Oxidative stress and biochemical indicators in blood of patients addicted to alcohol treated for acute ethylene glycol poisoning

Ethylene glycol (EG), in addition to its neurotoxic and nephrotoxic effects, evokes oxidative stress. The aim of this study was to assess the influence of the ethylene glycol on the biochemical indicators and oxidoreductive balance of patients treated for acute poisoning. The total study group consisted of 56 persons including 26 alcoholics who took EG as a substitute for ethyl alcohol in the course of alcohol dependence syndrome and 30 controls. Severity of poisoning, results of acid-base parameters, biochemical, and toxicological tests as well as biomarkers of the oxidative stress in blood were analyzed during the patients’ hospitalization. The key issue was to assess the oxidative stress and biochemical disturbances caused by EG and the type of treatment applied in the course of poisoning. Significant changes in some parameters were found both at time of diagnosis and after treatment initiation (ethanol as an antidote and hemodialysis). The most important differences included the activity of hepatic parameters (aspartate aminotransferase, AST) and oxidative stress markers like catalase (CAT); correlation of the lipid peroxidation products level (TBARS) with urea concentration has been shown. On the last day of the hospitalization, in some cases, the mutual correlation between the evaluated markers were observed, for example, between alanine transaminase (ALT) and glutathione reductase (GR), and urea concentration and glutathione level (GSH/GSSG). The concentration of ions (H+) had a major impact on the oxidoreductive balance, correlating with the elevated GR and GSH/GSSG levels.

Toxicity assessment of gelsenicine and the search for effective antidotes

Background Gelsenicine, one of the most toxic alkaloids of Gelsemium elegans Benth ( G. elegans), causes severe respiratory depression. However, its toxicity mechanisms are yet to be elucidated and no effective antidotes are available. Objective This study aimed to analyse the toxicity characteristics of gelsenicine. Methods Both acute and sub-acute toxicities were evaluated. Gelsenicine distribution and elimination in the central nervous system (CNS) and blood were observed. Effective antidotes for gelsenicine poisoning were screened. Results In the acute toxicity study, gelsenicine was highly toxic, and female rats exhibited greater sensitivity to gelsenicine than male rats (LD50 0.520 mg/kg vs 0.996 mg/kg, respectively). Death was primarily caused by respiratory failure. However, in the sub-acute toxicity study, no significant organ damage was observed. Gelsenicine was easily absorbed from the gastrointestinal tract and penetrated the blood–brain barrier, reaching peak concentrations in the CNS within 15 min and rapidly decreasing thereafter. Flumazenil or diazepam combined with epinephrine reversed gelsenicine toxicity and significantly improved survival rate in mice. Conclusions Gelsenicine is a highly toxic substance that affects nerve conduction without causing damage; the potential toxic mechanism is possibly associated with GABAA receptors. Our findings provide insights into the clinical treatment of gelsenicine -related poisoning and its toxicity mechanisms.

Frontal QRS-T angle as a predictive marker for myocardial damage in acute carbon monoxide poisoning

Introduction The present study was undertaken to investigate the prognostic value of the frontal QRS-T angle associated with adverse cardiac outcomes in patients with carbon monoxide (CO) poisoning in early stages in the emergency department. Materials and methods The data of 212 patients with CO poisoning who were admitted to the ED between January 2010 and May 2020 were retrospectively analyzed. The frontal QRS-T angle was obtained from the automatic reports of the EKG device. Results Compared to patients without myocardial damage, among patients with myocardial damage, statistically high creatinine, creatine kinase MB, cardiac troponin I, and frontal QRS-T angle values were found ( p < 0.001 for all parameters), while the saturation of arterial blood pH and arterial oxygen values were found to be lower ( p = 0.002 and p < 0.001, respectively). The frontal QRS-T angle values were correlated with creatine kinase, creatine kinase-MB, cardiac troponin I, and oxygen saturation (SpO2) in arterial blood (r = 0. 232, p = 0.001; r = 0. 253, p = < 0.001; r = 0. 389, p = < 0.001; r = −0. 198, p = 0.004, respectively). The optimum cut-off value of the frontal QRS-T angle was found to be 44.5 (area under the curve: 0.901, 95% confidence interval: 0.814–0.988, sensitivity: 87%, specificity: 84%). Conclusions The frontal QRS-T angle, a simple and inexpensive parameter that can be easily obtained from 12-lead surface electrocardiography, can be used as an early indicator in the detection of myocardial damage in patients with CO poisoning.

