Capsaicin, the pungent principle of peppers, ameliorates alcohol-induced acute liver injury in mice via modulation of matrix metalloproteinases

Alcohol, the most common cause for hepatic injury, may further deteriorate the hepatic tissue when left unattended. Capsaicin, the pungent principle of chilli peppers, possesses antioxidant and anti-inflammatory properties and is a proven dietary antioxidant in various ailments. However, its role in alcohol-induced hepatic injury is unclear. In this study, we investigated the effects of capsaicin on the hepatic tissue of mice treated with alcohol. Acute liver injury was induced in mice by oral gavage of 5 doses of 10 mL/kg of 50% ethyl alcohol at an interval of 12 h. The tissue antioxidant levels along with the mitochondrial functional parameters and matrix metalloproteinase levels were evaluated in the hepatic tissues of mice following alcohol challenge. The results showed that alcohol intake significantly attenuated the hepatic antioxidant levels and mitochondrial function. These changes were accompanied by enhanced serum hepatic injury markers and matrix metalloproteinases. However, capsaicin treatment (10 and 20 mg/kg, oral) throughout the experimental period caused a drastic improvement in the hepatic tissue of the alcohol-treated mice, reflected by the normalization of hepatic enzyme and protein levels along with restored histological alterations. These results indicate that capsaicin, as a dietary intervention, may prevent alcohol-induced acute liver injury.

Download Full-text

Acute liver injury associated with Oxyfluorfen toxicity

SAGE Open Medical Case Reports ◽

10.1177/2050313x211000454 ◽

2021 ◽

Vol 9 ◽

pp. 2050313X2110004

Author(s):

Selladurai Pirasath ◽

Ayshanie Gayanthika Samasundara Mudiyanselage ◽

Manosha Harshani Seneviratne

Keyword(s):

Sri Lanka ◽

Liver Injury ◽

Young Woman ◽

Broad Spectrum ◽

Hepatic Injury ◽

Acute Liver Injury ◽

Toxic Dose ◽

Acute Hepatic Injury ◽

Haem Biosynthesis ◽

Spectrum Control

Oxyfluorfen is a phenoxyphenyl-type herbicide which is used for broad-spectrum control of broadleaf and grassy weeds. Ingestion of toxic dose of oxyfluorfen can be fatal among animals. However, toxicity to humans are rare in literature. The alterations in haem biosynthesis (anaemia) and in liver are the primary toxic effects. There are no specific antidotes and none of the current treatments have proven efficacious till date. Therefore, prevention needs to be the utmost priority, and on exposure, aggressive decontamination should be initiated. Herein, we described an oxyfluorfen toxicity with acute hepatic injury in a young woman who presented with a deliberate self-harming with an oxyfluorfen poisoning in Sri Lanka.

Download Full-text

Mechanism of KLF4 Protection against Acute Liver Injury via Inhibition of Apelin Signaling

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/6140360 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Weitao Ji ◽

Hongyun Shi ◽

Hailin Shen ◽

Jing Kong ◽

Jiayi Song ◽

...

Keyword(s):

Liver Injury ◽

Signaling Pathway ◽

Acute Liver Injury ◽

Control Group ◽

Necrosis Factor Alpha ◽

Protein Levels ◽

Klf4 Expression ◽

Mrna And Protein Expression

Krüppel-like factor 4 (KLF4) is a key transcription factor that regulates genes involved in the proliferation or differentiation in different tissues. Apelin plays roles in cardiovascular functions, metabolic disease, and homeostatic disorder. However, the biological function of apelin in liver disease is still ongoing. In this study, we investigated the mechanism of KLF4-mediated protection against acute liver injury via the inhibition of the apelin signaling pathway. Mice were intraperitoneally injected with carbon tetrachloride (CCl4; 0.2 mL dissolved in 100 mL olive oil, 10 mL/kg) to establish an acute liver injury model. A KLF4 expression plasmid was injected through the tail vein 48 h before CCl4 treatment. In cultured LX-2 cells, pAd-KLF4 or siRNA KLF4 was overexpressed or knockdown, and the mRNA and protein levels of apelin were determined. The results showed that the apelin serum level in the CCl4-injected group was higher than that of control group, and the expression of apelin in the liver tissues was elevated while KLF4 expression was decreased in the CCl4-injected group compared to the KLF4-plasmid-injected group. HE staining revealed serious hepatocellular steatosis in the CCl4-injected mice, and KLF4 alleviated this steatosis in the mice injected with KLF4 plasmid. In vitro experiments showed that tumor necrosis factor-alpha (TNF-α) could downregulate the transcription and translation levels of apelin in LX-2 cells and also upregulate KLF4 mRNA and protein expression. RT-PCR and Western blotting showed that the overexpression of KLF4 markedly decreased basal apelin expression, but knockdown of KLF4 restored apelin expression in TNF-α-treated LX-2 cells. These in vivo and in vitro experiments suggest that KLF4 plays a key role in inhibiting hepatocellular steatosis in acute liver injury, and that its mechanism might be the inhibition of the apelin signaling pathway.

