Naringenin protects against isoniazid- and rifampicin-induced apoptosis in hepatic injury

Abstract

AIMTo explore the protective effects and mechanisms of naringenin (NRG) on hepatic injury induced by isoniazid (INH) and rifampicin (RIF).METHODSMale mice were randomly divided into four groups and treated for 14 d as follows: normal control group was administered intragastrically with normal saline solution alone; model group was administered intragastrically with INH (100 mg/kg) and RIF (100 mg/kg); low- and high-dosage NRG pretreatment groups were administered intragastrically with different doses of NRG (50 or 100 mg/kg) 2 h before INH and RIF challenge. Mice were killed 16 h after the last dose of drug treatment to determine activity of serum transaminases. Oxidative stress was evaluated by measuring hepatic glutathione (GSH) and superoxide dismutase (SOD) and malondialdehyde (MDA) levels. Histopathological changes in hepatic tissue were observed under the optical microscope. Hepatocyte apoptosis was measured by TUNEL assay and caspase-3 activation. Expression of Bcl-2 and Bax in liver was determined by western blot.RESULTSBoth low- and high-dosage NRG pretreatment obviously alleviated serum levels of alanine aminotransferase and aspartate aminotransferase, liver index, hepatic MDA content, and increased hepatic GSH content and SOD activity compared with the INH and RIF-treated group (44.71 ± 8.15 U/L, 38.22 ± 6.64 U/L vs 58.15 ± 10.54 U/L; 98.36 ± 14.78 U/L, 92.41 ± 13.59 U/L vs 133.05 ± 19.36 U/L; 5.34% ± 0.26%, 4.93% ± 0.25% vs 5.71% ± 0.28%; 2.76 ± 0.67 nmol/mgprot, 2.64 ± 0.64 nmol/mgprot vs 4.49 ± 1.12 nmol/mgprot; 5.91 ± 1.31 mg/gprot, 6.42 ± 1.42 mg/gprot vs 3.11 ± 0.73 mg/gprot; 137.31 ± 24.62 U/mgprot, 148.83 ± 26.75 U/mgprot vs 102.34 ± 19.22 U/mgprot; all P < 0.01 or 0.05). Histopathological evaluation showed obvious necrosis and inflammatory cell infiltration in liver of mice administered INH and RIF; however, mice pretreated with NRG showed minor hepatic injury. In addition, INH and RIF resulted in hepatocyte apoptosis, and NRG pretreatment dramatically suppressed INH- and RIF-induced hepatocytes apoptosis. Furthermore, NRG-mediated anti-apoptotic effects seemed to be in connection with its regulation of Bax and Bcl-2 protein expression in hepatic tissue.CONCLUSIONNRG might attenuate INH- and RIF-induced hepatic injury via suppression of oxidative stress and hepatocyte apoptosis.

By reducing oxidative stress, naringenin mitigates hyperglycaemia-induced upregulation of hepatic nuclear factor erythroid 2-related factor 2 protein

“…That naringenin increases SOD and GPx activity in non-diabetic animals, suggests that their production is highly inducible and depends on oxidative stress. Naringenin has previously been shown to protect against isoniazid-and rifampicin-induced apoptosis in hepatic injury, high glucose-induced mitochondriamediated apoptosis and hepatic oxidative events and regulation of eNOS expression in the liver in fructose-administered rats [29][30][31] in tandem with our results. Naringenin is a known powerful antioxidant with free radical quenching properties owing to its OH which have high affinity for ROS and RNS.…”

Karbontetraklorür İle Karaciğer Hasarı Oluşturulan Ratlarda Tribulus terrestris’in Antihiperlipidemik Etkisinin Araştırılması

“…CCl4 ile in vitro şartlarda oluşturulan zararda etkilenen birinci derecede karaciğer olsa da bu toksikasyon sonucu birçok organ ve sistem doğrudan ve dolaylı olarak etkilenmektedir [1][2][3]. CCl4'un düşük dozlarda uzun süreli uygulanması sonucu karaciğer hücrelerinde lipid dejenerasyonuna, doz arttıkça ise karaciğer hücrelerinin nekrozuna, paranşimde kanamalara neden olduğu gösterilmektedir [4][5][6]. CCl4 ile oluşturulan toksikasyonda hücre hasarı, lipid peroksidasyonundaki artışla doğru orantılıdır ve bu toksik etkinin, serbest radikallere dönüşümü ile olduğu belirlenmiştir.…”

Effect of mobile phone electromagnetic waves on rat testis and the possible ameliorating role of Naringenin : A histological study

“…Naringenin has wide range of biological pharmacological activities as anti-inflammatory [10] , anticancer [11] , antiatherogenic [12] and antioxidant [13] . It has also been reported to be hepatoprotective [14] , cardioprotective [15] and renoprotective [16] . Recently, NG protective effect against testicular toxicity induced by cisplatin (chemotherapeutic) [17] and permethrin (insecticide) was investigated [18] .…”