Hepatoprotective effects of total saponins isolated from Taraphochlamys affinis against carbon tetrachloride induced liver injury in rats

In this study, rats were orally treated with the total saponins of Taraphochlamys affinis (TSTA) daily with administration of CCl4 twice a week for 8 weeks. Compared to the normal control, CCl4 induced liver damage significantly increased the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in serum and decreased the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px), and glutathione reductase (GSH-Rd) in liver. Meanwhile content of hepatic malondialdehyde (MDA), which was oxidative stress marker, was increased. Histological finding also confirmed the hepatotoxic characterization in rats. Furthermore, proinflammatory mediators including tumor necrosis factor-α(TNF-α) in serum, prostaglandin E2 (PGE2), inducible enitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in liver were detected with elevated contents, while expression of xenobiotic metabolizing enzyme--cytochrome P4502E1 (CYP2E1) was inhibited. The results revealed that TSTA not only significantly reversed CCl4 originated changes in serum toxicity and hepatotoxic characterization, but also altered expression of hepatic oxidative stress markers and proinflammatory mediators, combined with restoring liver CYP2E1 level. The results indicated that protective effect of TSTA against CCl4-induced hepatic injury may rely on its effect on reducing oxidative stress, suppressing inflammatory responses and improving drug-metabolizing enzyme activity in liver.     

Preventive effect of neutropenia on carbon tetrachloride-induced hepatotoxicity in rats

The preventive effect of neutropenia on carbon tetrachloride (CCl4)-induced hepatotoxicity was examined in rats. In rats treated once with CCl4 (1 ml kg(-1), i.p.), the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), indices of liver cell damage, and the hepatic activity of myeloperoxidase (MPO), an index of tissue neutrophil infiltration, increased at 6 h after the intoxication and further increased at 24 h. The liver of CCl4 -treated rats showed an increase in the concentration of thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation, and decreases in superoxide dismutase (SOD) activity and reduced glutathione (GSH) concentration at 6 h after the intoxication followed by a further increase in TBARS concentration and further decreases in SOD activity and GSH concentration at 24 h with increased xanthine oxidase (XO) activity at 24 h. Neutropenic treatment with anti-rat neutrophil antiserum (2 ml kg(-1), i.p.) at 0.5 h after CCl4 intoxication attenuated the increases in serum ALT and AST activities and hepatic MPO activity and TBARS concentration and the decreases in hepatic SOD activity and GSH concentration found at 6 and 24 h after CCl4 intoxication and the increase in hepatic XO activity found at 24 h after the intoxication. This neutropenia reduced the necrotic and degenerative changes with inflammatory cell infiltration in the liver cell of CCl4 -treated rats. These results indicate that neutropenia prevents CCl4 -induced hepatotoxicity in rats by attenuating the disruption of hepatic reactive oxygen species metabolism mediated by neutrophils accumulating in the liver tissue.     

Protective effects of amburoside A, a phenol glucoside from Amburana cearensis, against CCl4-induced hepatotoxicity in rats

The aim of this study was to investigate the possible beneficial effects of amburoside A, AMB [4-(O-beta- D-glycopyranosyl)benzyl protocatechoate], against carbon tetrachloride (CCl (4)) toxicity in rats. AMB is a phenol glucoside from the Brazilian medicinal plant Amburana cearensis, popularly used for the treatment of respiratory tract affections. Acute AMB (25 and 50 mg/kg, I. P. or P. O.) treatments of CCl (4)-intoxicated rats significantly inhibited the increase in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, as compared to the group treated with CCl (4) only. Histological studies showed less centrolobular necrosis and inflammatory cell infiltrates in the liver of animals treated with AMB plus CCl (4), when compared to the group treated with CCl (4) alone. In hepatic tissues, AMB at both doses inhibited CCl (4)-induced thiobarbituric acid-reactive substances (TBARS) formation, indicating a blockade of CCl (4)-induced lipid peroxidation. AMB also reversed the decrement in glutathione contents of hepatic tissues in CCl (4)-intoxicated rats. Furthermore, it restored catalase activity to normal values, which was significantly increased after CCl (4) treatment. Our results indicate that CCl (4)-induced oxidative damage in hepatic tissues is reversed by AMB treatment. The protective effect of AMB is probably due to the phenolic nature of this glucoside.     

