999 ◽  
Vol 18 (5) ◽  
pp. 285-296
Author(s):  
Gene E. Schulze ◽  
Jim E. Proctor ◽  
Mark A. Dominick ◽  
Amy E. Weiss ◽  
Oliver P. Flint ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Nasal Mucosa ◽  
Olfactory Epithelium ◽  
Mucosal Injury ◽  
Separate Experiment ◽  
Toxic Metabolite ◽  
Respiratory Epithelial Cells ◽  
Nasal Injury ◽  
Respiratory Epithelial ◽  
Dose Dependent

One-month intranasal toxicity studies were conducted with BMS-181885 at doses of 1.5, 9, or 15 mg/animal/day in rats and 4, 24, or 40 mg/animal/day in monkeys. A 1-month intermittent intranasal toxicity study was also conducted in monkeys at doses of 3, 6, and 12 mg/animal 3 days per week. BMS-181885 was generally well tolerated in rats but resulted in dose-dependent nasal mucosal injury, primarily characterized by subacute inflammation of the nasal mucosa, and degeneration, single-cell necrosis, and/or erosion of the olfactory epithelium and, to a lesser extent, the respiratory epithelium. In monkeys, daily BMS-181885 administration was well tolerated and produced similar dose-dependent nasal injury primarily characterized by subacute inflammation of the nasal mucosa with degeneration and erosion of the olfactory epithelium. In a separate experiment, intermittent administration also resulted in dose-dependent nasal injury. In cultured rat nasal mucosal cells, BMS-181885 was toxic to olfactory epithelial cells with a range of mean IC50s between 44 and 291 μM. In contrast, BMS-181885 had no effect on respiratory epithelial cells up to its maximum solubility. Cytochrome P450 inhibition had no effect on the toxicity of BMS-181885 in olfactory epithelial cells but produced dose-dependent toxicity in respiratory epithelial cells, which was not present previously. The in vitro data suggest that parent drug, rather than a toxic metabolite, caused the drug-associated nasal mucosal injury.

scholarly journals Effect of sodium (S)-2-hydroxyglutarate in male, and succinic acid in female Wistar rats against renal ischemia-reperfusion injury, suggesting a role of the HIF-1 pathway

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9438
Author(s):  
Eduardo Cienfuegos-Pecina ◽  
Tannya R. Ibarra-Rivera ◽  
Alma L. Saucedo ◽  
Luis A. Ramírez-Martínez ◽  
Deanna Esquivel-Figueroa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Succinic Acid ◽  
Wistar Rats ◽  
Ischemia Reperfusion ◽  
The Other ◽  
Oxidative Stress Biomarkers ◽  
Stress Biomarkers ◽  
Female Wistar Rats ◽  
Dose Dependent ◽  
Nephroprotective Effect

