Research Article Details
| Article ID: | A37549 |
| PMID: | 15447754 |
| Source: | Am J Gastroenterol |
| Title: | Beneficial effects of tumor necrosis factor-alpha inhibition by pentoxifylline on clinical, biochemical, and metabolic parameters of patients with nonalcoholic steatohepatitis. |
| Abstract: | BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) has been incriminated to play an important role in the pathogenesis of nonalcoholic steatohepatitis (NASH). Pentoxifylline, a TNF-alpha inhibitor could prove useful in treating patients with NASH. METHODS: Eighteen patients (mean age, 34 +/- 7.8 yr) with histologically proven NASH and with persistently elevated ALT (>1.5 times) were given pentoxifylline at a dosage of 400 mg t.i.d. for 6 months. No lipid-lowering agent or antioxidants were concurrently advised. RESULTS: Impaired fasting glycemia, impaired glucose tolerance, diabetes mellitus, and hypertriglyceridemia were noted in 6, 35, 17, and 53% of the patients, respectively. After 6 months of therapy, fatigue improved (55.6 vs 20%, p= 0.016), but serum triglyceride (182 +/- 66 vs 160 +/- 55 mg/dl, p= 0.397), cholesterol (173 +/- 46 vs 162 +/- 40 mg/dl, p= 0.440), and body mass index (BMI) (27.3 +/- 3.1 vs 26 +/- 3.1 kg/m(2), p= 0.087) remained unchanged. Mean AST (66 +/- 29 vs 33 +/- 11 IU/l, p < 0.0001) and ALT (109 +/- 44 vs 47 +/- 20 IU/l, p < 0.0001) reduced significantly. ALT normalized in 23% at month 1 (p= 0.125), 35% at month 2 (p= 0.125), and 60% at month 6 (p= 0.008) of treatment. The insulin resistance index assessed by homeostatic metabolic assessment (HOMA(IR)) improved (5.1 +/- 3.4 vs 2.6 +/- 2, p = 0.046) and the serum TNF-alpha reduced significantly after therapy (22.15 +/- 2.49 vs 17 +/- 2.58 pg/ml, p = 0.011). The drug was well tolerated. CONCLUSIONS: In patients with NASH, pentoxifylline therapy effectively achieved significant clinical and biochemical improvement with reduction in HOMA(IR). These benefits are possibly mediated through suppression of TNF-alpha. |
| DOI: | 10.1111/j.1572-0241.2004.40220.x |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I13 | 3146 | Lipid metabolism disorder | An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism | disease of metabolism/ inherited metabolic disorder | Details |
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D266 | Pentoxifylline | Chemical drug | DB00806 | ADORA2A antagonist; ADORA1 antagonist; PDE4A inhibitor; PDE3B inhibitor; PDE4B inhibitor; PDE5A inhibitor; PDE8A inhibitor; PDE4C inhibitor; PDE11A inhibitor; PDE7A inhibitor; PDE7B inhibitor; PDE4D inhibitor; PDE3A inhibitor | Anti-inflammatory; Cardiovascular drug | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |