Prenatal arsenic exposure induces immunometabolic alteration and renal injury in rats
Arsenic (As) exposure is progressively associated with chronic kidney disease (CKD), a leading public health concern present worldwide. The adverse effect of As exposure on the kidneys of people living in As endemic areas have not been extensively studied. Furthermore, the impact of only prenatal ex...
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2022.1045692/full |
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| author | Radha Dutt Singh Radha Dutt Singh Ratnakar Tiwari Vineeta Sharma Vineeta Sharma Hafizurrahman Khan Hafizurrahman Khan Siddhartha Gangopadhyay Siddhartha Gangopadhyay Sukhveer Singh Sukhveer Singh Kavita Koshta Kavita Koshta Shagun Shukla Nidhi Arjaria Kapil Mandrah Kapil Mandrah Pankaj Ramji Jagdale Satyakam Patnaik Satyakam Patnaik Somendu Kumar Roy Somendu Kumar Roy Dhirendra Singh Ashok Kumar Giri Vikas Srivastava Vikas Srivastava |
| author_facet | Radha Dutt Singh Radha Dutt Singh Ratnakar Tiwari Vineeta Sharma Vineeta Sharma Hafizurrahman Khan Hafizurrahman Khan Siddhartha Gangopadhyay Siddhartha Gangopadhyay Sukhveer Singh Sukhveer Singh Kavita Koshta Kavita Koshta Shagun Shukla Nidhi Arjaria Kapil Mandrah Kapil Mandrah Pankaj Ramji Jagdale Satyakam Patnaik Satyakam Patnaik Somendu Kumar Roy Somendu Kumar Roy Dhirendra Singh Ashok Kumar Giri Vikas Srivastava Vikas Srivastava |
| author_sort | Radha Dutt Singh |
| collection | DOAJ |
| description | Arsenic (As) exposure is progressively associated with chronic kidney disease (CKD), a leading public health concern present worldwide. The adverse effect of As exposure on the kidneys of people living in As endemic areas have not been extensively studied. Furthermore, the impact of only prenatal exposure to As on the progression of CKD also has not been fully characterized. In the present study, we examined the effect of prenatal exposure to low doses of As 0.04 and 0.4 mg/kg body weight (0.04 and 0.4 ppm, respectively) on the progression of CKD in male offspring using a Wistar rat model. Interestingly, only prenatal As exposure was sufficient to elevate the expression of profibrotic (TGF-β1) and proinflammatory (IL-1α, MIP-2α, RANTES, and TNF-α) cytokines at 2-day, 12- and 38-week time points in the exposed progeny. Further, alteration in adipogenic factors (ghrelin, leptin, and glucagon) was also observed in 12- and 38-week old male offspring prenatally exposed to As. An altered level of these factors coincides with impaired glucose metabolism and homeostasis accompanied by progressive kidney damage. We observed a significant increase in the deposition of extracellular matrix components and glomerular and tubular damage in the kidneys of 38-week-old male offspring prenatally exposed to As. Furthermore, the overexpression of TGF-β1 in kidneys corresponds with hypermethylation of the TGF-β1 gene-body, indicating a possible involvement of prenatal As exposure-driven epigenetic modulations of TGF-β1 expression. Our study provides evidence that prenatal As exposure to males can adversely affect the immunometabolism of offspring which can promote kidney damage later in life. |
| first_indexed | 2024-04-10T23:44:34Z |
| format | Article |
| id | doaj.art-45a5d27a5b264731ad9fa8aa1eb3dd0c |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-04-10T23:44:34Z |
| publishDate | 2023-01-01 |
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| series | Frontiers in Medicine |
| spelling | doaj.art-45a5d27a5b264731ad9fa8aa1eb3dd0c2023-01-11T05:16:16ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2023-01-01910.3389/fmed.2022.10456921045692Prenatal arsenic exposure induces immunometabolic alteration and renal injury in ratsRadha Dutt Singh0Radha Dutt Singh1Ratnakar Tiwari2Vineeta Sharma3Vineeta Sharma4Hafizurrahman Khan5Hafizurrahman Khan6Siddhartha Gangopadhyay7Siddhartha Gangopadhyay8Sukhveer Singh9Sukhveer Singh10Kavita Koshta11Kavita Koshta12Shagun Shukla13Nidhi Arjaria14Kapil Mandrah15Kapil Mandrah16Pankaj Ramji Jagdale17Satyakam Patnaik18Satyakam Patnaik19Somendu Kumar Roy20Somendu Kumar Roy21Dhirendra Singh22Ashok Kumar Giri23Vikas Srivastava24Vikas Srivastava25Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, IndiaAcademy of Scientific and Innovative Research, New Delhi, IndiaSystems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, IndiaSystems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, IndiaDepartment of Biotechnology, Faculty of Engineering and Technology, Manav Rachna International Institute of Research and Studies, Faridabad, Haryana, IndiaSystems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, IndiaAcademy of Scientific and Innovative Research, New Delhi, IndiaSystems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, IndiaAcademy