Melatonin alleviates aluminium chloride-induced immunotoxicity by inhibiting oxidative stress and apoptosis associated with the activation of Nrf2 signaling pathway

Yu, Hongyan; Zhang, Jian; Ji, Qiang; Kobayashi, Yu; Wang, Peiyan; Song, Miao; Cao, Zheng; Zhang, Xueyan; Li, Yanfei

doi:10.1016/j.ecoenv.2019.01.095

Cited by 57 publications

(36 citation statements)

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“…In this study, it was observed that AlCl 3 intoxication significantly downregulated the expression level of the Nrf2 gene in the hepatic and renal tissues as compared with the CON group. These data are in agreement with those of Yu et al [ 38 ] and Xu et al [ 39 ], who found that Al toxicity is associated with Nrf2 deregulation. One of our most interesting results is that the administration of MEL 30 minutes before AlCl 3 upregulated the expression level of the Nrf2 gene in the liver and kidney of rats by more than 100% as compared with the AlCl 3 group.…”

Section: Discussionsupporting

confidence: 94%

The Protective Effects of Melatonin on Aluminum-Induced Hepatotoxicity and Nephrotoxicity in Rats

Othman

Fareid

Hameed

et al. 2020

Oxidative Medicine and Cellular Longevity

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Aluminum (Al) is a ubiquitous element with known toxicity for both humans and animals. Herein, we aimed to investigate the potential role of melatonin (MEL) in hepatotoxicity and nephrotoxicity following aluminum chloride (AlCl3) treatment in rats. Adult male rats were treated with AlCl3 (34 mg/kg bwt) for eight weeks. Exposure to AlCl3 enhanced the serum activities of the liver transaminases (alanine aminotransferase and aspartate aminotransferase) and increased the level of bilirubin, in addition to the serum kidney function markers urea and creatinine. AlCl3 intoxication boosted oxidative stress, as evidenced by increases in the levels of lipid peroxidation (LPO) and nitric oxide (NO) along with simultaneous decreases in the levels of glutathione (GSH), various antioxidant enzymes, and Nrf2 mRNA expression. MEL (5 mg/kg bwt) treatment repressed LPO and NO levels, whereas it augmented GSH content. The activities of the antioxidant enzymes GPx, SOD, CAT, and GR were also restored concomitantly when MEL was administered before AlCl3. MEL also suppressed the apoptotic effect of AlCl3 by enhancing Bcl-2 protein expression in the liver and kidney and decreasing the expression levels of proinflammatory cytokines. Histopathological findings in the liver and kidney tissues confirmed the beneficial effect of MEL against AlCl3 toxicity. These findings indicate that MEL prevents AlCl3 toxicity by enhancing the antioxidant defense system.

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Section: Discussionsupporting

confidence: 94%

The Protective Effects of Melatonin on Aluminum-Induced Hepatotoxicity and Nephrotoxicity in Rats

Othman

Fareid

Hameed

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Oxidative stress, lipid peroxidation Kattab et al, 2010;Exley, 2013;Abd-Elhady et al, 2013;Zhang et al, 2016;Yang et al, 2018;Yu et al, 2019 Pro-inflammatory: organ inflammation in lung, intestine, heart, and testis Fogarty et al, 1998;Verma et al, 2007;Lerner, 2007;Exley, 2013;Taiwo, 2014;de Chambrun et al, 2014;Gherardi et al, 2016;Martinez et al, 2017;Hangouche et al, 2017 Immunosupression: induces lymphocyte apoptosis and dysfunction, inhibits lymphocyte proliferation, causes macrophage dysfunction Nordal and Dahl, 1988;Kammalov et al, 2011;She et al, 2012;Zhu et al, 2014;Zhuang et al, 2016;Xu et al, 2018;Yu et al, 2019 Protein denaturation and transformation Exley et al, 2006;Mujika et al, 2018 Enzymatic stimulation or inhibition Ohsaka and Nomura, 2016 Metabolic impairment: impairs glycolysis and Kreb's cycle; promotes lipid and protein oxidation Xu et al 1990;Mailloux et al, 2006 Genotoxicity: reduced cell proliferation and differentiation, dysneurogenesis Nam et al, 2014 Amyloidogenic and anti-amyloidolytic Sakamoto et al, 2006;Xu et al, 2016 Acts as metalloestrogen, promotes proliferation and migration of breast cancer cells Bakir and Darbre, 2015;Darbre, 2016 Induces teratogenesis causing foetal and neonatal defects Malekshah et al, 2005;Wang et al, 2012;El Mazoudy and Bekhet, 2016 Disrupts mineral metabolism of Fe, P, Ca, Zn, Cu by altering intestinal absorption and cellular uptake…”

Section: Toxic Action or Effect Selected Referencesmentioning

confidence: 99%

“…Iron overload due to Al exposure has been shown to result in increased lipid peroxidation, DNA lesions, and apoptosis induced by reactive oxygen species (Bacon et al, 1983;Oteiza, 1994;Kell, 2009). Apoptosis of erythrocytes (eryptosis), lymphocytes and osteoblasts is also stimulated by Al ions (Niemoeller et al, 2006;Li et al, 2012;Xu et al, 2018;Yang et al, 2018;Yu et al, 2019). The oxidative injury was reported to activate the JNK apoptotic pathway in ostoblasts (Yang et al, 2018).…”

