Curcumin attenuates ochratoxin A and hypoxia co-induced liver injury in grass carp (Ctenopharyngodon idella) by dual targeting endoplasmic reticulum stress and apoptosis via reducing ROS content.

Background: Ochratoxin A (OTA) is a toxin widely found in aquafeed ingredients, and hypoxia is a common problem in fish farming. In practice, aquatic animals tend to be more sensitive to hypoxia while feeds are contaminated with OTA, but no studies exist in this area. This research investigated the multiple biotoxicities of OTA and hypoxia combined on the liver of grass carp and explored the mitigating effect of curcumin (CUR).

Methods: A total of 720 healthy juvenile grass carp (11.06 ± 0.05 g) were selected and assigned randomly to 4 experimental groups: control group (without OTA and CUR), 1.2 mg/kg OTA group, 400 mg/kg CUR group, and 1.2 mg/kg OTA + 400 mg/kg CUR group with three replicates each for 60 d. Subsequently, 32 fish were selected, divided into normoxia (18 fish) and hypoxia (18 fish) groups, and subjected to hypoxia stress for 96 h.

Results: CUR can attenuate histopathological damage caused by coming to OTA and hypoxia by reducing vacuolation and nuclear excursion. The alleviation of this damage was associated with the attenuation of apoptosis in the mitochondrial pathway by decreasing the expression of the pro-apoptotic proteins Caspase 3, 8, 9, Bax, and Apaf1 while increasing the expression of the anti-apoptotic protein Bcl-2, and attenuation of endoplasmic reticulum stress (ERS) by reducing Grp78 expression and chop levels. This may be attributed to the fact that the addition of CUR increased the levels of catalase (CAT) and glutathione reductase (GSH), increased antioxidant capacity, and ensured the proper functioning of respiratory chain complexes I and II, which in turn reduced the high production of reactive oxygen species (ROS), thus alleviating apoptosis and ERS.

Conclusions: In conclusion, our data demonstrate the effectiveness of CUR in attenuating liver injury caused by the combination of OTA and hypoxia. This study confirms the feasibility and efficacy of adding natural products to mitigate toxic damage to aquatic animals.