Protective effect of salvianic acid a on acute liver injury induced by carbon tetrachloride in rats

Previous research has shown that salvianic acid A [2-(3,4-dihydroxyphenyl)-2-hydroxy-propanoic acid, SA] extracted from Salvia miltiorrhiza BGE (Danshen) markedly inhibits lipid peroxidation of mitochondrial membrane of hepatic cells in vitro. The present study was conducted to examine protective effect of SA on liver injury induced by carbon tetrachloride (CCl4) and its possible mechanism in vivo. Male Sprague-Dawley rats weighing 180-200 g were used in the experiments. Five mmol/kg CCl4 in olive oil was given to rats i.p. Spectrophotometrical method was used to measure activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum, activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) as well as malondialdehyde (MDA) level in hepatic tissue and the rate of superoxide anion (O2*-) generation in hepatic submitochondrial particles. Hepatic histological structure was observed under light microscopy. CCl4 caused significant changes of activities of the enzymes, MDA level, and the rate of O2*- generation and histopathological changes of acute hepatic injury were noted. SA reversed the significant changes induced by CCl4. These results demonstrate that SA produces protective action on acute hepatic injury induced by CCl4 via an antioxidative mechanism.     

Suppressive effects of<Emphasis Type="Italic">Platycodon grandiflorum</Emphasis> on the progress of carbon tetrachloride-lnduced hepatic fibrosis

The suppressive effects of Platycodi Radix (Changkil: CK), the root of Platycodon grandiflorum A. DC (Campanulaceae), on the progress of acute carbon tetrachloride (CCl4)-induced hepatic fibrosis were investigated in the rat. CK significantly suppressed CCl4-induced hepatic necrosis and inflammation, as determined by the serum enzymatic activities of alanine and aspartate aminotransferase and serum tumor necrosis factor-alpha levels, in dose-dependent manners. In addition, the increased hepatic fibrosis after acute CCl4 treatment was suppressed by the administration of CK. CK also significantly prevented the elevation of hepatic alpha1 (I) procollagen (type I collagen) mRNA and alpha-smooth muscle actin (alpha-SMA) expressions in the liver of CCl4-intoxicated rats and also suppressed the induction of alpha-SMA and type I collagen in cultured hepatic stellate cells, in dose-dependent manners. These results suggest that the suppressive effects of CK against the progress of acute CCl4-induced hepatic fibrosis possibly involve mechanisms related to its ability to block both hepatic inflammation and the activation of hepatic stellate cells.     

肝乐宁粉针剂对实验性肝损伤的保护作用

研究肝乐宁粉针剂对实验性肝损伤的保护作用。方法：采用四氯化碳致小鼠和大鼠肝脏损伤,测定生化指标及观察病理组织学改变。结果：肝乐宁粉针剂能显著降低四氯化碳引起的急性肝损伤小鼠和慢性肝损伤大鼠血清丙氨酸氨基转换酶和天门冬氨酸氨基转换酶增高;亦能明显降低大鼠血清唾液酸和肝羟脯氨酸含量,升高血清总蛋白和白蛋白水平;病理组织学检查肝乐宁粉针剂明显减轻肝细胞的变性和坏死,并抑制慢性肝损伤胶原纤维形成。结论：肝乐宁粉针剂具有肝细胞保护及抗肝纤维化作用。     

Salidroside protects mice against CCl4-induced acute liver injury via down-regulating CYP2E1 expression and inhibiting NLRP3 inflammasome activation