of Scientific and Innovative Research, New Delhi, IndiaSystems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, IndiaAcademy of Scientific and Innovative Research, New Delhi, IndiaSystems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, IndiaAcademy of Scientific and Innovative Research, New Delhi, IndiaSystems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, IndiaAdvanced Imaging Facility, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, IndiaAcademy of Scientific and Innovative Research, New Delhi, IndiaRegulatory Toxicology Group, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, IndiaRegulatory Toxicology Group, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, IndiaAcademy of Scientific and Innovative Research, New Delhi, IndiaRegulatory Toxicology Group, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, IndiaAcademy of Scientific and Innovative Research, New Delhi, IndiaRegulatory Toxicology Group, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, IndiaRegulatory Toxicology Group, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, IndiaMolecular and Human Genetics Division, CSIR-Indian Institute of Chemical Biology, Kolkata, West Bengal, IndiaSystems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, IndiaAcademy of Scientific and Innovative Research, New Delhi, IndiaArsenic (As) exposure is progressively associated with chronic kidney disease (CKD), a leading public health concern present worldwide. The adverse effect of As exposure on the kidneys of people living in As endemic areas have not been extensively studied. Furthermore, the impact of only prenatal exposure to As on the progression of CKD also has not been fully characterized. In the present study, we examined the effect of prenatal exposure to low doses of As 0.04 and 0.4 mg/kg body weight (0.04 and 0.4 ppm, respectively) on the progression of CKD in male offspring using a Wistar rat model. Interestingly, only prenatal As exposure was sufficient to elevate the expression of profibrotic (TGF-β1) and proinflammatory (IL-1α, MIP-2α, RANTES, and TNF-α) cytokines at 2-day, 12- and 38-week time points in the exposed progeny. Further, alteration in adipogenic factors (ghrelin, leptin, and glucagon) was also observed in 12- and 38-week old male offspring prenatally exposed to As. An altered level of these factors coincides with impaired glucose metabolism and homeostasis accompanied by progressive kidney damage. We observed a significant increase in the deposition of extracellular matrix components and glomerular and tubular damage in the kidneys of 38-week-old male offspring prenatally exposed to As. Furthermore, the overexpression of TGF-β1 in kidneys corresponds with hypermethylation of the TGF-β1 gene-body, indicating a possible involvement of prenatal As exposure-driven epigenetic modulations of TGF-β1 expression. Our study provides evidence that prenatal As exposure to males can adversely affect the immunometabolism of offspring which can promote kidney damage later in life.https://www.frontiersin.org/articles/10.3389/fmed.2022.1045692/fullprenatalimmunometabolismmetabolic impairmenthypermethylationnephropathy and chronic kidney disease |
| spellingShingle | Radha Dutt Singh Radha Dutt Singh Ratnakar Tiwari Vineeta Sharma Vineeta Sharma Hafizurrahman Khan Hafizurrahman Khan Siddhartha Gangopadhyay Siddhartha Gangopadhyay Sukhveer Singh Sukhveer Singh Kavita Koshta Kavita Koshta Shagun Shukla Nidhi Arjaria Kapil Mandrah Kapil Mandrah Pankaj Ramji Jagdale Satyakam Patnaik Satyakam Patnaik Somendu Kumar Roy Somendu Kumar Roy Dhirendra Singh Ashok Kumar Giri Vikas Srivastava Vikas Srivastava Prenatal arsenic exposure induces immunometabolic alteration and renal injury in rats Frontiers in Medicine prenatal immunometabolism metabolic impairment hypermethylation nephropathy and chronic kidney disease |
| title | Prenatal arsenic exposure induces immunometabolic alteration and renal injury in rats |
| title_full | Prenatal arsenic exposure induces immunometabolic alteration and renal injury in rats |
| title_fullStr | Prenatal arsenic exposure induces immunometabolic alteration and renal injury in rats |
| title_full_unstemmed | Prenatal arsenic exposure induces immunometabolic alteration and renal injury in rats |
| title_short | Prenatal arsenic exposure induces immunometabolic alteration and renal injury in rats |
| title_sort | prenatal arsenic exposure induces immunometabolic alteration and renal injury in rats |
| topic | prenatal immunometabolism metabolic impairment hypermethylation nephropathy and chronic kidney disease |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2022.1045692/full |
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