镉可通过影响大鼠肠道菌群致大脑皮质氧化应激

doi:10.11843/j.issn.0366-6964.2025.07.045

Abstract

Abstract:

To explore whether cadmium can induce oxidative stress in the cerebral cortices by affecting the intestinal flora of rats, twenty 21-day-old female Wistar rats were randomly divided into control group (Con group) and cadmium group (Cd group) and pre-fed for 1 week. The rats in the Cd group were given cadmium chloride (CdCl₂) at a dose of 10 mg per kg of body weight by intragastric administration every day, while the rats in the Con group were given double distilled water at the same dose by intragastric administration (i.g.) every day. After 4 weeks, the fresh feces of the rats were collected to make fecal bacteria suspension, and then the cerebral cortices of the rats were dissected. In addition, twenty 21-day-old female Wistar rats were given mixed antibiotics for 1 week to construct a pseudo-aseptic model, and were randomly divided into fecal microbiota transplantation control group (FMTCon group) and fecal microbiota transplantation cadmium group (FMTCd group). The rats in the FMTCon group were given the above-mentioned fecal suspension of the rats in the Con group at a dose of 10 mL per kg of body weight by i.g. every day, and the rats in the FMTCd group were given the above-mentioned fecal suspension of the rats in the Cd group at a dose of 10 mL per kg of body weight by i.g. every day. After 4 weeks of treatment, the cerebral cortices of rats were dissected and collected. The contents of malondialdehyde (MDA) and reduced glutathione (GSH), the activities of total superoxide dismutase (T-SOD) and catalase (CAT) and the total antioxidant capacity (T-AOC) were detected by colorimetry. The protein expressions of nuclear factor E2-related factor 2 (Nrf2) and NADH quinone dehydrogenase 1 (NQO-1) were detected by Western blot. The results showed that compared with the Con group, the contents of MDA were significantly increased (P < 0.05), the contents of GSH, the activities of CAT and T-SOD, and the protein expressions of T-AOC, Nrf2 and NQO-1 were significantly decreased (P < 0.05) in the cerebral cortices of Cd group rats. Compared with FMTCon, the contents of MDA were significantly increased (P < 0.05), the content of GSH, the activities of CAT, the protein expressions of Nrf2 and NQO-1 were significantly decreased (P < 0.05), and the activities of T-SOD and T-AOC were decreased, but there were no significant difference (P>0.05) in the cerebral cortices of FMTCd group rats. The results suggested that cadmium could induce oxidative stress in the cerebral cortices by affecting the intestinal flora of rats.

Key words: cadmium, intestinal flora, rat, cerebral cortex, oxidative stress

CLC Number:

S856.9

LU Le, LUO Xianzu, HUANG Xinyu, ZOU Hui, GU Jianhong, LIU Xuezhong, BIAN Jianchun, LIU Zongping, YUAN Yan. Cadmium Can Induce Oxidative Stress in the Cerebral Cortices by Affecting the Intestinal Flora of Rats[J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(7): 3540-3547.

