A promising antifibrotic drug, pyridoxamine attenuates thioacetamide-induced liver fibrosis by combating oxidative stress, advanced glycation end products, and balancing matrix metalloproteinases

Alshanwani, Aliah R.; Hagar, Hanan; Shaheen, Sameerah; Alhusaini, Ahlam; Arafah, Maha; Faddah, L. M.; Alharbi, Fatima M B; Sharma, Arun K; Badr, Amira M.

doi:10.1016/j.ejphar.2022.174910

Cited by 21 publications

(7 citation statements)

References 53 publications

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“…Alpha-tocotrienol belongs to vitamin E, have antioxidant and anti-in ammatory effects, have been shown to be protective to liver function [42]. Pyridoxamine is a structural analog of vitamin B6 that could attenuate liver brosis by inhibiting the in ammatory cascades and combating oxidative stress [43]. Tryptophan and pipecolinic acid, the essential amino acid, has been reported that possesses the capacity to regulate host susceptibility to acute liver failure by regulating the activity of aryl hydrocarbon receptor [44].…”

Section: Discussionmentioning

confidence: 99%

Intestinal Microbiomics and Metabolomics Insights into the Hepatoprotective Effects of Lactobacillus paracasei CCFM1222 Against the Acute Liver Injury in Mice

Guo

Cui

Tang

et al. 2022

Probiotics & Antimicro. Prot.

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In recent years, acute liver injury (ALI) has received wide-range attention in the world due to its relatively high morbidity and mortality. This study aimed to explore the hepatoprotective effect of Lactobacillus paracasei CCFM1222 against lipopolysaccharide (LPS)-induced ALI mice, and further elaborate its mechanism of action from the perspective of intestinal microbiomics and metabolomics. The results displayed that L. paracasei CCFM1222 pretreatment signi cantly decreased the serum ALT, and AST levels, inhibited the releases of hepatic TNF-α, IL-1β, and IL-6 levels, and activated the SOD, CAT, and GSH-Px activities in LPS-treated mice. The cecal short-chain fatty acid (SCFAs) levels were increased in LPStreated mice with L. paracasei CCFM1222 pretreatment. In addition, L. paracasei CCFM1222 pretreatment remarkably shifted the intestinal microbiota composition, including the higher abundance of Faecalibaculum, Bi dobacterium, and lower abundance of Prevotellaceae NK3B31 group, which is positively associated with the cecal propionic, butyric, valeric, isobutyric, and isovaleric acids. The metabolomics based on UPLC-QTOF/MS revealed that L. paracasei CCFM1222 pretreatment signi cantly regulated the composition of feces metabolites in LPS-treated mice, especially the potential biomarkersrelated butanoate metabolism, vitamin B6 metabolism, D-glutamine and D-glutamate metabolism, tryptophan metabolism, caffeine metabolism, arginine biosynthesis, arginine, and proline metabolism. Moreover, L. paracasei CCFM1222 pretreatment remarkably regulated the expression of genes-associated ALI (including Tlr4, Myd88, Nf-kβ, iNOS, Cox2, Iκ-Bα, Nrf2, and Sirt-1). In conclusion, these results suggest the possibility that L. paracasei CCFM1222 supplementation has bene cial effects on preventing the occurrence and development of ALI by inhibiting the in ammatory responses, altering intestinal microbiota composition and their metabolites, and mediating the Tlr4/Nf-kβ pathway.

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Section: Discussionmentioning

confidence: 99%

Intestinal Microbiomics and Metabolomics Insights into the Hepatoprotective Effects of Lactobacillus paracasei CCFM1222 Against the Acute Liver Injury in Mice

Guo

Cui

Tang

et al. 2022

Probiotics & Antimicro. Prot.

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“…22 Several studies have reported an elevation in LPO byproducts, including MDA, in experimental models during oxidative stress. 47,48 Furthermore, antioxidants, including SOD, CAT, GSH, and glutathione peroxidase (GPx) were depleted in TAAinduced rats. 49 The oxidative stress milieu is maintained over time by the ability of intracellular ROS to induce mitochondrial production of excessive ROS.…”

Section: Discussionmentioning

confidence: 99%

“…TASO 2 , a metabolite of TAA, is itself a highly reactive ROS that causes LPO in hepatocyte membranes 22 . Several studies have reported an elevation in LPO byproducts, including MDA, in experimental models during oxidative stress 47,48 . Furthermore, antioxidants, including SOD, CAT, GSH, and glutathione peroxidase (GPx) were depleted in TAA‐induced rats 49 .…”

Section: Discussionmentioning

confidence: 99%

Coleus vettiveroides ethanolic root extract protects against thioacetamide‐induced acute liver injury in rats

