Hepatoprotective effects of Liv-52 on ethanol induced liver damage in rats

The mechanism of protective effects of Liv-52, a multiherbal hepatoprotective drug, on ethanol induced hepatic damage has been investigated. The results indicate that Liv-52 treatment prevents ethanol induced increase in the activity of the enzyme gamma-glutamyl transpeptidase. Concomitantly there was also a decrease in ethanol accentuated lipid peroxidation in liver following Liv-52 treatment. The activity of antioxidant enzymes; superoxide dismutase, glutathione peroxidase and the levels of glutathione were decreased following ethanol ingestion. Liv-52 treatment was found to have protective effects on the activity of superoxide dismutase and the levels of glutathione. The results obtained from the study indicate hepatoprotective nature of Liv-52 which might be attributed to its ability to inhibit lipid peroxidation.     

Hepatoprotective and antioxidant activity of N-Trisaccharide in different experimental rats

ObjectivesTo investigate the hepatoprotective, antioxidant and antihyperlipidemic effect of N-Trisaccharide isolated from Cucumis prophetarum (L.) on different experimental rats.MethodsN-Trisaccharide (25 and 50 mg/kg.b.w), silymarin (25 mg/kg) and glibenclamide (25 mg/kg) was orally administered once daily for 28 days and toxicity evaluation studies were carried out. Liver damage was assessed by determining DNA damage, serum enzyme activities and hepatic histopathology of carbon tetrachloride (CCl₄) induced hepatic injury in rats. Enzymatic and non enzymatic antioxidant levels in liver and kidney were determined and biochemical parameters such as, serum lipid profile, renal function markers were estimated in type 2 diabetic rats.ResultsDNA fragmentation analysis revealed the protective effect of N-Trisaccharide on liver DNA damage. Histopathological studies indicated that CCl₄-induced liver injury was less severe in N-Trisaccharide (25 and 50 mg/kg) treated group. Given at the above doses conferred significant protection against the hepatotoxic actions of CCl₄ in rats, reducing serum markers like SGOT, SGPT, ALP, creatinine and urea levels back to near normal (p < 0.05) compared to untreated rats. In diabetic rats, N-Trisaccharide treatment significantly reversed abnormal status of enzymatic and non-enzymatic antioxidants levels to near normal. Also, serum lipids such as TG, TC, LDL-C and VLDL-C levels were significantly (p < 0.05) reduced compared to diabetic untreated rats.ConclusionPresent study results confirm that N-Trisaccharide possesses significant antihyperlipidemic, antioxidant and hepatoprotective properties.     

Antibacterial and anti-inflammatory effects of genistein in Staphylococcus aureus induced osteomyelitis in rats

Methicillin-resistant Staphylococcus aureus (MRSA) is a highly infectious Gram-positive pathogen known to cause severe diseases such as endocarditis, food poisoning, pneumonia, osteomyelitis, and septicemia. MRSA is a major public health issue. Among these, osteomyelitis is inflammation of the bone caused by the invasion of the bacterial pathogen in the bones. Its prominent symptoms include fever, pain, and redness of bones. In the case of children, it affects the long bones of arms and legs, whereas in the case of adults it affects the hip, feet, and spine. Bacterial osteomyelitis can trigger pathological remodeling of bones and hence causes substantial morbidity and mortality. The present study aims to evaluate the isoflavone genistein's (5,7-dihydroxy-3-(4-hydroxyphenyl)−4H-1-benzopyran-4-one,4′,5,7 trihydroxyisoflavone) antimicrobial and anti-inflammatory effects against osteomyelitis induced by MRSA in male Wistar rats. Classification of the animals was into the following: sham (Group I), osteomyelitis (Group II, control), genistein (25 mg/kg body weight, Group III), and genistein (50 mg/kg body weight, Group IV). The rats did not receive any treatment for 4 weeks after bacterial inoculation. Genistein was then administered twice daily for 2 weeks. Bacterial growth, mean body weight bone infection status, and side effects of genistein treatment were assessed. Furthermore, lipid peroxidation, superoxide dismutase, glutathione (GSH) peroxidase, catalase, reduced GSH, tumor necrosis factor-α (TNF-α), and interleukin (IL)-6 were also determined. Two days after treatment, it was found that genistein significantly suppressed bacterial growth and reduced serum pro-inflammatory cytokines TNF-α and IL-6. Therefore, the study suggests that genistein could be a promising lead against MRSA-induced osteomyelitis.     

