microcystin-LR In Liver Research Articles

Identification and characterization of ABCC gene family and their roles in the response to intraperitoneal injection of microcystin-LR in liver of silver carp (Hypophthalmichthys molitrix)

Silver carp (Hypophthalmichthys molitrix) is a widely distributed food resource and phytoplankton predator in China, which has been used to control algal blooms. Silver carp is quite resistant to microcystins (MCs), which are typical hepatotoxins generated by toxic algae. ATP-Binding Cassette, Subfamily C (ABCC) transporter are critical detoxification genes that could export toxic substances out of the cell, and with regard to ABCC transporters in H. molitrix, current studies are limited. In order to investigate the roles of ABCC genes in excretion of MCs, the full-length transcriptome of silver carp was analyzed to screen a total of nine ABCC transporter genes, which were expressed ubiquitously in silver carp tissues, especially in the liver. Furthermore, microcystin-LR (MC-LR) intraperitoneal injection was performed, and the results showed that, except abcc2, abcc10 and abcc12, the expression of other ABCC genes increased rapidly within 1 h and then began to decline after 6 h. Among these five genes, abcc3 and abcc9 exhibited the most pronounced response, indicating that these two were the most preeminent detoxification genes of microcystin in ABCC genes family in silver carp. Meanwhile, the activities of glutathione-S-transferase (GST) were increased significantly, while the content of glutathione (GSH) demonstrated a dramatic decrease, implying that GST catalyzed binding of GSH and MC-LR, and then excreted through ABCC transporters. The findings of this study will be useful in further investigating the fundamental characteristics of silver carp and provide new insights into the potential function of ABCC genes in the detoxication of MC-LR.

The presence of polystyrene nanoplastics enhances the MCLR uptake in zebrafish leading to the exacerbation of oxidative liver damage

The accumulation of diminutive plastic waste in the environment, including microplastics and nanoplastics, has threatened the health of multiple species. Nanoplastics can adsorb the pollutants from the immediate environment, and may be used as carriers for pollutants to enter organisms and bring serious ecological risk. To evaluate the toxic effects of microcystin-LR (MCLR) on the liver of adult zebrafish (Danio rerio) in the presence of 70 nm polystyrene nanoplastics (PSNPs), zebrafish were exposed to MCLR alone (0, 0.9, 4.5 and 22.5 μg/L) and a mixture of MCLR + PSNPs (100 μg/L) for three months. The results indicated that groups with combined exposure to MCLR and PSNPs further enhanced the accumulation of MCLR in the liver when compared to groups only exposed to MCLR. Cellular swelling, fat vacuolation, and cytoarchitectonic damage were observed in zebrafish livers after exposure to MCLR, and the presence of PSNPs exacerbated these adverse effects. The results of biochemical tests showed the combined effect of MCLR + PSNPs enhanced MCLR-induced hepatotoxicity, which could be attributed to the altered levels of reactive oxygen species, malondialdehyde and glutathione, and activities of catalase. The expression of genes related to antioxidant responses (p38a, p38b, ERK2, ERK3, Nrf2, HO-1, cat1, sod1, gax, JINK1, and gstr1) was further performed to study the mechanisms of MCLR combined with PSNPs aggravated oxidative stress of zebrafish. The results showed that PSNPs could improve the bioavailability of MCLR in the zebrafish liver by acting as a carrier and accelerate MCLR-induced oxidative stress by regulating the levels of corresponding enzymes and genes.

Comparison of response indices to toxic microcystin-LR in blood of mice

In order to investigate the response indices to toxic microcystin-LR (MC-LR) in blood of mice, concentrations of free and total MC-LR in blood and tissues, accompanied by serous parameters in series including some enzymatic activities, hematology and the function of leukocytes, were determined in mice exposed to the toxin ranging from 3.125 to 25.000μgkg−1day−1 by intraperitoneal injection for 7days. On the 7th day, the ratios of mass of free MC-LR in serum to the mass of MC-LR in given dose were 3.843–4.555%, while the ratios of total MC-LR in liver were 34.465–38.567%. Comparing the overall experimental results, the three most sensitive indices are total MC-LR in the liver, the phagocytic index and reactive oxygen species (ROS) which have shown significant differences between the lowest dose group and the control group. Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and lactate dehydrogenase had proportional correlations with the MC-LR exposure doses, and the hematology of the majority of blood cells and the volume of erythrocytes were also influenced by the toxin. The alterations of some cytokines and the ROS of leukocytes were observed. The results of the studies suggest that measurement of MC-LR in blood is powerful and clear evidence to indicate that subjects have been exposed to MC-LR and can be used to discriminate from other causes leading to hepatic lesions although it is not as sensitive as other indices that are usually as useful complements to reflect the liver function.

The role of cysteine conjugation in the detoxification of microcystin-LR in liver of bighead carp (Aristichthys nobilis): a field and laboratory study

The role of glutathione (GSH) and cysteine (Cys) conjugates in the detoxification of microcystin-LR (MC-LR) in bighead carp (Aristichthys nobilis) was examined under laboratory and field conditions. Wild individuals of bighead carp were collected from 5 eutrophic lakes along the Yangtze River, while in laboratory experiment, bighead carp were injected intraperitoneally with 500μg purified MC-LR/kg body weight (bw). Contents of MC-LR and its glutathione (MC-LR-GSH) and cysteine conjugates (MC-LR-Cys) in the liver of bighead carp were determined by liquid chromatography electrospray ionization mass spectrum (LC-ESI-MS). In laboratory experiment, low concentrations of MC-LR-GSH (mean: 0.042μg/g dry weight (DW)) were always detectable, and the mean ratio of MC-LR-Cys to MC-LR-GSH was 6.55. While, in field study, relatively high MC-LR-Cys concentration (mean: 0.22μg/g DW) was detected, whereas MC-LR-GSH was occasionally detectable, and the average ratio of MC-LR-Cys to MC-LR-GSH was as high as 71.49. A positive correlation was found between MC-LR-Cys concentration in the liver of bighead carp and MC-LR content in seston from the five lakes (r=0.85). These results suggest that MC-LR-Cys might be much more important than MC-LR-GSH in the detoxification of MC-LR in fish liver, and that cysteine conjugation of MC-LR might be a physiological mechanism for the phytoplanktivorous bighead carp to counteract toxic cyanobacteria.