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

Abstract

Melamine (ML) is a common environmental contaminant, commonly used in food fraud, representing a serious health hazard and jeopardizing human and animal health. Recently, nootkatone (NK), a naturally occurring sesquiterpenoid, has garnered considerable attention due to its potential therapeutic advantages. We investigated the potential mechanisms underlying the protective effects of NK against ML-induced liver injury in rats. Five groups were utilized: control, ML, NK10, ML-NK5, and ML-NK10. ML induced substantial hepatotoxicity, including considerable alterations in biochemical parameters and histology. The oxidative distress triggered by ML increased the generation of malondialdehyde (MDA) and nitric oxide (NO) and decreased levels of reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) activities. In addition, decreased expression of nuclear factor-erythroid 2-related factor 2 (Nrf2) and increased nuclear factor kappa beta (NF-κB) expression levels were observed in hepatocytes, which indicated the occurrence of inflammatory changes following ML exposure. These alterations were alleviated by NK supplementation in a dose-dependent manner. The data revealed that the favorable effects of NK were attributed, at least in part, to its antioxidant and anti-inflammatory properties. Moreover, our results were supported by molecular docking studies that revealed a good fit and interactions between NK and antioxidant enzymes. Thus, the current study demonstrated that NK is a potential new food additive for the prevention or treatment of ML-induced toxicity.

Nootkatone Counteracts Melamine-Mediated Nephrotoxicity via Modulation of Intermediate Filament Proteins, Oxidative, Inflammatory, and Apoptotic Events

“…Increased NF-κB expression levels in hepatocytes of MM-exposed rats was observed which indicated that inflammatory reaction mediated by MM exposure. 58 In addition, MM induced oxidative and inflammatory stresses in macrophages and human embryonic kidney cells by activating the NF-κB/COX-2 and NOX/ROS pathways, besides increasing prostaglandin E2 production. 44 Therefore, a marked alteration in the inflammatory, and antioxidant markers in MM-intoxicated group might be attributed to the production of calcium oxalate crystals.…”

Grouping strategies for assessing and managing persistent and mobile substances

“…PMT/vPvM substances can be found in a wide range of applications and sources, including in industrial processes, fire-fighting foams, and consumer products such as food, cosmetics and furniture [15]. They can cause long-term harm to humans and the environment and are also costly and difficult to remove from drinking water [16][17][18][19].…”

Grouping strategies for assessing and managing persistent and mobile substances

“…PMT/vPvM substances can be found in a wide range of applications and sources, including in industrial processes, fire-fighting foams, and consumer products such as food, cosmetics and furniture [14]. They can cause longterm harm to humans and the environment and are also costly and difficult to remove from drinking water [15][16][17][18]. PMT/vPvM substances have been suggested to have an equivalent level of concern as persistent, bioaccumulative and toxic (PBT) substances or very persistent and very bioaccumulative (vPvB) substances.…”