Thymoquinone ameliorates bleomycin-induced reproductive toxicity in male Balb/c mice

Bleomycin (BL) is a powerful chemotherapy drug that has devastating effects on spermatogenic function and may make cancer survivors at risk of infertility. Protective effects of thymoquinone (TQ), a phytochemical compound with antioxidant and anticancer influences, were investigated on sperm parameters, testicular structures, and sexual hormones in BL-treated mice. Forty-eight adult male Balb/c mice were randomly divided into six groups. Control group received normal saline; BL group received 10 mg/kg BL; TQ7.5 group received 7.5 mg/kg TQ; TQ15 group received 15 mg/kg TQ; BL+TQ7.5 group received 10 mg/kg BL and 7.5 mg/kg TQ; BL + TQ15 group received 10 mg/kg BL and 15 mg/kg TQ. BL was intraperitoneally used every day through 35 days, and TQ was intraperitoneally injected 3 days before administration of BL and continued twice per week for 35 days. Results showed that BL significantly decreased count, viability, morphology, maturity, and progressive movement of sperm, testosterone, seminiferous tubule diameters, the ratio of testis weight to body weight, number of spermatogonia, spermatocytes, spermatids, and Sertoli cells per tubule, and expression of Bcl2l1 and Bcl2l1/Bax ratio, and increased the non-progressive movement and immotile sperm, intermediate and immature sperm, LH, FSH, and malondialdehyde levels, and tunica albuginea thickness compared to the control group ( p < .05). TQ at a level of 7.5 mg/kg ameliorated BL-induced toxicity on measured parameters and returned most of them to the level of the control group. These data suggested TQ in a dose-dependent manner may have positive effects on BL-induced toxicity of the testis in mice model.

Epicatechin ameliorative effects on methotrexate-induced hepatotoxicity in mice

Background Due to the fact that methotrexate is widely used both as an immunosuppressive drug and as a chemotherapy agent, many studies are needed to reduce the side effects of this drug on non-target organs. Purpose This study was designed to investigate the effects of epicatechin (Epi) on MTX (methotrexate)-induced hepatotoxicity in mice. Research Design After 1 week for adaptation, we randomly divided 42 male Naval Medical Research Institute mice into six groups: (I) control; (II) Epi (100 mg/kg, po); (III) MTX (20 mg/kg, i.p.) on the fifth day; and (IV, V, and VI) Epi (25, 50, and 100 mg/kg, po) + MTX (20 mg/kg, i.p.) on the fifth day. At day 10, the mice were sacrificed and serum factors, oxidative stress markers, and inflammatory cytokines were measured. Results MTX increased activity level of serum enzymes (alanine aminotransferase and aspartate aminotransferase), lipid peroxidation marker (malondialdehyde), and inflammatory factors including interleukin-1 beta, tumor necrosis factor-alpha, and nitric oxide. Furthermore, MTX decreased glutathione level and activity level of catalase, superoxide dismutase, and glutathione peroxidase. Epi was able to reduce the destructive effects of oxidative/antioxidant system imbalance and inflammatory reactions and also histopathological damage in MTX intoxicated mice. Epi pretreatment reduced liver dysfunction by improving the antioxidant defense system, anti-inflammatory effects, and alleviation of histopathological damage in MTX hepatotoxicity. Conclusions Accordingly, Epi can be used as a therapeutic agent in hepatotoxicity associated with MTX chemotherapy.