Salidroside (Sal), a natural phenolic compound isolated from Rhodiola sachalinensis, has been utilized as anti-inflammatory and antioxidant for centuries, however, its effects against liver injury and the underlying mechanisms are unclear. This study was designed to evaluate the protective effects and underlying mechanisms of Sal on carbon tetrachloride (CCl4)-induced acute liver injury (ALI) in mice. C57BL/6 mice were pretreated with Sal before CCl4 injection, the serum and liver tissue were collected to evaluate liver damage and molecular indices. The results showed that Sal pretreatment dose-dependently attenuated CCl4-induced acute liver injury, as indicated by lowering the activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and inhibiting hepatic pathological damage and apoptosis. In addition, Sal alleviated CCl4-primed oxidative stress and inflammatory response by restoring hepatic glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and inhibiting cytokines. Finally, Sal also down-regulated the expression of cytochrome P4502E1 (CYP2E1), and Nod-like receptor protein 3 (NLRP3) inflammasome activation in the liver of mice by CCl4. Our study demonstrates that Sal exerts its hepatoprotective effects on ALI through its antioxidant and anti-inflammatory effects, which might be mediated by down-regulating CYP2E1 expression and inhibiting NLRP3 inflammasome activation.     

恩施富硒藤茶水提液对四氯化碳致急性肝损伤小鼠的保护作用

目的 观察恩施富硒藤茶水提液对四氯化碳（CCl4）诱导的小鼠急性肝损伤的影响。方法用腹腔注射CCl4致小鼠急性肝损伤模型,测定不同剂量的恩施富硒藤茶水提液对肝损伤血清丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）活性、肝中超氧化物歧化酶（SOD）活性、肝中丙二醛（MDA）含量的影响。结果恩施富硒藤茶水提液具有剂量依赖性地降低CCl4致小鼠肝损伤血清ALT、AST值升高,降低肝组织匀浆中MDA的含量,增强SOD的活性（P〈0．01或P〈0．05）。结论恩施富硒藤茶水提液对CCl4致小鼠急性肝损伤具有一定的保护作用。     

Du-Zhong (Eucommia ulmoides Oliv.) leaves inhibits CCl4-induced hepatic damage in rats.

The protective effects of water extract of Du-Zhong (Eucommia ulmoides Oliv.) leaves (WEDZ) and its active compound (protocatechuic acid; PCA) on liver damage were evaluated by carbon tetrachloride (CCl4)-induced chronic hepatotoxicity in rats. Wistar rats were orally treated with WEDZ (0.1, 0.5, and 1.0 g/kg bw) or PCA (0.1 g/kg bw) with administration of CCl4 (0.5 ml/rat, 20% CCl4 in olive oil) for 28 consecutive days. It showed that CCl4-treated rats increased the relative organ weights of liver and kidney. CCl4-induced rats liver damage and significantly (p<0.05) increased the GOT, GPT, LDH and ALP levels in serum as compared with the control group. Treatment with WEDZ or PCA could decrease the GOT, GPT, LDH and ALP levels in serum when compared with CCl4-treated group. CCl4-treated rats also significantly (p<0.05) decreased the GSH content in liver and trolox equivalent antioxidant capacity (TEAC) in serum whereas increased (p<0.05) MDA content in liver as compared with the control group. Treatment with WEDZ or PCA also significantly (p<0.05) increased the GSH content and significantly (p<0.05) decreased the MDA content in liver. Administration of WEDZ or PCA could increase the activities of GPx, GRd and GST in liver. Liver histopathology showed that WEDZ or PCA reduced the incidence of liver lesions including hepatic cells cloudy swelling, lymphocytes infiltration, cytoplasmic vacuolization, hepatic necrosis and fibrous connective tissue proliferated induced by CCl4 in rats. The data suggest that oral administration with WEDZ for 28 consecutive days significantly decrease the intensity of hepatic damage induced by CCl4 in rats.     

Hepatoprotection of tea seed oil (Camellia oleifera Abel.) against CCl4-induced oxidative damage in rats.

