Melatonin ameliorates renal dysfunction in glyphosate- and hard water-treated mice

Ecotoxicology and Environmental Safety

卷:241

Xuan Wu¹  Qing Wu²  Jianying Hu³  Xiaoyan Zhang³  Lin Zhang⁴  Yi Wan⁴  Yingying Liu⁴  Fan Ding⁴ 

[1] Key Laboratory of Children’s Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China;

[2] Department of Nephrology, Zhongshan Hospital of Fudan University, Shanghai, China;

[3] Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing, China;

[4] School of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai, China;

关键词: Chronic interstitial nephritis in agricultural communities (CINAC);    Glyphosate;    Hard water;    Melatonin;    Endoplasmic reticulum (ER) stress;    Pyroptosis;   

DOI  :  

来源: DOAJ

【 摘 要 】

Chronic interstitial nephritis in agricultural communities (CINAC) is a severe and widespread disease that has been associated with environmental and occupational exposure to glyphosate and hard water. However, the potential underlying mechanisms remain incompletely understood. Melatonin is reported to exert protective effects on the kidney, but whether melatonin can attenuate renal tubular injury in mice exposed to glyphosate combined with hard water is unclear. Here, mice were treated with high doses and environmentally relevant doses of glyphosate (100 mg/kg·bw and 0.7 mg/L, respectively) and/or hard water (2500 mg/L CaCO3 and 250 mg/L Ca2+, respectively) via their drinking water for 12 weeks. We found that high-dose glyphosate or hard water treatment significantly increased the levels of biomarkers of renal damage, including β2-microglobulin, neutrophil gelatinase-associated lipid carrier protein, and/or albumin, in the urine; these increased biomarker levels were correlated with obvious morphological changes, and all of these changes were also observed in animals exposed to environmentally relevant doses of glyphosate and/or high Ca2+ water. Melatonin (10 mg/kg·bw, intraperitoneal injection, daily for 12 weeks) administered concomitantly with high doses of glyphosate and hard water inhibited the glyphosate- and hard water-induced increases in the levels of kidney injury biomarkers and changes in morphology; this result was intriguing. Additionally, glyphosate combined with hard water at both high and environmentally relevant doses significantly upregulated the expression of the endoplasmic reticulum (ER) stress marker proteins Bip, ATF6, and PERK as well as the pyroptosis-related proteins (NLRP3 and caspase 1 signaling proteins) in renal tissues. Similarly, melatonin significantly attenuated the increased ER stress and pyroptosis induced by high doses of glyphosate and hard water. In summary, we conclude that exposure to glyphosate and hard water at both high doses and environmentally relevant doses causes renal dysfunction in mice, and this dysfunction can be attenuated by melatonin, possibly through the inhibition of ER stress and pyroptosis. Our results support the notion that melatonin may have therapeutic potential for the treatment of chronic kidney diseases.

【 授权许可】

Unknown