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Hesperetin attenuated acetaminophen-induced hepatotoxicity by inhibiting hepatocyte necrosis and apoptosis, oxidative stress and inflammatory response via upregulation of heme oxygenase-1 expression.
Abstract Acetaminophen (APAP) is a common antipyretic and analgesic drug, but its overdose can induce acute liver failure with lack of effective therapies. Hesperetin, a dihydrogen flavonoid compound, has been revealed to exert multiple pharmacological activities. Here, we explored the protective effects and mechanism of hesperetin on APAP-induced hepatotoxicity. The results showed that pretreatment with hesperetin dose-dependently attenuated APAP-induced acute liver injury in mice, as measured by alleviated serum enzymes activities, hepatic pathological damage and apoptosis. Moreover, hesperetin mitigated APAP-in...
Source: International Immunopharmacology - March 25, 2020 Category: Allergy & Immunology Authors: Wan J, Kuang G, Zhang L, Jiang R, Chen Y, He Z, Ye D Tags: Int Immunopharmacol Source Type: research

GLT25D2 Is Critical for Inflammatory Immune Response to Promote Acetaminophen-Induced Hepatotoxicity by Autophagy Pathway
In conclusion, our study proves that the upregulated expression of GLT25D2 decreased autophagy contributing to APAP-induced hepatotoxicity by mediating the inflammatory immune regulatory mechanism.
Source: Frontiers in Pharmacology - September 17, 2020 Category: Drugs & Pharmacology Source Type: research

Human superoxide dismutase 1 attenuates quinoneimine metabolite formation from mefenamic acid.
In conclusion, we found that SOD1 can serve as a detoxification enzyme for quinoneimines to protect from drug-induced toxicity. PMID: 33259822 [PubMed - as supplied by publisher]
Source: Toxicology - November 28, 2020 Category: Toxicology Authors: Ogiso T, Fukami T, Zhongzhe C, Konishi K, Nakano M, Nakajima M Tags: Toxicology Source Type: research

Caveolin-1 Alleviates Acetaminophen-Induced Fat Accumulation in Non-Alcoholic Fatty Liver Disease by Enhancing Hepatic Antioxidant Ability via Activating AMPK Pathway
In this study, seven-week-old C57BL/6 male mice (18–20 g) were raised under similar conditions for in vivo experiment. In vitro, L02 cells were treated with A/O (alcohol and oleic acid mixture) for 48 h, and APAP was added at 24 h for further incubation. The results showed that the protein expression of the AMPK/Nrf2 pathway was enhanced after CAV1 upregulation. The effects of CAV1 on fat accumulation, ROS, and the AMPK/Nrf2 anti-oxidative pathway were reduced after the application of CAV1-siRNA. Finally, treatment with compound C (an AMPK inhibitor) prevented CAV1 plasmid-mediated alleviation of oxidative stress and ...
Source: Frontiers in Pharmacology - July 7, 2021 Category: Drugs & Pharmacology Source Type: research

The Relationship between Prohibitin 1 Expression, Hepatotoxicity Induced by Acetaminophen, and Hepatoprotection by S-Adenosylmethionine in AML12 Cells
In this study, we sought to understand the regulation of mRNA expression in relation to APAP and GSH metabolism by Phb1 in normal mouse AML12 hepatocytes. We used two different Phb1 silencing levels: high-efficiency (HE, >90%) and low-efficiency (LE, 50- 60%). In addition, the siRNA-transfected cells were further pretreated with 0.5 mM of Sadenosylmethionine (SAMe) for 24 h before treatment with APAP at different doses (1-2 mM) for 24 h. The expression of APAP metabolism-related and antioxidant genes such as Cyp2e1 and Ugt1a1 were increased during SAMe pretreatment. Moreover, SAMe increased intracellular GSH concentrati...
Source: Journal of Microbiology and Biotechnology - October 31, 2022 Category: Biotechnology Authors: Eunhye Cho Soohan Jung Jina Kim Kwang Suk Ko Source Type: research

Caveolin-1 alleviates acetaminophen-induced vascular oxidative stress and inflammation in non-alcoholic fatty liver disease
In conclusion, our findings confirmed that CAV1 exerts a protective effect against vascular injury by inhibiting oxidative stress and inflammation through the PKC/MAPK pathway. Therefore, restoration of CAV1 may have clinical benefits in reducing APAP-induced vascular damage in NAFLD patients.PMID:36596386 | DOI:10.1016/j.freeradbiomed.2022.12.095
Source: Free Radical Biology and Medicine - January 3, 2023 Category: Biology Authors: Dongdong Fu Shuai Wu Xiangfu Jiang Tingyu You Yu Li Jiao Xin Xiaowen Feng Jiagen Wen Yan Huang Chengmu Hu Source Type: research

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