Interleukin-7 as a potential therapeutic target for alleviating hepatic fibrosis in a mice model induced by carbon tetrachloride: implications for fitness and exercise

The effects of interleukin-7 (IL-7) on the carbon tetrachloride (CCL4) induced hepatic fibrosis were investigated in this study. Thirty-six female BALB/C mice were randomized into group A (control group) injected with saline, group B (fibrotic model group) and group C (IL-7 intervention group). Histopathological changes were observed by HE, Masson as well as reticular fiber staining. The apoptosis cells and hepatic stellate cell (HSC) were detected from the tissues, and the expressions of Bax and Bcl-2 gene were also detected. The results of histological HE, Masson and reticular fiber staining showed that compared with group B, the degree of inflammation and fibrosis of the tissue were statistically reduced in group C. Compared with sub-group B and C, the degree of reduce inflammation of the liver and inhibit hepatic fibrosis were more obviously with the extension of treatment time. The inflammatory activity and liver fibrosis score were statistical significant between groups (P<0.05), the highest score was group B, followed by group C. The apoptosis cells were similar between fibrotic model group and IL-7 intervention group, while the HSC count was obviously higher in group B compared to the other two groups. The Bax gene was up-regulated when intervened with IL-7 for hepatic fibrosis and Bcl-2 showed to the contrary. IL-7 could inhibit hepatic fibrosis in mice induced by CCL4 and reduce liver inflammation process. The anti-fibrosis mechanism might be involved in inducing apoptosis through P53 pathway regulated Bcl-2 and Bax genes. (AU)

Protective effect of the total flavonoids from Apocynum venetum L. on carbon tetrachloride-induced hepatotoxicity in vitro and in vivo

Apocynum venetum L., belonging to the family Apocynaceae, is a popular medicinal plant, which is commonly used in the treatment of hypertension, neurasthenia, and hepatitis in China. In the present study, the total flavonoids (TFs) were prepared from the leaves of A. venetum, and its protective effects on carbon tetrachloride (CCl4)-induced hepatotoxicity in a cultured HepG2 cell line and in mice were investigated. Cell exposed to 0.4% CCl4 (v/v) for 6 h led to a significant decrease in cell viability, increased LDH leakage, and intracellular reactive oxygen species (ROS). CCl4 also induced cell marked apoptosis, which was accompanied by the loss of mitochondrial membrane potential (MMP). Pretreatment with TFs at concentrations of 25, 50, and 100 μg/mL effectively relieved CCl4-induced cellular damage in a dose-dependent manner. In vivo, TFs (100, 200, and 400 mg/kg BW) were administered via gavage daily for 14 days before CCl4 treatment. The high serum ALT and AST levels induced by CCl4 were dose-dependently suppressed by pretreatment of TFs (200 and 400 mg/kg BW). Histological analysis also supported the results obtained from serum assays. Furthermore, TFs could prevent CCl4-caused oxidative damage by decreasing the MDA formation and increasing antioxidant enzymes (CAT, SOD, GSH-Px) activities in liver tissues. In summary, both in vitro and in vivo data suggest that TFs, prepared from A. venetum, showed a remarkable hepatoprotective and antioxidant activity against CCl4-induced liver damage

Role of Anise on the hepatotoxicity induced by carbon tetrachloride in adult male albino rats

Oxidative stress induced by free radicals is known to be a common cause of liver damage and hepatic fibrosis. Anise oil and its compounds have been identified to have antioxidant, anti-inflammatory and antifibrinogenic properties that may play a role in the management of hepatic disorders and promote liver regeneration. Thus, the purpose of the study was to evaluate the effects of anise oil on hepatotoxicity induced by carbon tetrachloride in adult male albino rats. Sixty male albino rats were divided into control group, CCL4-treated group that was injected with 1 mg /kg CCL4 intraperitoneally (ip), CCL4+anise oil-treated group that was injected with 1 mg /kg of CCL4 and 0.5 ml/ kg of anise oil (ip), and anise oil-treated group that was injected with 0.5 ml/kg of anise oil. Animals received treatment for 4 weeks and sacrificed 24 hours after the last administration. Livers were removed and processed for light and electron microscopy analysis. The CCL4-treated group revealed loss of normal architecture of hepatic lobules, steatosis, necrosis, cholestasis, portal congestion and progressed grading of lobular inflammation, ballooning degeneration and fibrosis. On the other hand, the CCL4 + anise group showed reduced liver damage and increased signs of regeneration. We conclude that anise oil has a protective effect on liver damage caused by CCL4and promotes liver regeneration (AU)