The oil of tea seed (Camellia oleifera Abel.) is used extensively in China for cooking. This study was designed to evaluate the effects of tea seed oil on CCl(4)-induced acute hepatotoxicity in rats. Male SD rats (200+/-10 g) were pre-treated with tea seed oil (50, 100, and 150 g/kg diet) for six weeks before treatment with a single dose of CCl(4) (50% CCl(4), 2 mL/kg of bw, intraperitoneally), the rats were sacrificed 24h later, and blood samples were collected for assaying serum biochemical parameters. The livers were excised for evaluating peroxidation products and antioxidant substances, as well as the activities of antioxidant enzymes. Pathological histology was also performed. The results showed that a tea seed oil diet significantly (p<0.05) lowered the serum levels of hepatic enzyme markers (alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase), inhibited fatty degeneration, reduced the content of the peroxidation product malondialdehyde, and elevated the content of GSH. Pre-treatment of animals with tea seed oil (150 g/kg diet) could increase the activities of glutathione peroxidase, glutathione reductase and glutathione S transferase in liver when compared with CCl(4)-treated group (p<0.05). Therefore, the results of this study show that a tea seed oil diet can be proposed to protect the liver against CCl(4)-induced oxidative damage in rats, and the hepatoprotective effect might be correlated with its antioxidant and free radical scavenger effects.     

Hepatoprotective Effects of the Polysaccharide Isolated from Tarphochlamys affinis (Acanthaceae) against CCl(4)-Induced Hepatic Injury

This study was designed to investigate the protective effects of the polysaccharide isolated from Tarphochlamys affinis (PTA) against CCl(4)-induced hepatotoxicity in rats. Liver injury was induced in rats by the administration of CCl(4) twice a week for 2 weeks. During the experiment, the model group received CCl(4) only; the treatment groups received various drugs plus CCl(4), whereas the normal control group received an equal volume of saline. Compared with the CCl(4) group, PTA significantly decreased the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in the serum and increased the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) in the liver. Moreover, the content of hepatic malondialdehyde (MDA) was reduced. Histological findings also confirmed the anti-hepatotoxic characterisation. In addition, PTA significantly inhibited the proinflammatory mediators, such as prostaglandin E(2) (PGE(2)), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and myeloperoxidase (MPO). Further investigation showed that the inhibitory effect of PTA on the pro-inflammatory cytokines was associated with the down-regulation of nuclear factor-kappa B (NF-κB). In brief, our results show that the protective effect of PTA against CCl(4)-induced hepatic injury may rely on its ability to reduce oxidative stress and suppress inflammatory responses.     

彩虹明樱蛤多糖对小鼠急性化学性肝损伤的保护作用

目的研究彩虹明樱蛤多糖(MIP)对CCl4致小鼠急性化学性肝损伤的保护作用。方法 MIP对小鼠连续腹腔注射7 d,以0.1%CCl4橄榄油溶液经腹腔注射,建立小鼠急性化学性肝损伤模型,测定给药后模型小鼠肝指数,检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)活性,测定肝组织匀浆中丙二醛(MDA)含量和超氧化物歧化酶(SOD)、谷胱甘肽(GSH)的活性及观察肝脏病理学变化。结果 MIP中、高剂量组(80,160 mg/kg)均能显著降低CCl4致急性肝损伤小鼠血清ALT、AST活性(P<0.01),降低肝脏MDA含量(P<0.01),增强SOD和GSH活力(P<0.01或0.05),并能明显改善肝组织的病理学损伤,但对肝指数无明显影响。结论 MIP对CCl4致小鼠急性化学性肝损伤有保护作用。     

Protective effects of Pycnogenol on carbon tetrachloride-induced hepatotoxicity in Sprague-Dawley rats.

