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Clinical application of doxorubicin is limited because of its potential side effects. The present study examined whether naringin had protective actions on doxorubicin‐induced liver injury. Male BALB/c mice and alpha mouse liver 12 (AML‐12) cells were used in this paper. The results showed that AML‐12 cells treated with naringin significantly reduced cell injury, reactive oxygen species release and apoptosis level; Moreover, naringin notably alleviated liver injury by decreasing aspartate transaminase, alanine transaminase and malondialdehyde, and increasing superoxide dismutase, glutathione and catalase levels. Mechanism researches indicated that naringin increased the expression levels of sirtuin 1 (SIRT1), and inhibited the downstream inflammatory, apoptotic and oxidative stress signaling pathways. Further validation was obtained by knocking down SIRT1 in vitro, which proved the effects of naringin on doxorubicin‐induced liver injury. Therefore, naringin is a valuable lead compound for preventing doxorubicin‐induced liver damage by reducing oxidative stress, inflammation, and apoptosis via up‐regulation of SIRT1. [ABSTRACT FROM AUTHOR]

Severe acetaminophen (APAP)‐induced hepatic damage is the second most common cause for hepatic transplantation. Clinically, hepatic damage caused by APAP is treated using N‐acetyl‐L‐cysteine, which can induce numerous side effects. Naringin, a bioflavonoid abundant in grapefruit and other citrus fruits, displays marked antiinflammatory and antioxidant activities. Herein, we aimed to investigate the potential mechanism underlying naringin‐mediated protection against APAP‐induced acute hepatotoxicity. We observed that naringin afforded protection against APAP‐induced acute liver failure in mice. Importantly, pretreatment with naringin before APAP administration further increased antioxidant enzyme expression, inhibited the production of proinflammatory cytokines, and activated apoptotic pathways. Furthermore, we observed that the protective effect was associated with the upregulation of cation transport regulator‐like protein 2 (CHAC2) and nuclear factor erythroid derived‐2‐related factor 2 (Nrf2). Notably, CHAC2 knockdown inhibited Nrf2 activation and naringin‐mediated antioxidant, antiinflammatory, and antiapoptotic effects in APAP‐induced liver injury. Likewise, si‐Nrf2 blocked the protective effect of naringin against APAP‐induced liver injury. Collectively, our results indicate that naringin may be a potent CHAC2 activator, alleviating APAP‐induced hepatitis via CHAC2‐mediated activation of the Nrf2 pathway. These data provide new insights into mechanisms through which CHAC2 regulates APAP‐induced liver injury by targeting Nrf2, which should be considered a novel therapeutic target. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) leads to myocardial cell damage and irreversible heart failure, which limits the clinical application of DOX. Naringin has biological functions of inhibiting inflammation, oxidative stress and apoptosis. Our aim was to investigate whether Naringin could prevent DOX-related cardiotoxicity in mice. Naringin was administered by gavage and mice were intraperitoneally injected with doxorubicin (1 mg/kg/day) for 15 days. H&E, Masson, TUNEL and others experiments were examined. NRVMs and H9C2 cells were treated with Naringin and DOX in vitro. Using IF, ELISA and Western Blot to detect the effect of Naringin and ECHS1 on cells. The results showed that Naringin could prevent DOX related cardiac injury, inhibit cardiac oxidative stress, inflammation and apoptosis in vivo and in vitro. Inhibition of ECHS1 could interfere the effect of Naringin on DOX-induced myocardial injury. Naringin may provide a new cardiac protective tool for preventing the cardiotoxicity of anthracycline drugs. [ABSTRACT FROM AUTHOR]