Through its genoprotective, mitochondrial bioenergetic modulation, and antioxidant effects, Fucoxanthin and its metabolite minimize Ochratoxin A-induced nephrotoxicity in HK-2 human kidney cells.

BACKGROUND

Ochratoxin A (OTA) is a mycotoxin with reported multiorgan toxicity, especially kidney toxicity. Fucoxanthin (FX) and its hydrolyzed metabolite Fucoxanthinol (FXL) have reno-protective antioxidant and anti-inflammatory properties. This study evaluates the nephroprotective effects of FX and FLX on OTA-induced renal cytotoxicity using the HK-2 cell line.

METHODS

Molecular docking was used to study the binding affinities with the main proteins of the studied pathways. Various in-vitro assays were used to test the hypothesis, including MTT, mitochondrial bioenergetics, oxidative stress, and apoptosis biomarkers.

RESULTS

Docking revealed binding affinities of the tested chemicals with mitochondria, oxidative stress, and apoptosis. Data showed that OTA has a dose-dependent cytotoxic effect on HK-2 cells. Notably, FX and FXL improved cell viability. A significant deregulation of normal cellular pathways including genotoxicity (DNA damage percentage), mitochondrial bioenergetics disruption (PDH, α-KG, MCI and MCIII complexes activities, ATP levels and mitochondrial membrane potential), downregulation of some mitochondrial genes (ND1, ND5, CO-1 and ATP6/8) expression, mitophagy inhibition (PARK1 and parkin), Oxidative stress induction (ROS and TBARS), oxidative stress genes downregulation (HO-1 and Nrf2), antioxidant enzymatic activity reduction (ROS and CAT), and apoptotic mediator markers elevation (Caspases- 3, 8 and 9, and Bax/Bcl-2 ratio) were observed in OTA mono-treated cells compared to untreated control cells. All parameters were markedly normalized by combining FX or FLX with OTA, providing more protection in FXL co-treated samples.

CONCLUSION

Our results suggest that FX and FXL may be effective novel therapies for treating OTA-induced nephrotoxicity in vitro.