Clusterin protects against Cr(VI)-induced oxidative stress-associated hepatotoxicity by mediating the Akt-Keap1-Nrf2 signaling pathway

Ma, Yu; Li, Siwen; Tang, Sixuan; Ye, Shuzi; Liang, Ningjuan; Liang, Yuehui; Xiao, Fang

doi:10.1007/s11356-022-19118-w

Cited by 9 publications

(6 citation statements)

References 46 publications

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“…Cr(VI)-induced oxidative stress is accompanied by damage to hepatocyte cell membranes, after which aminotransferases enter the blood plasma (Hassan et al, 2019). Therefore, changes in blood aminotransferases activity are an important indicator of the structural and functional state of the liver (Ma et al, 2022). We only observed a tendency to increase in ALT, AST activity in the blood plasma of rats of group IV relative to group III.…”

Section: Resultsmentioning

confidence: 58%

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Features of the influence of S-ethyl-4-aminobenzene thiosulfonate on some biochemical parameters of rat blood under the condition of Cr(VI) intoxication

2023

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Background. The main pathway of Cr(VI) cytotoxicity is activation of oxidative stress in cells of living organisms, resulting in an imbalance of blood biochemical parameters. Our recent studies indicate that S-ethyl-4-aminobenzenethiosulfonate (ETS), which belongs to thiosulfonate compounds, is able to reduce intensity of Cr(VI)-induced oxidative stress in liver tissue of rats. It is known that oxidative stress induced by Cr(VI) causes liver and kidney tissue damage with a subsequent imbalance of blood biochemical parameters. Therefore, the aim of this study was to evaluate the potential ability of ETS to prevent Cr(VI)-induced disorders of some biochemical blood parameters, which are important biomarkers of Cr(VI) intoxication. Materials and Methods. The object of the research was the separate biochemical parameters of the blood of rats with Cr(VI)-induced oxidative stress after prior exposure to ETS. Two experimental groups of male Wistar rats were intoxicated once per day intraperitoneally with K2Cr2O7 dissolved in physiological saline solution for 7 or 14 days. Two other experimental groups were pretreated once per day intragastrically with ETS dissolved in oil before the period of 7 or 14-day K2Cr2O7 intoxication. We measured total protein, creatinine and urea level, as well as determined the activity of aminotransferases in the blood plasma of rats. Results. Intraperitoneal injection of K2Cr2O7 (dissolved in physiological saline solution at a dose of 2.5 mg Cr(VI)/kg body weight) for 7 and 14 days causes a decrease in total protein level and leads to elevation of plasma creatinine level and urea concentration. The activity of blood aminotransferases increases due to Cr(VI) toxicity. The 14-day exposure to ETS (dissolved in oil at a dose 100 mg/kg body weight) prior to the period of Cr(VI) intoxication is characterized by a smaller percentage increase in the level of creatinine, urea and activity of alanine aminotransferase (ALT) in the blood plasma of rats. Conclusion. Cr(VI)-induced toxicity causes an imbalance in biochemical blood parameters. Cr(VI) induces a total protein decrease and leads to an increase in the level of the studied biochemical parameters of blood plasma, which are markers of damage to the liver (aminotransferases) and kidneys (creatinine, urea). In contrast, exposure to ETS for 14 days prior to the period of Cr(VI) intoxication causes percentage decrease in creatinine, urea accumulation and percentage reduction of ALT hyper-activation in the blood of rats. However, the levels of creatinine, urea and ALT activity in this case remained significantly higher than those in the control group. In conclusion, pretreatment with ETS (100 mg/kg) for 2 weeks helps to reduce the level of Cr(VI)-induced disturbances of some blood biochemical parameters, but does not normalize them.

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Section: Resultsmentioning

confidence: 58%

“…Literature sources also indicate that Cr(VI)induced inflammatory processes in the liver and kidneys leads to a decrease in De Ritis ratio due to accumulation of ALT in blood plasma. Experimental data indicate that moderate and severe liver damage is characterized by de Ritis coefficients <1.0 (Ma et al, 2022;Buchko et al, 2021).…”

Section: Resultsmentioning

confidence: 99%

Features of the influence of S-ethyl-4-aminobenzene thiosulfonate on some biochemical parameters of rat blood under the condition of Cr(VI) intoxication

2023

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“…The levels of lipid peroxidation and protein carbonyl group content in mice exposed to hexavalent chromium (Cr(VI)) were increased, and a large number of ROS were produced in the body. At the same time, the activities of SOD, glutathione S-transferase, GSH, total mercaptan (TT), CAT, and cholinesterase were decreased, which induced oxidative stress leading to liver cell damage, causing the increase of aspartate aminotransferase and alanine aminotransferase [ 79 ].…”

