PMID- 34124373 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220423 IS - 2391-5412 (Electronic) IS - 2391-5412 (Linking) VI - 16 IP - 1 DP - 2021 TI - Hyperhomocysteinemia exacerbates ischemia-reperfusion injury-induced acute kidney injury by mediating oxidative stress, DNA damage, JNK pathway, and apoptosis. PG - 537-543 LID - 10.1515/biol-2021-0054 [doi] AB - BACKGROUND: Hyperhomocysteinemia (HHcy) plays an important role in the progression of many kidney diseases; however, the relationship between HHcy and ischemia-reperfusion injury (IRI)-induced acute kidney injury (IRI-induced AKI) is far from clear. In this study, we try to investigate the effect and possible mechanisms of HHcy on IRI-induced AKI. METHODS: Twenty C57/BL6 mice were reared with a regular diet or high methionine diet for 2 weeks (to generate HHcy mice); after that, mice were subgrouped to receive sham operation or ischemia-reperfusion surgery. Twenty four hour after reperfusion, serum creatinine, blood urea nitrogen, and Malondialdehyde (MDA) were measured. H&E staining for tubular injury, western blot for gammaH2AX, JNK, p-JNK, and cleaved caspase 3, and TUNEL assay for tubular cell apoptosis were also performed. RESULTS: Our results showed that HHcy did not influence the renal function and histological structure, as well as the levels of MDA, gammaH2AX, JNK, p-JNK, and tubular cell apoptosis in control mice. However, in IRI-induced AKI mice, HHcy caused severer renal dysfunction and tubular injury, higher levels of oxidative stress, DNA damage, JNK pathway activation, and tubular cell apoptosis. CONCLUSION: Our results demonstrated that HHcy could exacerbate IRI-induced AKI, which may be achieved through promoting oxidative stress, DNA damage, JNK pathway activation, and consequent apoptosis. CI - (c) 2021 Mei Zhang et al., published by De Gruyter. FAU - Zhang, Mei AU - Zhang M AD - Department of Biomedicine, Guizhou University School of Medicine, Guizhou University, Guiyang 550025, Guizhou, People's Republic of China. FAU - Yuan, Jing AU - Yuan J AD - Division of Nephrology, Guizhou Provincial People's Hospital, Guizhou Provincial Institute of Nephritic & Urinary Disease, No. 83 East ZhongShan Road, Guiyang 550002, Guizhou, People's Republic of China. FAU - Dong, Rong AU - Dong R AD - Division of Nephrology, Guizhou Provincial People's Hospital, Guizhou Provincial Institute of Nephritic & Urinary Disease, No. 83 East ZhongShan Road, Guiyang 550002, Guizhou, People's Republic of China. FAU - Da, Jingjing AU - Da J AD - Division of Nephrology, Guizhou Provincial People's Hospital, Guizhou Provincial Institute of Nephritic & Urinary Disease, No. 83 East ZhongShan Road, Guiyang 550002, Guizhou, People's Republic of China. FAU - Li, Qian AU - Li Q AD - Division of Nephrology, Guizhou Provincial People's Hospital, Guizhou Provincial Institute of Nephritic & Urinary Disease, No. 83 East ZhongShan Road, Guiyang 550002, Guizhou, People's Republic of China. FAU - Hu, Ying AU - Hu Y AD - Division of Nephrology, Guizhou Provincial People's Hospital, Guizhou Provincial Institute of Nephritic & Urinary Disease, No. 83 East ZhongShan Road, Guiyang 550002, Guizhou, People's Republic of China. FAU - Yu, Fangfang AU - Yu F AD - Division of Nephrology, Guizhou Provincial People's Hospital, Guizhou Provincial Institute of Nephritic & Urinary Disease, No. 83 East ZhongShan Road, Guiyang 550002, Guizhou, People's Republic of China. FAU - Ran, Yan AU - Ran Y AD - Division of Nephrology, Guizhou Provincial People's Hospital, Guizhou Provincial Institute of Nephritic & Urinary Disease, No. 83 East ZhongShan Road, Guiyang 550002, Guizhou, People's Republic of China. FAU - Zha, Yan AU - Zha Y AD - Division of Nephrology, Guizhou Provincial People's Hospital, Guizhou Provincial Institute of Nephritic & Urinary Disease, No. 83 East ZhongShan Road, Guiyang 550002, Guizhou, People's Republic of China. FAU - Long, Yanjun AU - Long Y AD - Division of Nephrology, Guizhou Provincial People's Hospital, Guizhou Provincial Institute of Nephritic & Urinary Disease, No. 83 East ZhongShan Road, Guiyang 550002, Guizhou, People's Republic of China. LA - eng PT - Journal Article DEP - 20210529 PL - Poland TA - Open Life Sci JT - Open life sciences JID - 101669614 PMC - PMC8165256 OTO - NOTNLM OT - JNK signaling pathway OT - acute kidney injury OT - hyperhomocysteinemia OT - ischemia-reperfusion injury OT - oxidative stress COIS- Conflict of interest: The authors state no conflict of interest. EDAT- 2021/06/15 06:00 MHDA- 2021/06/15 06:01 PMCR- 2021/05/29 CRDT- 2021/06/14 09:54 PHST- 2020/11/09 00:00 [received] PHST- 2021/04/01 00:00 [revised] PHST- 2021/04/22 00:00 [accepted] PHST- 2021/06/14 09:54 [entrez] PHST- 2021/06/15 06:00 [pubmed] PHST- 2021/06/15 06:01 [medline] PHST- 2021/05/29 00:00 [pmc-release] AID - biol-2021-0054 [pii] AID - 10.1515/biol-2021-0054 [doi] PST - epublish SO - Open Life Sci. 2021 May 29;16(1):537-543. doi: 10.1515/biol-2021-0054. eCollection 2021.