Download Full-text

Systemic and hepatic hemodynamic changes in acute liver injury

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1997.272.3.g617 ◽

1997 ◽

Vol 272 (3) ◽

pp. G617-G625 ◽

Cited By ~ 5

Author(s):

A. J. Makin ◽

R. D. Hughes ◽

R. Williams

Keyword(s):

Blood Flow ◽

Liver Injury ◽

Hepatic Injury ◽

Acute Liver Injury ◽

Venous Blood ◽

Marked Change ◽

Arterial Blood Flow ◽

Venous Flow ◽

Subsequent Increase ◽

Arterial Blood

Systemic and hepatic circulatory changes were studied in rats over the course of acute liver injury. Hepatic injury was induced by intraperitoneal injection of D-galactosamine (1.1 g/kg), and systemic and hepatic hemodynamics were measured over a 72-h period using a radioactive microsphere technique with direct measurement of arterial, portal venous, and hepatic venous blood oxygen content. Cardiac output increased to a maximum at 48 h, producing a marked increase (450%) in hepatic arterial blood flow so that it became the dominant supply of oxygen at the time of maximal hepatic injury. A subsequent increase in portal venous flow resulted in an overall increase in total hepatic blood flow of 500%. At this point the oxygen delivery by the hepatic arterial and portal venous systems was equal. These circulatory changes returned to control values by 72 h with recovery of liver function. These results demonstrate the development of a hyperdynamic circulation and a marked change in the normal relationship between portal venous and hepatic arterial blood flows that occur during hepatic injury.

Download Full-text

Polydatin alleviates alcohol-induced acute liver injury in mice: Relevance of matrix metalloproteinases (MMPs) and hepatic antioxidants

Phytomedicine ◽

10.1016/j.phymed.2017.01.013 ◽

2017 ◽

Vol 27 ◽

pp. 23-32 ◽

Cited By ~ 16

Author(s):

Meghana Koneru ◽

Bidya Dhar Sahu ◽

Sagarika Gudem ◽

Madhusudana Kuncha ◽

Halley Gora Ravuri ◽

...

Keyword(s):

Liver Injury ◽

Matrix Metalloproteinases ◽

Acute Liver Injury

Download Full-text

Protective Effect of Lactiplantibacillus plantarum 1201 Combined with Galactooligosaccharide on Carbon Tetrachloride-Induced Acute Liver Injury in Mice

Nutrients ◽

10.3390/nu13124441 ◽

2021 ◽

Vol 13 (12) ◽

pp. 4441

Author(s):

Zhongyue Ren ◽

Yalan Huo ◽

Qimeng Zhang ◽

Shufang Chen ◽

Huihui Lv ◽

...

Keyword(s):

Carbon Tetrachloride ◽

Liver Injury ◽

Dietary Intervention ◽

Acute Liver Injury ◽

Intestinal Flora ◽

Intestinal Barrier ◽

16S Rrna Gene Sequencing ◽

Research Direction ◽

Hepatic Function ◽

Rrna Gene

Acute liver injury (ALI) has a high mortality rate of approximately 20–40%, and it is imperative to find complementary and alternative drugs for treating ALI. A carbon tetrachloride (CCl4)-induced ALI mouse model was established to explore whether dietary intervention can alleviate ALI in mice. Intestinal flora, intestinal integrity, biomarkers of hepatic function, systemic inflammation, autophagy, and apoptosis signals were detected through a real-time PCR, hematoxylin-eosin staining, 16S rRNA gene sequencing, and so on. The results showed that Lactiplantibacillus plantarum 1201 had a strongly antioxidant ability, and galactooligosaccharide (GOS) could boost its growth. Based on these findings, the combination of L. plantarum 1201 and GOS, the synbiotic, was applied to prevent CCl4-induced ALI in mice. The current research proved that GOS promoted the intestinal colonization of L. plantarum 1201, and the synbiotic improved the antioxidant capacity of the host, regulated the intestinal flora, repaired the intestinal barrier, inhibited the activation of the MAPK/NF-κB pathway, and then inhibited the apoptosis and autophagy pathways, relieving inflammation and liver oxidation; thereby, the ALI of mice was alleviated. These results suggest that synbiotics may become a new research direction for liver-protecting drugs.

