Hepatoprotective efficacy of certain flavonoids against microcystin induced toxicity in mice

Abstract

Toxic cyanobacteria (blue-green algae) water blooms have become a serious problem in several industrialized areas of the world. Microcystin-LR (MC-LR) is a cyanobacterial heptapeptide that represents acute and chronic hazards to animal and human health. Identification of suitable chemprotectants against microcystin is essential considering human health hazards. In the present study, we have evaluated the protective efficacy of three flavanoids namely quercetin (200 mg/kg), silybin (400 mg/kg), and morin (400 mg/kg)] pretreatment against microcystin toxicity (0.75 LD(50), 57.5 microg/kg) in mice. Various biochemical variables were measured to study the recovery profile of protected animals at 1- and 3-days post-toxin treatment. The serum alanine amino transferase (ALT) shows 17-fold increase in MC-LR treated animals compared with control group at 1 day. The silybin and quercetin group showed a decrease in level of ALT compared with MC-LR group but still higher than control group. No significant protection was observed with aspartate aminotransaminase (AST) and lactate dehydrogenase (LDH) levels in flavanoid-treated groups at 1-day post-treatment. But at 3 days, the serum levels of AST and ALT were normalized to control values, but the serum LDH levels were still significantly higher than the control group. No significant changes were observed in glutathione peroxidase and reduced glutathione levels at both 1- and 3-day postexposure. The catalase activity shows a significant decrease in quercetin-treated animals at 3-day postexposure. The protein phosphatase was significantly inhibited in MC-LR group compared to control. The silybin pretreated group showed recovery after 1 day. At 3 days, the PPAse activity was reversed to control values in all the flavanoid-treated groups. Immunoblotting analysis showed microcystin-PPAse adduct in liver tissues of toxin-treated as well as flavanoid-treated mice even after 3 days. The results of this study show that flavanoids, quercetin, silybin, and morin could reverse the hepatotoxic effects of MC-LR in vivo.

Plant Bioactive Metabolites and Drugs Produced by Endophytic Fungi of Spermatophyta

“…Silymarin is a bioactive extract of the fruits of milk thistle (Silybum marianum), containing seven flavolignans with reported antitumor and hepatoprotective properties [149,150]. Three of these compounds, silybin A, silybin B, and isosilybin A have been extracted as fermentation products of a strain of Aspergillus iizukae isolated from the leaves of S. marianum.…”

Assessment of the Antioxidant Activity of Silybum marianum Extract and Its Protective Effect against DNA Oxidation, Protein Damage and Lipid Peroxidation

“…Silybum marianum seeds contain more than seven fl avonolignans. Many studies have reported the biological evaluation of silymarin, such as in cancer chemoprevention and hepatoprotection (1,2). Silymarin has the ability to scavenge free radicals, it has been found to increase the production of glutathione in hepatocytes and the activity of superoxide dismutase in erythrocytes (3).…”

Silibinin Induced Autophagic and Apoptotic Cell Death in HT1080 Cells Through a Reactive Oxygen Species Pathway

“…Our previous studies have shown that silibinin exhibited an anti-apoptotic effect on isoproterenol-treated rat cardiac myocytes by reducing the expression of inducible nitric oxide synthase (iNOS) (7) and by increasing superoxide dismutase (SOD) activity (8). Subsequently, silibinin was detected to promote sustained superoxide (O 2 •− ) production, which had a protective effect, as exogenous SOD markedly enhanced silibinininduced apoptosis (9). In this study, silibinin displayed a cytotoxic effect on human fibroblast cells HT1080 through induction of reactive oxygen species (ROS) generation.…”