Abstract
BackgroundThe first line anti-tuberculosis drugs isoniazid (INH), rifampicin (RIF) and pyrazinamide (PZA) continues to be the effective drugs in the treatment of tuberculosis, however, the use of these drugs is associated with toxic reactions in tissues, particularly in the liver, leading to hepatitis. Silymarin, a standard plant extract with strong antioxidant activity obtained from S. marianum, is known to be an effective agent for liver protection and liver regeneration. The aim of this study was to investigate the protective actions of silymarin against hepatotoxicity caused by different combinations of anti-tuberculosis drugs.MethodsMale Wistar albino rats weighing 250–300 g were used to form 6 study groups, each group consisting of 10 rats. Animals were treated with intra-peritoneal injection of isoniazid (50 mg/kg) and rifampicin (100 mg/kg); and intra-gastric administration of pyrazinamid (350 mg/kg) and silymarin (200 mg/kg). Hepatotoxicity was induced by a combination of drugs with INH+RIF and INH+RIF+PZA. Hepatoprotective effect of silymarin was investigated by co-administration of silymarin together with the drugs. Serum biochemical tests for liver functions and histopathological examination of livers were carried out to demonstrate the protection of liver against anti-tuberculosis drugs by silymarin.ResultsTreatment of rats with INH+RIF or INH+RIF+PZA induced hepatotoxicity as evidenced by biochemical measurements: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities and the levels of total bilirubin were elevated, and the levels of albumin and total protein were decreased in drugs-treated animals. Histopathological changes were also observed in livers of animals that received drugs. Simultaneous administration of silymarin significantly decreased the biochemical and histological changes induced by the drugs.ConclusionThe active components of silymarin had protective effects against hepatotoxic actions of drugs used in the chemotherapy of tuberculosis in animal models. Since no significant toxicity of silymarin is reported in human studies, this plant extract can be used as a dietary supplement by patients taking anti-tuberculosis medications.
Highlights
The first line anti-tuberculosis drugs isoniazid (INH), rifampicin (RIF) and pyrazinamide (PZA) continues to be the effective drugs in the treatment of tuberculosis, the use of these drugs is associated with toxic reactions in tissues, in the liver, leading to hepatitis
The serum Alanine transaminase (ALT), Aspartate transaminase (AST) and alkaline phosphatase (ALP) activities of the control group and the silymarin-control group did not show any significant difference when compared with baseline values (Figures 1, 2, 3)
This study showed that silymarin has a significant protective action against the hepatotoxicity induced by the drugs used in the treatment of tuberculosis
Summary
The first line anti-tuberculosis drugs isoniazid (INH), rifampicin (RIF) and pyrazinamide (PZA) continues to be the effective drugs in the treatment of tuberculosis, the use of these drugs is associated with toxic reactions in tissues, in the liver, leading to hepatitis. Rifampicin (RIF), isoniazid (INH), pyrazinamid (PZA) and ethambutol are first line drugs used for the treatment of tuberculosis. The active metabolite is pyrazinoic acid that inhibits fatty acid synthesis in M. tuberculosis [3]. This drug is used in the initial two months of treatment to reduce the duration of therapy, and is not used alone [4]. Ethambutol inhibits the synthesis of some metabolites in actively growing M. tuberculosis, causing impairment of cell metabolism, arrest of multiplication, and cell death [5]
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