Download Full-text

Ascites management by cell-free concentrated ascites reinfusion therapy during recovery from drug-induced acute liver injury: a case report

Journal of Medical Case Reports ◽

10.1186/s13256-020-02507-5 ◽

2020 ◽

Vol 14 (1) ◽

Cited By ~ 1

Author(s):

Koya Yasuda ◽

Mea Asou ◽

Tomohiko Asakawa ◽

Makoto Araki

Keyword(s):

Liver Injury ◽

Liver Regeneration ◽

Hepatic Injury ◽

Acute Liver Injury ◽

Artery Bypass ◽

Severe Disease ◽

International Normalized Ratio ◽

Cardiac Complications ◽

Massive Ascites ◽

Drug Induced

Abstract Background The symptoms of drug-induced hepatic injury are manifold; however, the presence of ascites indicates a severe disease condition. The rapid accumulation of ascites is distressing and requires palliative treatment. Because many cases are addressed by repeated large-volume paracentesis, often resulting in impairment due to protein and electrolyte loss, a different approach is required. Case presentation A 61-year-old Japanese man on maintenance dialysis was admitted to our hospital with acute liver injury. Our patient was diagnosed as having drug-induced liver injury due to warfarin or diltiazem, which started immediately after coronary artery bypass grafting 7 months previously. One month after admission, our patient’s hepatic encephalopathy remained grade 1 and his prothrombin time international normalized ratio was maintained at < 1.5. However, the liver was markedly atrophied with massive ascites. Although liver transplantation was desired, he was considered unfit for transplantation because of his renal and cardiac complications. Therefore, we devised a strategy to manage the massive ascites with cell-free concentrated ascites reinfusion therapy while awaiting liver regeneration. At first, cell-free concentrated ascites reinfusion therapy was required frequently because ascites accumulated rapidly. But the fluid retention interval was gradually extended as intended, and cell-free concentrated ascites reinfusion therapy was withdrawn after 8 months. During that time, the size of his liver increased from 1419 cm3 to 1587 cm3 on computed tomography. Conclusions Cell-free concentrated ascites reinfusion therapy is an apheresis therapy in which ascites are collected aseptically by paracentesis, concentrated, and then reinfused intravenously. This treatment has the advantage of preserving nutrition by reusing the fluid. Previously, cell-free concentrated ascites reinfusion therapy was used only for the management of ascites in patients with cirrhosis or carcinomatous peritonitis. This case suggests that palliation and maintenance of nutritional status with cell-free concentrated ascites reinfusion therapy may be useful as an adjunct to liver regeneration in drug-induced hepatic injury.

Download Full-text

AICAR-Induced AMPK Activation Inhibits the Noncanonical NF-κB Pathway to Attenuate Liver Injury and Fibrosis in BDL Rats

Canadian Journal of Gastroenterology and Hepatology ◽

10.1155/2018/6181432 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 7

Author(s):

Haoyang Zhu ◽

Yichao Chai ◽

Dinghui Dong ◽

Nana Zhang ◽

Wenyan Liu ◽

...

Keyword(s):

Liver Injury ◽

Hepatic Injury ◽

Protective Role ◽

Ampk Activation ◽

Ductular Reaction ◽

Protein Levels ◽

Chronic Cholestasis ◽

Duct Ligation ◽

Amp Activated Protein Kinase ◽

Cholestatic Diseases

Background. To evaluate the AMP-activated protein kinase- (AMPK-) mediated signaling and NF-κB-related inflammatory pathways that contribute to cholestatic diseases in the bile duct ligation (BDL) rat model of chronic cholestasis and verify the protective role of 5-Aminoimidazole-4-carboxamide1-β-D-ribofuranoside (AICAR) against hepatic injury and fibrosis triggered by cholestasis-related inflammation. Methods. Animals were randomly divided into three groups: sham-operated group, BDL group, and BDL+ AICAR group. Cholestatic liver injury was induced by common BDL. Two weeks later, rats in BDL+AICAR group started receiving AICAR treatment. Hepatic pathology was examined by haematoxylin and eosin (H&E) and sirius red staining and hydroxyproline assay was performed in evaluating the severity of hepatic cirrhosis. Real-time PCR and Western blot were performed for RNA gene expression of RNA and protein levels, respectively. Results. The BDL group showed liver injury as evidenced by histological changes and elevation in serum biochemicals, ductular reaction, fibrosis, and inflammation. The mRNA expression of canonical NF-κB inflammatory cytokines such as TNF-α, IL-1β, TGF-β, and the protein of noncanonical NF-κB, P100, and P52 was upregulated in the livers of BDL rats. The BDL rats with the administration of AICAR could induce AMPK activation inhibiting the noncanonical NF-κB pathway to attenuate liver injury and fibrosis in BDL rats. Conclusion. The BDL model of hepatic cholestatic injury resulting in activation of Kupffer cells and recruitment of immune cells might initiate an inflammatory response through activation of the NF-κB pathway. The AMPK activator AICAR significantly alleviated BDL-induced inflammation in rats by mainly inhibiting the noncanonical NF-κB pathway and thus protecting against hepatic injury and fibrosis triggered by BDL.

