Functional and toxicological consequences of metabolic bioactivation of methapyrilene via thiophene S-oxidation: Induction of cell defence, apoptosis and hepatic necrosis

Mercer, Amy E.; Regan, Sophie; Hirst, Charlotte; Graham, Emma E.; Antoine, Daniel J.; Benson, Craig A.; Williams, Dominic P.; Foster, John R.; Kenna, J. Gerry; Park, B. Kevin

doi:10.1016/j.taap.2009.05.027

Cited by 22 publications

(12 citation statements)

References 31 publications

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“…Although infusion of MSCs often results in attenuation or improvement of liver disease, current studies have not provided definitive evidence that MSCs have a capability to differentiate into functional hepatocytes in vivo 91–95 . In turn, these improvements could be attributed to the secretion of soluble factors by MSCs, rather then transdifferentiation into hepatocytes.…”

Section: Progress In Developing Therapies For Liver Fibrosismentioning

confidence: 95%

Anti-fibrogenic strategies and the regression of fibrosis

Kisseleva

Brenner

2011

Best Practice & Research Clinical Gastroenterology

148

110

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Liver fibrosis is an outcome of many chronic diseases, and often results in cirrhosis, liver failure, and portal hypertension. Liver transplantation is the only treatment available for patients with advanced stage of fibrosis. Therefore, alternative methods are required to develop new strategies for anti-fibrotic therapy. Available treatments are designed to substitute for liver transplantation or bridge the patients, they include inhibitors of fibrogenic cytokines such as TGF-β1 and EGF, inhibitors of rennin angiotensin system, and blockers of TLR4 signaling. Development of liver fibrosis is orchestrated by many cell types. However, activated myofibroblasts remain the primary target for anti-fibrotic therapy. Hepatic stellate cells and portal fibroblasts are considered to play a major role in development of liver fibrosis. Here we discuss the origin of activated myofibroblasts and different aspects of their activation, differentiation and potential inactivation during regression of liver fibrosis.

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Section: Progress In Developing Therapies For Liver Fibrosismentioning

confidence: 95%

Anti-fibrogenic strategies and the regression of fibrosis

Kisseleva

Brenner

2011

Best Practice & Research Clinical Gastroenterology

148

110

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“…원물질 의 활성화란 독성을 유발하기 위해 세포 및 인체를 구성하는 거 대분자인 당, 단백질, DNA 그리고 지질 등과의 결합 능력이나 라디칼(radical)을 생성할 수 있는 능력을 의미한다 (Park et al, 2014). 대부분 부식을 비롯하여 자극성 및 감작성 등의 피부손상 도 원물질의 활성화에 기인하다 (Mercer et al, 2009;Madden et al, 2017;Weston et al, 2014). 활성화는 자연분해(natural decomposition) 및 cytochrome P450 등과의 효소에 의한 과 정인 생화학적 전환으로 이루어진다 (Park et al, 2014 (Agner & Serup, 1990;Barel et al, 2014;Nizioł-Łukaszewska et al, 2017;Rhein et al, 2006).…”

Section: 일반적으로 화학물질의 독성은 원물질(Parent Compound)unclassified

Initial Toxicity Screening Techniques of Skin Contact Materials Using Glutathione

Heo¹,

An²,

Yoon³

et al. 2019

Asian J Beauty Cosmetol

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Purpose: We developed a glutathione-containing screening (GCS) system capable of confirming toxicity at the substance screening stage aimed at reducing the time and cost of the cosmetic raw material development stage. Methods: Based on genotoxicity testing, a GCS system, comprising a direct and indirect system, was developed to reduce the time and cost to identify toxicity during the screening of candidate cosmetic substances. Toxicity potential was confirmed by identifying changes in the content of total glutathione (GSH), which conjugates only toxic substances, and those in the glutathione disulfide (GSSG)/GSH ratio. Results: Heptanal, a positive control substance in skin irritation tests, showed a decrease in total GSH and was identified as a direct-acting toxicant. Eugenol, a positive control substance in skin sensitization tests, showed a decrease in total GSH and an altered GSSG/GSH ratio and was identified as an indirect-acting toxicant. Conclusion: The GCS system could identify toxicity characteristics of skin irritation and sensitization. However, more positive chemicals are required to induce skin irritation or sensitization to challenge a chemical's toxic classification such as irritation or sensitization according to the GCS system, direct and indirect systems.

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“… 36 The regional hepatic injury pattern observed after administration of methapyrilene and allyl alcohol to rats, consists of periportal necrosis. 36 , 37 Importantly, differential zonal responses to hepatotoxins, assists in dissecting more sensitive mechanistic details, which are highly unlikely to be observed in in vitro models. For example, the periportal rat hepatotoxin, methapyrilene, elicits initial glutathione depletion in periportal hepatocytes, whilst stimulating glutathione synthesis and adaptation in centrilobular hepatocytes.…”

Section: Physiological Replication In In Vitro Modmentioning

confidence: 99%