S‐allyl cysteine, an active ingredient of garlic, attenuates acute liver dysfunction induced by lipopolysaccharide/<scp>d</scp>‐galactosamine in mouse: Underlying mechanisms

Rousta, Ali Mohammad; Mirahmadi, Seyed-Mohamad-Sadegh; Shahmohammadi, Alireza; Ramzi, Samira; Baluchnejadmojarad, Tourandokht; Roghani, Mehrdad

doi:10.1002/jbt.22518

Cited by 11 publications

(6 citation statements)

References 68 publications

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“…To minimize damaging effects of oxidative stress, antioxidants including SOD, catalase, and GSH are determining defensive factors 62 . Increment of such beneficial factors protects tissues against oxidative stress consequences via cleansing free radicals 19 63 . Acetaminophen administration at a high dose elevates hepatic ROS and MDA and reduces level of antioxidants 64 which is also seen in this study.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Potential of Isorhamnetin following Acetaminophen-Induced Hepatotoxicity through Targeting NLRP3/NF-κB/Nrf2

et al. 2022

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Acetaminophen (APAP)-induced acute liver injury (ALI) is the principal cause of acute liver failure (ALF) in some countries including the United States and with few available treatments. Isorhamnetin is a bioflavonoid that is found in medicinal plants like Hippophae rhamnoides L. and Ginkgo biloba L. with promising potential to regulate inflammatory responses. In this study, we evaluated the possible effect of isorhamnetin in prevention of APAP-induced ALI and analyzed further the involvement of oxidative stress and inflammation-associated factors. Male C57BL/6 mice were given isorhamnetin (25 or 100 mg/kg b.w., p.o.) three times at 48, 24, and 1 h before APAP administration (300 mg/kg b.w., i.p.). Functional indicators of liver injury were measured as well as analysis of oxidative stress- and inflammation-associated indices and liver histopathology was also conducted. Isorhamnetin at the higher dose of 100 mg/kg significantly lowered serum levels of ALT, ALP, and AST in addition to reduction of ROS, TBARS, IL-6, TNFα, NF-kB, NLRP3, caspase 1, and MPO and significantly prevented reduction of GSH, SOD activity, sirtuin 1, and Nrf2. Additionally, isorhamnetin alleviated pathological changes of the liver tissue and suitably reversed NF-kB and Nrf2 immunoreactivity. These findings show protective effect of isorhamnetin against acetaminophen-induced liver injury through reducing oxidative stress, inflammation, and pyroptosis which is attributed to its regulation of NF-kB, Nrf2, NLRP3, and sirtuin 1.

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Section: Discussionmentioning

confidence: 99%

Therapeutic Potential of Isorhamnetin following Acetaminophen-Induced Hepatotoxicity through Targeting NLRP3/NF-κB/Nrf2

et al. 2022

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“…Betaine can prevent/protect against apoptosis induced by an array of agents [ 24 , 46 , 47 , 48 ]. Strategies increasing the anti-apoptotic armamentarium of hepatocytes have been shown to beneficially impact the outcome of fulminant hepatic failure [ 56 , 57 , 58 , 59 , 60 , 61 , 62 ]. In this study, we show that betaine is also effective in protecting against LPS-GalN-induced apoptosis in RD mice.…”

Section: Discussionmentioning

confidence: 99%

“…We believe that betaine pretreatment prevents SAM depletion and thereby prevents the hypomethylation of ribosomal RNA induced by GalN treatment and the “priming” of hepatocytes to subsequent damage [ 67 , 68 ]. While many agents have been used to ameliorate LPS/GalN liver damage [ 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 69 , 70 , 71 , 72 ], betaine is inexpensive, bioavailable [ 73 , 74 ], and has no consistent relation with cancer, cardiovascular risk, or risk factors [ 75 ], making it a safe therapeutic.…”

Section: Discussionmentioning

confidence: 99%

Susceptibility of Asialoglycoprotein Receptor-Deficient Mice to LPS/Galactosamine Liver Injury and Protection by Betaine Administration

