Hepatoprotective activity of the ethanolic extract of Morus indica roots from Indian Bodo tribes

The roots of Morus species are well described in the Pharmacopoeia of the People's Republic of China (ChP) for its traditional use in treating liver fibrosis due to its hepatoprotective property. However, little is known about the hepatoprotective effect of the roots of Morus indica L. (RoMi), and the pharmacological mechanism(s) are uncertain due to its intricacy. Therefore, this study evaluates the hepatoprotective activity of the ethanolic extract of RoMi (eRoMi) against the CCl4-induced in-vivo animal model at different dosages (100 and 200 mg/kg BW) in comparison with silymarin as a positive control. The hepatoprotective activity of eRoMi was evaluated by measuring the levels of serum biomarkers, hepatic antioxidant enzymes and was verified by histological studies. Interestingly, 1,2-bis(trimethylsilyl) benzene, 1,4-phenylenebis (trimethylsilane), 2,4,6-cycloheptatriene-1-one, 3,5-bis-trimethylsilyl and α-amyrin were the active components found in eRoMi as detected by GC–MS. Oral administration of eRoMi (200 mg/kg BW) to rats significantly protected serum biochemical parameters (increased ALT, AST, LDH, bilirubin and GGT as well as depletion of antioxidant enzymes and hepatic GSH) and elevation in hepatic lipid peroxidation as compared to CCl4-treated rats. The hematological indices such as erythrocytes, hemoglobin, monocytes and lymphocytes were also normal in eRoMi-treated rats. The histopathological evaluation indicated a significant restoration of liver structure as compared to silymarin. This study is the first scientific validation for the traditional use of eRoMi to understand its hepatoprotective activity.

Pregnancy Is Enough to Provoke Deleterious Effects in Descendants of Fructose-Fed Mothers and Their Fetuses

The role of fructose in the global obesity and metabolic syndrome epidemic is widely recognized. However, its consumption is allowed during pregnancy. We have previously demonstrated that maternal fructose intake in rats induces detrimental effects in fetuses. However, these effects only appeared in adult descendants after a re-exposure to fructose. Pregnancy is a physiological state that leads to profound changes in metabolism and hormone response. Therefore, we wanted to establish if pregnancy in the progeny of fructose-fed mothers was also able to provoke an unhealthy situation. Pregnant rats from fructose-fed mothers (10% w/v) subjected (FF) or not (FC) to a fructose supplementation were studied and compared to pregnant control rats (CC). An OGTT was performed on the 20th day of gestation, and they were sacrificed on the 21st day. Plasma and tissues from mothers and fetuses were analyzed. Although FF mothers showed higher AUC insulin values after OGTT in comparison to FC and CC rats, ISI was lower and leptinemia was higher in FC and FF rats than in the CC group. Accordingly, lipid accretion was observed both in liver and placenta in the FC and FF groups. Interestingly, fetuses from FC and FF mothers also showed the same profile observed in their mothers on lipid accumulation, leptinemia, and ISI. Moreover, hepatic lipid peroxidation was even more augmented in fetuses from FC dams than those of FF mothers. Maternal fructose intake produces in female progeny changes that alter their own pregnancy, leading to deleterious effects in their fetuses.

Hepatoprotective Activity of Leaves Extract of Bauhinia acuminata (Linn) against CCl4 Induced Hepatotoxicity in Albino Rats

The purpose of this study was to see if ethanolic and aqueous extracts of Bauhinia acuminatea (Linn.) had any hepatoprotective activity against CCl4-induced albino rats. The levels of biochemical parameters (SGOT, SGPT and ALP) were reduced and the levels of hepatic antioxidant enzymes such as GSH and CAT were decreased whereas the level of hepatic lipid peroxidation (MDA) was elevated byCCl4 induction in Albino rats when compared with the normal group. The ethanolic and aqueous extract of Bauhinia acuminata (Linn.) and Silymarin treated animal groups showed significant decrease in activities of different biochemical parameters like SGOT, SGPT, ALP and lipid peroxidase i.e., MDA level which were elevated by carbon tetrachloride (CCl4) intoxication, at doses of 200 and 400 mg/kg and increased the level of antioxidant enzymes such as GSH and CAT. The high dose of ethanolic extracts (400 mg/kg) was more effective as compared to low dose (200 mg/kg). So, it was concluded from the result that the ethanolic extract of Bauhinia acuminata (Linn.) possesses significant hepatoprotective activity compared to aqueous extracts against CCl4 induced hepatotoxicity in rats.

