Effects of MC-LR on histological structure and cell apoptosis in the kidney of grass carp (Ctenopharyngodon idella)

He, Li; Liu, Lin; Lin, Changgao; Ruan, Jiming; Liang, Ximei; Zhou, Ying; Wei, Lili

doi:10.1007/s10695-020-00833-5

Cited by 16 publications

(4 citation statements)

References 36 publications

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“…It had been reported that mitochondria serve as the central mediators of MC-LR cytotoxicity, initiating different signaling pathways [ 49 ]. In the present study, the ultrastructural analysis observed swollen and broken mitochondria in MC-LR-treated HEK293 cells, along with partial autophagosomes and increased lysosomes, which is in parallel with the results of He’s group [ 25 ].…”

Section: Discussionsupporting

confidence: 91%

“…A study with 3 different doses (25,75, and 100 µg/kg body weight) of MC-LR treatment in grass carp suggested that MC-LR could lead to the structural destruction of the kidneys, and massive swollen mitochondrial and vacuolar degeneration was found using transmission electron microscopy [25]. In addition, apoptosis features such as chromatin concentration and cell contraction were observed in the high-dose infected group [26].…”

Section: Introductionmentioning

confidence: 99%

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Microcystin-LR-Exposure-Induced Kidney Damage by Inhibiting MKK6-Mediated Mitophagy in Mice

Yao

Liu

Yang

et al. 2023

Toxins

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Previous studies have reported that microcystin-LR (MC-LR) levels are highly correlated with abnormal renal function indicators, suggesting that MC-LR is an independent risk factor for kidney damage. However, the evidence for the exact regulation mechanism of MC-LR on kidney damage is still limited, and further in-depth exploration is needed. In addition, the mitochondria-related mechanism of MC-LR leading to kidney damage has not been elucidated. To this end, the present study aimed to further explore the mechanism of mitophagy related to kidney damage induced by MC-LR through in vitro and in vivo experiments. Male C57BL/6 mice were fed with a standard rodent pellet and exposed daily to MC-LR (20 μg/kg·bw) via intraperitoneal injections for 7 days. Moreover, HEK 293 cells were treated with MC-LR (20 μM) for 24 h. The histopathological results exhibited kidney damage after MC-LR exposure, characterized by structurally damaged nephrotomies, with inflammatory cell infiltration. Similarly, a significant increase in renal interstitial fibrosis was observed in the kidneys of MC-LR-treated mice compared with those of the control group (CT) mice. MC-LR exposure caused impaired kidney function, with markedly increased blood urea nitrogen (BUN), creatinine (Cr), and uric acid (UA) levels in mice. Ultrastructural analysis exhibited obviously swollen, broken, and disappearing mitochondrial crests, and partial mitochondrial vacuoles in the MC-LR-treated HEK 293 cells. The Western blotting results demonstrated that exposure to MC-LR significantly increased the protein expressions of MKK6, p-p38, and p62, while the expression of mitophagy-related proteins was significantly inhibited in the kidneys of mice and HEK293 cells, including parkin, TOM20, and LC3-II, indicating the inhibition of mitophagy. Therefore, our data suggest that the inhibition of MKK6-mediated mitophagy might be the toxicological mechanism of kidney toxicity in mice with acute exposure to MC-LR.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Microcystin-LR-Exposure-Induced Kidney Damage by Inhibiting MKK6-Mediated Mitophagy in Mice

Yao

Liu

Yang

et al. 2023

Toxins

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“…Some studies indicate that As could cause oxidative stress, inflammation, and renal apoptosis by activating the PI3K/AKT signaling pathway [ 57 , 58 ]. In addition, MCs and As both can increase the expression of Bax and p53 and enhance the activity of caspase-3 to induce oxidative stress and apoptosis of renal cells [ 50 , 58 , 59 ]. Although current studies have shown that MCs and As have some common toxic effects and mechanisms on the kidney, further experiments still are needed to explore and verify the combined mechanism, which is the key to the prevention and treatment of renal insufficiency and deterioration of CKD.…”

Section: Discussionmentioning

confidence: 99%

Combination Effect of Microcystins and Arsenic Exposures on CKD: A Case-Control Study in China

Hong

Zhu

Deng

et al. 2023

Toxins

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Evidence has shown that exposure to environmental pollutants such as microcystins (MCs), arsenic (As), and cadmium (Cd) can lead to the occurrence and development of chronic kidney disease (CKD). There is a synergistic effect between MCs and Cd. However, the combined effect of MCs and As exposures on CKD remains unclear. In Hunan province, China, 135 controls and 135 CKD cases were enrolled in a case-control study. Serum MCs, plasma As and Cd concentrations were measured for all participants. We investigated the association between MCs/As and CKD risk using conditional logistic regression. The additive model explored the interaction effect, and the Bayesian kernel machine regression (BKMR) models investigated the combined effects of MCs, As, and Cd on CKD. The results showed that MCs and As were significantly associated with CKD risk. Participants in the highest MCs concentration had a 4,81-fold increased risk of CKD compared to those in the lowest quartile (95% confidence interval [CI]: 1,96 to 11,81). The highest quartile of As concentrations corresponded to an adjusted odds ratio of 3.40 (95% CI: 1.51, 7.65) relative to the lowest quartile. MCs/As and CKD risk exhibited significant dose–response correlations (all p for trend < 0.01). In addition, a positive interaction effect of MCs and As on CKD was also reported. The CKD risk due to interaction was 2.34 times (95% CI: 0.14, 4.54) relative to the CKD risk without interaction, and the attributable proportion of CKD due to interaction among individuals with both exposures was 56% (95% CI: 0.22, 0.91). In the BKMR, the combined effect of MCs, As, and Cd was positively associated with CKD. In conclusion, both MCs and As are independent risk factors for CKD, exerting a synergistic effect between them. Combined exposure to MCs, As, and Cd can increase the risk of CKD.

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“…The purification of MCs is problematic, resulting in the difficulty of obtaining sufficient standard reagents for MCs. 18 Fortunately, imprinting with a dummy template provides an opportunity to reduce costs. A segment of the MC molecule is used instead of MCs as templates for synthesizing MIPs.…”

Section: Introductionmentioning

confidence: 99%

A dummy molecularly imprinted ratiometric fluorescence nanosensor for the sensitive detection of guanidyl-microcystins in environmental water

Bai

et al. 2023

Analyst

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Effects of MC-LR on histological structure and cell apoptosis in the kidney of grass carp (Ctenopharyngodon idella)

Cited by 16 publications

References 36 publications

Microcystin-LR-Exposure-Induced Kidney Damage by Inhibiting MKK6-Mediated Mitophagy in Mice

Microcystin-LR-Exposure-Induced Kidney Damage by Inhibiting MKK6-Mediated Mitophagy in Mice

Combination Effect of Microcystins and Arsenic Exposures on CKD: A Case-Control Study in China

A dummy molecularly imprinted ratiometric fluorescence nanosensor for the sensitive detection of guanidyl-microcystins in environmental water

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