METHODS: Hepatotoxicity was induced in adult female Wistar rats using carbon tetrachloride (CCl4 ). Thirty-six rats were randomly divided into six groups with six rats in each group: Group 1 (normal control group), Group 2 (received only CCl 4 ), Group 3 (CCl 4 +low dose BM-MSCs), Group 4 (CCl 4 +high dose BM-MSCs), Group 5 (CCl 4 + silymarin), Group 6 (CCl 4 +silymarin+high dose BM-MSCs). Thirty days after the treatment, blood samples were collected for hepatocyte growth factor estimation. The rats were then killed, bone marrow was extracted for chromosomal aberration assay. Liver tissue was processed for evaluating the DNA fragmentation assay, histopathology, and scanning electron microscopy study.
RESULTS: Combination treatment of silymarin and high dose BM-MSCs significantly (P liver tissue samples. The combination treatment produced significant hepatoprotective effect which was supported by histopathology and scanning electron microscopy study.
CONCLUSION: Results indicate that the treatment of BM-MSCs in combination with silymarin had a better hepatoprotective and antimutagenic effect and represents a novel strategy for the treatment of hepatotoxicity.
RESULTS: The amount of total phenolics was estimated to be 70.83 mg Gallic Acid Equivalent (GAE) per gram of dry extract. The antioxidant activity of the L. edodes extract was 39.0% at a concentration of 1 mg/mL and was also concentration dependant, with an EC(50) value of 4.4 mg/mL. Different groups of animals (Wister albino mice) were administered paracetamol (1 g/kg, p.o.). L. edodes extract at a dose of 200 mg/kg was administered to the paracetamol treated mice for seven days. The effects of L. edodes extract on serum transaminases (SGOT, SGPT), alkaline phosphatase (ALP) and bilirubin were measured in the paracetamol-induced hepatotoxic mice. L. edodes extract produced significant (p < 0.05) hepatoprotective effects by decreasing the activity of serum enzymes and bilirubin.
CONCLUSIONS: From these results, it was suggested that L. edodes extract could perhaps protect liver cells from paracetamol-induced liver damage by its antioxidative effect on hepatocytes, hence diminishing or eliminating the harmful effects of toxic metabolites of paracetamol.
METHODS: A group of mice (n = 5) treated orally with a single dose (5000 mg/kg) of MEDL was first subjected to the acute toxicity study using the OECD 420 model. In the hepatoprotective study, six groups of rats (n = 6) were used and each received as follows: Group 1 (normal control; pretreated with 10% DMSO (extract's vehicle) followed by treatment with 10% DMSO (hepatotoxin's vehicle) (10% DMSO +10% DMSO)), Group 2 (hepatotoxic control; 10% DMSO +3 g/kg APAP (hepatotoxin)), Group 3 (positive control; 200 mg/kg silymarin +3 g/kg APAP), Group 4 (50 mg/kg MEDL +3 g/kg APAP), Group 5 (250 mg/kg MEDL +3 g/kg APAP) or Group 6 (500 mg/kg MEDL +3 g/kg APAP). The test solutions pre-treatment were made orally once daily for 7 consecutive days, and 1 h after the last test solutions administration (on Day 7th), the rats were treated with vehicle or APAP. Blood were collected from those treated rats for biochemical analyses, which were then euthanized to collect their liver for endogenous antioxidant enzymes determination and histopathological examination. The extract was also subjected to in vitro anti-inflammatory investigation and, HPLC and GCMS analyses.
RESULTS: Pre-treatment of rats (Group 2) with 10% DMSO failed to attenuate the toxic effect of APAP on the liver as seen under the microscopic examination. This observation was supported by the significant (p liver enzymes of alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP), and significant (p liver cells architecture with increase in dose of the extract. MEDL also demonstrated a low to none inhibitory activity against the respective LOX- and NO-mediated inflammatory activity. The HPLC and GCMS analyses of MEDL demonstrated the presence of several non-volatile (such as rutin, gallic acid etc.) and volatile (such as methyl palmitate, shikimic acid etc.) bioactive compounds.
CONCLUSION: MEDL exerts hepatoprotective activity against APAP-induced intoxication possibly via its ability to partly activate the endogenous antioxidant system and presence of various volatile and non-volatile bioactive compounds that might act synergistically to enhance the hepatoprotective effect.