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The potential effects of pomegranate (Punica granatum) juice on carbon tetrachloride-induced nephrotoxicity in rats

The purpose of this study was to evaluate the effect of pomegranate (Punica granatum) in inhibiting and reversing the nephrotoxicity of carbon tetrachloride, a potent oxidative stress inducer which induces cellular kidney damage. Rats were intraperitoneally injected with carbon tetrachloride (2 mL/kg body weight) which produced severe renal tissue damage, as demonstrated by decreased uric acid and dramatic elevation of urea and creatinine. In addition, carbon tetrachloride injection caused oxidative stress in rats, as evidenced by increased lipid peroxidation and nitrite/nitrate (NOx) concentrations in the renal tissue, along with a remarkable reduction in superoxide dismutase, catalase, glutathione transferase, glutathione reductase, glutathione peroxidase activities and glutathione content. We suggested that pomegranate juice was able to elevate the antioxidant defense system, clean up free radicals, lessen oxidative damages and protect the kidney against carbon tetrachloride-induced toxicity, thus having a potential protective effect (AU)

Protective effects of curcumin, alpha-lipoic acid, and N-acetylcysteine against carbon tetrachloride-induced liver fibrosis in rats

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Liver fibrosis is a major health problem that can lead to the development of liver cirrhosis and hepatocellular carcinoma. On the other hand, several antioxidants have been shown to possess protective effect against liver fibrosis. Therefore, in the present work, the effectiveness of curcumin, alpha-lipoic acid, and N-acetylcysteine in protecting against carbon tetrachloride (CCl4)-induced liver fibrosis as well as the mechanism(s) implicated in this protective effect was studied. The antioxidants used in this study resulted in hepatoprotective effect as evident by substantial (..) (AU)

Acetyl-L-carnitine prevents carbon tetrachloride-induced oxidative stress in various tissues of Wistar rats

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Acetyl-L-carnitine (ALCAR) has been shown to prevent experimental selenite cataractogenesis, a manifestation of oxidative stress, but little is known about its potential in other settings of oxidative stress. The present study was based on the hypothesis that ALCAR prevents carbon tetrachloride (CCl4)-induced oxidative stress in vital tissues. Male albino Wistar rats were divided into three groups, each of six rats. Group I (control) rats received only vehicle (1 ml/kg b.w.) for 4 days; Group II (CCl4-exposed, untreated) rats received CCl4 (2 ml/kg b.w.) on the second and third days and vehicle on the first and fourth days; Group III (CCl4-exposed, ALCAR-treated) rats received ALCAR (200 mg/kg b.w.) for 4 days and CCl4 on the second and third days. All administrations were made intraperitoneally. After the experimental period, significantly (P < 0.05) elevated mean serum levels of aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase were observed in Group II rats when compared to Group I and Group III rats. The mean levels of vitamin C, vitamin E, and reduced glutathione and the mean activities of superoxide dismutase, catalase, and glutathione peroxidase were significantly (P < 0.05) lower in samples of hemolysate and of liver, kidney, and brain tissues of Group II rats than those in Group I and Group III rats. The mean level of lipid peroxidation was significantly (P < 0.05) higher in Group II rats than that in Group I and Group III rats. Moreover, the CCl4-induced upregulation of inducible nitric oxide synthase expression was prevented by ALCAR in the liver and brain tissues. These results suggest that ALCAR is able to prevent the CCl4-induced oxidative stress (AU)

The hepatoprotective effect of coumarin and coumarin derivates on carbon tetrachloride-induced hepatic injury by antioxidative activities in rats