Figures/Tables 4

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References 37

1	PEANA M , PELUCELLI A , CHASAPIS C T , et al. Biological effects of human exposure to environmental cadmium[J]. Biomolecules, 2022, 13 (1): 36.
2	WANG B , DU Y L . Cadmium and its neurotoxic effects[J]. Oxid Med Cell Longev, 2013, 2013, 898034.
3	郭宝福, 刘祥萍, 王艳莉, 等. 芦蒿中重金属铅、镉污染现状及溯源分析[J]. 东南大学学报: 医学版, 2021, 40 (6): 826- 830.
	GUO B F , LIU X P , WANG Y L , et al. Pollution status and traceability analysis of heavy metals lead and cadmium in artemisia selengensis[J]. Journal of Southeast University: Medical Science Edition, 2021, 40 (6): 826- 830.
4	LAMTAI M , AZIRAR S , ZGHARI O , et al. Melatonin ameliorates cadmium-induced affective and cognitive impairments and hippocampal oxidative stress in rat[J]. Biol Trace Elem Res, 2021, 199 (4): 1445- 1455.
5	PARI L , MURUGAVEL P . Diallyl tetrasulfide improves cadmium induced alterations of acetylcholinesterase, ATPases and oxidative stress in brain of rats[J]. Toxicology, 2007, 234 (1-2): 44- 50.
6	JIMÉNEZ-ORTEGA V , CANO-BARQUILLA P , SCACCHI P A , et al. Cadmium-induced disruption in 24-h expression of clock and redox enzyme genes in rat medial basal hypothalamus: prevention by melatonin[J]. Front Neurol, 2011, 2, 13.
7	KENSLER T W , WAKABAYASHI N , BISWAL S . Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway[J]. Annu Rev Pharmacol Toxicol, 2007, 47, 89- 116.
8	BAIRD L , DINKOVA-KOSTOVA A T . The cytoprotective role of the Keap1-Nrf2 pathway[J]. Arch Toxicol, 2011, 85 (4): 241- 272.
9	TAGUCHI K , MOTOHASHI H , YAMAMOTO M . Molecular mechanisms of the Keap1-Nrf2 pathway in stress response and cancer evolution[J]. Genes Cells, 2011, 16 (2): 123- 140.
10	陈嘉兴, 吴礼康, 田亚锋, 等. 转录因子NF-E2相关因子2信号通路在金属污染物毒理学作用中的机制及其研究进展[J]. 环境与健康杂志, 2017, 34 (5): 466- 470.
	CHEN J X , WU L K , TIAN Y F , et al. Role of transcription factor NF-E2-related factor 2 signaling pathway in toxicity of metal pollutants: a review of recent studies[J]. Journal of Environment and Health, 2017, 34 (5): 466- 470.
11	GENCHI G , SINICROPI M S , LAURIA G , et al. The effects of cadmium toxicity[J]. Int J Environ Res Public Health, 2020, 17 (11): 3782.
12	LI X J , BREJNROD A D , ERNST M , et al. Heavy metal exposure causes changes in the metabolic health-associated gut microbiome and metabolites[J]. Environ Int, 2019, 126, 454- 467.
13	HE X W , QI Z D , HOU H , et al. Structural and functional alterations of gut microbiome in mice induced by chronic cadmium exposure[J]. Chemosphere, 2020, 246, 125747.
14	HEIJTZ R D , WANG S G , ANUAR F , et al. Normal gut microbiota modulates brain development and behavior[J]. Proc Natl Acad Sci U S A, 2011, 108 (7): 3047- 3052.
15	COBLEY J N , FIORELLO M L , BAILEY D M . 13 reasons why the brain is susceptible to oxidative stress[J]. Redox Biol, 2018, 15, 490- 503.
16	王光亮. 镉暴露对DSS诱导小鼠结肠炎的促进作用及机制研究[D]. 天津: 天津科技大学, 2021.
	WANG G L. The promoting effect and mechanism of cadmium exposure on DSS-induced colitis in mice[D]. Tianjin: Tianjin University of Science and Technology, 2021. (in Chinese)
17	OLSON C A , VUONG H E , YANO J M , et al. The gut microbiota mediates the anti-seizure effects of the ketogenic diet[J]. Cell, 2018, 174 (2): 497.
18	REIKVAM D H , EROFEEV A , SANDVIK A , et al. Depletion of murine intestinal microbiota: effects on gut mucosa and epithelial gene expression[J]. PLoS One, 2011, 6 (3): e17996.
19	郑文璐, 李莉, 王昆, 等. 肠道微生物群移植和益生菌补充剂对妊娠期糖尿病大鼠抗炎症、抗氧化及妊娠结局的影响[J]. 中国微生态学杂志, 2024, 36 (6): 657-664, 670.
	ZHENG W L , LI L , WANG K , et al. Effects of fecal microbiota transplantation and probiotic supplementation on anti-inflammation, antioxidation and pregnancy outcome in gestational diabetic rats[J]. Chinese Journal of Microecology, 2024, 36 (6): 657-664, 670.
20	TSENTSEVITSKY A N , ZAKYRJANOVA G F , PETROV A M . Cadmium desynchronizes neurotransmitter release in the neuromuscular junction: key role of ROS[J]. Free Radic Biol Med, 2020, 155, 19- 28.
