The potential protective role of folic acid against acetaminophen-induced hepatotoxicity and nephrotoxicity in rats

Abstract

Folic acid (FA), is a group B vitamin, has high reactive oxygen radicals quenching ability, resulting in protection against oxidative damage in aerobic cell. Acetaminophen (N-acetyl-p-aminophenol, APAP) is a nonsteroidal anti-inflammatory drug, and can promote oxidative damage in liver and kidney tissues. The aim of this study was to investigate whether folic acid has protective effects on oxidative liver and kidney injury caused by experimental APAP toxication. Forty female Sprague dawley rats were divided into 5 groups; control, APAP, FA, APAP+FA, and APAP+N-acetylcysteine (NAC) groups. APAP toxication was induced by oral gavage (3 g/kg bodyweight). FA (20 mg/kg bodyweight) and NAC (150 mg/kg bodyweight) were given by oral gavage to the specified groups. Oxidant and antioxidant parameter were determined in liver and kidney tissues. In addition, the liver and kidney tissues were histological evaluated. When compared with APAP group, superoxide dismutase (SOD) and catalase activities and glutathione levels were statistically higher, malondialdehyde (MDA) level and myeloperoxidase activity (except liver tissue) were statistically lower in both APAP+FA and APAP+NAC. Liver and kidney MDA level and kidney SOD activity were significantly lower in APAP+NAC group compared with APAP+FA group. Co-administration of NAC with APAP was found to provide protection, but hepatic cords were defective in some places and some glomerular tubules also had dilatation. Necrotic areas was reduced in the liver and the glomerular structure was in good condition in the APAP+FA group. As a result, FA might have a protective effect against APAP-induced hepato-nephrotoxicity and oxidative stress in rat.

Keywords: acetaminophen; folic acid; oxidative stress; rat; toxicity.

Fig. 1.

Liver central veins (CV) and parenchyma image of experimental groups. A. Control group. Bar: 50 µm. H&E stain. B. APAP group. Bar: 100 µm. Necrotic areas (arrows) H&E stain. C. FA group. Bar: 50 µm. H&E stain. D. APAP+FA group. Bar: 50 µm. H&E stain. E. APAP+NAC group. Bar: 50 µm. H&E stain.

Fig. 2.

Kidney image of experimental groups. G: Glomerulus. A. Control group. Bar: 50 µm. H&E stain. B. APAP group. *: Enlarged Bowman spacing. V: Dilated tubules. Hyaline cast (arrows) Bar: 50 µm. H&E stain. C. FA group. Bar: 50 µm. H&E stain. D. APAP+FA group. Bar: 50 µm. H&E stain. E. APAP+NAC group. Bar: 50 µm. H&E stain.