The role of PGC-1α and metabolic signaling pathway in kidney injury following chronic administration with 3-MCPD as a food processing contaminant.

3-Monochloropropane-1,2-diol (3-MCPD) as a byproduct of food processing and a carcinogenic agent has attracted much attention in the last decades. Kidney is the main target organ that is sensitive to the toxicity of 3-MCPD. Due to limited evidence about possible 3-MCPD toxicity, we design an investigation to determine the role of mitochondrial biogenesis following chronic oral administration of 3-MCPD (2, 4, 8 and 32 mg/kg) for 2 months in male C57 mice. The present study evaluated the affects of 3-MCPD in modulating metabolic signalling which is associated with Il-18, PGC-1α, Nrf-2 and Sir3 which are the major transcription factors. Our data confirms controversial behaviors after chronic exposure with 3-MCPD. Over expression of the PGC-1α and Sir3 and IL-18 were observed after exposure with 2,4 & 8 mg kg-1  day-1 of 3-MCPD. In front, PGC-1α down-regulation occurs at the highest dose (32 mg/kg) resulted in kidney injury. Based on the findings, PGC-1α plays an important role in the restoration of the mitochondrial function during the recovery from chronic kidney injury. We suggest that the PGC-1α can be consider as a therapeutic target in prevention and treatment of kidney injury after chronic exposure of 3-MCPD. PRACTICAL APPLICATIONS: 3-Monochloropropane-1, 2-diol (3-MCPD) existed in several foods, can induce nephrotoxicity, progressive nephropathy and renal tubule dilation following acute and chronic exposure. It revealed that 3-MCPD toxicity is related to metabolites which can cause oxidative stress and activation of cell death signaling. It seems that cytotoxicity of 3-MCPD has disruptive effect on kidney cells due to rise in ROS production and decrease in mitochondrial membrane permeability. These effects can lead to MPT pore opening, cytochrome c release and activation of programed cell death signaling pathway. Therefore, present study was investigated the role of PGC-1a and the metabolic signaling involved in 3-MCPD-induced nephrotoxicity for the first time. Our data revealed that up-regulation of mitochondrial biogenesis following chronic exposure with 3-MCPD accelerates recovery of mitochondrial and cellular function in kidney by deacetylation of histones, overexpression of transcription factors (PGC-1α, Nrf-2, and Sir3) and maintaining cellular homeostasis.