Background Ischemia–reperfusion (IR) injury is the main cause of delayed graft function in solid organ transplantation. Hypoxia-inducible factors (HIFs) control the expression of genes related to preconditioning against IR injury. During normoxia, HIF-α subunits are marked for degradation by the egg-laying defective nine homolog (EGLN) family of prolyl-4-hydroxylases. The inhibition of EGLN stabilizes HIFs and protects against IR injury. The aim of this study was to determine whether the EGLN inhibitors sodium (S)-2-hydroxyglutarate [(S)-2HG] and succinic acid (SA) have a nephroprotective effect against renal IR injury in Wistar rats. Methods (S)-2HG was synthesized in a 22.96% yield from commercially available L-glutamic acid in a two-step methodology (diazotization/alkaline hydrolysis), and its structure was confirmed by nuclear magnetic resonance and polarimetry. SA was acquired commercially. (S)-2HG and SA were independently evaluated in male and female Wistar rats respectively after renal IR injury. Rats were divided into the following groups: sham (SH), nontoxicity [(S)-2HG: 12.5 or 25 mg/kg; SA: 12.5, 25, or 50 mg/kg], IR, and compound+IR [(S)-2HG: 12.5 or 25 mg/kg; SA: 12.5, 25, or 50 mg/kg]; independent SH and IR groups were used for each assessed compound. Markers of kidney injury (BUN, creatinine, glucose, and uric acid) and liver function (ALT, AST, ALP, LDH, serum proteins, and albumin), proinflammatory cytokines (IL-1β, IL-6, and TNF-α), oxidative stress biomarkers (malondialdehyde and superoxide dismutase), and histological parameters (tubular necrosis, acidophilic casts, and vascular congestion) were assessed. Tissue HIF-1α was measured by ELISA and Western blot, and the expression of Hmox1 was assessed by RT-qPCR. Results (S)-2HG had a dose-dependent nephroprotective effect, as evidenced by a significant reduction in the changes in the BUN, creatinine, ALP, AST, and LDH levels compared with the IR group. Tissue HIF-1α was only increased in the IR group compared to SH; however, (S)-2HG caused a significant increase in the expression of Hmox1, suggesting an early accumulation of HIF-1α in the (S)-2HG-treated groups. There were no significant effects on the other biomarkers. SA did not show a nephroprotective effect; the only changes were a decrease in creatinine level at 12.5 mg/kg and increased IR injury at 50 mg/kg. There were no effects on the other biochemical, proinflammatory, or oxidative stress biomarkers. Conclusion None of the compounds were hepatotoxic at the tested doses. (S)-2HG showed a dose-dependent nephroprotective effect at the evaluated doses, which involved an increase in the expression of Hmox1, suggesting stabilization of HIF-1α. SA did not show a nephroprotective effect but tended to increase IR injury when given at high doses.

scholarly journals Preclinical Study on the Ameliorating Effect of L-Ascorbic Acid for the Oxidative Stress of Caused by Chronic Administration of Organic Nitrates in Cardiovascular Diseases

2021 ◽  
Author(s):  
Ahmed M Hamdan ◽  
Zuhair M. Mohammedsaleh ◽  
Aalaa Aboelnour ◽  
Sherif M.H. Elkhannishi
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Ascorbic Acid ◽  
Chronic Administration ◽  
Stress Factors ◽  
Male Rats ◽  
Oxidative Stress Marker ◽  
Organic Nitrates ◽  
Dependent Manner ◽  
Dose Dependent

Abstract PurposeThe therapeutic activity of Glyceryl trinitrate (GTN) is mainly regulated by liberating nitric oxide (NO) and reactive nitrogen species (RNS). During this biotransformation, oxidative stress and lipid peroxidation inside the red blood cells (RBCs) occur. The principal objective of our research is to explain the ameliorating effect of L-ascorbic acid for the deleterious effects of chronic administration of nitrovasodilator drugs. MethodsWe studied some biochemical parameters for the oxidative stress using groups of high sucrose/fat (HSF) diet Wistar male rats chronically orally administered ISMN. Afterwards, we evaluated the role of L-ascorbic acid against these biochemical changes. ResultsChronic treatment with organic nitrates caused elevated serum levels of lipid peroxidation, hemoglobin derivatives as methemoglobin and carboxyhemoglobin, rate of hemoglobin autoxidation, the cellular levels of pro-inflammatory cytokines marker (NF-κB) and apoptosis markers (caspase-3) in myocardium muscles in a dose dependent manner. Meanwhile, such exposure caused decline in the enzymatic effect of superoxide dismutase (SOD), glutathione (GSH) and catalase activity (CAT) accompanied with a decrease of in the level of mitochondrial oxidative stress marker (nrf2) in myocardium muscles and decrease in the serum iron and total iron binding capacity (TIBC) in a dose dependent manner. Concomitant treatment with L-ascorbic acid significantly diminished these changes for all examined parameters.ConclusionChronic administration of organic nitrates leads to the alteration of the level of oxidative stress factors in the myocardium tissue due to generation of reactive oxygen species. Using vitamin C can effectively ameliorate such intoxication to overcome the nitrate tolerance.

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