Hepatoprotective efficacy of certain flavonoids against microcystin induced toxicity in mice.
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.
Jayaraj
R
R
Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474002, India.
Deb
Utsab
U
Bhaskar
A S B
AS
Prasad
G B K S
GB
Rao
P V Lakshmana
PV
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001427:Bacterial Toxins / Q000633:toxicity; D002374:Catalase / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008387:Marine Toxins / Q000633:toxicity; D051379:Mice; D052998:Microcystins / Q000633:toxicity*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D011794:Quercetin / Q000494:pharmacology*; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology; D047309:Flavones
D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D001427:Bacterial Toxins; D002374:Catalase; D005419:Flavonoids; D005978:Glutathione; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D007770:L-Lactate Dehydrogenase; D008387:Marine Toxins; D052998:Microcystins; D010744:Phosphoric Monoester Hydrolases; D020011:Protective Agents; D011794:Quercetin; D000077385:Silybin; D012838:Silymarin; C008548:morin; D047309:Flavones; C057862:cyanoginosin LR