Hepatoprotective activity of Abutilon indicum on experimental liver damage in rats.

The aqueous extract of Abutilon indicum was tested for hepatoprotective activity against carbon tetrachloride- and paracetamol-induced hepatotoxicities in rats. A. indicum exhibited significant hepatoprotective activity by reducing carbon tetrachloride- and paracetamol-induced change in bio-chemical parameters that was evident by enzymatic examination. The plant extract may interfere with free-radical formation, which may conclude in hepatoprotective action. Acute toxicity studies revealed that the LD50 value is more than the dose of 4 g/kg body wt.     

Hepatoprotective effects of IL-22 on fulminant hepatic failure induced by d-galactosamine and lipopolysaccharide in mice

Interleukin-22 (IL-22), a member of the IL-10 cytokine family that is produced by activated Th22, Th1 and Th17 cells as well as natural killer cells, plays an important role in increase of innate immunity, protection from damage and enhancement of regeneration. Here, we examined the effects of IL-22 on acute liver failure model induced by d-galactosamine (GalN) and lipopolysaccharide (LPS). Administration of recombinant human IL-22 (rhIL-22) reduced the death rate markedly and prevented mice from severe hepatic injury, as evidenced by decreased serum alanine aminotransferase (ALT) and total bilirubin (T.Bil) activity as well as improved histological signs in liver. Furthermore, IL-22 treatment decreased the hepatic malondialdehyde (MDA) contents and increased the reduced glutathione levels. Serum tumor necrosis factor α (TNF-α) level and hepatic caspase-3 activity were significantly lower in mice administrated with IL-22. Moreover, IL-22 treatment significantly enhanced activation of STAT3 and up-regulated the expression of Bcl-xL, heme oxygenase-1 (HO-1) and redox factor-1 (Ref-1) in the liver injury induced by GalN/LPS. Collectively, these data indicate that IL-22 can provide critical protection against GalN/LPS-induced liver injury through anti-apoptotic, anti-oxidant and anti-inflammatory actions.     

Structural alterations in rat myocardium induced by chronic l-arginine and l-NAME supplementation

Structural changes affecting cardiomyocyte function may contribute to the pathophysiological remodeling underlying cardiac function impairment. Recent reports have shown that endogenous nitric oxide (NO) plays an important role in this process. In order to examine the role of NO in cardiomyocyte remodeling, male rats were acclimated to room temperature (22 ± 1 °C) or cold (4 ± 1 °C) and treated with 2.25% l-arginine·HCl or 0.01% l-NAME (N^ω-nitro-l-arginine methyl ester)·HCl for 45 days. Untreated groups served as controls. Right heart ventricles were routinely prepared for light microscopic examination. Stereological estimations of volume densities of cardiomyocytes, surrounding blood vessels and connective tissue, as well as the morphometric measurements of cardiomyocyte diameters were performed. Tissue sections were also analyzed for structural alterations. We observed that both l-arginine and l-NAME supplementation induced cardiomyocyte hypertrophy, regardless of ambient temperature. However, cardiomyocyte hypertrophy was associated with fibrosis and extra collagen deposition only in the l-NAME treated group. Taken together, our results suggest that NO has a modulatory role in right heart ventricle remodeling by coordinating hypertrophy of cardiomyocytes and fibrous tissue preventing cardiac fibrosis.     

Hepatoprotective effects of phosphatidylserine liposomes on carbon tetrachloride-induced hepatotoxicity in rats

It has been proposed carbon tetrachloride (CCl₄) intoxication due to the production of free radicals and serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) overload results hepatotoxicity. Phosphatidylserine (PS) has shown antioxidant activity in numerous studies. Therefore, this study was aimed to investigate the effects of PS liposomes treatment against the CCl₄-induced hepatotoxicity in a rat model. Male Wistar rats were treated with PS (10 mg/kg, oral) or phosphatidylcholine liposomes (PC) (10 mg/kg, oral) for 3 days before CCl₄ (2 ml/kg; ip once on the third day) injection. The serum level of ALT, AST, and ALP were measured. Also, antioxidant assays were performed. Administration of PS with CCl₄ significantly inhibited alterations in the serum levels of AST, ALP (^**P < 0.01), and ALT (^***P < 0.001) compared with control group. Furthermore, measurement of malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) levels indicated that PS significantly reduced reactive oxygen species. The results of the present study showed the hepatoprotective effects of PS against CCl₄-induced hepatotoxicity in rats.     