Section: Toxic Action or Effect Selected Referencesmentioning

confidence: 99%

“…The activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH) are affected by Al exposure because of oxidative stress (Oteiza et al, 1993a;Julka and Gill, 1996;Campbell et al, 1999). Abnormal increases in levels of malondealdehyde (MDA) and thiobarbituric acid reactive substances (TBARS) were reported along with decreased levels of antioxidants such as GSH, GPx, SOD, and CAT in tissue homogenates of rats exposed to Al (Anane and Creppy, 2001;Gonzalez et al, 2007;Newairy et al, 2009;Khattab et al, 2010;Bai et al, 2012;Exley, 2013;Abd-Elhady et al, 2013;Zhang et al, 2016;Yu et al, 2019).…”

Section: Toxic Action or Effect Selected Referencesmentioning

confidence: 99%

“…Toxic exposure to Al causes immunotoxicity leading to inhibition of lymphocyte and macrophage functions (Nordal et al, 1988;Zhu et al, 2014a). Immunosuppression arises from oxidative stress which is associated with apoptosis of lymphocytes (Yu et al, 2019) and damage to thymocytes and lymphocytes (Kamalov et al, 2011). Immune functions of splenic B-and T-lymphocytes were inhibited in vitro by reduction of lymphocyte proliferation, cytokine secretion and proportions of CD-3(+) and CD-4(+) lymphocytes .…”

Section: Toxic Action or Effect Selected Referencesmentioning

confidence: 99%

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Aluminium toxicosis: a review of toxic actions and effects

Igbokwe

Igwenagu

Igbokwe

2019

Interdisciplinary Toxicology

257

149

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Aluminium (Al) is frequently accessible to animal and human populations to the extent that intoxications may occur. Intake of Al is by inhalation of aerosols or particles, ingestion of food, water and medicaments, skin contact, vaccination, dialysis and infusions. Toxic actions of Al induce oxidative stress, immunologic alterations, genotoxicity, pro-inflammatory effect, peptide denaturation or transformation, enzymatic dysfunction, metabolic derangement, amyloidogenesis, membrane perturbation, iron dyshomeostasis, apoptosis, necrosis and dysplasia. The pathological conditions associated with Al toxicosis are desquamative interstitial pneumonia, pulmonary alveolar proteinosis, granulomas, granulomatosis and fibrosis, toxic myocarditis, thrombosis and ischemic stroke, granulomatous enteritis, Crohn’s disease, inflammatory bowel diseases, anemia, Alzheimer’s disease, dementia, sclerosis, autism, macrophagic myofasciitis, osteomalacia, oligospermia and infertility, hepatorenal disease, breast cancer and cyst, pancreatitis, pancreatic necrosis and diabetes mellitus. The review provides a broad overview of Al toxicosis as a background for sustained investigations of the toxicology of Al compounds of public health importance.

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Probiotic‐fermented Qushi decoction alleviates reserpine‐induced spleen deficiency syndrome by regulating spleen function and gut microbiota dysbiosis

et al. 2023

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BACKGROUNDSpleen deficiency syndrome (SDS) is associated with elevated inflammatory factors and dysregulation of gastrointestinal motility hormones and intestinal microbiota. Qushi decoction (QD), a traditional formula, has not been reported using modern scientific research methods for changes in its probiotic fermented QD (FQD) composition and its potential mechanisms to alleviate SDS. Therefore, the aim of this study was to investigate the splenic protection of FQD in SDS rats by modulating gastrointestinal motility hormones and intestinal microbiota.RESULTSThe results showed that FQD increased total polysaccharides, total protein, total flavonoids and the other active ingredients compared to QD, effectively improved splenic inflammation and apoptosis in SDS rats, and modulated gastrointestinal motility hormones to alleviate diarrhea and other symptoms. In addition, the dysregulation of the gut microbiota was reversed by increasing the levels of Bifidobacterium and decreasing the levels of Escherichia–Shigella and Proteobacteria, which may be related to the regulation of bacterial metabolites to alleviate SDS.CONCLUSIONThese results suggest that FQD is an effective formula for improving SDS. Our findings show that FQD beneficial to the implications for the treatment of SDS. © 2023 Society of Chemical Industry.

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Melatonin alleviates aluminium chloride-induced immunotoxicity by inhibiting oxidative stress and apoptosis associated with the activation of Nrf2 signaling pathway

Cited by 57 publications

References 57 publications

The Protective Effects of Melatonin on Aluminum-Induced Hepatotoxicity and Nephrotoxicity in Rats

The Protective Effects of Melatonin on Aluminum-Induced Hepatotoxicity and Nephrotoxicity in Rats

Aluminium toxicosis: a review of toxic actions and effects

Probiotic‐fermented Qushi decoction alleviates reserpine‐induced spleen deficiency syndrome by regulating spleen function and gut microbiota dysbiosis

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