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 Group 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.
Highlights
Diazepam is reported to be effective as an acute and chronic anticonvulsant in cats
Hepatic necrosis is the most serious adverse event reported in cats, so some neurologists do not recommend the use of diazepam as a maintenance anticonvulsant in cats
Serum concentrations of ALT, AST, Alkaline Phosphatase (ALP), Lactate Dehydrogenase (LDH) and total and direct bilirubin were measured in an automated chemical analyzer (BT 3000 Plus, Biotechnica, Milan, Italy) using diagnostic kits (Pars Azmoon Co., Tehran, Iran) before diazepam administration and 24, 48, 72 and 96 h thereafter
Summary
It has been used to treat problems such as inappropriate elimination associated with anxiety, urine marking or spraying, fear aggression and over grooming, as well as to stimulate appetite (Maddison et al, 2002) It is the most commonly used anticonvulsant followed by phenobarbitone and pentobarbital. Concurrent administration with other drugs that compete with the cytochrome P450 enzyme system may decrease the rate of metabolism of diazepam. This adverse effect should be carefully considered before administering diazepam to cats, especially on a long-term or recurrent basis. The present study was conducted to evaluate the hepatoprotective action of silymarin as the standard drug for evaluation of prophylactic and therapeutic effects on diazepam-induced hepatotoxicity in cats
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