Animal Kernicterus Models: Progress and Challenges

Amini, Naser; Bakhshayesh, Babak; Ramezani, Sara; Sarmadi, Vahid Hosseinpour; Milan, Peiman Brouki; Ashraf, Seyedeh Sara; Larijani, Ghazaleh; Gharahgheshlagh, Soheila Naderi; Derakhshanmehr, Bahareh; Mohebbi, Seyedeh Lena; Joghataei, Mohammad Taghi

doi:10.1016/j.brainres.2021.147624

Cited by 4 publications

(6 citation statements)

References 27 publications

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“…The etiology of hyperbilirubinemia Is very complex; It is one of the most common diseases of newborns, and it also occurs in people in various conditions, such as hepatitis, cirrhosis, sepsis, liver transplantation and heart surgery [ 46 ]. Studies [ 46 , 47 , 48 , 49 , 50 , 51 , 52 ] have shown that hyperbilirubinemia and liver injury interact with each other. When liver clearance is low [ 53 ], hyperbilirubinemia may occur.…”

Section: Discussionmentioning

confidence: 99%

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A Novel Drug with Potential to Treat Hyperbilirubinemia and Prevent Liver Damage Induced by Hyperbilirubinemia: Carbon Dots Derived from Platycodon grandiflorum

Chen

et al. 2023

Molecules

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Platycodon grandiflorum (PG) is a traditional Chinese medicine with a long history, but its active compounds have not been reported. In this study, novel carbon dots (CDs), PG-based CDs (PGC-CDs), were discovered and prepared from PG via calcinations and characterized by transmission electron microscopy; high-resolution transmission electron microscopy; X-ray diffraction, fluorescence, ultraviolet-visible, and Fourier-transform infrared spectrometers; X-ray photoelectron spectroscopy; and high-performance liquid chromatography. In addition, the safety and antioxidant activity of PGC-CDs was evaluated by RAW264.7 cells and LO2 cells. The therapeutic effects of PGC-CDs on hyperbilirubinemia and liver protection were evaluated in a bilirubin-induced hyperbilirubinemia mice model. The experiment confirmed that the diameter range of PGC-CDs was from 1.2 to 3.6 nm. PGC-CDs had no toxicity to RAW264.7 cells and LO2 cells at a concentration of 3.91 to 1000 µg/mL and could reduce the oxidative damage of cells caused by H2O2. PGC-CDs could inhibit the increase levels of bilirubin and inflammation factors and increase the levels of antioxidants and survival rate, demonstrating that PGC-CDs possessed anti-inflammatory and anti-oxidation activity. PGC-CDs may reduce the content of bilirubin, so as to reduce a series of pathological lesions caused by bilirubin, which has potential in treating hyperbilirubinemia and preventing liver damage induced by hyperbilirubinemia.

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Section: Discussionmentioning

confidence: 99%

“…The hyperbilirubinemia model Induced by the direct Injection of bilirubin Is a stable, economical and simple model [ 49 ]. This study provided a reference for the establishment of a liver damage model induced by hyperbilirubinemia.…”

Section: Discussionmentioning

confidence: 99%

A Novel Drug with Potential to Treat Hyperbilirubinemia and Prevent Liver Damage Induced by Hyperbilirubinemia: Carbon Dots Derived from Platycodon grandiflorum

Chen

et al. 2023

Molecules

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“…Although rodent models of hyperbilirubinemia and bilirubin-induced neurological damage (BIND) have been developed before, alternative models are still needed to recapitulate newborn hyperbilirubinemia to the full extent ( Amini et al, 2021 ). Here, the first zebrafish hyperbilirubinemia model is generated via exposure of early zebrafish larvae to external bilirubin.…”

Section: Discussionmentioning

confidence: 99%

“…Induction of hemolysis by drug administration or direct injection of bilirubin into the brain are among the methods to induce newborn hyperbilirubinemia ( Rice and Shapiro, 2008 ; Song et al, 2014 ; Amini et al, 2017 ). Each model has its own advantages and disadvantages, as well as technical challenges, and the need for in vivo models that will allow mechanistic studies to be performed to understand BIND mechanisms and develop preventive strategies is not fulfilled ( Amini et al, 2021 ; Pranty et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

A zebrafish model for studying the mechanisms of newborn hyperbilirubinemia and bilirubin-induced neurological damage

Guzelkaya,

Onal,

Gelinci

et al. 2023

Front. Cell Dev. Biol.