Rasineni

Lee

McVicker

et al. 2020

Biology

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Background: Work from our laboratory has shown that the ethanol-induced increase in apoptotic hepatocellular death is closely related to the impairment in the ability of the asialoglycoprotein receptor (ASGP-R) to remove neighboring apoptotic cells. In this study, we assessed the role of ASGP-R in fulminant liver failure and investigated whether prior treatment with betaine (a naturally occurring tertiary amine) is protective. Methods: Lipopolysaccharide (LPS; 50 μg/kg BW) and galactosamine (GalN; 350 mg/kg BW) were injected together to wild-type and ASGP-R-deficient mice that were treated for two weeks prior with or without 2% betaine in drinking water. The mice were sacrificed 1.5, 3, or 4.5 h post-injection, and tissue samples were collected. Results: LPS/GalN injection generate distinct molecular processes, which includes increased production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), thus causing apoptosis as evident by increased caspase-3 activity. ASGP-R deficient animals showed increased liver caspase activities, serum TNF-α and IL-6 levels, as well as more pronounced liver damage compared with the wild-type control animals after intraperitoneal injection of LPS/GalN. In addition, prior administration of betaine was found to significantly attenuate the LPS/GalN-induced increases in liver injury parameters. Conclusion: Our work underscores the importance of normal functioning of ASGP-R in preventing severe liver damage and signifies a therapeutic role of betaine in prevention of liver injuries from toxin-induced fulminant liver failure.

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“…The dose of the mixture was in accordance with previous studies. 17 , 18 First, mice received 30 or 60 mg/kg Rb1 by intraperitoneal injection for 3 days, while the control group and D-GalN/LPS group received the same volume of 0.9% saline for 3 days. On the third day, 1 h after the final Rb1 or 0.9% saline injection, the D-GalN/LPS group, the D-GalN/LPS+30 mg/kg Rb1 group and the D-GalN/LPS+60 mg/kg Rb1 group received D-GalN/LPS injection for the induction of ALI, while the control group was given the same volume of 0.9% saline.…”

Section: Methodsmentioning

confidence: 99%

Ginsenoside Rb1 Reduces D-GalN/LPS-induced Acute Liver Injury by Regulating TLR4/NF-κB Signaling and NLRP3 Inflammasome

Liu¹,

Liu²,

Liu³

et al. 2021

J Clin Transl Hepatol

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Background and Aims:The effect of ginsenoside Rb1 on D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver injury (ALI) is unknown. The aim of this study was to evaluate the effect of ginsenoside Rb1 on ALI and its underlying mechanisms. Methods: Mice were pretreated with ginsenoside Rb1 by intraperitoneal injection for 3 days before D-GalN/LPS treatment, to induce ALI. The survival rate was monitored every hour for 24 h, and serum biochemical parameters, hepatic index and histopathological analysis were evaluated to measure the degree of liver injury. ELISA was used to detect oxidative stress and inflammatory cytokines in hepatic tissue and serum. Immunohistochemistry staining, RT-PCR and western blotting were performed to evaluate the expression of toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), and NLR family, pyrin domain-containing 3 protein (NLRP3) in liver tissue and Kupffer cells (KCs). Results: Ginsenoside Rb1 improved survival with D-GalN/LPS-induced ALI by up to 80%, significantly ameliorated the increased alanine and aspartate transaminase, restored the hepatic pathological changes and reduced the levels of oxidative stress and inflammatory cytokines altered by D-GalN/LPS. Compared to the control group, the KCs were increased in the D-GalN/ LPS groups but did not increase significantly with Rb1 pretreatment. D-GalN/LPS could upregulate while Rb1 pretreatment could downregulate the expression of interleukin (IL)-1β, IL-18, NLRP3, apoptosis associated speck-like protein containing CARD (ASC) and caspase-1 in isolated KCs. Furthermore, ginsenoside Rb1 inhibited activation of the TLR4/NF-κB signaling pathway and NLRP3 inflammasome induced by D-GalN/LPS administration. Conclusions: Ginsenoside Rb1 protects mice against D-GalN/LPS-induced ALI by attenuating oxidative stress and the inflammatory response through the TLR4/NF-κB signaling pathway and NLRP3 inflammasome activation.

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S‐allyl cysteine, an active ingredient of garlic, attenuates acute liver dysfunction induced by lipopolysaccharide/d‐galactosamine in mouse: Underlying mechanisms

Cited by 11 publications

References 68 publications

Therapeutic Potential of Isorhamnetin following Acetaminophen-Induced Hepatotoxicity through Targeting NLRP3/NF-κB/Nrf2

Therapeutic Potential of Isorhamnetin following Acetaminophen-Induced Hepatotoxicity through Targeting NLRP3/NF-κB/Nrf2

Susceptibility of Asialoglycoprotein Receptor-Deficient Mice to LPS/Galactosamine Liver Injury and Protection by Betaine Administration

Ginsenoside Rb1 Reduces D-GalN/LPS-induced Acute Liver Injury by Regulating TLR4/NF-κB Signaling and NLRP3 Inflammasome

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