Protective Effect of Diosgenin Against Carbon Tetrachloride and Cisplatin Induced Hepatotoxicity in Rats

Abstract

Background: Activation of hepatic stellate cells (HSC) plays central role in the development of liver fibrosis. In HSC activation, the transforming growth factor-β1 (TGF-β1) is considered to be the main stimuli factor. Diosgenin are the steroidal saponin and found in Trigonella foenum graecum Linn (Fenugreek) and some other species of Dioscorea. Diosgenin attenuates HSC activation by inhibiting transforming growth factor-β. Aim: In present study an attempt was made to explore the effect of diosgenin on liver fibrosis. Methods: Liver fibrosis was induced in rats by carbon tetrachloride (CCl 4 ) 1 ml/kg intraperitoneally twice a week for 28 days and cisplatin 3mg/kg intraperitoneally at 0, 1, 3 week for 4 weeks. The extent of liver fibrosis was assessed by measuring the weight of liver and levels of total bilirubin (TBL), hydroxyproline (HP) and serum enzymes due to deposition of extracellular matrix (ECM). Results: The administration of diosgenin reduced the liver weight of CCl 4 and cisplatin treated animals and reduced the TBL, HP level and serum enzymes significantly and inhibited liver fibrosis induced by CCl 4 and cisplatin. Conclusion: The result obtained in the present investigation, Diosgenin treatment exerted significant hepatoprotective effect in animals by inhibiting ECM deposition and HSCs activation.

Therapeutic Potential of Diosgenin in Amelioration of Carbon Tetrachloride-Induced Murine Liver Injury

“…Damage to the hepatocytes promotes the release of enzymes into the bloodstream and ultimately causes an increase in the serum levels of AST and ALT [14]. The production of free radicals due to the hepatotoxic effects of CCL4 causes oxidative damage to the hepatocytes, thereby promoting the leakage of liver enzymes into the circulation [17]. Serum albumin level is an-other parameter determining liver function, which decreases in the end stage liver diseases.…”

“…This steroidal sapogenin prevented liver fibrosis and ameliorated liver function. Diosgenin could decrease serum levels of liver enzymes, total bilirubin, and hydroxyproline [17]. Another study suggested that diosgenin is a potential agent to prevent the development of NAFLD and reduce serum ALT levels through the adenosine monophosphate-activated protein kinase (AMPK) and liver X receptor (LXR) signaling pathways [14].…”

“…Another study indicated that diosgenin alleviated nonalcoholic steatohepatitis and also reduced the serum levels of liver enzymes [16]. Diosgenin effect against hepatotoxicity induced by CCL4 and cisplatin was also investigated and diosgenin could decrease serum levels of liver enzymes [17]. However, the impact of diosgenin administration (for 8 weeks) on the liver oxidant-antioxidant status of animals injected with CCL4 has not yet been evaluated.…”

L-carnitine Protects Cisplatin Induced Liver Fibrosis in Experimental Animals via Reducing Oxidative and Nitrosative Stress

“…Assessment of Biochemical paradigms such as AST, ALP, ALT, TB and HP was conducted as per the manufacturer's protocol and the literature avalable. 15…”

Literature review on hepatoprotective effects of diosgenin: possible mechanisms of action

“…Liver content of hydroxyproline and ECM deposition, prominent markers of liver fibrosis, were also reduced by diosgenin. Diosgenin, probably via inhibiting the activation of hepatic stellate cells (HSCs), prevented liver fibrosis development ( Nimbalkar et al, 2018 ).…”