Cypermethrin and/or sulfamethoxazole exposure effect on apoptosis and endoplasmic reticulum of grass carp cardiomyocyte

With the soar use range of pesticides and antibiotics in agricultural production, the pollution of surrounding runoff has become more severe; thus, the health and safety of non-target species such as fish are at risk. Excessive amounts of cypermethrin (CMN, 0.651 mg/l) and sulfamethoxazole (SMZ, 0.3 mg/l) are known to trigger oxidative stress and endoplasmic reticulum stress, resulting in toxic effects on cells. The damage degree of poisons on grass carp and the effect of the corresponding axis pathway PERK/eif2 alpha/CHOP are still unknown. Therefore, our study set up two single poison groups (CMN/SMZ) and a combined poison group (CMN&SMZ) to detect this pathway and related indicators. After detection, the content of MDA both in CMN and SMZ group myocardium tissue was increased, while the SOD, CAT activity and GSH levels were decreased. Apoptosis-related genes (Bax, PUMA, P53 and Caspase-3/9), inflammation-related genes (TNF-alpha, iNOS and IL-1 beta/6/8), ER stress pathway PERK/eif2 alpha/CHOP and related genes (ATF6, IRE1a and GRP78) were all increased; in contrast, the anti-apoptotic gene Bcl-2 was down-regulated. From the overall trend observation, the apoptosis proportion of car-diomyocytes in the combined poison group was higher than that of the single poison. In summary, this study shows that CMZ and SMZ can induce oxidative stress and subsequent ER stress in grass carp cardiomyocytes by regulating the PERK/eif2 alpha/CHOP signaling axle, thereby inducing apoptosis, and followed by inflammatory responses. The combined effect of the CMZ and SMZ mixture was severer than that of a single poison (CMZ or SMZ), so it can be inferred that the damage degree of grass carp myocardium tissue would be aggravated with the appearance of CMZ or/and SMZ. The experimental results of this study have suggestions and warnings for the toxicological research of CMZ and SMZ and the management of industrial and ecological balance.