A Novel Method for Preparation of Animal Models of Liver Damage: Liver Targeting of Carbon Tetrachloride in Rats.

Abstract

Animal models prepared by treatment with toxic compounds such as a carbon tetrachloride have been used to examine drug disposition in hepatic diseases. However, it is possible that these compounds accumulate and cause damage to other organs as they are administered systemically. In this study, we used the liver surface application technique to deliver a toxic compound to the liver to prepare an appropriate animal model in which only the liver is significantly damaged. To restrict the absorption area in the liver, a cylindrical diffusion cell was attached to the liver surface of male Wistar rats. Twenty-four hours after direct addition of carbon tetrachloride to the diffusion cell, plasma levels of glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT), and hepatic malondialdehyde (MDA) concentration were increased, while there were no changes in plasma creatinine or renal MDA level. On the other hand, not only GOT, GPT and hepatic MDA, but also creatinine and renal MDA levels were markedly increased by p.o. and i.p. administration of carbon tetrachloride, suggesting renal damage. These results indicated that the animal models of liver damage prepared by utilizing drug delivery techniques to accumulate toxic compounds in the liver would enable us to investigate the precise effects of hepatic disorder on drug disposition.

Pharmacokinetic Behavior of Micafungin in Rats with Carbon Tetrachloride-Induced Acute Hepatic Failure

“…Thus, CCl 4 -treated rats are widely used as common pathological models of acute hepatic failure in pharmacokinetic experiments. [10][11][12][13][14][15][16][17][18] Marked elevation in the activities of ALT and AST was confirmed in CCl 4 -treated rats, indicating the development of liver injury. CCl 4 intoxication is involved in reducing hepatic blood flow as well as the activities of hepatic enzymes responsible for drug metabolism, 14,19) and it has been reported that the elimination clearance of many drugs that undergo hepatic removal is markedly reduced in CCl 4 -treated rats.…”

In vivo antioxidant effect of aqueous root bark, stem bark and leaves extracts of Vitex doniana in CCl4 induced liver damage rats

“…The decrease in the kidneys activities of SOD and CAT after exposing rats to CCl 4 was also reported by Ragıp et al [31] . The non significant increase in TBARS of kidney tissue as compared to liver may be as a result of the fact that CCl 4 systemically applied on rats is found to be distributed in a higher concentration in the liver when compared to the kidneys [32] . There was no significant (P>0.05) difference between the kidney level of TBARS in the normal control and all the induced groups.…”

Protective Effects of Antioxidants on the Experimental Liver and Kidney Toxicity in Mice

“…Ogawa et al (20) suggested that the event related with the kidneys and liver are dependant to independent etiologies. CCl 4 systemically applied on rats were reported to be distributed in a higher concentration in the liver when compared to the kidneys (21). Multiple number of studies showed tissue damage in many organs, mainly in the liver induced by CCL 4 (18).…”