Mohamed Azar,

Ezhilarasan,

Shree Harini

et al. 2023

Cell Biochemistry & Function

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Acute liver injury is caused by various factors, including oxidative stress and inflammation. Coleus vettiveroides, an ayurvedic medicinal plant, is known to possess antioxidant, antibacterial, and antidiabetic properties. In this current study, we investigated the protective effect of C. vettiveroides ethanolic root extract (CVERE) against thioacetamide (TAA)‐induced acute liver injury in rats. A single dose of TAA (300 mg/kg, b.w., i.p.) was administered to induce acute liver injury. The treatment groups of rats were concurrently treated with CVERE (125 and 250 mg/kg, b.w., p.o.) and silymarin (100 mg/kg, b.w., p.o.), respectively. After 24 h of the experimental period, TAA‐induced liver injury was confirmed by increased activity of serum transaminases and malondialdehyde levels in liver tissue, decreased levels of antioxidants, upregulated expression of the inflammatory marker gene, and altered liver morphology. Whereas CVERE simultaneous treatment inhibited hepatic injury and prevented the elevation of serum aspartate and alanine transaminases, alkaline phosphatase, and lactate dehydrogenase activities. CVERE attenuated TAA‐induced oxidative stress by suppressing lipid peroxidation and restoring antioxidants such as superoxide dismutase, catalase, and reduced glutathione. Further, CVERE treatment was found to inhibit nuclear factor κB‐mediated inflammatory signaling, as indicated by downregulated pro‐inflammatory cytokines including tumor necrosis factor‐α and interleukin‐1β. Our findings suggest that CVERE prevents TAA‐induced acute liver injury by targeting oxidative stress and inflammation.

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“…23 Regulation of TIMPs is poorly understood, but several candidate drugs, including caffeine, omeprazole, statins, and Rho kinase inhibitors, have been shown to inhibit TIMP function or decrease TIMP expression in cell cultures and other models. [47][48][49][50][51][52] Two significant limitations of this in vitro study are the use of a simple gelatin substrate to stand in for the complex arrangement of the ECM and the use of MMP-2 as a sole representative protease for inhibition. Both of these factors may have influenced the findings.…”

Section: Discussionmentioning

confidence: 99%

“…Because MMP enhancement has received more attention than TIMP suppression as a therapeutic strategy for glaucoma, these findings, which suggest that TIMP dysregulation might be the more powerful force in TM ECM changes in CPACG, could have important implications for future work 23 . Regulation of TIMPs is poorly understood, but several candidate drugs, including caffeine, omeprazole, statins, and Rho kinase inhibitors, have been shown to inhibit TIMP function or decrease TIMP expression in cell cultures and other models 47–52 …”

Section: Discussionmentioning

confidence: 99%

Relative ability of aqueous humor from dogs with and without primary angle‐closure glaucoma and ADAMTS10 open‐angle glaucoma to catalyze or inhibit collagenolysis

Pumphrey,

Harman,

Anderson

et al. 2023

Veterinary Ophthalmology

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ObjectiveThe objective of the study was to compare the ability of aqueous humor (AH) from dogs with primary angle‐closure glaucoma (CPACG), companion dogs without overt evidence of CPACG, and Beagles with and without ADAMTS10 open‐angle glaucoma (ADAMTS10‐OAG) to catalyze or inhibit collagenolysis.Animals studiedSeventeen normal pet dogs, 27 dogs with CPACG, 19 Beagles with ADAMTS10‐OAG, and 4 unaffected Beagles.ProceduresA fluorescein‐based substrate degradation assay was used to assess AH proteolytic capacity. Samples were then assayed using the same substrate degradation assay, with recombinant activated matrix metalloproteinase‐2 (MMP‐2) added to measure protease inhibition effects.ResultsFor the protease activity assay, relative fluorescence (RF) for AH from normal pet dogs was 13.28 ± 2.25% of control collagenase while RF for AH from dogs with CPACG was 17.47 ± 4.67%; RF was 8.57 ± 1.72% for ADAMTS10‐OAG Beagles and 7.99 ± 1.15% for unaffected Beagles. For the MMP‐2 inhibition assay, RF for AH from normal dogs was 34.96 ± 15.04% compared to MMP‐2 controls, while RF from dogs with CPACG was 16.69 ± 7.95%; RF was 85.85 ± 13.23% for Beagles with ADAMTS10‐OAG and 94.51 ± 8.36% for unaffected Beagles. Significant differences were found between dogs with CPACG and both normal pet dogs and dogs with ADAMTS10‐OAG and between normal pet dogs and both groups of Beagles.ConclusionsAH from dogs with CPACG is significantly more able to catalyze proteolysis and inhibit MMP‐2 than AH from normal dogs or dogs with ADAMTS10‐OAG. Results suggest that pathogenesis may differ between CPACG and ADAMTS10‐OAG.

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A promising antifibrotic drug, pyridoxamine attenuates thioacetamide-induced liver fibrosis by combating oxidative stress, advanced glycation end products, and balancing matrix metalloproteinases

Cited by 21 publications

References 53 publications

Intestinal Microbiomics and Metabolomics Insights into the Hepatoprotective Effects of Lactobacillus paracasei CCFM1222 Against the Acute Liver Injury in Mice

Intestinal Microbiomics and Metabolomics Insights into the Hepatoprotective Effects of Lactobacillus paracasei CCFM1222 Against the Acute Liver Injury in Mice

Coleus vettiveroides ethanolic root extract protects against thioacetamide‐induced acute liver injury in rats

Relative ability of aqueous humor from dogs with and without primary angle‐closure glaucoma and ADAMTS10 open‐angle glaucoma to catalyze or inhibit collagenolysis

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