Hepatoprotective Activity of Sharbat Deenar, against Carbon Tetrachloride-Induced Hepatotoxicity in Rats

Polyherbal formulation Sharbat Deenar is a very popular unani medicine in Bangladesh. It is usually used for different kinds of liver disorders. In absence of reliable and inadequate hepatoprotective agents in conventional medicine, the herbal preparations are preferred for liver diseases. The present study was designed to evaluate the hepatoprotective activity of Sharbat Deenar on carbon tetrachloride (CCl4) induced hepatotoxicity in male Long-Evans albino rats. Group I served as normal control and received neither formulation nor carbon tetrachloride. Group II received only CCl4 1mL/kg body weight of rat intraperitoneally for consecutive 14 days. Group III received CCl4 1mL/kg body weight of rat intraperitoneally and Silymarin, in dose 50mg/kg body weight of rat orally. Group IV received CCl4 1mL/kg body weight of rat intraperitoneally and Sharbat Deenar 1mL/kg body weight of rat for the same 14 consecutive days. At the end of the study, hepatoprotective activity was evaluated by the levels of total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). Histopathological study of rat liver was also carried out. The results showed that polyherbal formulation Sharbat Deenar exhibited a significant hepatoprotective effect. Such an outcome seems to be the synergistic effect of all ingredients of tested herbal formulation. Although this study suggests that Sharbat Deenar may be used to cure or minimize various liver diseases, it needs further study to attain the clarity of mechanism and safety.

Hepatotoxicity Induced by Arsenic Trioxide in Adult Mice and Their Progeny

In this investigation, we have evaluated the effects of arsenic trioxide on hepatic function in pregnant and lactating Swiss albino mice and their suckling pups. Experiments were carried out on female mice given 175 ppm As2O3 in their drinking water from the 14th day of pregnancy until day 14 after delivery. Our results showed a significant decrease in plasma levels of total protein and albumin, cholesterol and triglyceride in As2O3 treated mice and their pups. The hyperbilirubinemia and the increased plasma total alkaline phosphatase activity suggested the presence of cholestasis. Transaminase activities as well as lactate deshydrogenase activity in plasma, known as biomarkers of hepatocellular injury, were elevated indicating hepatic cells’ damage after treatment with As2O3. Exposure to arsenic led to an increase of liver thiobarbituric acid reactive substances level along with a concomitant decrease in the activities of superoxide dismutase, catalase and glutathione peroxidase and in glutathione.

Protective Effect of Saponin Extract from the Root of Garcinia kola (Bitter kola) against Paracetamol- Induced Hepatotoxicity in Albino Rats

Liver disorders are one of the major problems of the world. Despite its frequent occurrence, high morbidity and high mortality, its medical management is currently inadequate. This study was designed to evaluate the hepatoprotective effect of saponin extract of the root of Garcinia kola on the integrity of the liver of paracetamol induced wistar albino rats. Twenty five (25) male adult wistar albino rats were divided into five (5) groups. Group I was the Control group that received distilled water only, group II was the negative control that received 2 g/kg of paracetamol on the 13th day, and group III, IV and V were pre-treated with 100, 200 and 400mg/kg of the saponin extract before inducing the liver damage on the 13th day with 2 g/kg of paracetamol. Twenty four (24) h after administration, the rats were sacrificed and blood samples were collected. The serum Alanine Transaminase (ALT), Aspartate Transaminase (AST), Alkaline Phosphatase (ALP) activities, Bilirubin and conjugated bilirubin, glucose and protein concentrations were evaluated. The liver was fixed immediately in Formalin and was processed and stained in Haematoxylin and Eosin (H&E). Administration of saponin extract from the root of Garcinia kola significantly decreased paracetamol induced elevated enzymes in the test group. Also histological observations showed that saponin extract of the root of Garcinia kola exhibited a significant liver protection against the toxicant as evident by the cells trying to return to normal. Saponin extract from the root of Garcinia kola indicated a protection of structural integrity of the hepatocytic cell membrane and regeneration of the damaged liver.