Download Full-text

Patchouli oil isolated from the leaves of Pogostemon cablin ameliorates ethanol-induced acute liver injury in rats via inhibition of oxidative stress and lipid accumulation

RSC Advances ◽

10.1039/c8ra02422g ◽

2018 ◽

Vol 8 (43) ◽

pp. 24399-24410 ◽

Cited By ~ 8

Author(s):

Qiong-Hui Huang ◽

Xue Wu ◽

Xiao-Hong Chen ◽

Jia-Zhen Wu ◽

Zi-Ren Su ◽

...

Keyword(s):

Oxidative Stress ◽

Alcohol Consumption ◽

Liver Injury ◽

Lipid Accumulation ◽

Hepatic Injury ◽

Acute Liver Injury ◽

Metabolic Disturbance ◽

Excessive Alcohol Consumption ◽

Pogostemon Cablin ◽

Excessive Alcohol

Excessive alcohol consumption can cause serious hepatic injury which is associated with oxidative stress and fatty metabolic disturbance.

Download Full-text

Polysaccharides from Enteromorpha prolifera protect against carbon tetrachloride-induced acute liver injury in mice via activation of Nrf2/HO-1 signaling, and suppression of oxidative stress, inflammation and apoptosis

Food & Function ◽

10.1039/d0fo00575d ◽

2020 ◽

Vol 11 (5) ◽

pp. 4485-4498

Author(s):

Fuchuan Guo ◽

Xinyun Zhuang ◽

Mengyuan Han ◽

Wenting Lin

Keyword(s):

Oxidative Stress ◽

Carbon Tetrachloride ◽

Liver Injury ◽

Hepatic Injury ◽

Acute Liver Injury ◽

Reactive Intermediates ◽

Enteromorpha Prolifera ◽

Hepatic Oxidative Stress

EPP protected against hepatic injury induced by CCl4-derived reactive intermediates through the suppression of hepatic oxidative stress, inflammation, and apoptosis.

Download Full-text

Phenylpropionc acid produced by gut microbiota alleviates acetaminophen-induced hepatotoxicity

10.1101/811984 ◽

2019 ◽

Author(s):

Sungjoon Cho ◽

Xiaotong Yang ◽

Kyoung-Jae Won ◽

Vanessa Leone ◽

Nathaniel Hubert ◽

...

Keyword(s):

Liver Injury ◽

Gut Microbiota ◽

Hepatic Injury ◽

Gut Bacteria ◽

Toxic Metabolite ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

Protein Levels ◽

Cyp 2E1 ◽

Gut Microbe

ABSTRACTAcetaminophen (APAP) overdose causes hepatic injury and is major contributor to acute liver injury cases. To investigate potential roles of gut microbiota in APAP-induced liver injury, C57BL/6 mice from Jackson (JAX) or Taconic (TAC) were challenged with APAP. TAC mice were more susceptible to APAP toxicity, and this disappeared upon co-housing of JAX and TAC mice. When the cecum contents from JAX and TAC mice were transplanted to germ-free mice, the mice that received TAC gut microbiota exhibited more significant hepatotoxicity after APAP administration. Non-targeted metabolomic analysis using portal vein serum and liver tissue of the mice led to identification of 19 metabolites the levels of which are associated with JAX or TAC gut microbiota. A gut bacteria-derived metabolite phenylpropionic acid (PPA) levels in cecum contents and blood were higher in mice harboring JAX gut microbiota. PPA supplementation in drinking water alleviated APAP-induced hepatotoxicity in TAC mice. This was accompanied by reduced hepatic protein levels of cytochrome P450 (CYP) 2E1, the enzyme responsible for APAP bioactivation to a toxic metabolite. This illustrates a gut microbe-liver interaction mediated by a gut bacteria-derived metabolite in modulating drug-induced liver injury.

Download Full-text