Hydrogen Sulfide Attenuates Carbon Tetrachloride-Induced Hepatotoxicity, Liver Cirrhosis and Portal Hypertension in Rats

Abstract

BackgroundHydrogen sulfide (H2S) displays vasodilative, anti-oxidative, anti-inflammatory and cytoprotective activities. Impaired production of H2S contributes to the increased intrahepatic resistance in cirrhotic livers. The study aimed to investigate the roles of H2S in carbon tetrachloride (CCl4)-induced hepatotoxicity, cirrhosis and portal hypertension.Methods and FindingsSodium hydrosulfide (NaHS), a donor of H2S, and DL-propargylglycine (PAG), an irreversible inhibitor of cystathionine γ-lyase (CSE), were applied to the rats to investigate the effects of H2S on CCl4-induced acute hepatotoxicity, cirrhosis and portal hypertension by measuring serum levels of H2S, hepatic H2S producing activity and CSE expression, liver function, activity of cytochrome P450 (CYP) 2E1, oxidative and inflammatory parameters, liver fibrosis and portal pressure. CCl4 significantly reduced serum levels of H2S, hepatic H2S production and CSE expression. NaHS attenuated CCl4-induced acute hepatotoxicity by supplementing exogenous H2S, which displayed anti-oxidative activities and inhibited the CYP2E1 activity. NaHS protected liver function, attenuated liver fibrosis, inhibited inflammation, and reduced the portal pressure, evidenced by the alterations of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), albumin, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and soluble intercellular adhesion molecule (ICAM)-1, liver histology, hepatic hydroxyproline content and α-smooth muscle actin (SMA) expression. PAG showed opposing effects to NaHS on most of the above parameters.ConclusionsExogenous H2S attenuates CCl4-induced hepatotoxicity, liver cirrhosis and portal hypertension by its multiple functions including anti-oxidation, anti-inflammation, cytoprotection and anti-fibrosis, indicating that targeting H2S may present a promising approach, particularly for its prophylactic effects, against liver cirrhosis and portal hypertension.

Hydrogen Sulfide Attenuates sFlt1-Induced Hypertension and Renal Damage by Upregulating Vascular Endothelial Growth Factor

“…Moreover, BP-lowering effects of H 2 S have also been previously reported in various other models of both experimental and spontaneous hypertension in rats. [38][39][40] It is known that H 2 S-induced vasorelaxation is mainly mediated by the opening of K ATP channels in vascular smooth muscle cells. 22 However, in this study, the antihypertensive effect of H 2 S is accompanied by an increase in plasma VEGF, which itself is a vasodilator.…”

Hydrogen Sulfide, the Next Potent Preventive and Therapeutic Agent in Aging and Age-Associated Diseases

“…Additionally, H 2 S can inhibit the expression of proinflammatory factors by downregulating NF-B activation or by upregulating heme oxygenase 1 expression (24-28). Moreover, H 2 S may help regulate various functions of the human body with its cytoprotective, antifibrotic, antiapoptotic, and angiogenic properties (29)(30)(31)(32). Taken together, these known functions of H 2 S imply an important role in aging and age-associated diseases (Table 1).…”

Influence of hypolipidemic agents on the level of steatogenic and fibrogenic modulators in rats with non-alcoholic fatty liver disease associated with hyperhomocysteinemia

“…Нещодавно встановлено, що розвиток стеатозу та фіброзу печінки може асоціюватись з порушенням продукції таких медіаторів як гідроген сульфід (Н 2 S) [7,8] та інсуліноподібний фактор росту-1 (IGF-1) [9].…”

“…З 61-ої доби і до завершення досліду 6 груп щурів з НАЖХП+ +ГГЦ були переведені на стандартну дієту (СД), що постачала 21 % ккал за рахунок жирів, 62 % ккал за рахунок вуглеводів, 17 % ккал за рахунок протеїнів. На цьому фоні тваринам 4-х груп упродовж 14 та 28 діб 1 раз на добу в/шл вводились гіполіпідемічні засоби -симвастатин (групи 5, 6) або препарат ω-3 ПНЖК (групи 7,8). Симвастатин вводили в дозі 20 мг/кг маси щура на 1 % крохмальному гелі (1 мл/ 100 г маси), препарат ω-3 ПНЖК -в дозі 150 мг/ кг маси (1,5 мл препарату змішували з 8,5 мл рафі-нованої соняшникової олії і вводили із розрахунку 0,1 мл/ 100 г маси), щурі груп порівняння (групи 3 та 4) отримували еквівалентну кількість розчинників (1 % крохмальний гель та рафіновану соняшникову олію).…”