Combination of Sitagliptin and Silymarin ameliorates liver fibrosis induced by carbon tetrachloride in rats

Sokar, Samia Salem; El-Sayad, Magda El-Sayed; Ghoneim, Mai El-Sayed; Shebl, Abdelhadi M.

doi:10.1016/j.biopha.2017.02.010

Cited by 48 publications

(23 citation statements)

References 71 publications

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“…In recent years, increased GGT levels has been recognized as a risk factor for advanced liver fibrosis [47]. Moreover, it has been demonstrated in animal studies that sitagliptin can reduce liver fibrosis by alleviating oxidative stress [48,49].Therefore, the partial decrease in GGT may indicate the potential role of sitagliptin in the treatment of NAFLD by relieving oxidative stress, as well as the reduced risk of developing liver fibrosis and accompanied diseases, like diabetes and insulin resistance. Serum ALT is a known biomarker of hepatic inflammation.…”

Section: Discussionmentioning

confidence: 99%

Effects and Safety of Sitagliptin in Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

et al. 2020

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Non-alcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease. However, the treatment is limited. The aim of this meta-analysis was to evaluate the effects and safety of sitagliptin, a selective inhibitor of dipeptidyl peptidase-4 (DPP-4I), in treating NAFLD. Studies were sourced from electronic databases including PubMed, CENTRAL (Cochrane Controlled Trials Register), Embase, Medline, Web of Science, Clinical Trials, and CNKI to identify all randomized controlled clinical trials (RCTs) and non-RCTs in adult patients with NAFLD. Key outcomes were changes in serum levels of liver enzymes and improvement in hepatic histology and fat content measured by imaging or liver biopsy. Stata14.0 and RevMan5.3 were used for the meta-analysis. Seven studies with 269 NAFLD patients were included. Compared to the control group, sitagliptin treatment improved serum gamma-glutamyl transpeptidase (GGT) levels in the RCT subgroup (SMD = 0.79, 95% CI: 0.01–1.58). However, there was no significant improvement in serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels following sitagliptin treatment. Four of the included studies performed liver imaging, but sitagliptin treatment did not result in a significant reduction in liver fat content. Only five participants developed sitagliptin-related gastrointestinal discomfort. Our study suggests that sitagliptin effects individuals with NAFLD by improving serum GGT. Although sitagliptin is safe and well tolerated in NAFLD patients, it exerts no beneficial effects on liver transaminase and liver fat content in these patients.

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Section: Discussionmentioning

confidence: 99%

Effects and Safety of Sitagliptin in Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

et al. 2020

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“…It was introduced as a hepatoprotective agent few years ago (Tsai et al, 2008). It offers hepatoprotection in various toxic models of experimental liver diseases in vivo through its free radicals scavenging properties, enhancing the endogenous antioxidant defense systems and stabilizing effect on the cytoplasmic membranes (Sokar et al, 2017). In addition, it stimulates protein synthesis, glucuronidation, protects against glutathione depletion and plays role in the regeneration of liver tissue.…”

Section: Silymarinmentioning

confidence: 99%

“…DPP4 is also highly expressed in liver, and plays a role in the fibronectin-mediated interaction of hepatocytes with ECM and is expressed on the surface of activated HSCs. Moreover, it was reported that its serum activity and mRNA levels were significantly increased in tetrachloromethane-induced cirrhotic rats and in nonalcoholic fatty liver disease (NAFLD) compared to that in control livers (Sokar et al, 2017).…”

Section: Sitagliptin Combined With Silymarinmentioning

confidence: 99%

“…The effect was found to be mainly through the inhibition of hepatic oxidative stress and augmentation of anti-oxidant defenses, attenuating the activation of hepatic stellate cells via reduction of αSMA expression in liver, inhibiting the fibrogenesis and proliferation of activated HSCs response via inhibiting the release of TGFβ1, and inhibition of proinflammatory cytokines as IL-6. Interestingly, this combination may be useful for patients with type 2 Diabetes Mellitus accompanied by liver injury (Sokar et al, 2017).…”

Section: Sitagliptin Combined With Silymarinmentioning

confidence: 99%

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Naturally Derived Compounds Used for Prevention or Regression of Experimentally Induced Liver Fibrosis

Adel

2019

Al-Azhar Journal of Pharmaceutical Sciences

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Liver fibrosis is a common health problem that is associated with mortality and morbidity worldwide. The inappropriate tissue repair of damaged liver results in oversynthesis and deposition of fibrillar collagen. It is usually associated with progressive pathological and biochemical changes that ultimately lead to structural and metabolic abnormalities and hepatic scarring. If not properly treated, liver fibrosis may develop to cirrhosis and hepatocellular carcinoma within few years. Blocking this progression, therefore, could be an effective and potential strategy for survival. The only effective approach to treating advanced liver fibrosis is transplantation. Understanding its etiology and pathophysiology, however, could help to investigate therapeutic pathophysiology based treatment of liver fibrogenesis. Recently several promising natural based treatment methods interfering with cytokines signaling pathway involved in fibrogenesis have been investigated offering new potential therapeutic intervention. The aim of the present updated review is to identify the natural antifibrotic options that have been studied in animal models with liver fibrosis for the treatment of this pathological conditions enabling prevention or at least regression of its progression.

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“…Recently,silymarin (SLY) have received attention for treatment of liver disease and dysfunction, and to promote liver regeneration (10). SLY increases the detoxification capacity of the liver by elevating the amount of glutathione, a strong antioxidant that is exposed to oxidative stress in the liver.…”

Section: Introductionmentioning

confidence: 99%

Investigation of the positive effects of silymarin on valproic acid-induced liver damage in rats

Aktaş

Armağan

2019

Adıyaman Üniversitesi Sağlık Bilimleri Dergisi

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In this study; We aimed to investigate the possible hepatoprotective effects of silymarin against hepatic damage in valproic acid-induced rats using histological and biochemical evaluations. Method: Experimental procedures were performed on 21 male Sprague Dawley rats. Rats were seperated into three groups: group 1, control; group 2, valproic acid; group 3, valproic acid + silymarin. The groups were administered 500 mg/kg/day valproic acidand 100 mg/kg/daysilymarin for 14 days, except control group. Results: Silymarin treatment decreased the levels of serumgamma glutamyl transferase, alanine amino transferase, aspartate aminotransferase and increreased serum albumin levelssignificantly (p<0.05). In addition, increased amount of malondialdehyde and decreased levels of glutathione with valproic acid were significantly suppressed by silymarin in liver tissue (p<0.05).The combination of silymarinwith valproic acid reduced loss of body weight in the present study. Histologically, the extent of liver damage was remarkably lower in the valproic acid+silymarin group (p<0.005). When the valproic acid + silymarin group compared to the valproic acid group; it was determined that antioxidant activity was increased, oxidative stress. Conclusion: This study revealed that the liver injury induced by valproic acid was attenuated with silymarin administration. Silymarincan protect rat liver against valproic acid induced injury by its anti-oxidative effect, and might be useful for reducing the severity of liver injury.

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Combination of Sitagliptin and Silymarin ameliorates liver fibrosis induced by carbon tetrachloride in rats

Cited by 48 publications

References 71 publications

Effects and Safety of Sitagliptin in Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

Effects and Safety of Sitagliptin in Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

Naturally Derived Compounds Used for Prevention or Regression of Experimentally Induced Liver Fibrosis

Investigation of the positive effects of silymarin on valproic acid-induced liver damage in rats

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