Oxidative damage is implicated in the pathogenesis of various liver injuries. In the present study the ability of Pycnogenol (PYC) as an antioxidant to protect against CCl4-induced oxidative stress and hepatotoxicity in rats was investigated. Four experimental groups of six rats each were constructed: a vehicle control group received the respective vehicles (distilled water and corn oil) only; a CCl4 group received a 14-day repeated intraperitoneal (i.p.) dose of distilled water and then a single oral dose of CCl4 at 1.25 ml/kg; and the CCl4&PYC 10 and CCl4&PYC 20 groups received a 14-day repeated i.p. dose of PYC 10 and 20 mg/kg, respectively, and then a single oral dose of CCl4 at 1.25 ml/kg. Hepatotoxicity was assessed 24 h after the CCl4 treatment by measurement of serum aminotransferase (AST) and alanine aminotransferase (ALT) activities, hepatic malondialdehyde (MDA) and glutathione (GSH) concentrations, and catalase, superoxide dismutase (SOD), and glutathione-S-transferase (GST) activities. The results were confirmed histopathologically. The single oral dose of CCl4 produced significantly elevated levels of serum AST and ALT activities. Histopathological examinations showed extensive liver injuries, characterized by extensive hepatocellular degeneration/necrosis, fatty changes, inflammatory cell infiltration, congestion, and sinusoidal dilatation. In addition, an increased MDA concentration and decreased GSH, catalase, SOD, and GST were observed in the hepatic tissues. On the contrary, PYC treatment prior to the administration of CCl4 significantly prevented the CCl4-induced hepatotoxicity, including the elevation of serum AST and ALT activities and histopathological hepatic lesions, in a dose-dependent manner. Moreover, MDA and GSH levels and catalase, SOD, and GST activities in hepatic tissues were not affected by administration of CCl4, indicating that the pretreatment of PYC efficiently protects against CCl4-induced oxidative damage in rats. The results indicate that PYC has a protective effect against acute hepatotoxicity induced by the administration of CCl4 in rats, and that the hepatoprotective effects of PYC may be due to both the inhibition of lipid peroxidation and the increase of antioxidant activity.     

虎杖提取物对小鼠急性肝损伤的保护作用

目的观察虎杖提取物对cch诱导的小鼠急性肝损伤的保护作用。方法采用CCl4诱导小鼠急性肝损伤模型,测定血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AsT）、肝组织超氧化物歧化酶（S（）D）活性及丙二醛（MDA）含量。结果cch诱导的小鼠急性肝损伤摸型,血清ALT、AST明显升高,肝组织SOD活性明显降低,MDA含量显著升高（P〈0．01）;虎杖提取物能显著降低血清ALT,AST,明显提高肝组织SOD活性,降低肝组织MDA含量（P〈0．01）。结论虎杖提取物具有降酶及抗氧化的作用。对CCh诱导的小鼠急性肝损伤具有一定的保护作用。     

The protective effects of Hibiscus sabdariffa extract on CCl4-induced liver fibrosis in rats.

Dried flower Hibiscus sabdariffa L. (HSE) extracts, a local soft drink material and medicinal herb, were studied for their protective effects against liver fibrosis induced using carbon tetrachloride (CCl(4)) in rats. Male Wistar rats were administered CCl(4) by intraperitoneal injection for 7weeks and received a normal diet or normal diet with various HSE doses (1-5%) for 9weeks. HSE significantly reduced the liver damage including steatosis and fibrosis in a dose dependent manner. Moreover, HSE significantly decreased the elevation in plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT). It also restored the decrease in glutathione content and inhibited the formation of lipid peroxidative products during CCl(4) treatment. In the primary culture, HSE also significantly inhibited the activation of the hepatic stellate cells. These results suggested that HSE may protect the liver against CCl(4)-induced fibrosis. This protective effect appears due to HSEs antioxidant properties.     

