Low doses of fumonisin B1 exacerbate ochratoxin A-induced renal injury in mice and the protective roles of heat shock protein 70

Haolei Li; Wenmiao He; Dongmei Yue; Mengmeng Wang; Xin Yuan; Kehe Huang

doi:10.1016/j.cbi.2022.110240

Low doses of fumonisin B1 exacerbate ochratoxin A-induced renal injury in mice and the protective roles of heat shock protein 70

Chem Biol Interact. 2023 Jan 5:369:110240. doi: 10.1016/j.cbi.2022.110240. Epub 2022 Oct 27.

Authors

Haolei Li¹, Wenmiao He¹, Dongmei Yue¹, Mengmeng Wang¹, Xin Yuan¹, Kehe Huang²

Affiliations

¹ College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, China; Institute of Animal Nutritional Health, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, China.
² College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, China; Institute of Animal Nutritional Health, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, China. Electronic address: khhuang@njau.edu.cn.

PMID: 36397609
DOI: 10.1016/j.cbi.2022.110240

Abstract

Fumonisin B1 (FB1) and ochratoxin A (OTA) possess nephrotoxicity to animals and widely co-exist in food and feedstuffs. FB1 rarely, while OTA often, causes toxicosis in animals. Heat shock protein 70 (Hsp70) resists lung injury induced by pneumolysin, but whether Hsp70 could remission mycotoxins-induced renal injury is still unknown. The present study aims to explore the impacts of nontoxic doses of FB1 on OTA-induced nephrotoxicity and the protective roles of Hsp70. In the mycotoxins-challenge experiment, ICR mice were co-exposed to nontoxic doses of FB1 (0, 0.2, 0.5, 1.0 mg/kg bw, IP) and toxic dose of OTA (0.4 mg/kg bw, IP) for 16 d. The results showed that the levels of BUN, Cr, MDA in serum, the Cyto C in renal tubes or glomerulus, pro-apoptosis genes and p-JNK protein expression in kidney were significantly increased. Histopathological results revealed the glomerular swelling. The above all indexes were dose-dependent. In the protection experiment, the mice were pretreated with the eukaryotic plasmid of pEGFP-C3-Hsp70, these increasing parameters in the mycotoxins-challenge experiment were reversed. In vitro, after pK-15 cells were treated with 8 μM FB1 and 5 μM OTA for 48 h, the mitochondrial membrane potential was significantly reduced, mitochondrial ROS was remarkably increased, more Cyto C was leaked from mitochondria into cytoplasm, and pro-apoptosis genes were significantly up-regulated. After the Hsp70 level was up-regulated by pEGFP-C3-Hsp70 or ML346 in pK-15 cells, these above indexes were reversed. However, activation of JNK by anisomycin significantly suppressed the protective effects of Hsp70. Our results demonstrate that the nontoxic doses of FB1 exacerbate the toxic dose of OTA-induced renal injury, while Hsp70 alleviates renal injury by inhibiting the JNK/MAPK signaling pathway. Hsp70 up-regulation may be an efficient strategy for protecting against tissue damage and bio-function impairment induced by co-exposure to FB1 and OTA.

Keywords: Fumonisins B1; Heat shock protein 70; Mitochondrial reactive oxygen species; Ochratoxin A; Protective effects; c-Jun N-Terminal kinase.

MeSH terms

Animals
Drug-Related Side Effects and Adverse Reactions*
HSP70 Heat-Shock Proteins / genetics
Kidney
Mice
Mice, Inbred ICR
Mycotoxins* / toxicity

Substances

ochratoxin A
fumonisin B1
HSP70 Heat-Shock Proteins
Mycotoxins