Hepatoprotective effects of whey protein on D-galactosamine-induced hepatitis and liver fibrosis in rats

The hepatoprotective effects of whey protein on two injections of D-galactosamine (300 mg/kg, i.p.) were investigated in rats fed a modified AIN-93M diet formulated with a protein source of casein or whey for 16 d. The whey protein-containing diet clearly suppressed an increase in plasma alanine and aspartate aminotransferase activity, lactate dehydrogenase and bilirubin, which are hepatitis markers, and also hyaluronic acid, a fibrosis marker. In addition, it suppressed histopathological signs of portal fibrosis, bile duct proliferation, and perivenular sclerosis. These results suggest that supplementation with whey protein can help prevent the development of hepatitis and portal fibrosis.     

Hepatoprotective effects of Hibiscus, Rosmarinus and Salvia on azathioprine-induced toxicity in rats

As an anti-metabolite, Azathioprine inhibits the de novo and salvage pathways of purine synthesis. Intraperitoneal injection of this drug results in not only lymphocyte suppression but also toxicity to bone marrow, gastrointestinal tract, and liver. This Azathioprine-induced hepatotoxicity was found to be associated with oxidative damage. Plants with antioxidative properties have been traditionally used to prevent diseases associated with free radicals. In this report, we used water extracts of three herbal plants that have been commonly used for treating many illnesses (Hibiscus sabdariffa, Rosmarinus officinalis and Salvia officinalis). Here we show their novel hepatoprotective effects against Azathioprine-induced hepatotoxicity in rats. Typically, administration of Azathioprine induces oxidative stress through depleting the activities of antioxidants and elevating the level of malonialdehyde in liver. This escalates levels of alanine aminotransferase, and aspartate aminotranferase in serum. Pretreatment with any of the three herbal plants used in this investigation proved to have a protective effect against Azathioprine-induced hepatotoxicity. Animals pretreated with water extracts from any of the three herbs under investigation not only failed to show necrosis of the liver after azathioprine administration, but also retained livers that, for the most part, were histologically normal. In addition, these herbs blocked the induced elevated levels of alanine aminotransferase and aspartate aminotranferase in serum. The Azathioprine-induced oxidative stress was relieved to varying degrees by the examined herbal extracts. This effect was evident through reducing malonialdehyde levels and releasing the inhibitory effect of Azathioprine on the activities of glutathione, catalase and superoxide dismutase. To our knowledge, this report is the first that shows hepatoprotective effects of Hibiscus, Rosmarinus and Salvia species against Azathioprine-induced acute liver damage.     

Effects of an anti-inflammatory agent of benzamide structure, dexamethasone and indomethacin on experimental cerebral edema induced by phospholipase 2 in rats

Only a few molecules show any efficacy against brain edema. Different methods such as brain copper-wire implantation or arachidonic acid injection are used in the research of active drugs. A new model, involving injection of phospholipase A2, is described. The effect of an anti-inflammatory compound, N-(4,6-dimethyl 2-pyridinyl) benzamide, was evaluated on the three different experimental brain edemas mentioned above; dexamethasone and indomethacin were used as reference drugs. The studied molecule is, like dexamethasone, active on the three brain edema models. It has no direct inhibitory effect on phospholipase A2, cannot block cyclooxygenase activity but does reduce prostaglandin biosynthesis. Other factors, such as dopaminergic and alpha 2-adrenergic agonist activities, could also interfere.     

Immunohistochemical examination of anti-inflammatory and anti-apoptotic effects of hesperetin on trinitrobenzene sulfonic acid induced colitis in rats

The trinitrobenzene sulfonic acid (TNBS) induced colitis model is used to investigate the pathogenesis of ulcerative colitis. Colon inflammation and apoptosis are associated with tissue damage in ulcerative colitis. Hesperetin is a natural flavonoid that exhibits antioxidative, anti-inflammatory and anti-apoptotic properties. We investigated the effects of hesperetin on tumor necrosis factor-alpha (TNF-α), protein tyrosine phosphatase, receptor type C (CD45), caspase-3 and Bax expressions in TNBS in induced colitis model in rats. Male rats were divided into three groups: control group treated with 1 ml physiological saline, colitis group, and colitis + hesperetin group treated with TNBS and hesperetin. Hesperetin treatment was applied for 10 days starting 3 days prior to colitis induction. At the end of the experiment, TNF-α, CD45, caspase-3 and Bax expressions in colon tissue were determined using indirect immunohistochemistry. Increased immunoreactivity of both inflammation markers, TNF-α, CD45, and apoptotic markers, caspase-3 and Bax, was detected in the colitis group. Hesperetin treatment effected significant reduction of all parameters. Hesperetin treatment prevents colon damage owing to its anti-inflammatory and anti-apoptotic effects.     

