Arsenic aggravates oxidative stress causing hepatic alterations and inflammation in diabetic rats

Souza, Ana Cláudia Ferreira; Bastos, Daniel Silva Sena; Santos, Felipe Couto; Sertorio, Marcela Nascimento; Ervilha, Luiz Otávio Guimarães; Gonçalves, Reggiani Vilela; Oliveira, Leandro Licursi de; Machado‐Neves, Mariana

doi:10.1016/j.lfs.2018.08.054

Cited by 39 publications

(21 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The normality of the results was evaluated by Shapiro–Wilk test. As diabetic rats drink more water than non‐diabetic animals (Ge et al ., ), and we provided arsenic solution ad libitum to simulate the conditions faced in the environment (Souza et al ., ), three separated Student's t ‐tests were performed to compare the results. Thus, data from negative control and diabetes control groups were compared to validate the injuries caused by STZ‐induced diabetes.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Combined effects of arsenic exposure and diabetes on male reproductive functions

et al. 2019

Self Cite

View full text Add to dashboard Cite

Background: It is known that exposure to either arsenic or hyperglycemia can induce male reproductive damages. However, their combined effects on male reproductive organs are still unclear. Therefore, the present study investigated morphological and functional parameters of the testis, epididymis, and spermatozoa in diabetic rats exposed to arsenate. Materials and methods: Diabetes was induced in male rats by intraperitoneal streptozotocin injection. While a set of healthy and diabetic animals received saline solution (negative control and diabetes control, respectively), the other set received 10 mg/L sodium arsenate (arsenic control and diabetes + arsenic groups, respectively) for 40 days in drinking water. Testosterone concentration, daily sperm production, sperm counts in the testis and epididymis, and sperm parameters were evaluated in the groups. Moreover, testis and epididymis were subjected to antioxidant enzymes analysis, micromineral determination, and histopathological evaluation. Results: Arsenate exposure reduced serum testosterone concentration in healthy animals and worsened this reduction in diabetic rats. In addition, the number of spermatozoa in testis and epididymis tissues, as well as the daily sperm production, was decreased in these groups. Sperm parameters such as motility, morphology, and integrity of acrosomal and plasma membranes were impaired in health animals exposed to arsenate. The combination of diabetes and arsenate, in turn, increased only the percentage of spermatozoa with abnormal morphology. Moreover, the proportion of arsenic increased in the testis and epididymis of both groups receiving arsenate. Its bioaccumulation in these organs caused an imbalance in antioxidant enzymes activities and mineral content in healthy animals, enhancing these changes in diabetic rats. Testicular pathologies occurred mainly in animals co-exposed to diabetes and arsenate. Conclusion: Our results indicate that arsenate exposure enhances several damages to male reproductive functions in diabetic rats, mainly by impairing testosterone levels and inducing nitrosative stress in testis and epididymis.

show abstract

Section: Methodsmentioning

confidence: 99%

“…Of note, polydipsia is an important symptom of diabetes (Ge et al ., ), and drinking water is the main source of arsenic contamination (Orloff et al ., ). Therefore, diabetic individuals living in arsenic‐exposed areas might be suffering extensive health damages, posing a serious problem for public health (Souza et al ., ).…”

Section: Introductionmentioning

confidence: 97%

Combined effects of arsenic exposure and diabetes on male reproductive functions

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…Among them, the liver, as the primarily metabolic and detoxifying organ, is already confirmed as a susceptible toxicity target to arsenic 8 . Recent studies have indicated that chronic arsenic exposure through environmental media with high levels of arsenic could result in increased risks of various hepatic diseases, such as hepatomegaly, fibrosis, cirrhosis, and even liver cancer 9,10 . Though the severity and types of liver injury caused by arsenic are different, the pathological process with abnormal inflammatory response is common.…”

Section: Introductionmentioning

confidence: 99%

Imbalanced inflammatory response in subchronic arsenic‐induced liver injury and the protective effects of Ginkgo biloba extract in rats: Potential role of cytokines mediated cell–cell interactions

