Aristolactam I (ALI) is an active component derived from some Traditional Chinese medicines (TCMs), and also the important metabolite of aristolochic acid. Long-term administration of medicine-containing ALI was reported to be related to aristolochic acid nephropathy (AAN), which was attributed to ALI-induced nephrotoxicity. However, the toxic mechanism of action involved is still unclear. Recently, pathogenic ferroptosis mediated lipid peroxidation was demonstrated to cause kidney injury. Therefore, this study explored the role of ferroptosis induced by mitochondrial iron overload in ALI-induced nephrotoxicity, aiming to identify the possible toxic mechanism of ALI-induced chronic nephropathy. Our results showed that ALI inhibited HK-2 cell activity in a dose-dependent manner and significantly suppressed glutathione (GSH) levels, accompanying by significant increases in intracellular 4-hydroxynonenal (4-HNE) and intracellular iron ions. Moreover, the ALI-mediated cytotoxicity could be reversed by deferoxamine mesylate (DFO). Compared with other inhibitors, Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, obviously alleviated ALI-induced cytotoxicity. Furthermore, we have shown that ALI could remarkably increase the levels of superoxide anion and ferrous ions in mitochondria, and induce mitochondrial damage and condensed mitochondrial membrane density, the morphological characteristics of ferroptosis, all of which could be reversed by DFO. Interestingly, ALI dose-dependently inhibited these protein contents of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and glutathione peroxidase 4 (GPX4), which could be partly rescued by Tin-protoporphyrin IX (SnPP) and mitoTEMPO co-treatment. In conclusion, our results demonstrated that mitochondrial iron overload-mediated antioxidant system inhibition would assist ALI-induced ferroptosis in renal tubular epithelial cells, and Nrf2-HO-1/GPX4 antioxidative system could be an important intervention target to prevent medicine containing ALI-induced nephropathy.

The objective of this study was to determine the effect fresh celery powder and starter culture (FCP+SC), blanching celery powder and starter culture (BCP+SC) had on the quality characteristics of indirectly cured sausages, Two treatments (TRT) (TRT 1: FCP+SC, 0.3%FCP+0.033%WBL-45; TRT 2: BCP+SC, 0.3%BCP+0.033%WBL-45 ), Negative Control (NC) (no-nitrite-added control), Positive Control (PC) (0.1%sodium nitrite-added control) were investigated. Residual nitrite levels throughout storage is always higher in PC than FCP+SC and BCP+SC(P < 0.05), but in TBARS, PC is better than FCP+SC and BCP+SC(P < 0.05). Few differences existed between TRTs and PC for a* and gel strength. The processing methods investigated to manufacture “naturally cured” in this study were applied for products instead of sodium nitrite.

The purpose of this study was to meet the regulations of “natural product”, fermented celery powder (FCP) were selected in this research to evaluate its ability to restrain Listeria monocytogenes growth in the naturally cured sausage, and also the effectiveness on quality and sensory attributes of the sausages. The content of nitrite is 150mg/kg in each group. The FCP were assessed at both their intrinsic pH and at a pH adjusted approach that of a sausage product. The results are the FCP treatments can substitute conventional sodium nitrite to the growth of Listeria monocytogenes in the sausage without negatively impact the quality and sensory attributes of the products. In addition, the adjusted FCP treatments were more effective than conventional nitrite.