Abstract
Liver is considered as the first target for the toxic effects of toxins and other xenobiotics, and this can be attributed to its role as a site which receive all absorbed xenobiotics from the gastrointestinal tract and its role as a major site for biotransformation of xenobiotics. The present study was designed to evaluate the possible hepatoprotective effect of benfotiamine against CCl4-induced hepatotoxicity in rats. The study was conducted on 48 male albino rats; the animals were allocated into 8 groups (6 rats in each group) and treated as follow: 4 groups treated with oral doses of either normal saline, benfotiamine (100 mg/kg), thiamine (100 mg/kg), N-acetylcystein (400 mg/kg) only without induction of hepatic damage. The other 4 groups were treated as indicated previously with induction of hepatic damage with CCl4; at the end of treatment period, rats were scarified, blood samples obtained and livers excised for the assessment of the oxidative stress parameters (MDA and GSH), cholesterol and triglycerides levels. Additionally, serum levels of total bilirubin, albumin, total protein and the activities of ALT, AST and ALP enzymes were evaluated before and after treatment with benfotiamine. Tissue sections were prepared for evaluation of histopathological changes. The results indicated that benfotiamine has the ability to protect hepatic tissue against the toxicity induced by CCl4, revealed through reduction of serum levels of TSB and liver enzymes, decrease in the hepatic tissue MDA levels and elevation of GSH there. Histological evaluation of tissue sections prepared for this purpose confirmed the previous finding. In conclusion, benfotiamine is capable to protect liver tissue against CCl4-induced toxicity in rats more than thiamine.
 Key words: Benfotiamine, CCl4, Hepatotoxicity
Highlights
The liver plays a central role in carbohydrate, protein and fat metabolism and allows the detoxification of various xenobiotics
(1) Toxic injury occurs in the liver more often than other organs, because all ingested substances that are absorbed are first presented to the liver and that the liver is responsible for the metabolism and elimination of many substances.[1]Many xenobiotics such as acetaminophen, CCl4,and yellow phosphorus produce liver damage in a predictable and dose-dependent manner; the most frequent mechanism of hepatocellular injury involves production of injurious metabolites by the cytochrome P450 system. [2,3] Preventive care can significantly reduce the progression of liver disease. [4]
Administration of Benfotiamine results in increased intracellular thiamine diphosphate levels, a cofactor of transketolase enzyme; activation of this enzyme by thiamine may reduce superoxide overproduction through directing advanced glycation and lipoxidation end products substrates to the pentose phosphate pathway.[7,8] The data presented in this work showed a significant decline in MDA level and increase in GSH level in animals treated with Benfotiamine and thiamine prior to CCl4 administration, this might be attributed to the up-regulation of transketolase but could be a positive side effect of Benfotiamine, which show an intrinsic antioxidative activity by itself.[37]. It is important to mention that the effect of Benfotiamine was much better than thiamine concerning GSH levels
Summary
The liver plays a central role in carbohydrate, protein and fat metabolism and allows the detoxification of various xenobiotics. It regulates the synthesis and secretion of bile. [1] Toxic injury occurs in the liver more often than other organs, because all ingested substances that are absorbed are first presented to the liver and that the liver is responsible for the metabolism and elimination of many substances.[1]Many xenobiotics such as acetaminophen, CCl4 ,and yellow phosphorus produce liver damage in a predictable and dose-dependent manner; the most frequent mechanism of hepatocellular injury involves production of injurious metabolites by the cytochrome P450 system. [13] Activation of Akt (protein kinase B) has been demonstrated to stimulate eNOS activity, increase the bioavailability of NO and reduce the generation of ROS. Activation of the hexosamine pathway with subsequent decrease in the accumulation of deleterious glucose metabolites seems to be involved, second, normalization of PKC activity along with prevention of nuclear factor kappa B (NF-κB) activation has been found in retinas, and third, correction of imbalances in the polyol pathway by decreasing aldose reductase activity, sorbitol concentrations and intracellular glucose levels seems to play a role. [7] Absorption of benfotiamine was better than thiamine itself, and levels of thiamine and thiamine pyrophosphate (TPP) remain higher for longer period of time. [18] Absorption of thiamine in the form of benfotiamine is found to be five times greater than the absorption of the conventional thiamine supplements, and because of greatest intracellular access of benfotiamine, its tissue availability and effects are more impressive, especially in the brain and muscles. [19] The present study was designed to evaluate the possible protective effect of benfotiamine against CCL4-induced hepatotoxicity in rats
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