Potential therapeutic effects of induced pluripotent stem cells on induced salivary gland cancer in experimental rats

Salivary gland neoplasms exhibit complex histopathology in a variety of tumor types and treatment options depend largely on the stage of the cancer. Induced pluripotent stem cells (iPS) have been investigated for treating induced salivary gland cancer and for restoring salivary gland function. We investigated iPS treatment for salivary gland cancer both in vitro and in vivo. For our study in vitro, we re-programmed human skin fibroblasts to form iPS cells using a plasmid containing Oct4, Sox2, L-MYC and LIN28. For our study in vivo, we used 30 white male albino rats divided into the following groups of 10: group 1 (control): rats were injected with phosphate-buffered saline (PBS), group 2 induced squamous cell carcinoma (SCC): rat submandibular glands were injected with squamous carcinoma cells (SCC), group 3 (induced SCC/iPS): SCC treated rats treated with 5 × 106 iPS cells. Submandibular glands from rats of all groups were examined histologically and real time PCR was performed for amylase, and COX I and COX II gene expression. We confirmed that submandibular gland specimens included tumor tissue before starting treatment with iPS. iPS treated cases exhibited regeneration of salivary glands, although minor degenerative and vascularization changes remained. The acinar cells regained their proper organization, but continued to exhibit abnormal activity including hyperchromatism. iPS cells may be useful for treating salivary gland carcinomas.     

Hepatoprotective activity of Azadirachta indica leaves on paracetamol induced hepatic damage in rats.

Effect of A. indica leaf extract on serum enzyme levels (glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, acid phosphatase and alkaline phosphatase) elevated by paracetamol in rats was studied with a view to observe any possible hepatoprotective effect of this plant. It was interesting to observe that serum enzyme levels were much elevated in paracetamol induced animals than in those receiving a combination of paracetamol and lead extract. It is stipulated that the extract treated group was protected from hepatic cell damage caused by paracetamol induction. The findings were further confirmed by histopathological study of liver.     

Hepatoprotective activity of ellagic acid against carbon tetrachloride induced hepatotoxicity in rats

Administration of CCl4 to normal rats and consequent oral feeding with ellagic acid (50 mg/kg) provided a significant protection against the biochemical alterations in serum and liver produced by CCl4. In vitro experiments showed that liver microsomes from animals treated with ellagic acid and CCl4, decreased lipid peroxidation compared to microsome prepared from rats exposed to CCl4 alone.     

Hepatoprotective effects of Arctium lappa Linne on liver injuries induced by chronic ethanol consumption and potentiated by carbon tetrachloride

Arctium lappa Linne (burdock) is a perennial herb which is popularly cultivated as a vegetable. In order to evaluate its hepatoprotective effects, a group of rats (n = 10) was fed a liquid ethanol diet (4 g of absolute ethanol/ 80 ml of liquid basal diet) for 28 days and another group (n = 10) received a single intraperitoneal injection of 0.5 ml/kg carbon tetrachloride (CCl(4)) in order to potentiate the liver damage on the 21st day (1 day before the beginning of A. lappa treatment). Control group rats were given a liquid basal diet which did not contain absolute ethanol. When 300 mg/kg A. lappa was administered orally 3 times per day in both the 1-day and 7-day treatment groups, some biochemical and histopathological parameters were significantly altered, both in the ethanol group and the groups receiving ethanol supplemented with CCl(4). A. lappa significantly improved various pathological and biochemical parameters which were worsened by ethanol plus CCl(4)-induced liver damage, such as the ethanol plus CCl(4)-induced decreases in total cytochrome P-450 content and NADPH-cytochrome c reductase activity, increases in serum triglyceride levels and lipid peroxidation (the deleterious peroxidative and toxic malondialdehyde metabolite may be produced in quantity) and elevation of serum transaminase levels. It could even restore the glutathione content and affect the histopathological lesions. These results tended to imply that the hepatotoxicity induced by ethanol and potentiated by CCl(4) could be alleviated with 1 and 7 days of A. lappa treatment. The hepatoprotective mechanism of A. lappa could be attributed, at least in part, to its antioxidative activity, which decreases the oxidative stress of hepatocytes, or to other unknown protective mechanism(s).     