Diosgenin inhibits the proliferation of gastric cancer cells via inducing mesoderm posterior 1 down-regulation-mediated alternative reading frame expression

Introduction Whether and how mesoderm posterior 1 (MESP1) plays a role in the proliferation of gastric cancer cells remain unclear. Methods The expression of MESP1 was compared in 48 human gastric cancer tissues and adjacent normal tissues. Knockdown of MESP1 was performed to investigate the role of MESP1 in the proliferation and apoptosis of BGC-823 and MGC-803 gastric cancer cells. Knockdown of alternative reading frame (ARF) was performed to study the role of ARF in the inhibitory effect of MESP1 knockdown on cell proliferation in gastric cancer cells. Mouse subcutaneous xenograft tumor model bearing BGC-823 cells was used to investigate the role of MESP1 in the growth of gastric tumor in vivo. The effect of seven active ingredients from T. terrestris on MESP1 expression was tested. The anti-cancer effect of diosgenin was confirmed in gastric cancer cells. MESP1 dependence of the anti-cancer effect of diosgenin was confirmed by MESP1 knockdown. Results MESP1 was highly expressed in human gastric cancer tissues ( p < 0.05). MESP1 knockdown induced apoptosis and up-regulated the expression of ARF in gastric cancer cells ( p < 0.05). Knockdown of ARF attenuated the anti-cancer effect of MESP1 knockdown ( p < 0.05). In addition, MESP1 knockdown also suppressed tumor growth in vivo ( p < 0.05). Diosgenin inhibits both mRNA and protein expression of MESP1 ( p < 0.05). MESP1 knockdown attenuated the anti-cancer effect of diosgenin ( p < 0.05). Conclusions MESP1 promotes the proliferation of gastric cancer cells via inhibiting ARF expression. Diosgenin exerts anti-cancer effect through inhibiting MESP1 expression in gastric cancer cells.

Pomegranate extract ameliorates renal ischemia/reperfusion injury in rats via suppressing NF-κB pathway

Inflammation and oxidative stress are the major pathways involved in ischemia–reperfusion (I/R)-induced renal injury. This study was designed to evaluate the potential effect of pomegranate against I/R-induced renal injury. I/R injury was induced in nephrectomized rats by unilateral occlusion of the left renal pedicle for 45 min followed by 24 h of perfusion. Pomegranate succeeded to decrease serum levels of creatinine, potassium, and urea nitrogen, along with increasing creatinine clearance. Pomegranate also decreased I/R-induced changes in histopathological examination. Pomegranate attenuated the renal inflammatory response reflected by the suppression of nuclear factor κB p65 DNA binding activity, the upregulation of inhibitory protein kappa B-alpha mRNA expression, the downregulation of mRNA and protein expression of tumor necrosis factor α, in addition to the reduced myeloperoxidase activity and mRNA expression. Additionally, pomegranate attenuated oxidative stress likely through the modulation of lipid peroxidation and antioxidant levels reflected by the decreased MDA content and the increased glutathione level and superoxide dismutase activity. Results confirm the potential protective effect of pomegranate against I/R-induced renal injury through its anti-inflammatory and anti-oxidant effects mediated through the upregulation of inhibitory protein kappa B-alpha, the inhibition of NF-κB activity, and the associated TNF-α release, neutrophil infiltration, and oxidative stress.

DAPK1 may be a potential biomarker for arterial aneurysm in clinical treatment and activated inflammation levels in arterial aneurysm through NLRP3 inflammasome by Beclin1

