Evaluation of the Protective Effect of Silibinin Against Diazinon Induced Hepatotoxicity and Free-Radical Damage in Rat Liver

Abstract

Background:Diazinon (0,0-Diethyl 0-(1-6-methyl-2-isoprophyl 4 pyrimidinyl) phosphorothioate) (DI) is a very effective organophosphate pesticide, used widely in agriculture. Consequently, data on poisoning cases secondary to DI exposure are important. The DI may affect a variety of tissues, including liver. Silibinin is a pharmacologically active constitute of Silybum marianum, with documented antioxidant activity.Objectives:The aim of our study was to evaluate both histopathologically and biochemically whether silibinin is protective in DI induced liver damage.Materials and Methods:Thirty two Wistar albino rats were divided into four groups, as follows: 1) control group - oral corn oil was given; 2) DI group - rats were administered orally 335 mg/kg in the corn oil solution; 3) Silibinin group - 100 mg/kg/day silibinin was given alone orally, every 24 hours for 7 days; 4) Silibinin + DI group - DI plus silibinin was given. All rats were sacrificed at the end of experiment. Superoxide dismutases (SOD), glutathione peroxidase (GPX), nitric oxide (NO) and myeloperoxidase (MPO) were investigated in serum and liver tissue. In addition, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzyme activities were evaluated. The liver tissue was evaluated histopathologically with Hematoxilin & Eosin dye.Results:Biochemically, ALT, AST, NO, MPO in serum and NO, MPO in liver tissue were found to be significantly higher in DI group, compared to control group (P < 0.001). In Group Silibinin + DI, serum AST, ALT, NO, MPO levels were significantly lower (P < 0.01), and both serum and tissue SOD activities were significantly higher, compared to DI group (P < 0.001). Diazinon induced histopathological changes in liver tissue were: severe sinusoidal dilatation, moderate disruption of the radial alignment of hepatocytes around the central vein, severe vacuolization in the hepatocyte cytoplasm, inflammation around central vein and portal region. In rats receiving both DI and silibinin, the DI induced changes accounted for less sinusoidal dilatation, vacuolization in the hepatocyte cytoplasm and the inflammation around central vein and portal region (P < 0.05).Conclusions:The DI was found to induce liver damage by oxidative stress mechanisms. Silibinin reduced the oxidative stress by inducing antioxidant mechanisms, thereby showing protective effect against DI induced liver damage. Further studies with silibinin should be performed regarding DI toxicity.

Adverse effects of organophosphorus pesticides on the liver: a brief summary of four decades of research

“…Acute high dose of diazinon caused hypertrophy and swelling of hepatocytes, vacuolisation of cytoplasm, and macrovascular steatosis (39). Forty-minute inhalation of diazinon every other day in pregnant mice induced a dosedependent increase in the hepatocyte area, hepatocyte apoptosis, and a decrease in the sinusoid area of the foetal liver (40).…”

“…There is strong evidence that both are increased by dimethoate, monocrotophos, methyl parathion, dichlorvos, fenitrothion, o m e t h o a t e , c h l o r p y r i f o s , 2 -b u t e n o i c a c i d -3 -(diethoxyphosphinothioyl) methyl ester (RPR-II), diazinon, and methidathion (21,33,39,(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64). It is interesting to note that the increases in AST and ALT are often accompanied by increases in the inflammatory mediator tumour necrosis factor alpha (TNF-α) (39,49,51,65). In humans, higher AST and ALT were reported in tobacco farmworkers in India (66) and farm workers in Gadap Karachi, Pakistan exposed to a mixture of pesticides, including OPs (67).…”

Investigation of the positive effects of silymarin on valproic acid-induced liver damage in rats

“…VPA (as Convulex 500 mg capsules) from Liba Co. (İstanbul, Turkey). Silymarin was obtained as Legalon fort (100 mg/kg capsules)from Madaus Co.(İstanbul, Turkey).VPA and SLY doses were determined based on previous studies, respectively (5,12).…”

“…The VPA group was given VPA peros 500 mg / kg / day for 14 th days (5).The VPA + SLY group was received 500 mg / kg VPA and 100 mg / kg / day SLY peros for 14 th days (12).Body weights were recorded at the beginning and the end of the study. Liver weights were recorded at the end of the experiment.…”

“…It promotes hepatocyte regeneration by stimulating RNA and DNA polymerase synthesis (11). The binding to the receptors in the membranes prevents the binding of toxins in these regions thereby reducing drug-induced hepatocellular damage (12). It is used in the treatment of diseases such as alcohol, toxin and viral hepatitis (13).…”