Hepatoprotective and antioxidant effect of tender coconut water on carbon tetrachloride induced liver injury in rats

Hepatoprotective and antioxidant effects of tender coconut water (TCW) were investigated in carbon tetrachloride (CCl4)-intoxicated female rats. Liver damage was evidenced by the increased levels of serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) and decreased levels of serum proteins and by histopathological studies in CCl4-intoxicated rats. Increased lipid peroxidation was evidenced by elevated levels of thiobarbituric acid reactive substance (TBARS) viz, malondialdehyde (MDA), hydroperoxides (HP) and conjugated dienes (CD), and also by significant decrease in antioxidant enzymes activities, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (Gpx) and glutathione reductase (GR) and also reduced glutathione (GSH) content in liver. On the other hand, CCl4-intoxicated rats treated with TCW retained almost normal levels of these constituents. Decreased activities of antioxidant enzymes in CCl4-intoxicated rats and their reversal of antioxidant enzyme activities in TCW treated rats, shows the effectiveness of TCW in combating CCl4-induced oxidative stress. Hepatoprotective effect of TCW is also evidenced from the histopathological studies of liver, which did not show any fatty infiltration or necrosis, as observed in CCl4-intoxicated rats.     

Attenuation of cyclophosphamide induced toxicity by squalene in experimental rats

Cyclophosphamide (CP) is a widely used antineoplastic drug, which could cause toxicity of the normal cells due to its toxic metabolites. In this study, the protective role of squalene (SQ) towards the tissue defense system in the toxicity induced by CP (150 mg/kg b.w., twice, in 2 consecutive days) was studied in the experimental rats. The significant (P < 0.05) alterations in the levels of enzymic [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR)] and non-enzymic antioxidants [total reduced glutathione (GSH), Vitamin E (Vit.E), Vitamin C (Vit.C) and ceruloplasmin] of the heart, red blood cell (RBC) hemolysate and plasma were investigated in the CP toxicity. Alterations in the levels of thiobarbutric acid reactive substance (TBARS) in heart, RBC hemolysate and plasma were also observed as a measure of lipid peroxidation (LPO). These pathological alterations due to CP administration were attenuated by the oral treatment of SQ at a dose of 0.4 ml/day/rat. These observations demonstrate the protective role of SQ towards the tissue defense system of the rats in the CP induced toxicity.     

Hepatoprotective activity of Leucas hirta against CCl4 induced hepatic damage in rats

Methanol and aqueous leaf extracts of L. hirta demonstrated hepatoprotective activity against carbon tetrachloride induced liver damage in rats. The parameters studied were serum total bilirubin, total protein, alanine transaminase, aspartate transaminase and alkaline phosphatase activities. The hepatoprotective activity was also supported by histopathological studies of liver tissue. Results of the biochemical studies of blood samples of CCl4 treated animals showed significant increase in the levels of serum markers and decrease in total protein level reflecting the liver injury caused by CCl4. Whereas blood samples from the animals treated with methanol and aqueous leaf extracts showed significant decrease in the levels of serum markers and increase in total protein indicating the protection of hepatic cells. The results revealed that methanol leaf extract followed by aqueous extract of L. hirta could afford significant protection against CCl4 induced hepatocellular injury.     

Hepatoprotective effects of purple potato extract against D-galactosamine-induced liver injury in rats

We investigated the hepatoprotective effect of purple potato extract (PPE) against D-galactosamine (GalN)-induced liver injury in rats. PPE (400 mg) was administered once daily for 8 d, and then GalN (250 mg/kg of body weight) was injected at 22 h before the rats were killed. Serum tumor necrosis factor alpha (TNF-alpha), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and asparate aminotranferase (AST) levels increased significantly after injection of GalN, but PPE inhibited GalN-induced alterations in serum TNF-alpha, LDH, ALT, and AST levels. Hepatic lipid peroxide and glutathione levels in the control + GalN group were higher and lower respectively than those in the control group, and those in the PPE + GalN group did not differ from that in the control group. The lipid peroxide level in hepatic microsomes treated with 2,2'-azobis (2-amidinopropane) dihydrochloride in the PPE group was significantly lower than that in the control group. This suggests that PPE has hepatoprotective effects against GalN-induced hepatotoxicity via inhibition lipid peroxidation and/or inflammation in rats.