Dong

Liu

Wang

et al. 2021

Environmental Toxicology

View full text Add to dashboard Cite

Arsenic is a well‐known environmental toxicant and carcinogen, which has been epidemiologically proved related to the increased hepatic disorders. Researches have shown that aseptic inflammation and abnormal immune response are associated with arsenic‐induced liver injury. However, the immunotoxic effects of liver have not been extensively characterized. Ginkgo biloba extract (GBE), a natural products of G. biloba leaves with proven anti‐inflammatory and potential immunoregulatory activities, was used as intervention agent to explore its protective effects on arsenic‐induced hepatotoxicity. Thus, the underlying mechanism of the immunotoxic effects on arsenic‐induced liver injury were investigated in 2.5, 5.0, and 10.0 mg/kg NaAsO2 of Wistar rats for 16 weeks. Subsequently, GBE was used as intervention agent in 50 mg/kg for 6 weeks after cessation of arsenic exposure. The ratio of Th17 to Treg cells in peripheral blood as well as the secretion of inflammatory cytokines IL‐17A, IL‐6, TGF‐β1, and IL‐10 in serum and liver were detected. Meanwhile, the notable activation of aseptic inflammation‐related molecule TLR4 and its downstream targets MyD88 and NF‐κB in the liver were observed. In this work, we confirmed that subchronic exposed to arsenic triggered the infiltration of inflammatory cells in rat liver, coupled with obvious histopathological changes and aberrant hepatic serum biochemical parameters. Meanwhile, imbalanced immune response was verified by the notable abnormal ratio of Th17 to Treg cells in peripheral blood as well as the secretion of inflammatory cytokines IL‐17A, IL‐6, TGF‐β1, and IL‐10 in serum and liver of arsenic exposed rats. Further, the level of TLR4, MyD88, and NF‐κB in liver both transcription and translation activity were raised. Subsequently, GBE markedly mitigated arsenic‐induced liver injury, most impressively, post treatment with GBE prominently suppressed the overactivated inflammatory‐related TLR4‐MyD88‐NF‐κB pathway and evidently decreased the secretion of inflammation cytokines. Meanwhile, the disturbance of pro‐ and anti‐inflammatory response was reversed. We concluded that the disruption of pro‐ and anti‐inflammatory T‐cells balance caused by cytokines mediated cell–cell interactions may be one of the mechanisms underlying arsenic‐induced liver injury and that GBE intervention exerts an evidence protective effects, which might be closely associated with the suppression of inflammatory‐related TLR4 pathway.

show abstract

“…Morphological markers of VE dysfunction are endotheliocytes circulating in the blood, their fragments and precursors and smooth muscle cells of blood vessels (Fink et al, 2010). When the VE is damaged, blood levels of many substances increase, which are considered as biochemical markers of VE Jomova et al, 2011;Souza et al, 2018Souza et al, 2018Ellinsworth, 2015Jomova et al, 2011;Lim et al, 2011Moon et al, 2017Zhou et al, 2011Ellinsworth, 2015Jomova et al, 2011;Souza et aerobic type of energy metabolism of endotheliocytes predisposes them to disruption of ATP resynthesis in acute hypoxia (Zlacká & Zeman, 2021). In high-altitude illness, this leads to damage to the pulmonary circulatory system endothelium, manifested by pulmonary vasoconstriction and hypertension, non-productive cough, focal infiltrates on chest X-ray and ground glass on computed tomography (Paralikar, 2012).…”

Section: Dysfunctional Vementioning

confidence: 99%

Endogenous humoral determinants of vascular endothelial dysfunction as triggers of acute poisoning complications

Ivnitsky

Schäfer²,

Rejniuk

et al. 2022

J of Applied Toxicology

View full text Add to dashboard Cite

The vascular endothelium is not only the semipermeable membrane that separates tissue from blood but also an organ that regulates inflammation, vascular tone, blood clotting, angiogenesis and synthesis of connective tissue proteins. It is susceptible to the direct cytotoxic action of numerous xenobiotics and to the acute hypoxia that accompanies acute poisoning. This damage is superimposed on the preformed state of the vascular endothelium, which, in turn, depends on many humoral factors. The probability that an exogenous toxicant will cause lifethreatening dysfunction of the vascular endothelium, thereby complicating the course of acute poisoning, increases with an increase in the content of endogenous substances in the blood that disrupt endothelial function. These include ammonia, bacterial endotoxin, indoxyl sulfate, para-cresyl sulfate, trimethylamine N-oxide, asymmetric dimethylarginine, glucose, homocysteine, low-density and very-lowdensity lipoproteins, free fatty acids and products of intravascular haemolysis. Some other endogenous substances (albumin, haptoglobin, haemopexin, biliverdin, bilirubin, tetrahydrobiopterin) or food-derived compounds (ascorbic acid, rutin, omega-3 polyunsaturated fatty acids, etc.) reduce the risk of lethal vascular endothelial dysfunction. The individual variability of the content of these substances in the blood contributes to the stochasticity of the complications of acute poisoning and is a promising target for the risk reduction measures. Another feasible option may be the repositioning of drugs that affect the function of the vascular endothelium while being currently used for other indications.

show abstract

Arsenic aggravates oxidative stress causing hepatic alterations and inflammation in diabetic rats

Cited by 39 publications

References 44 publications

Combined effects of arsenic exposure and diabetes on male reproductive functions

Combined effects of arsenic exposure and diabetes on male reproductive functions

Imbalanced inflammatory response in subchronic arsenic‐induced liver injury and the protective effects of Ginkgo biloba extract in rats: Potential role of cytokines mediated cell–cell interactions

Endogenous humoral determinants of vascular endothelial dysfunction as triggers of acute poisoning complications

Contact Info

Product

Resources

About