Theophylline, an old drug with multi-faceted effects: Its potential benefits in immunological liver injury in rats

Hussein, Reeham Mohamed; Elsirafy, Osama Mahmod; Wahba, Yousria Saad; Kawy, Hala Salah Abdel; Hasanin, Amany Helmy; Hamam, Ghada Galal

doi:10.1016/j.lfs.2015.06.028

Cited by 10 publications

(7 citation statements)

References 47 publications

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“…Moreover, the area percentage of collagen fibers stained with Masson trichrome in sections of the liver showed an increase in the percentage area of cells that were stained by Masson's trichrome after treatment with Con A and a reduction of the stained area in the combination group. Histological staining to confirm the deposition of collagen has been done by Hussein RM and it revealed deposition of collagen after administration of Con A which was confirmed by the results of this study [30].…”

Section: Discussionsupporting

confidence: 82%

Hepatoprotective Effects of Suberoylanilide Hydroxamic Acid (A Histone Deacetylase Inhibitor) in Immunological Liver Injury in Rats

Alhaddad

Kawy

Ramadan

et al. 2019

JPRI

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One of the main reasons for the development of chronic liver disease is autoimmune hepatitis (AIH). There is no clear etiological factor for AIH occurrence and no drug has been approved for its treatment. Vorinostat, a Histone deacetylase inhibitor (HDACi) has been shown to reduce inflammation. Our aim was to explore the therapeutic potential of vorinostat in a rat model of AIH induced by Concanavalin A (Con A). The rats were randomly divided into 4 groups; control group, con A (20 mg/kg/iv/wk) group, vorinostat (15 mg/kg/day p.o) group and Con A with vorinostat group. Blood and liver samples were collected at the end of the fourth and eighth weeks for biochemical and histopathological examinations. Results revealed that administration of Con A elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) liver enzymes, which were reduced to 52.8% and to 61.8% respectively on simultaneous administration of Vorinostat as compare to Con A group. Furthermore, Vorinostat reduced fibrosis and diminished apoptosis as deduced by the decrease in the hepatic hydroxyproline content of the liver and tumor necrosis factor-alpha levels. Relative gene expression analysis of interleukin 1b and transforming growth factor beta were significantly decreased in groups treated with vorinostat. Histopathological analysis showed that administration of vorinostat significantly restored the well organized structure of the liver, decreased initial inflammation produced by Con A, reduced liver fibrosis and mitigated hepatic stellate cell’s activities. In conclusion, administration of vorinostat in Con A model of autoimmune hepatitis, significantly decreased liver inflammation and fibrosis. So vorinostat might show a novel therapeutic approach for management of autoimmune hepatitis and its obstacles.

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Section: Discussionsupporting

confidence: 82%

Hepatoprotective Effects of Suberoylanilide Hydroxamic Acid (A Histone Deacetylase Inhibitor) in Immunological Liver Injury in Rats

Alhaddad

Kawy

Ramadan

et al. 2019

JPRI

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“…It is shown that taurine has a significant therapeutic effect on CHF by reducing myocytehypertrophy and fibrosis [32]. Theophylline, another metabolite upregulated by YQFM, is also proved to have an antifibrosis effect by decreasing the expression of TGF‐β [33]. It is reported that theophylline could inhibit TGF‐β‐induced collagen I synthesis, α‐SMA expression, and fibroblast proliferation to improve lung fibrosis [34].…”

Section: Discussionmentioning

confidence: 99%

HPLC‐QTOF/MS‐based metabolomics to explore the molecular mechanisms of Yiqi Fumai Lyophilized Injection in heart failure mice

Yuan

Liu

Lai

et al. 2021

J of Separation Science

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Chronic heart failure is a common and fatal disease triggered by loss of normal cardiac function. Yiqi Fumai Lyophilized Injection is widely used in the treatment of cardiovascular diseases, especially chronic heart failure. In this study, a model of chronic heart failure in mice was established with permanent coronary artery ligation followed by Yiqi Fumai Lyophilized Injection intervention for 14 days. Then, the endogenous metabolites of mice plasma and urine samples were screened through nontargeted metabolomics techniques. The results indicated that Yiqi Fumai Lyophilized Injection treatment changed the metabolic pattern of chronic heart failure and regulated valine, leucine, and isoleucine biosynthesis, taurine and hypotaurine metabolism, histidine metabolism and arginine biosynthesis, etc. Finally, the cardioprotective mechanism of Yiqi Fumai Lyophilized Injection was further verified in the mouse model of chronic heart failure and angiotensin II‐induced cardiac fibroblasts based on metabolomics. The results showed that Yiqi Fumai Lyophilized Injection could inhibit myocardial fibrosis to improve chronic heart failure. This study firstly elucidated the metabolic network and pathways regulated by Yiqi Fumai Lyophilized Injection, which might facilitate the realization of the clinically accurate application of Yiqi Fumai Lyophilized Injection in the treatment of chronic heart failure.

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“…It prevents the translocation of the proinflammatory transcription factor nuclear factor-kB (NF-kB) into the nucleus [25], and inhibits histone deacetylase-2 activation [26]. In animal studies, theophylline effectively reduced the inflammation in liver tissues and alleviated the liver damage by decreasing IFN-g and TGF-b in liver tissues of rats with immunological hepatic injury induced by concanavalin A (Con A) [27]. Spontaneous superoxide release by alveolar macrophages and mononuclear cells was significantly reduced by therapeutically achievable concentrations of theophylline was also found [28].…”

Section: Discussionmentioning

confidence: 99%

Association of pre-hospital theophylline use and mortality in chronic obstructive pulmonary disease patients with sepsis

Shih

Chen

Chu

et al. 2017

Respiratory Medicine

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Theophylline, an old drug with multi-faceted effects: Its potential benefits in immunological liver injury in rats

Cited by 10 publications

References 47 publications

Hepatoprotective Effects of Suberoylanilide Hydroxamic Acid (A Histone Deacetylase Inhibitor) in Immunological Liver Injury in Rats

Hepatoprotective Effects of Suberoylanilide Hydroxamic Acid (A Histone Deacetylase Inhibitor) in Immunological Liver Injury in Rats

HPLC‐QTOF/MS‐based metabolomics to explore the molecular mechanisms of Yiqi Fumai Lyophilized Injection in heart failure mice

Association of pre-hospital theophylline use and mortality in chronic obstructive pulmonary disease patients with sepsis

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