Background Death-associated protein kinase (DAPK1) is one of the positive regulators of apoptosis, and it is widely involved in apoptosis induced by multiple pathways. We examined that the function of DAPK1 in Clinical treatment of arterial aneurysm and its underlying mechanisms. Arterial aneurysm is a common cerebrovascular disease with high disability and fatality rate. Objectives Male C57BL/6 mice or DAPK1−/− mice were injected with 50 mg/kg pentobarbital sodium and then were injected with angiotensin II (AngII) infusion for vivo model. hASMCs (Human artery smooth muscle cell) were treated with murine recombinant IL-6 (20 ng ml−1; Cell Signaling) for vitro model. Results DAPK1 gene, mRNA expression, and protein expression were induced in mice of arterial aneurysm. DAPK1 mRNA expression was increased and Area Under Curve was 0.9075 in patients with arterial aneurysm. Knockout of DAPK1 decreased inflammation and vascular injury in mice model of arterial aneurysm. Beclin1/NLRP3 (NACHT, LRR, and PYD domains-containing protein 3) signal pathway is a critical downstream effector of DAPK1 by TAP production. The regulation of Beclin1 participated in the effects of DAPK1 on inflammation of arterial aneurysm by ATP-dependent NLRP3 inflammasome. The regulation of NLRP3 participated in the effects of DAPK1 on inflammation of arterial aneurysm. Conclusion Collectively, our data indicated that DAPK1 may be a potential biomarker for arterial aneurysm in clinical treatment and activated inflammation levels in arterial aneurysm through NLRP3 inflammasome by Beclin1. DAPK1 might be a key pathogenic event underlying excess inflammation of arterial aneurysm.

Exposure to a “safe” dose of environmental pollutant bisphenol A elevates oxidative stress and modulates vasoactive system in hypertensive rats

Due to the prevalence of hypertension (one of the major risk factors of CVD) in the population, it is necessary to explore the adverse effects of daily tolerable and “safe” dose of bisphenol A (BPA) under hypertensive conditions. The current study exposed the Nω-nitro-l-arginine methyl ester (L-NAME, 40 mg/kg b.w/day) induced hypertensive Wistar rats to BPA (50 μg/kg b.w/day) by oral administration along with appropriate controls for 30 days period. The results illustrate that a ‘safe’ dose of BPA does not influence the systolic blood pressure (SBP) and levels of circulatory biomarkers of tissue damage. On the other hand, BPA exposure significantly ( p < 0.05) elevates the thiobarbituric acid reactive substances (TBARS) content in plasma and tissues (heart, aorta, liver and kidney) in hypertensive rats when compared with respective control (BPA alone exposed) rats. Similarly, a significant modulation of ROS generation in RBC, plasma nitric oxide (NO) level and angiotensin-converting enzyme (ACE) activity was observed only under hypertensive milieu. In conclusion, the observed adverse effects during ‘safe’ dose of BPA exposure are specific to the hypertensive condition. Therefore, a precise investigation to explore the effects of BPA exposure in vulnerable hypertensive populations is highly suggested.

Effect of nano zinc oxide on proliferation and toxicity of human gingival cells

Background Periodontal dressing is used to cover the gum surface and protect the wound after periodontal surgery. Nanomaterials have been widely applied in dentistry in recent years. Zinc oxide (ZnO) is one of the main components of periodontal dressing. Aim This study aims to explore the toxicity ZnO nanoparticles (ZnO NPs) causes to human gingival fibroblast cells (HGF-1) and its effect on cell proliferation. Methods First, we identified and analyzed HGF-1, including cell morphology, growth curve, and immunohistochemistry staining. Then, we treated HGF-1 with ZnO NP. Cell viability, the integrity of the cell membrane, oxidative damage, and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release assay, fluorescent probe, and flow cytometry. Furthermore, the expression of murine double minute 2 (MDM2) and p53 was determined by quantitative real-time polymerase chain reaction (qPCR) and Western blotting. We finally overexpressed MDM2 in HGF-1 to verify the relationship between MDM2 and cell proliferation. Results Our research indicated ZnO NPs did not affect cell proliferation at low concentrations. However, high-concentration ZnO NP inhibited cell proliferation, destroyed the integrity of cell membranes, and induced oxidative stress and apoptosis. In addition, high concentration of ZnO NPs inhibited the proliferation of HGF-1 by regulating the expression of MDM2 and p53. Conclusion High concentration of ZnO NP caused toxicity to HGF-1 cells and inhibited cell proliferation by regulating MDM2 and p53 expression.