Study of oxidative stress in isoniazid-induced hepatic injury in young rats with and without protein-energy malnutrition.
The role of oxidative stress as a mechanism of hepatic injury caused by isoniazid (INH) was investigated in young growing rats. The interaction of moderate and severe degree of protein-energy malnutrition (PEM) was also investigated. Hepatic injury was produced by giving 50 mg/kg/day of INH for 2 weeks. Liver showed kupffer cell hyperplasia along with patchy sinusoidal congestion in hematoxylin (H) and eosin (E) staining. However, diffuse microglobules of oil red O' positive fat globules could be demonstrated in frozen sections stained with oil red O'. The concomitant elevation of serum ALT/AST added support to the histopathologic injury. Electronmicroscopic analysis revealed the proliferation of rough endoplasmic reticulum in INH-treated groups. The glutathione and related thiols were decreased significantly by INH both in blood and liver tissues, indicating a decrease in protective mechanism. Glutathione reductase activity was elevated concomitantly in both the tissues. A significant decrease in the activity of glutathione peroxidase and catalase is again indicative of diminished capacity to handle the disposal of hydrogen peroxide (H2O2) and lipid peroxides. All these alterations indicated that the damage to the liver cell could well be operating through the inefficient disposal of superoxides (O-2) and H2O2. A profound decrease in the protective mechanism further aggravated the picture in moderate and severe PEM, which was observed with INH alone.
Sodhi
C P
CP
Department of Gastroenterology and Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Rana
S V
SV
Mehta
S K
SK
Vaiphei
K
K
Attri
S
S
Thakur
S
S
Mehta
S
S
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D003593:Cytoplasm / Q000737:chemistry / Q000648:ultrastructure; D005629:Frozen Sections; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007538:Isoniazid; D015227:Lipid Peroxidation / Q000502:physiology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008107:Liver Diseases / Q000503:physiopathology*; D008297:Male; D008854:Microscopy, Electron; D018384:Oxidative Stress / Q000502:physiology*; D010088:Oxidoreductases / Q000378:metabolism; D011502:Protein-Energy Malnutrition / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar
D010088:Oxidoreductases; D005982:Glutathione Transferase; D005978:Glutathione; D007538:Isoniazid