Protective effects of total flavonoids of Bidens bipinnata L. against carbon tetrachloride-induced liver fibrosis in rats

Bidens bipinnata L. is well known in China as a traditional Chinese medicine and has been used to treat hepatitis in clinics for many years. In a previous study we found that total flavonoids of Bidens bipinnata L. (TFB) had a protective effect against carbon tetrachloride (CCl4)-induced acute liver injury in mice. Now this study was designed to investigate its therapeutic effect against CCl4-induced liver fibrosis in rats and to determine, in part, its mechanism of action. The liver fibrosis model was established by subcutaneous injection of 50% CCl4 twice a week for 18 weeks. TFB (40, 80 and 160 mg kg(-1)) was administered by gastrogavage daily from the 9th week. The results showed that TFB (80 and 160 mg kg(-1)) treatment for 10 weeks significantly reduced the elevated liver index (liver weight/body weight) and spleen index (spleen weight/body weight), elevated levels of serum transaminases (alanine aminotransferase and aspartate aminotransferase), hyaluronic acid, type III procollagen and hepatic hydroxyproline. In addition, TFB markedly inhibited CCl4-induced lipid peroxidation and enhanced the activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase. Moreover, TFB (80 and 160 mg kg(-1)) treatment improved the morphologic changes of hepatic fibrosis induced by CCl4 and suppressed nuclear factor (NF)-kappaB, alpha-smooth muscle actin (SMA) protein expression and transforming growth factor (TGF)-beta1 gene expression in the liver of liver fibrosis of rats. In conclusion, TFB was able to ameliorate liver injury and protect rats from CCl4-induced liver fibrosis by suppressing oxidative stress. This process may be related to inhibiting the induction of NF-kappaB on hepatic stellate cell activation and the expression of TGF-beta1.     

Protective effect of saponins derived from the roots of Platycodon grandiflorum against carbon tetrachloride induced hepatotoxicity in mice

The purpose of this study was to investigate the protective effects of the saponins isolated from the root of Platycodi Radix (Changkil saponins: CKS) on carbon tetrachloride (CCl(4))-induced hepatotoxicities in mice. Pretreatment with CKS prior to the administration of CCl(4) significantly prevented the increase in serum alanine aminotransferase and aspartate aminotransferase activities and hepatic lipid peroxidation formation. In addition, CKS prevented CCl(4)-induced apoptosis and necrosis, as indicated by a liver histopathologic study and DNA laddering. To determine whether Fas/Fas ligand (FasL) pathway involved in CCl(4)-induced acute liver injury, Fas and FasL proteins and caspase-3, -8 activities were tested by western blotting and ELISA. CKS markedly decreased CCl(4)-induced Fas/FasL protein expression levels and in turn attenuated CCl(4)-induced caspase-3, -8 activities in mouse livers. Additionally, CKS protected the CCl(4)-induced depletion of hepatic glutathione levels. The effect of CKS on CYP2E1, the major isozyme involved in CCl(4) bioactivation, was investigated. Treatment with CKS resulted in a significant decrease in the CYP2E1-dependent hydroxylation of aniline. In addition, CKS exhibited antioxidant effects on FeCl(2)-ascorbate induced lipid peroxidation in liver homogenates, and on superoxide radical scavenging activity. These findings suggest that the protective effects of CKS against CCl(4)-induced acute liver injury possibly involve mechanisms related to its ability to block CYP2El-mediated CCl(4) bioactivation and its free radical scavenging effects, and that is also protects against Fas/FasL pathway mediated apoptosis.     

藤茶双氢杨梅树皮素对实验性慢性肝损伤的保护作用

目的：探讨从藤茶提取的双氢杨梅树皮素（APS）对慢性肝损伤的保护作用。方法：采用四氯化碳（CCl4）建立小鼠慢性肝损模型，并给予APS观察其对实验鼠血清丙氨酸氨基转移酶（ALT），天门冬氨酸氨基转移酶（AST）活性，总蛋白（TP），白蛋白（ALB），透明质酸（HA）含量和肝组织羟脯氨酸（HyP）含量的影响及肝组织病理改变的影响。结果：APS明显降低血清ALT，AST活性，血清HA含量和肝组织HyP含量，明显增高血清TP和ALB含量，同时可减轻实验鼠肝组织病理改变的程度。结论：APS对CCL4所致实验性慢性肝损伤具有明显的保护作用。