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Coumarins are a vast group of natural compounds and some of them possess antioxidant activities. The comparison of the antioxidant activity of some coumarins with various chemical molecular structure has not been investigated in previous studies. Therefore, this study was aimed to investigate the hepatoprotective effect against carbon tetrachloride (CCl4) -induced hepatic injury by coumarin (1,2-benzopyrone) and coumarin derivatives, esculetin (6,7-dihydroxycoumarin), scoparone (6,7-dimethoxycoumarin), and 4-methylumbelliferone (7-hyroxy-4-methyl) in male Sprague–Dawley rats. Product of lipid peroxidation, malondialdehyde (MDA), activities of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) were evaluated for oxidative stress in hepatic injury. Gamma glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH) were detected in plasma as a biomarker of hepatic injury. Significantly elevated levels of MDA and lowered levels of SOD and CAT activities were observed in liver of rats exposed to CCl4, when compared to control values. Similarly, administration of CCl4 increased LDH and GGT levels in serum. Pre-treatment of rats with esculetin (35 mg kg−1, orally) and scoparone (35 mg kg−1, orally) significantly prevented CCl4-induced decrease in MDA levels and increase in SOD and CAT, whereas 4-methylumbelliferone (35 mg kg−1) and coumarin (30 mg kg−1) had no effect against CCl4-induced rise in serum enzymes. Esculetin and scoparone also showed protective properties as was evidenced in reduced LDH and GGT levels in serum. The results of this study indicate that the chemical structures of coumarins play an important role in the prevention of oxidative stress (AU)

Comparison of vitamin E, L-carnitine and melatonin in ameliorating carbon tetrachloride and diabetes induced hepatic oxidative stress

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This study aimed to investigate whether treatments with vitamin E, L-carnitine and melatonin can protect against CCl4 and diabetes-induced hepatic oxidative stress. Hepatic oxidative stress was performed in rats through 50% v/v carbon tetrachloride (CCl4) (1 ml/kg/3days, i.p.), and through diabetes mellitus induced by streptozotocin (STZ) (40 mg/kg, i.p.). Vitamin E (100 mg/kg/day, i.p), L-carnitine (300 mg/kg/day, i.p.) and melatonin (10 mg/kg/day, i.p.) were injected for a period of 6 weeks. Thereafter, changes in serum glucose level, liver function tests, hepatic malondialdehyde (MDA) content, hepatic reduced glutathione (GSH) content, hepatic superoxide (..) (AU)

Análisis fitofarmacológico de los frutos de Luffa acutangula para determinar su actividad antihepatotóxica / Phytopharmacological screening of Luffa acutangula fruits for its antihepatotoxic activity

Se examinó el extracto acuoso y etanólico (100 mg/kg) de Luffa acutangula Linn (frutos) para determinar la actividadantihepatotóxica en ratas druckrey mediante la hepatotoxicidad inducida por tetracloruro de carbono (CCl4)y paracetamol (PCM). Se demostró que el extracto posee un efecto hepatoprotector signifi cativo, ya que reduce losniveles séricos de transaminasas (SGPT y SGOT), fosfatasa alcalina (ALP) y bilirrubina. La signifi cativa actividadhepatoprotectora de Luffa acutangula es comparable a la de la silimarina, agente hepatoprotector estándar, lo quejustifi ca su uso en afecciones del hígado

The ethanolic and aqueous extract (100mg/kg) of Luffa acutangula Linn(fruits) was examined for antihepatotoxic activityin druckrey rats by inducing hepatotoxicity with Carbon tetrachloride(CCl4) and Paracetamol(PCM). The extracthas shown to posses signifi cant hepatoprotective effect by lowering the serum level of transaminases (SGPT & SGOT),Alkaline phosphatase (ALP) and bilirubin. The signifi cant hepatoprotective activity of Luffa acutangula is comparableto that standard hepatoprotective agent silymarin, which justify its use in liver affection

Intoxicación por dicloropropano: comunicación de 2 casos / Dicloropropane intoxication: communication of 2 cases

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