Protective Effects Of Solanium Nigrum Methanolic Extract Against Isoniazid/Rifampicin Induced Hepatotoxicity In Rats

Abdel Hameed Fayed,Azza Hassan,Taha Attia,Elbatran A,Abeer Salama,Ismaiel Ismaiel

doi:10.21608/javs.2019.63436

Abstract

Drug-induced liver injury (DILI) is the major health problem that resulted from uses of many drugs especially from serious adverse effect of antituberculosis (ATT) drugs. forty eight rats (200-250g) were allocated into six groups (8 rats in each group), and treated as follow: group I: received normal saline orally; group II: received INH/RFP (50 mg/Kg/day of each) for 28 days orally; group III: received Silymarin (50 mg/kg/day) + INH/RFP for 28 days orally; group IV: received SNME(250 mg/Kg/day) + INH/RFP for 28 days orally; group V: received SNME (500 mg/Kg/day) + INH/RFP for 28 days orally; group VI, received SNME (1000 mg/Kg/day) + INH/RFP for 28 days orally. Co-administration of herbal plant (SNME) with INH/RFP reduced elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and (bilirubin total &direct) levels but also decreased the elevated malondialdehyde (MDA) & tumor necrosis factor-α (TNF-α) contents in liver homogenate. Moreover, co-administration of herbal plant (SNME) with INH/RFP increased glutathione peroxidase (GPX) & adiponectin activity. Solanum nigrum administration to rats, in present study, led to a remarkable alteration of histological changes observed in INH/RFP group. It is concluded that Solanum nigrum might be considered as adjuvant drug in treatment of liver disorder and/or as hepatoprotective therapy with anti-tubercular drugs.

Highlights

Preparation of Alcoholic Extract This extract were obtained by the following steps: Grinding SN fruits in blender till obtain powder, maceration with petroleum ether to remove fatty substances and the marc was further exhaustively extracted with 70% ethanol for 3 days (3 X 5L), Soaking this powder in methyl alcohol for seven days with rotation every day, Filtration by using piece of cotton, separation by filtration and concentration on rotavapour (Buchi, USA) and dring in lyophilizer (Labconco, USA) under reduced pressure, repeat extraction was carried out, the extract will be stored in an airtight container in a refrigerator below 10 °C
The regimen of RIF/INH is more effective in tuberculosis (TB) but Rifampicin addition to regimen induces isoniazid hydrolase, increasing hydrazine production resulting in increased risk of hepatotoxicity (Steele et al, 1991; Tayal et al, 2007)
The current study revealed that administration of Solanum nigrum resulted in mitigating RIF/INH oxidative effects and achieving cellular protection against oxidative stress, this manifested by a decrease in the levels of MDA and increased the activity of glutathione peroxidase (GPx) as compared to hepatotoxic rats. the lipid peroxidation is a state of destructive process of liver cells causing elevations in MDA level and failure of antioxidant defense mechanisms these actions were remolded by action of Solanum nigrum fruit extact supplementation (Gupta et al, 2009) so this beneficial antioxidative activity of the extract might be considered as an adjuvant drug in liver disorders treatment (Lee et al, 2005; Sankaran, 2012)

Summary

Introduction

Co-administration of herbal plant (SNME) with INH/RFP reduced elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and (bilirubin total &direct) levels and decreased the elevated malondialdehyde (MDA) & tumor necrosis factor-α (TNF-α) contents in liver homogenate. Co-administration of herbal plant (SNME) with INH/RFP increased glutathione peroxidase (GPX) & adiponectin activity. Solanum nigrum administration to rats, in present study, led to a remarkable alteration of histological changes observed in INH/RFP group. It is concluded that Solanum nigrum might be considered as adjuvant drug in treatment of. Several factors such as acute or chronic liver disease, high incidence of viral hepatitis, malnutrition as well as indiscriminate use of tuberculosis (TB) drugs, this hepatotoxicity may be resemble viral hepatitis (Makhlouf et al, 2008; Yu et al, 2010)

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