Protective Effects of Rheum Turkestanicum Janischagainst Diethylnitrosamine-Induced Hepatocellular Carcinoma in Rats

Aim of the study Hepatocellular carcinoma (HCC) is common cancer that causes many deaths worldwide. Recent studies have reported anti-cancer effects of R. turkestanicum against various cell lines including leukemia cervical tumor, and breast cancer. In this study, we aimed to identify the effect of R. turkestanicum against diethylnitrosamine (DEN)-induced HCC. Methods Wistar rats were divided into four groups of control, DEN, DEN + 100 mg/kg or 400 mg/kg of hydroethanolic extract of the plant roots. Results After four months, the animals in the DEN group showed HCC foci in the liver, an increase of hepatic lipid peroxidation, attenuation of hepatic antioxidant capacity, an increase of blood liver enzymes (ALT, AST, and ALP), bilirubin, albumin, creatinine, glucose, and reduction of the body weight. The plant extract could decrease the levels of liver enzymes, total bilirubin, direct bilirubin, albumin, urea, and creatinine in the blood. Also, the extract attenuated oxidative stress and improved pathological changes in the liver. Quantitative real-time PCR revealed a decrease in gene expression of Wnt/β-catenin and Akt and an increase in PTEN as the tumor suppressor gene. Conclusion The extract of R. turkestanicum reduced DEN-induced liver changes through inhibiting oxidative stress and attenuating the expression of Wnt/β-catenin and Akt and elevating PTEN expression.

Comparative Studies on the Hepatoprotective Effect of White and Coloured Rice Bran Oil against Acetaminophen-Induced Oxidative Stress in Mice through Antioxidant- and Xenobiotic-Metabolizing Systems

Rice bran oil (RBO) comprises various nutrients and phytochemicals which exhibit several health benefits. There are no studies regarding the functional effects of different colours of RBO. This study was aimed to compare the constituents and antioxidant activities of white rice bran oil (WRBO) and coloured rice bran oil (CRBO). Each RBO showed similar free fatty acid profiles. However, greater amounts of vitamin E, phytosterols, carotenoids, and chlorophylls were found in CRBO, which had lower γ-oryzanol content than WRBO. Oxidative stress was induced in male mice by an overdose of acetaminophen (APAP) at 300 mg/kg body weight. The mice were then fed with RBO at the equivalent dose to 100 mg/kg body weight of γ-oryzanol three hours later and sacrificed six hours after APAP treatment. The administration of 100 mg γ-oryzanol equivalent in CRBO ameliorated APAP-induced hepatotoxicity in mice more strongly than 100 mg γ-oryzanol equivalent in WRBO, as evidenced by the significant reduction of serum ALT, hepatocellular necrosis, and hepatic lipid peroxidation. CRBO could improve xenobiotic-metabolizing and antioxidant enzyme activities, including glutathione S -transferase, superoxide dismutase, glutathione peroxidase, and glutathione reductase, and also increase mRNA expression of various antioxidant-responsive genes. Vitamin E, phytosterols, carotenoids, and chlorophyll might be the protective compounds in CRBO that alleviate APAP-induced hepatotoxicity through the interruption of APAP metabolism and the activation of antioxidant systems at both transcriptional and enzymatic levels. These findings might provide a protective role of CRBO on oxidative stress associated with several degenerative diseases.

Dietary Iron Overload Differentially Modulates Chemically-Induced Liver Injury in Rats

Hepatic iron overload is well known as an important risk factor for progression of liver diseases; however, it is unknown whether it can alter the susceptibility to drug-induced hepatotoxicity. Here we investigate the pathological roles of iron overload in two single-dose models of chemically-induced liver injury. Rats were fed a high-iron (Fe) or standard diet (Cont) for four weeks and were then administered with allyl alcohol (AA) or carbon tetrachloride (CCl4). Twenty-four hours after administration mild mononuclear cell infiltration was seen in the periportal/portal area (Zone 1) in Cont-AA group, whereas extensive hepatocellular necrosis was seen in Fe-AA group. Centrilobular (Zone 3) hepatocellular necrosis was prominent in Cont-CCl4 group, which was attenuated in Fe-CCl4 group. Hepatic lipid peroxidation and hepatocellular DNA damage increased in Fe-AA group compared with Cont-AA group. Hepatic caspase-3 cleavage increased in Cont-CCl4 group, which was suppressed in Fe-CCl4 group. Our results showed that dietary iron overload exacerbates AA-induced Zone-1 liver injury via enhanced oxidative stress while it attenuates CCl4-induced Zone-3 liver injury, partly via the suppression of apoptosis pathway. This study suggested that susceptibility to drugs or chemical compounds can be differentially altered in iron-overloaded livers.