21	TSIKAS D . Assessment of lipid peroxidation by measuring malondialdehyde (MDA) and relatives in biological samples: analytical and biological challenges[J]. Anal Biochem, 2017, 524, 13- 30.
22	BECKMAN J S , KOPPENOL W H . Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly[J]. Am J Physiol, 1996, 271 (5 Pt 1): C1424- C1437.
23	任娜, 张暄梓, 郝小燕, 等. 核黄素对羔羊生长性能、氮代谢及血清生化和抗氧化指标的影响[J]. 动物营养学报, 2023, 35 (5): 3183- 3189.
	REN N , ZHANG X Z , HAO X Y , et al. Effects of riboflavin on growth performance, nitrogen metabolism and serum biochemical and antioxidant indices of lambs[J]. Chinese Journal of Animal Nutrition, 2023, 35 (5): 3183- 3189.
24	ZHANG W H , XU W C , WEN S Q , et al. Puerarin alleviates cadmium-induced rat neurocyte injury by alleviating Nrf2-mediated oxidative stress and inhibiting mitochondrial unfolded protein response[J]. Ecotoxicol Environ Saf, 2022, 247, 114239.
25	TANG K K , LIU X Y , WANG Z Y , et al. Trehalose alleviates cadmium-induced brain damage by ameliorating oxidative stress, autophagy inhibition, and apoptosis[J]. Metallomics, 2019, 11 (12): 2043- 2051.
26	YU J J , MENG J H , QIN Z W , et al. Dysbiosis of gut microbiota inhibits NMNAT2 to promote neurobehavioral deficits and oxidative stress response in the 6-OHDA-lesioned rat model of Parkinson's disease[J]. J Neuroinflammation, 2023, 20 (1): 117.
27	DING Y X , LI X , LIU Y T , et al. Protection mechanisms underlying oral administration of chlorogenic acid against cadmium-induced hepatorenal injury related to regulating intestinal flora balance[J]. J Agric Food Chem, 2021, 69 (5): 1675- 1683.
28	BOKOLIYA S C , DORSETT Y , PANIER H , et al. Procedures for fecal microbiota transplantation in murine microbiome studies[J]. Front Cell Infect Microbiol, 2021, 11, 711055.
29	XIAO W P , SU J B , GAO X J , et al. The microbiota-gut-brain axis participates in chronic cerebral hypoperfusion by disrupting the metabolism of short-chain fatty acids[J]. Microbiome, 2022, 10 (1): 62.
30	IBRAHIM F , HALTTUNEN T , TAHVONEN R , et al. Probiotic bacteria as potential detoxification tools: assessing their heavy metal binding isotherms[J]. Can J Microbiol, 2006, 52 (9): 877- 885.
31	NIES D H . Efflux-mediated heavy metal resistance in prokaryotes[J]. FEMS Microbiol Rev, 2003, 27 (2-3): 313- 339.
32	ALKHALIFAH E A R , ALOBAID A A , ALMAJED M A , et al. Cardamom extract alleviates the oxidative stress, inflammation and apoptosis induced during acetaminophen-induced hepatic toxicity via modulating Nrf2/HO-1/NQO-1 pathway[J]. Curr Issues Mol Biol, 2022, 44 (11): 5390- 5404.
33	HE J , ZHOU D , YAN B . Eriocitrin alleviates oxidative stress and inflammatory response in cerebral ischemia reperfusion rats by regulating phosphorylation levels of Nrf2/NQO-1/HO-1/NF-κB p65 proteins[J]. Ann Transl Med, 2020, 8 (12): 757.
34	SALEH H M , EL-SAYED Y S , NASER S M , et al. Efficacy of α-lipoic acid against cadmium toxicity on metal ion and oxidative imbalance, and expression of metallothionein and antioxidant genes in rabbit brain[J]. Environ Sci Pollut Res Int, 2017, 24 (31): 24593- 24601.
35	ALMEER R S , ALBASHER G I , ALARIFI S , et al. Royal jelly attenuates cadmium-induced nephrotoxicity in male mice[J]. Sci Rep, 2019, 9 (1): 5825.
36	ALHARTHY S A , ZUGHAIBI T A , VIJ P , et al. Mirtazapine attenuated cadmium-induced neuronal intoxication by regulating Nrf2 and NF-κB/TLR4 signals[J]. Toxicol Mech Methods, 2023, 33 (8): 675- 687.
37	SAEEDI B J , LIU K H , OWENS J A , et al. Gut-resident Lactobacilli activate hepatic Nrf2 and protect against oxidative liver injury[J]. Cell Metab, 2020, 31 (5): 956- 968.

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Cadmium Can Induce Oxidative Stress in the Cerebral Cortices by Affecting the Intestinal Flora of Rats

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