Nontoxic Concentration of Ochratoxin A Aggravates Renal Fibrosis Induced by Adriamycin/Cyclosporine A Nephropathy via TGF-β1/SMAD2/3.

Ochratoxin A (OTA) is the most common contaminant in food and feed, which causes nephrotoxicity. Studies revealed that a low level of OTA contamination could also cause physiological dysfunction. Chronic kidney disease (CKD) has become an important public health problem with increasing morbidity. However, the potential effect of nontoxic OTA on CKD remains uncertain. In this study, adriamycin (ADR) and cyclosporine A (CSA) were used to stimulate glomerular nephropathy and tubular nephropathy, respectively. Renal injury was aggravated due to OTA (0.25 mg/kg) exposure in the mouse nephropathy models, assessing by renal histomorphology and the detection of blood urea nitrogen (BUN) and serum creatine (SCr) levels. We noticed that nontoxic dosage of OTA increased the expression of fibrotic factors, α-smooth muscle actin (α-SMA), and Vimentin in a nephropathic mouse, which indicated the exacerbation of ADR/CSA-induced renal fibrosis. We conducted in vitro experiments in glomerular mesangial cells and renal tubular epithelial cells. Nontoxic concentration of OTA was found to exacerbate the cytotoxicity of ADR/CSA and intensify renal fibrosis by activating TGF-β1/SMAD2/3. Thus, this study may provide convincing evidence for the prevention of CKD aggravation and the renewal of food hygiene standards in mycotoxin contamination.