Influence of Pomegranate (Punica granatum L.) on Dimethoate Induced Hepatotoxicity in Rats

Pomegranate (Punica granatum L.) is an ancient fruit of great medical interest and rich source of antioxidants. Pesticides as dimethoate play a crucial role in the occurrence many diseases in plants, animal and human. Therefore the ability of Pomegranate (Punica granatum L.) to alleviate hepatotoxicity induced by organophosphate pesticide dimethoate was investigated. Albino male rats were divided randomly into 4 groups and kept at 7 animals per group in an environmentally controlled condition for 6 weeks. The first group was served as a control group (basal diet), the second group fed on basal diet supplemented with 5% freeze dried pomegranate seeds, the third group fed on 20 ppm dimethoate contaminated diet and the last group fed on dimethoate contaminated diet supplemented with 5% freeze dried pomegranate seeds. The results revealed that administration of dimethoate caused high significant increased in liver functions: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) activities as well as lipid peroxide (malonaldhyde, MDA); on the other hand high significant decreased on glutathione (GSH), glutathione peroxidase (GPx), albumin and total protein were observed. However addition of 5% freeze dried pomegranate seeds significantly improved all previously mentioned parameters. These results indicate the dimethoate induced hepatotoxicity and highlight the protective effect of pomegranate seeds as a potential protective agent against dimethoate induced hepatotoxicity. This may be attributed to the powerful antioxidants (polyphenols, total phenols, and total flavonoids) which present in high levels in pomegranate as well as improving the immunity by activation of antioxidant enzymes GSH and GPx.

Protective Effect of Hesperidin against Cyclophosphamide Hepatotoxicity in Rats

The protective effect of hesperidin was investigated in rats exposed to liver injury induced by a single intraperitoneal injection of cyclophosphamide (CYP) at a dose of 150 mg kg-1. Hesperidin treatment (100 mg kg-1/day, orally) was applied for seven days, starting five days before CYP administration. Hesperidin significantly decreased the CYP-induced elevations of serum alanine aminotransferase, and hepatic malondialdehyde and myeloperoxidase activity, significantly prevented the depletion of hepatic glutathione peroxidase activity resulted from CYP administration. Also, hesperidin ameliorated the CYP-induced liver tissue injury observed by histopathological examination. In addition, hesperidin decreased the CYP-induced expression of inducible nitric oxide synthase, tumor necrosis factor-α, cyclooxygenase-2, Fas ligand, and caspase-9 in liver tissue. It was concluded that hesperidin may represent a potential candidate to protect against CYP-induced hepatotoxicity.

Camel Thorn Has Hepatoprotective Activity against Carbon Tetrachloride or Acetaminophen Induced Hepatotoxicity, but Enhances the Cardiac Toxicity of Adriamycin in Rodents

In this study the administration of 660 mg/kg of the ethanolic extract of the Alhagigraecorum (Camel Thorn)to mice, showed a significant decrease in the level of transaminases in animals treated with a combination of CTE plus carbon tetrachloride (CCl4) or acetaminophen as compared to animals receiving CCl4 or acetaminophen alone. Histopatological investigation also confirmed that, camel thorn extract protects liver against damage-induced either by carbon tetrachloride or acetaminophen. On the other hand the cardiac toxicity produced by adriamycine was significantly increased in the presence of the ethanolic extract of camel thorn. Our study suggested that camel thorn can protect the liver against the injury produced by carbon tetrachloride or acetaminophen, with unexpected increase in the cardiac toxicity –induced by adriamycin in rodents.

A Nanosensor System Based On Disuccinimydyl–CYP2E1 for Amperometric Detection of the Anti-Tuberculosis Drug, Pyrazinamide

Pyrazinamide (PZA) is among the first-line pro-drugs  in the tuberculosis (TB) combination chemotherapy used to treat  Mycobacterium tuberculosis. Numerous reports have suggested that  hepatotoxicity due to pyrazinamide in patients is due to inappropriate  dosing. It is, therefore necessary to develop sensitive and reliable  techniques for determining the PZA metabolic profile of diagnosed  patients promptly and at point-of-care. This study reports the  determination of PZA based on nanobiosensor systems developed  from disuccinimidyl octanedioate modified Cytochrome P450-2E1  (CYP2E1) electrodeposited on gold substrates derivatised with  (poly(8-anilino-1-napthalene sulphonic acid) PANSA/PVP-AgNPs  nanocomposites. The rapid and sensitive amperometric PZA  detection gave a dynamic linear range of 2µM to 16µM revealing a  limit of detection of 0.044µM and a sensitivity of 1.38µA/µM. The  Michaelis-Menten parameters; KM, KM app and IMAX were calculated to  be 6.0µM, 1.41µM and 1.51x10-6 A, respectively, indicating a  nanobiosensor suitable for use in serum.