Pecan pericarp extract protects against carbon tetrachloride-induced liver injury through oxidative mechanism in rats

The purpose of this study was to quantify the proanthocyanidin content of pecan (Carya illinoinensis) pericarp extract (PPE) and to assess its useful impacts against carbon tetrachloride (CCl4)-induced hepatotoxicity. Rats were randomly divided into four groups: Group 1: received intraperitoneal injection of saline solution, Group 2: was injected with PPE (25 mg/kg body weight) for 10 consecutive days, Group 3: received CCl4 (0.5 ml/kg, subcutaneous injection), Group 4: was coadministred with PPE + CCl4. The CCl4 was administered every 3 days during 10 days. Results revealed the presence of a high amount of total proanthocyanidins in the PPE (81.01 ± 0.21 mg TAE.g−1DW). CCl4 injection induced significant reductions in hepatic antioxidants but increased hepatic lipid peroxidation (LPO) as well as serum injury biomarkers. However, cotreatment with PPE significantly (P < 0.05) inverted CCl4-induced increase in plasma alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase activities, respectively to 74%, 77%, 60%, and 82% compared with CCl4 group. No significant toxic effects were observed following treatment with plant extract alone. PPE cotreatment also decreased significant (P < 0.05) the hepatic malondialdehyde formation (21%) and enhanced the liver catalase activity (107%) in CCl4-intoxicated rats. The histopathological examination showed inflammatory infiltration and degenerative changes in the hepatic tissue following CCl4 injection. The hepatoprotective activity of PPE against CCl4 exposure was supported by the maintenance of structural integrity of liver histopathology. In conclusion, the current study illustrated that PPE pretreatment significantly improved all examined parameters, restored the hepatic architecture and successfully alleviates oxidative damage induced by CCl4 intoxication.

4-HNE Immunohistochemistry and Image Analysis for Detection of Lipid Peroxidation in Human Liver Samples Using Vitamin E Treatment in NAFLD as a Proof of Concept

Lipid peroxidation is a common feature of liver diseases, especially non-alcoholic fatty liver disease (NAFLD). There are limited validated tools to study intra-hepatic lipid peroxidation, especially for small specimen. We developed a semi-quantitative, fully automated immunohistochemistry assay for the detection of 4-hydroxynoneal (4-HNE) protein adducts, a marker of lipid peroxidation, for adaptation to clinical diagnostics and research. We used Hep G2 cells treated with 4-HNE to validate specificity, sensitivity, and dynamic range of the antibody. Staining and semi-quantitative automated readout were confirmed in human needle-biopsy liver samples from subjects with NAFLD and normal liver histology. The ability to detect changes in lipid peroxidation was tested in paired liver biopsies from NAFLD subjects, obtained before and after 4 weeks of treatment with the antioxidant vitamin E (ClinicalTrials.gov NCT01792115, n=21). The cellular calibrator was linear and NAFLD patients had significantly higher levels of 4-HNE adducts compared to controls ( p=0.02). Vitamin E treatment significantly decreased 4-HNE ( p=0.0002). Our findings demonstrate that 4-HNE quantification by immunohistochemistry and automated image analysis is feasible and able to detect changes in hepatic lipid peroxidation in clinical trials. This method can be applied to archival and fresh samples and should be considered for use in assessing NAFLD histology.

Chemoprotective Effect of Leaf Extracts of Cecropia distachya Huber (Urticaceae) in Mice Submitted to Oxidative Stress Induced by Cyclophosphamide

The objective of this work was to evaluate the chemoprotective effects of the embaúba Cecropia distachya Huber (two methanolic fractions: F1 and F2) on oxidative stress induced by cyclophosphamide (75 mg kg-1) in mice, as well as phytochemical analyzes by LC-MS/MS. In the experimental model, the fractions increased the hepatic and cardiac catalase (CAT), reduced glutathione (GSH) of the kidney and the heart. F1 increased platelet levels (PLT), hemogram (RBC), hematocrit (HCT) and hemoglobin (Hb) and F1 reduced hepatic lipid peroxidation (TBARS) and aspartate aminotransferase (AST) activity increased. F1 was attributed to possible hypoglycemic activity and possible immunosuppressive effects and F2 presented antimutagenic activity. In some cases, the fractions were also hepatotoxic. These results demonstrated that the fractions stimulate the antioxidant defenses, being hypoglycemic (F1) and antimutagenic (F2), and, the harmful effects attributed to the fractions may be the association of compounds that were not elucidated in this work.