H2S exposure-induced oxidative stress promotes LPS-mediated hepatocyte autophagy through the PI3K/AKT/TOR pathway.

Hydrogen sulfide (H2S), a common air pollutant and toxic gas, is detrimental to organisms and the environment. Exposure to highly concentrated H2S can induce oxidative stress and autophagy. However, the mechanism underlying the liver damage caused by H2S has not been identified. Lipopolysaccharide (LPS), the key component of endotoxin, can induce oxidative stress and autophagy. For this experiment, we used one-day-old chickens as model organisms to evaluate the effects of H2S combined with LPS on oxidative stress and autophagy. The four groups (control group, LPS group, H2S group and H2S-LPS group) were observed by electron microscopy, detected by oxidative stress kit, analyzed by quantitative real-time quantitative PCR, and analyzed by Western blot. We found that the activities of antioxidant enzymes (superoxide dismutase, antioxidant glutathione, catalase, and glutathione peroxidase) decreased in the H2S group compared to those in the control group; however, malondialdehyde levels in the H2S group increased. Molecular-level studies showed that the expression of genes associated with the PI3K/ AKT/ TOR pathways in the H2S group decreased, whereas the expression of other autophagy-related genes (Beclin1, ATG5 and the ratio of LC3-II/ LC3-I) increased compared to that in the control group. These findings suggest that H2S caused oxidative stress and induced autophagy through the PI3K/ AKT/ TOR pathway in chicken liver cells. Additionally, exposure to H2S aggravated LPS-induced oxidative stress and autophagy injury. Capsule: Aerial exposure to H2S can cause oxidative stress in chicken livers and induce autophagy through the PI3K/AKT/TOR pathway, and can aggravate LPS-induced oxidative stress and autophagy.

Effects of Atrazine and Chlorpyrifos on Autophagy-Related Genes in the Brain of Common Carp: Health-Risk Assessments.

This study assessed the impacts of atrazine (ATR), chlorpyrifos (CPF), and a combined ATR/CPF exposure on the brain of common carp (Cyprinus carpio L.). The carp were sampled after a 40-days exposure to CPF and ATR, individually or in combination, followed by a 40-days recovery period to measure autophagy and antioxidant activity. The results indicate that the anti-superoxide anion and anti-hydroxy radical activities decreased upon exposure to ATR, CPF, and the ATR/CPF combination but increased after a subsequent 40-days recovery period. Quantitative real-time PCR and Western blot analyses revealed that the mRNA and protein levels of LC3B and dynein in common carp decreased significantly after exposure to ATR and CPF alone or in combination. Moreover, the mRNA and protein levels of beclin1 gene decreased significantly only in the 116 and 11.3 µg/L treatment groups. However, the mRNA and protein levels of all tested genes increased significantly after a 40-days recovery. Transmission electron microscope demonstrated the occurrence of autolysosomes in the recovery groups but not in the exposure groups. These results suggest that exposure to ATR, CPF, or their combination promotes oxidative stress and autophagic responses in the brain of common carp.

Effect of atrazine and chlorpyrifos exposure on cytochrome P450 contents and enzyme activities in common carp gills.

Chlorpyrifos (CPF) and atrazine (ATR) are the most widely used organophosphate insecticides and triazine herbicides, respectively, worldwide. This study aimed at investigating the effects of ATR, CPF and mixture on common carp gills following 40-d exposure and 40-d recovery experiments. Cytochrome P450 content, activities of aminopyrine N-demethylase (APND) and erythromycin N-demethylase (ERND) and the mRNA levels of the CYP1 family (CYP1A, CYP1B, and CYP1C) were determined. In total, 220 common carps were divided into eleven groups, and each group was treated with a specific concentration of ATR (4.28, 42.8 and 428 µg/L), CPF (1.16, 11.6 and 116 µg/L) or ATR-CPF mixture (1.13, 11.3 and 113 µg/L). The results showed that P450 content and activities of APND and ERND in fish exposed to ATR and mixture were significantly higher than those in the control group. After the 40-d recovery treatment (i.e., depuration), the P450 content and the activities of APND and ERND in fish decreased to the background levels. A similar tendency was also found in the mRNA levels of the CYP1 family (CYP1A, CYP1B, and CYP1C) in common carp gills. The CPF-treated fish showed no significant difference from the control groups, except for a significant CYP1C induction. These results indicated that CYP enzyme levels are induced by ATR but were only slightly affected by CPF in common carp gills. In addition, the ATR and CPF exposure showed an antagonistic effect on P450 enzymes in common carp gills.

Effects of atrazine and chlorpyrifos on the production of nitric oxide and expression of inducible nitric oxide synthase in the brain of common carp (Cyprinus carpio L.).

The study aimed to investigate the effects of atrazine (ATR), chlorpyrifos (CPF), and the mixture of them on nitric oxide (NO) and inducible nitric oxide synthase (iNOS) in the brain of common carp. The triazine herbicide ATR and the organophosphorus insecticide CPF are frequently and extensively applied in agriculture all over the world. 220 Carps were averagely divided into eleven groups according to the different treatments and concentration, including the exposure and recovery experiments. In the present study, we investigated production of NO, iNOS activity and iNOS mRNA and protein expression in the brain of the common carp after a 40d exposure to ATR, CPF, alone or in combination, and a 40d recovery treatment. The results showed that the activity of iNOS and production of NO were significantly higher in all groups of fish exposed to high doses ATR, CPF and their mixture compared to control fish. After a 40d recovery treatment, iNOS activity and production of NO were lower than in the corresponding exposure groups in all the recovery groups. The mRNA and protein levels of iNOS were significantly higher in the high-dose group of ATR and CPF compared to control group, but were significantly lower in the group of the mixture of ATR and CPF compared to control group. Results indicated that NO and iNOS were involved in oxidative stress and brain tissue damage induced by ATR, CPF, and their mixture. Thus, the information presented in this study is helpful to understand the mechanism of ATR-, CPF- and ATR/CPF-mixture-induced neurotoxicity in fish.