Abstract
The beneficial effect of curcumin (CU) on dietary AGEs (dAGEs) involves blocking the overexpression of proinflammatory cytokine genes in the heart and kidney tissues of experimental mice. The animals were divided into six groups (n = 6/group) and were fed a heat-exposed diet (dAGEs) with or without CU for 6 months. Their blood pressure (BP) was monitored by a computerized tail-cuff BP-monitoring system. The mRNA and protein expression levels of proinflammatory genes were analyzed by RT-PCR and western blot, respectively. A marked increase in BP (108 ± 12 mmHg vs 149 ± 15 mmHg) accompanied by a marked increase in the heart and kidney weight ratio was noted in the dAGE-fed mice. Furthermore, the plasma levels of proinflammatory molecules (C5a, ICAM-1, IL-6, MCP-1, IL-1β and TNF-α) were found to be elevated (3-fold) in dAGE-fed mice. mRNA expression analysis revealed a significant increase in the expression levels of inflammatory markers (Cox-2, iNOS, and NF-κB) (3-fold) in cardiac and renal tissues of dAGE-fed mice. Moreover, increased expression of RAGE and downregulation of AGER-1 (p < 0.001) were noticed in the heart and kidney tissues of dAGE-fed mice. Interestingly, the dAGE-induced proinflammatory genes and inflammatory responses were neutralized upon cotreatment with CU. The present study demonstrates that dietary supplementation with CU has the ability to neutralize dAGE-induced adverse effects and alleviate proinflammatory gene expression in the heart and kidney tissues of experimental mice.
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Acknowledgements
Dr. EV acknowledges the Department of Biotechnology (DBT), India, for financial support in the form of a major research project (D.O.BT/PR6259/FNS/20/587/2012). BS thanks the Department of Biotechnology (DBT) and the Indian Council of Medical Research (ICMR) for research fellowships. KK thanks the Indian Council of Medical Research (ICMR) for the senior research fellowship (SRF).
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12012_2021_9697_MOESM1_ESM.tif
Supplementary Fig. 1 (A-C) shows the texture, browning index and N ε-CML levels in the basal and heat-exposed AIN-76 diets (72°C and 90°C). Values are expressed as the mean ± SEM (n = 3). **p < 0.05, AIN-76 basal diet vs AIN-76 heat-exposed diet 72°C, *** p<0.01, AIN-76 basal diet vs AIN-76 heat-exposed diet 90°C. Supplementary file1 (TIF 32267 KB)
12012_2021_9697_MOESM2_ESM.tif
Supplementary Fig. 2 (A-D) shows the mRNA expression levels of hypertrophic marker genes in the heart and kidney tissue of the control and experimental groups of mice. BD - basal diet, HED – heat-exposed diet, N ε-CML – N ε-CML mixed basal diet, HED + CU - HED diet cotreated with curcumin, N ε-CML + CU – N ε-CML mixed diet cotreated with curcumin and BD+CU – basal diet alone treated with curcumin. The data are represented as box and whisker plots; the box represents the 1st and 3rd quartiles, and the heavy bar represents the median value. a p < 0.001 and b p<0.01, BD-fed mice vs HED- and N ε-CML mixed basal diet-fed mice, respectively; a*p<0.05, HED vs HED + CU cotreated mice, b*p<0.05, N ε-CML vs N ε-CML +CU cotreated mice; ns - Nonsignificant changes in BD + CU-alone treated vs control mice. Supplementary file2 (TIF 22119 KB)
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Sowndhar Rajan, B., Krishnan, K. & Vellaichamy, E. Diet-Derived Advanced Glycation End Products (dAGEs) Induce Proinflammatory Cytokine Expression in Cardiac and Renal Tissues of Experimental Mice: Protective Effect of Curcumin. Cardiovasc Toxicol 22, 35–51 (2022). https://doi.org/10.1007/s12012-021-09697-4
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DOI: https://doi.org/10.1007/s12012-021-09697-4