MENU ▼
Read by QxMD icon Read
search
OPEN IN READ APP
JOURNAL ARTICLE

Telmisartan and/or chlorogenic acid attenuates fructose-induced non-alcoholic fatty liver disease in rats: Implications of cross-talk between angiotensin, the sphingosine kinase/sphingoine-1-phosphate pathway, and TLR4 receptors

Iman Alqarni, Yieldez A Bassiouni, Amira M Badr, Rehab A Ali
Biochemical Pharmacology 2019, 164: 252-262
31004566
Renin-angiotensin-aldosterone system (RAS) has been implicated in non-alcoholic fatty liver disease (NAFLD); the most common cause of chronic liver diseases. There is accumulating evidence that altered TLR4 and Sphingosine kinase 1(SphK1)/sphingosine1phosphate (S1P) signaling pathways are key players in the pathogenesis of NAFLD. Cross talk of the sphingosine signaling pathway, toll-4 (TLR4) receptors, and angiotensin II was reported in various tissues. Therefore, the aim of this study was to define the contribution of these two pathways to the hepatoprotective effects of telmisartan and/or chlorogenic acid (CGA) in NAFLD. CGA is a strong antioxidant that was previously reported to inhibit angiotensin converting enzyme. Male Wistar rats were treated with either high-fructose, with or without telmisartan, CGA, telmisartan + CGA for 8 weeks. Untreated NAFL rats showed characteristics of NAFLD, as evidenced by significant increase in the body weight, insulin resistance, and serum hepatotoxicity markers (Alanine and Aspartate transaminases) and lipids as compared to the negative control group, in addition to characteristic histopathological alterations. Treatment with either telmisartan and/or CGA improved aforementioned parameters, in addition to upregulation of antioxidant enzymes (Superoxide dismutase and Glutathione peroxidase). Effect of inhibiting RAS on both sphingosine pathway and TLR4 was evident by the suppressing effect of telmisartan and/or CGA on high fructose-induced upregulation of hepatic SPK1 and S1P, in addition to concomitant up-regulation of Sphingosine-1-Phosphate receptor (S1PR)3 protein level and increased expression of S1PR1 and TLR4. As TLR4 and SPK/S1P signaling pathways play important roles in the progression of liver inflammation, the effect on sphingosine pathway and TLR4 was associated with decreased concentrations of inflammatory markers, enzyme kB kinase (IKK), nuclear factor-kB and tumor necrosis factor-α as compared to untreated NAFL group. In conclusion, the present data strongly suggests the cross-talk between angiotensin, the Sphingosine SPK/S1P Axis and TLR4 Receptors, and their role in the pathogenesis of fructose-induced NAFLD, and the protection afforded by drugs inhibiting RAS.

Comments

You need to log in or sign up for an account to be able to comment.

No comments yet, be the first to post one!

Trending on Read

Available on the App Store

Available on the Play Store
Remove bar
Read by QxMD icon Read
31004566
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"