Nitrofurantoin‐Induced Hepatic and Pulmonary Biochemical Changes in Mice Fed Different Vitamin E Doses

Abstract

The hepatic and pulmonary effects of nitrofurantoin (40 mg/kg, intraperitoneally) were determined at 4 and 24 hr following its administration in mice fed for 10 weeks with a vitamin E sufficient, deficient or enriched diet. Liver glutathione (GSH) was reduced by nitrofurantoin at 4 hr but was unchanged 20 hr later. Nitrofurantoin did not affect liver glutathione peroxidase, glutathione reductase or superoxide dismutase activities. Liver catalase activities were decreased by nitrofurantoin at 4 hr. Lung GSH levels were increased whilst glutathione peroxidase activity was decreased at 4 and 24 hr. Lung glutathione reductase activity was reduced in certain groups. Nitrofurantoin did not affect lung superoxide dismutase, but catalase was decreased at 24 hr. Liver malondialdehyde levels were increased by nitrofurantoin in the vitamin E deficient group whilst lung malondialdehyde levels remained unchanged. Both liver and lung malondialdehyde levels were unaffected by vitamin E supplementation when compared to the vitamin E-sufficient group. These results suggest that nitrofurantoin (40 mg/kg) was deleterious to the liver and lung. Nitrofurantoin-induced lipid peroxidation was seen in vitamin E deficiency but an increase in dietary vitamin E content did not provide additional protection compared to the recommended daily allowance. The antioxidant activities of alpha-tocopherol and gamma-enriched tocotrienol were similar.

Pharmacological potential of tocotrienols: a review

“…Regulation of the balance between production of reactive oxygen species (ROS) by cellular processes and its removal by antioxidant defense system maintains normal physiological processes. The antioxidant activities of tocotrienols are mediated through induction of antioxidant enzymes such as superoxide dismutase [ 108 , 109 ], NADPH: quinoneoxidoreductase [ 110 ], and glutathione peroxidase [ 111 ], which quench free radicals such as superoxide radicals [ 112 ]. Effects of tocotrienols on antioxidant defense system in various animal models have been studied from time to time.…”

“…Tocopherol and γ-tocotrienol have been shown to prevent the nitrofurantoin induced damage in rat liver when administered for 10 weeks. The extract characteristically inhibited hepatic lipid peroxidation [ 111 ]. Tocotrienol also significantly increased the percent viability of cultured rat hepatocytes prepared from rats treated with diethylnitrosamine (DEN) and 2-acetylaminofluorene (AAF).…”

Tocotrienols, the vitamin E of the 21st century: Its potential against cancer and other chronic diseases

“…The antioxidant activities of this vitamin E (tocotrienols) are mediated through induction of antioxidant enzymes such as superoxide dismutase [18, 19], NADPH:quinone oxidoreductase [20], and glutathione peroxidase [21], which quench free radicals such as superoxide radicals [22] (Table 1). The antiproliferative activity of tocotrienols are mediated through modulation of growth factors such as vascular endothelial growth factor (VEGF)[23], basic fibroblast growth factor (bFGF) [24] and transforming growth factor beta (TGF-β) [25], HER2/neu [26], and interleukin-6 (IL-6) [27].…”

Potential role of cysteine and methionine in the protection against hormonal imbalance and mutagenicity induced by furazolidone in female rats

“…Nitrofuran drugs were found to induce oxidative stress leading to the decrease of sulphydryl groups and ascorbic acid concentration (Ali, 1992) as well as the decrease of catalase and glutathione, glutathione peroxidase and reductase with concomitant increase in lipid peroxidation (Adam et al, 1996). Antioxidants have been found to have potential role in mitigation of chemicals-induced oxidative damage (Patra et al, 2001;Ramanathan et al, 2002;Aly, 2003, 2005) and can protect the cells from oxygen radical-generated chromosomal injury (Weitberg et al, 1985).…”