Section: Major Toxicity Mechanisms Induced By Mycotoxins and Heavy Me...mentioning

confidence: 99%

Detoxification of Selenium Yeast on Mycotoxins and Heavy Metals: a Review

Sun

Chen

Xiong

et al. 2023

Biol Trace Elem Res

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Mycotoxins are secondary metabolites produced by specific fungi. More than 400 different mycotoxins are known in the world, and the concentration of these toxins in food and feed often exceeds the acceptable limit, thus causing serious harm to animals and human body. At the same time, modern industrial agriculture will also bring a lot of environmental pollution in the development process, including the increase of heavy metal content, and often the clinical symptoms of low/medium level chronic heavy metal poisoning are not obvious, thus delaying the best treatment opportunity. However, the traditional ways of detoxification cannot completely eliminate the adverse effects of these toxins on the body, and sometimes bring some side effects, so it is essential to find a new type of safe antidote. Trace element selenium is among the essential mineral nutrient elements of human and animal bodies, which can effectively remove excessive free radicals and reactive oxygen species in the body, and has the effects of antioxidant, resisting stress, and improving body immunity. Selenium is common in nature in inorganic selenium and organic selenium. In previous studies, it was found that the use of inorganic selenium (sodium selenite) can play a certain protective role against mycotoxins and heavy metal poisoning. However, while it plays the role of antioxidant, it will also have adverse effects on the body. Therefore, it was found in the latest study that selenium yeast could not only replace the protective effect of sodium selenite on mycotoxins and heavy metal poisoning, but also improve the immunity of the body. Selenium yeast is an organic selenium source with high activity and low toxicity, which is produced by selenium relying on the cell protein structure of growing yeast. It not only has high absorption rate, but also can be stored in the body after meeting the physiological needs of the body for selenium, so as to avoid selenium deficiency again in the short term. However, few of these studies can clearly reveal the protective mechanism of yeast selenium. In this paper, the detoxification mechanism of selenium yeast on mycotoxins and heavy metal poisoning was reviewed, which provided some theoretical support for further understanding of the biological function of selenium yeast and its replacement for inorganic selenium. The conclusions suggest that selenium yeast can effectively alleviate the oxidative damage by regulating different signaling pathways, improving the activity of antioxidant enzymes, reversing the content of inflammatory factors, regulating the protein expression of apoptosis-related genes, and reducing the accumulation of mycotoxins and heavy metals in the body.

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“…As Nrf2 has already been reported to regulate HO-1 expression (an antioxidant enzyme), the authors decided to focus their interest on this transcription factor. They demonstrated that the increase in Nrf2 is coordinated with a Cr(VI)-dependent induction of HO-1 via the Akt pathway [128].…”

Section: Nuclear Factor E2-related Factor 2 (Nrf2)mentioning

confidence: 99%

The Ins and Outs of Clusterin: Its Role in Cancer, Eye Diseases and Wound Healing

Gross,

Guérin,

Socol

et al. 2023

IJMS

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Clusterin (CLU) is a glycoprotein originally discovered in 1983 in ram testis fluid. Rapidly observed in other tissues, it was initially given various names based on its function in different tissues. In 1992, it was finally named CLU by consensus. Nearly omnipresent in human tissues, CLU is strongly expressed at fluid–tissue interfaces, including in the eye and in particular the cornea. Recent research has identified different forms of CLU, with the most prominent being a 75–80 kDa heterodimeric protein that is secreted. Another truncated version of CLU (55 kDa) is localized to the nucleus and exerts pro-apoptotic activities. CLU has been reported to be involved in various physiological processes such as sperm maturation, lipid transportation, complement inhibition and chaperone activity. CLU was also reported to exert important functions in tissue remodeling, cell–cell adhesion, cell–substratum interaction, cytoprotection, apoptotic cell death, cell proliferation and migration. Hence, this protein is sparking interest in tissue wound healing. Moreover, CLU gene expression is finely regulated by cytokines, growth factors and stress-inducing agents, leading to abnormally elevated levels of CLU in many states of cellular disturbance, including cancer and neurodegenerative conditions. In the eye, CLU expression has been reported as being severely increased in several pathologies, such as age-related macular degeneration and Fuch’s corneal dystrophy, while it is depleted in others, such as pathologic keratinization. Nevertheless, the precise role of CLU in the development of ocular pathologies has yet to be deciphered. The question of whether CLU expression is influenced by these disorders or contributes to them remains open. In this article, we review the actual knowledge about CLU at both the protein and gene expression level in wound healing, and explore the possibility that CLU is a key factor in cancer and eye diseases. Understanding the expression and regulation of CLU could lead to the development of novel therapeutics for promoting wound healing.

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Clusterin protects against Cr(VI)-induced oxidative stress-associated hepatotoxicity by mediating the Akt-Keap1-Nrf2 signaling pathway

Cited by 9 publications

References 46 publications

Features of the influence of S-ethyl-4-aminobenzene thiosulfonate on some biochemical parameters of rat blood under the condition of Cr(VI) intoxication

Features of the influence of S-ethyl-4-aminobenzene thiosulfonate on some biochemical parameters of rat blood under the condition of Cr(VI) intoxication

Detoxification of Selenium Yeast on Mycotoxins and Heavy Metals: a Review

The Ins and Outs of Clusterin: Its Role in Cancer, Eye Diseases and Wound Healing

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