Cannabidiol Treatment Ameliorates Acetaminophen-Induced Hepatotoxicity in Mice

The possible therapeutic effect of cannabidiol, the major non-psychotropic Cannabis constituent, was investigated against acute hepatotoxicity induced by a single oral dose of acetaminophen (500mg/kg) in mice. Cannabidiol (two intraperitoneal injections, 5mg/kg, each) was given 1 hour and 12 hours following acetaminophen administration. Acetaminophen administration caused significant elevations of serum alanine aminotransferase, and hepatic malondialdehyde, and nitric oxide levels, and a significant decrease in hepatic reduced glutathione. Cannabidiol significantly attenuated the deterioration in the measured biochemical parameters resulted from acetaminophen administration. Also, histopathological examination showed that cannabidiol markedly attenuated ameliorated acetaminophen-induced liver tissue damage. These results emphasize that cannabidiol represents a potential therapeutic option to protect against acetaminophen hepartotoxicity which is a common clinical problem.

Protein Profiling in Alanine Aminotransferase Induced Patient cohort using Acetaminophen

Sensitive and predictive DILI (Drug Induced Liver Injury) biomarkers are needed in drug R&D to improve early detection of hepatotoxicity. The discovery of DILI biomarkers that demonstrate the predictive power to identify individuals at risk to DILI would represent a major advance in the development of personalized healthcare approaches. In this healthy volunteer acetaminophen study (4g/day for 7 days, with 3 monitored nontreatment days before and 4 after), 450 serum samples from 32 subjects were analyzed using protein profiling by antibody suspension bead arrays. Multiparallel protein profiles were generated using a DILI target protein array with 300 antibodies, where the antibodies were selected based on previous literature findings of putative DILI biomarkers and a screening process using pre dose samples from the same cohort. Of the 32 subjects, 16 were found to develop an elevated ALT value (2Xbaseline, responders). Using the plasma profiling approach together with multivariate statistical analysis some novel findings linked to lipid metabolism were found and more important, endogenous protein profiles in baseline samples (prior to treatment) with predictive power for ALT elevations were identified.

Aqueous Extract of Flacourtia indica Prevents Carbon Tetrachloride Induced Hepatotoxicity in Rat

Carbon tetrachloride (CCl4) is a well-known hepatotoxin and exposure to this chemical is known to induce oxidative stress and causes liver injury by the formation of free radicals. Flacourtia indica commonly known as 'Baichi' has been reported as an effective remedy for the treatment of a variety of diseases. The objective of this study was to investigate the hepatoprotective activity of aqueous extract of leaves of Flacourtia indica against CCl4 induced hepatotoxicity. Animals were pretreated with the aqueous extract of Flacourtia indica (250 & 500 mg/kg body weight) for one week and then challenged with CCl4 (1.5 ml/kg bw) in olive oil (1:1, v/v) on 7th day. Serum marker enzymes (ALP, AST, ALT, Total Protein & Total Bilirubin) and TBARS level (Marker for oxidative stress) were estimated in all the study groups. Alteration in the levels of biochemical markers of hepatic damage like AST, ALT, ALP, Total Protein, Total Bilirubin and lipid peroxides (TBARS) were tested in both CCl4 treated and extract treated groups. CCl4 has enhanced the AST, ALT, ALP and the Lipid peroxides (TBARS) in liver. Treatment of aqueous extract of Flacourtia indica leaves (250 & 500 mg/kg) exhibited a significant protective effect by altering the serum levels of AST, ALT, ALP, Total Protein, Total Bilirubin and liver TBARS. These biochemical observations were supported by histopathological study of liver sections. From this preliminary study it has been concluded that the aqueous extract of the leaves of Flacourtia indica protects liver against oxidative damages and could be used as an effective protector against CCl4 induced hepatic damage. Our findings suggested that Flacourtia indica possessed good hepatoprotective activity