Melamine induced changes in histopathology of the main organs and transcriptional levels of MAPK signaling genes in kidneys of female mice

Abstract

Melamine is an important chemical raw material used in industries, which has potential health risks to animals and humans. Current research mainly focuses on the toxic effects of high‐dose melamine ingestion. However, there are few reports on whether melamine at the current limited standard dose has adverse effects on various tissues and organs, and whether there are sensitive target genes for risk evaluation. For this, 24 female Kunming mice were fed 0, 1.8‐, 3.6‐, and 7.2‐ mg/kg/d melamine via drinking water for consecutive 28 days, respectively. The morphological changes of the ovarian, hepatic, and renal tissues were firstly observed. The results demonstrated that the histopathology of ovary, liver, and especially in kidney had been altered by melamine intake in female. And then, the transcriptional levels of MAPK signaling genes including p38, ERK1, ERK2, JNK1, and JNK2 in kidneys were investigated by real‐time PCR. The data showed that ERK1 and p38 mRNAs expressions were up‐regulated significantly by melamine, suggesting that ERK1 and p38 transcriptional levels in the kidney might to be considered as candidate targets for lower‐dose melamine toxicity. This study not only provides potential targets for the diagnosis and prevention of melamine damage, but also helps to assess the health risks of the current minimum allowable levels of melamine in food and environment.

Leucine‐rich repeat kinase 2 is protective during acute kidney injury through its activation of autophagy in podocytes

“…Here we have chosen IR‐induced and LPS‐induced AKI as our research models, since they could well represent two common clinical situations, ischemic organ injury and sepsis. As for the cell signaling pathways underlying AKI, multiple key pathway mediators including Nrf2, MAPK, NLRP3, and NF‐κB have been reported in ischemic injury, nephrotoxic agent‐induced AKI, and LPS‐induced AKI 27,29–31,33–35 . In the current study, however, we revealed the pivotal role of autophagy in IR‐induced and LPS‐induced AKI.…”

“…As for the cell signaling pathways underlying AKI, multiple key pathway mediators including Nrf2, MAPK, NLRP3, and NF-κB have been reported in ischemic injury, nephrotoxic agentinduced AKI, and LPS-induced AKI. 27,[29][30][31][33][34][35] In the current study, however, we revealed the pivotal role of autophagy in IR-induced and LPS-induced AKI.…”

“…Over decades, researchers have struggled to identify the aetiologies and pathophysiological processes of AKI of different types. In regards to aetiologies, AKI could be clinically divided into three types 26 : prerenal AKI mainly due to ischemic organ injury; renal AKI caused by the damage to the kidney itself, a complicated AKI group that might involve a variety of environmental nephrotoxic materials such as melamine, lithium, bisphenol A, frequently applied nonsteroidal anti-inflammatory drugs, and even gamma irradiation [27][28][29][30][31][32] ; and postrenal AKI resulting from urinary flow obstruction. Here we have chosen IR-induced and LPS-induced AKI as our research models, since they could well represent two common clinical situations, ischemic organ injury and sepsis.…”

Nootkatone Mitigated Melamine-Evoked Hepatotoxicity by Featuring Oxidative Stress and Inflammation Interconnected Mechanisms: In Vivo and In Silico Approaches

“…ML is a common pollutant and carcinogen that threatens human and animal health, and has sparked major global concerns [ 29 ]. It is widely dispersed in the environment including water and soil [ 30 ], and has been incriminated as a substance in food adulteration [ 31 ].…”

“…It is widely dispersed in the environment including water and soil [ 30 ], and has been incriminated as a substance in food adulteration [ 31 ]. The liver is the primary organ for metabolism and detoxification and one of the organs most seriously affected by ML exposure [ 10 , 29 ].…”