Streptozotocin (STZ)-Induced Diabetes Affects Tissue Trace Element Content in Rats in a Dose-Dependent Manner

Karganov, M. Yu.; Алчинова, И. Б.; Tinkov, Alexey A.; Medvedeva, Yu. S.; Lebedeva, M. A.; Ajsuvakova, Olga P.; Polyakova, M. V.; Skalnaya, Margarita G.; Burtseva, T. I.; Нотова, С. В.; Хлебникова, Н. Н.; Skalny, Anatoly V.

doi:10.1007/s12011-020-02090-2

Cited by 13 publications

(6 citation statements)

References 37 publications

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“…Thus, the higher food intake and increased DMT1 expression found in H tissue could be associated with the increase in mineral serum and tissue values. These results are consistent with other previously published data [ 42 ]. Regarding Mn, the H and HV groups increased net retention.…”

Section: Discussionsupporting

confidence: 94%

“…Thus, Mn increased in serum and the liver, suggesting a positive correlation between intake and the Mn content in these tissues ( Table 3 ). Karganov et al described how Mn was deposited in the liver (without changes in other tissues, such as serum or spleen) in diabetic rats [ 42 ]. Furthermore, V supplementation enhanced Mn uptake in HepG2 cells [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

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Effect of Bis(maltolato)oxovanadium(IV) on Zinc, Copper, and Manganese Homeostasis and DMT1 mRNA Expression in Streptozotocin-Induced Hyperglycemic Rats

Sánchez-González

Moreno

Aranda

et al. 2022

Biology

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Our aim was to examine whether vanadium (IV) corrects alterations in zinc, copper and manganese homeostasis, observed in streptozotocin-induced hyperglycemic rats, and whether such changes are related to divalent metal transporter 1 (DMT1) mRNA expression, and antioxidant and proinflammatory parameters. Four groups of Wistar rats were examined: control; hyperglycemic (H); hyperglycemic treated with 1 mg V/day (HV); and hyperglycemic treated with 3 mg V/day (HVH). Vanadium was supplied in drinking water as bis(maltolato)oxovanadium(IV) for five weeks. Zinc, copper and manganese were measured in food, excreta, serum and tissues. DMT1 mRNA expression was quantified in the liver. Hyperglycemic rats showed increased Zn and Cu absorption and content in the liver, serum, kidneys and femurs; DMT1 expression also increased (p < 0.05 in all cases). HV rats showed no changes compared to H rats other than decreased DMT1 expression (p < 0.05). In the HVH group, decreased absorption and tissular content of studied elements (p < 0.05 in all cases) and DMT1 expression compared to H (p < 0.05) were observed. Liver zinc, copper and manganese content correlated positively with glutathione peroxidase activity and negatively with catalase activity (p < 0.05 in both cases). In conclusion, treatment with 3 mg V/d reverted the alterations in zinc and copper homeostasis caused by hyperglycemia, possibly facilitated by decreased DMT1 expression.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Effect of Bis(maltolato)oxovanadium(IV) on Zinc, Copper, and Manganese Homeostasis and DMT1 mRNA Expression in Streptozotocin-Induced Hyperglycemic Rats

Sánchez-González

Moreno

Aranda

et al. 2022

Biology

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“…However, the present limited study showed that copper aggravated diabetic cardiomyopathy mainly by increasing the extracellular matrix by activating TGF-beta/Smad signaling or oxidative stress [ 3 ]. It remaines elusive how copper directly influences the function of cardiomyocytes in diabetic cardiomyopathy [ 10 , 14 , 15 ], and there is no relevant study on the underpinning mechanism of copper overload-induced cuproptosis in diabetic cardiomyopathy.…”

Section: Discussionmentioning

confidence: 99%

“…This experimental evidence indicated that copper homeostasis might play an important role in maintaining cardiac function. However, how copper ions influence cardiac function in diabetic cardiomyopathy remains elusive [ 10 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

ATF3/SPI1/SLC31A1 Signaling Promotes Cuproptosis Induced by Advanced Glycosylation End Products in Diabetic Myocardial Injury