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Unresolved neonatal hyperbilirubinemia may lead to the accumulation of excess bilirubin in the body, and bilirubin in neural tissues may induce toxicity. Bilirubin-induced neurological damage (BIND) can result in acute or chronic bilirubin encephalopathy, causing temporary or lasting neurological dysfunction or severe damage resulting in infant death. Although serum bilirubin levels are used as an indication of severity, known and unknown individual differences affect the severity of the symptoms. The mechanisms of BIND are not yet fully understood. Here, a zebrafish newborn hyperbilirubinemia model is developed and characterized. Direct exposure to excess bilirubin induced dose- and time-dependent toxicity linked to the accumulation of bilirubin in the body and brain. Introduced bilirubin was processed by the liver, which increased the tolerance of larvae. BIND in larvae was demonstrated by morphometric measurements, histopathological analyses and functional tests. The larvae that survived hyperbilirubinemia displayed mild or severe morphologies associated with defects in eye movements, body posture and swimming problems. Interestingly, a plethora of mild to severe clinical symptoms were reproduced in the zebrafish model.

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“…Induction of hemolysis by drug administration or direct injection of bilirubin into the brain are among methods to induce newborn hyperbilirubinemia (12)(13)(14). Each model has its own advantages and disadvantages, as well as technical challenges; and need for in vivo models that will allow mechanistic studies to be performed for understanding BIND mechanisms and develop preventive strategies is not fulfilled (8,15). Zebrafish model can offer advantages such as ease of live imaging throughout embryonic and larval stages, ease of chemical exposure and genetic modifications.…”

Section: Introductionmentioning

confidence: 99%

A zebrafish model for studying mechanisms of newborn hyperbilirubinemia and bilirubin induced neurological damage

Guzelkaya,

Onal,

Gelinci

et al. 2023

Preprint

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Unresolved neonatal hyperbilirubinemia may lead to accumulation of excess bilirubin in the body, and bilirubin in the neural tissues may induce toxicity. Bilirubin induced neurological damage (BIND) can result in acute or chronic bilirubin encephalopathy, causing temporary or lasting neurological dysfunction or severe damage resulting in infant death. Although serum bilirubin levels are used as an indication of severety, known and unknown individual differences affect the severity of the symptoms. The mechanisms of BIND have not been fully understood yet. Here, a zebrafish newborn hyperbilirubinemia model is developed and characterized. Direct exposure to excess bilirubin induced dose and time dependent toxicity linked to the accumulation of bilirubin in the body and brain. Introduced bilirubin was processed by liver which increased the tolerance of larvae. BIND in larvae was demonstrated by morphometric measurements, histopathological analyses and functional tests. The larvae that survived hyperbilirubinemia displayed mild or severe morphologies associated with defects in eye movements, body posture and swimming problems. Interestingly, the plethora of mild to severe clinical symptoms were reproduced in the zebrafish model.

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Animal Kernicterus Models: Progress and Challenges

Cited by 4 publications

References 27 publications

A Novel Drug with Potential to Treat Hyperbilirubinemia and Prevent Liver Damage Induced by Hyperbilirubinemia: Carbon Dots Derived from Platycodon grandiflorum

A Novel Drug with Potential to Treat Hyperbilirubinemia and Prevent Liver Damage Induced by Hyperbilirubinemia: Carbon Dots Derived from Platycodon grandiflorum

A zebrafish model for studying the mechanisms of newborn hyperbilirubinemia and bilirubin-induced neurological damage

A zebrafish model for studying mechanisms of newborn hyperbilirubinemia and bilirubin induced neurological damage

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