Differential hepatoprotective mechanisms of rutin and quercetin in CCl4-intoxicated BALB/cN mice

Abstract

Aim: To investigate the mechanisms underlying the protective effects of quercetin-rutinoside (rutin) and its aglycone quercetin against CCl 4 -induced liver damage in mice. Methods: BALB/cN mice were intraperitoneally administered rutin (10, 50, and 150 mg/kg) or quercetin (50 mg/kg) once daily for 5 consecutive days, followed by the intraperitoneal injection of CCl 4 in olive oil (2 mL/kg, 10% v/v). The animals were sacrificed 24 h later. Blood was collected for measuring the activities of ALT and AST, and the liver was excised for assessing Cu/Zn superoxide dismutase (SOD) activity, GSH and protein concentrations and also for immunoblotting. Portions of the livers were used for histology and immunohistochemistry. Results: Pretreatment with rutin and, to a lesser extent, with quercetin significantly reduced the activity of plasma transaminases and improved the histological signs of acute liver damage in CCl 4 -intoxicated mice. Quercetin prevented the decrease in Cu/Zn SOD activity in CCl 4 -intoxicated mice more potently than rutin. However, it was less effective in the suppression of nitrotyrosine formation. Quercetin and, to a lesser extent, rutin attenuated the inflammation in the liver by down-regulating the CCl 4 -induced activation of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α) and cyclooxygenase (COX-2). The expression of inducible nitric oxide synthase (iNOS) was more potently suppressed by rutin than by quercetin. Treatment with both flavonoids significantly increased NF-E2-related factor 2 (Nrf2) and heme oxygenase (HO-1) expression in injured livers, although quercetin was less effective than rutin at an equivalent dose. Quercetin more potently suppressed the expression of transforming growth factor-β1 (TGF-β1) than rutin. Conclusion: Rutin exerts stronger protection against nitrosative stress and hepatocellular damage but has weaker antioxidant and antiinflammatory activities and antifibrotic potential than quercetin, which may be attributed to the presence of a rutinoside moiety in position 3 of the C ring.

Therapeutic detoxification of quercetin against carbon tetrachloride-induced acute liver injury in mice and its mechanism

“…Some previous studies have already demonstrated that quercetin can prevent CCl 4 -induced acute liver injury when given several days before CCl 4 intoxication (Janbaz et al, 2004;Domitrović et al, 2012;Cui et al, 2014). From the results of ALT/AST analysis and histological observations, our study demonstrates that quercetin can ameliorate CCl 4 -induced acute liver injury when it is given 30 min after CCl 4 intoxication.…”

“…Various reports show that quercetin has neuro-protection, anti-tumor, antiinflammation, anti-oxidant, and anti-diabetic effects (Chirumbolo, 2010;Kelly, 2011;Dajas, 2012). Furthermore, some reports demonstrate that quercetin can ameliorate various toxin-induced liver injuries, such as ethanol and acetaminophen (Vicente-Sánchez et al, 2008;Liu et al, 2010;Yousef et al, 2010;de David et al, 2011;Domitrović et al, 2012). However, the concrete-engaged signals in regulating the protection of quercetin against liver injuries are not very clear.…”

“…It have already demonstrated that pretreatment of mice or rats with quercetin for five consecutive days can prevent CCl 4 -induced acute liver injury (Janbaz et al, 2004;Domitrović et al, 2012;Cui et al, 2014). However, whether quercetin can also alleviate CCl 4 -induced acute liver injury, when it is given after intraperitoneal (i.p.)…”

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“…[50] The high amount of quercetin present in EAE attenuated the inflammation by down-regulating the CCl 4 -induced activation of nuclear factor-kappa B, tumor necrosis factor-α and cyclooxygenase and showed hepatoprotective effects. [51] …”

Antioxidant activity and free radical scavenging potential of alpha lipoic acid and quercetin against Al2O3 nanoparticle-induced toxicity in mice

“…We have demonstrated the antioxidant potential of quercetin and lipoic acid against metal/ metalloid-induced oxidative stress in mice. [13][14][15] The present study was aimed at investigating the comparative protective efficacy of alpha-lipoic acid and quercetin against nanoparticle induced oxidative injury. Liver was selected as the major organ for investigation as it is the major target for free radical attack leading to lipid peroxidation.…”