Huo

Wang

Shi

et al. 2023

IJMS

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Cuproptosis resulting from copper (Cu) overload has not yet been investigated in diabetic cardiomyopathy (DCM). Advanced glycosylation end products (AGEs) induced by persistent hyperglycemia play an essential role in cardiotoxicity. To clarify whether cuproptosis was involved in AGEs-induced cardiotoxicity, we analyzed the toxicity of AGEs and copper in AC16 cardiomyocytes and in STZ-induced or db/db-diabetic mouse models. The results showed that copper ionophore elesclomol induced cuproptosis in cardiomyocytes. It was only rescued by copper chelator tetrathiomolybdate rather than by other cell death inhibitors. Intriguingly, AGEs triggered cardiomyocyte death and aggravated it when incubated with CuCl2 or elesclomol–CuCl2. Moreover, AGEs increased intracellular copper accumulation and exhibited features of cuproptosis, including loss of Fe–S cluster proteins (FDX1, LIAS, NDUFS8 and ACO2) and decreased lipoylation of DLAT and DLST. These effects were accompanied by decreased mitochondrial oxidative respiration, including downregulated mitochondrial respiratory chain complex, decreased ATP production and suppressed mitochondrial complex I and III activity. Additionally, AGEs promoted the upregulation of copper importer SLC31A1. We predicted that ATF3 and/or SPI1 might be transcriptional factors of SLC31A1 by online databases and validated that by ATF3/SPI1 overexpression. In diabetic mice, copper and AGEs increases in the blood and heart were observed and accompanied by cardiac dysfunction. The protein and mRNA profile changes in diabetic hearts were consistent with cuproptosis. Our findings showed, for the first time, that excessive AGEs and copper in diabetes upregulated ATF3/SPI1/SLC31A1 signaling, thereby disturbing copper homeostasis and promoting cuproptosis. Collectively, the novel mechanism might be an alternative potential therapeutic target for DCM.

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“…Studies indicated a link between the disorders included in the metabolic syndrome and the status of trace elements. ese are basically focused on diabetes, in humans [15,16] and animals [17], obesity, in humans [18][19][20] and animals [21], and those who enclose dyslipidemia, delimited to only one or not many trace elements such as copper, magnesium, and selenium [2,[22][23][24]. Regarding the interrelationship of quercetin, trace elements, and metabolic syndrome, studies are scarce and also quite limited to diabetes [10] and obesity [21].…”

Section: Introductionmentioning

confidence: 99%

Quercetin Beneficial Role in the Homeostatic Variation of Certain Trace Elements in Dyslipidemic Mice

Муселин

Cristina

Dumitrescu

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Quercetin’s role in the homeostasis of certain trace elements in dyslipidemia induced in mice was assessed. Methods. Forty BALB/c mice were allocated into 4 groups as follows: control; HFD, received fat diet; HFD + Q group, received HFD +500 mg/L quercetin; and blank control (Q)—normal food + 500 mg/L quercetin in drinking water. Results. By analyzing the values of total proteins, albumins, cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, and the levels of several trace elements in blood and organs, we perceived a statistically significant increase ( ∗ ∗ , p < 0.01 ) of TP, ALB, TC, TGE, and LDL-c. A nonsignificant decrease was ascertained to HDL-c value in the HFD and quercetin groups ( p > 0.05 ). In the HFD group, all analyzed elements in the kidney and spleen increased, also Cu, Li, Mg, Mn, Pb, and of B, Ba, Cr, Cd, Cu, Fe, Li, Mn, Ni, Pb, and Zn in the heart increased, but furthermore, Ag, B, Ba, Cd, Cr, Fe, Ni, and Zn in blood, Ag and Zn in the liver, and Cd in the spleen decreased. In the HFD group who received quercetin, elements (except B) were decreased in kidney and liver, also increased Ag, Ba, Cr, Fe, Li, Ni, Zn in blood, but similarly, Ag, B, Ba, Cd, Cu, Mn, and Pb declined in the spleen and heart. Conclusions. Results proved the quercetin beneficial role.

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Streptozotocin (STZ)-Induced Diabetes Affects Tissue Trace Element Content in Rats in a Dose-Dependent Manner

Cited by 13 publications

References 37 publications

Effect of Bis(maltolato)oxovanadium(IV) on Zinc, Copper, and Manganese Homeostasis and DMT1 mRNA Expression in Streptozotocin-Induced Hyperglycemic Rats

Effect of Bis(maltolato)oxovanadium(IV) on Zinc, Copper, and Manganese Homeostasis and DMT1 mRNA Expression in Streptozotocin-Induced Hyperglycemic Rats

ATF3/SPI1/SLC31A1 Signaling Promotes Cuproptosis Induced by Advanced Glycosylation End Products in Diabetic Myocardial Injury

Quercetin Beneficial Role in the Homeostatic Variation of Certain Trace Elements in Dyslipidemic Mice

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