Evaluation of Prophylactic and Therapeutic Effects of Silymarin on Diazepam-Induced Hepatotoxicity in Cats

Abstract

Problem statement: Diazepam is commonly administered for seizure control and appetite stimulant in cats. Cats may develop acute fatal hepatic necrosis after receiving oral diazepam for several days. The aim of this study was to detect the protective action of silymarin on diazepam-induced hepatotoxicity in cats. Approach: About 25 healthy cats were randomly allotted to five equal groups. Animals in group A were given diazepam (repeated dose 2.5 mg kg −1 , p.o. q 12 h for 4 days); group B consisted of cats that received silymarin (30 mg kg −1 , p.o. q 12 h for 4 days) concurrent with diazepam administration; group C were received silymarin like group B, but 24 h after diazepam administration; group D were received silymarin like groups C, but 48 h after diazepam administration; group E were received silymarin like group D, but 72 h after diazepam administration. The serum concentrations of Alanine Amino Transferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), Lactate Dehydrogenase (LDH) and total and direct bilirubin were measured before diazepam administration and 24, 48, 72 and 96 h later as indices of liver injury. Results: Repeated oral administration of diazepam significantly elevated serum concentrations of ALT, AST, ALP, LDH and total and direct bilirubin in cats of group A, after 48 h. In both the groups (B and C) receiving silymarin, levels of serum enzyme activities and total and direct bilirubin remained within the normal values, but the group D and E which received silymarin 48 h and 72h later, levels of serum enzyme activities and total and direct bilirubin were increased with comparison to before diazepam administration. Conclusion: It was concluded that silymarin can protect liver tissue against oxidative stress in cats with diazepam intoxication particular in the first 24 h after exposure.

The Effects of Diazepam on Selected Blood Enzymes Activity and Prostate Specific Antigen of Adult Male Wistar Rats

“…The increase in the activity of AST was dosedependent with high doses having more serum AST activity than the lower doses. This finding supports the findings of [16] and [17] whose results indicated considerable increase in the serum activity of ALT in rats and cats respectively in the administration of diazepam. A high level of AST in the serum is an indicator of mitochondrial damage in mostly the centrilobular regions of the liver.…”

“…Results obtained in this study showed that administration of diazepam significantly (p ≤ 0.05) increase serum LDH levels in all test groups when compared to control from week 1 to 4. This result supports the study carried out by [17] whose findings showed that repeated oral administration of diazepam significantly elevated LDH. Although elevated LDH levels could also be as a result of its release from damaged cells from various part of the body as well as the liver due to exposure to drugs, elevated LDH levels together with higher activities of ALT, AST and ALP as an indication that the increase is of hepatic origin [23] .…”

“…The Biochemical studies showed that daily administration of diazepam significantly (p<0.05) elevated serum activity of alanine aminotranferase in all test groups when compared with the control group. This finding is in support of the study of [16] and [17] whose results showed significant increase in the serum activity of ALT in rats and cats in the administration of diazepam. The largest amount of ALT is in the cytosol of hepatic parenchymal cells [18] .…”

“…This makes it primarily a biomarker of hepatobilary effects [23] . Result obtained in this study agrees with the work of [17] whose results showed that continuous oral administration of diazepam considerably elevated serum concentration of ALT, AST & ALP but differs from the works of [16] whose results showed that chronic administration of diazepam caused significant reduction in ALP activity. These differences could be attributed to the fact that in long term administration, the effect of diazepam begins to wear off.…”

A Test for Two-Sample Repeated Measures Designs: Effect of High-Dimensional Data

“…Repeated measurements across time (occasion, drug or treatment) on the same subject (e.g., patient, animal, cell culture, block) are frequently observed in several scientific fields, for example in medicine, pharmaceutical, agriculture, industrial and social sciences (Zangiabadi and Ahrari, 2005;Sharifi et al, 2008;Arbabi et al, 2009;Tu and Koh, 2010;Mosallanejad et al, 2011). This type of data commonly called univariate repeated measures data (Davis, 2002).…”