Acute oral dose of sodium nitrite induces redox imbalance, DNA damage, metabolic and histological changes in rat intestine

Abstract

Industrialization and unchecked use of nitrate/nitrite salts for various purposes has increased human exposure to high levels of sodium nitrite (NaNO2) which can act as a pro-oxidant and pro-carcinogen. Oral exposure makes the gastrointestinal tract particularly susceptible to nitrite toxicity. In this work, the effect of administration of a single acute oral dose of NaNO2 on rat intestine was studied. Animals were randomly divided into four groups and given single doses of 20, 40, 60 and 75 mg NaNO2/kg body weight. Untreated animals served as the control group. An NaNO2 dose-dependent decline in the activities of brush border membrane enzymes, increase in lipid peroxidation, protein oxidation, hydrogen peroxide levels and decreased thiol content was observed in all treated groups. The activities of various metabolic and antioxidant defense enzymes were also altered. NaNO2 induced a dose-dependent increase in DNA damage and DNA-protein crosslinking. Histopathological studies showed marked morphological damage in intestinal cells. The intestinal damage might be due to nitrite-induced oxidative stress, direct action of nitrite anion or chemical modification by reaction intermediates.

The Noncanonical Pathway for In Vivo Nitric Oxide Generation: The Nitrate-Nitrite-Nitric Oxide Pathway

“…In contrast, a recent report using an acute supraphysiological dose of NaNO 2 (20, 40, 60, and 75 mg/kg b.wt. ) in rats demonstrated dose-dependent increase in abnormal structure and significant morphologic damage in the intestine in animals examined 24 hours postdose (Ansari et al, 2017), although the relevance of these acute doses to human gut physiology is unclear, and previous reports in rats using similar doses have not shown the same effect (Roediger et al, 1986).…”

Curcumin protects sodium nitrite-induced hepatotoxicity in Wistar rats

“…It is also employed in the industry for other purposes including flavour-enhancing, microbial growth inhibition and prevention of fat oxidation, thereby delaying rancidity. In addition, it also is used in the manufacturing of dyes, nitrous compounds and chemicals used in production of rubber [1]. Apart from the benefits offered by NaNO 2 in the food and other industries, other associated beneficial activities include its medicinal use for bronchodilation and vasodilation, its use as an antidote for poisonous chemicals, and other health roles at low physiological concentrations [2].…”

“…However, there have been reports of induced toxicities in several organs following acute exposure to high concentrations or chronic exposure to low doses of NaNO 2 . A single acute exposure to NaNO 2 at doses ranging between 20–75 mg/kg body weight resulted in organ damage in rats [1]. Several anthropogenic activities, such as the use of nitrogenous fertilizers to improve yield of crops and improper treatment of industrial and sewage wastes, have contributed greatly to the increased concentration of nitrite in the environment [3].…”

“…Several anthropogenic activities, such as the use of nitrogenous fertilizers to improve yield of crops and improper treatment of industrial and sewage wastes, have contributed greatly to the increased concentration of nitrite in the environment [3]. Levels of nitrite greater than the acceptable limit also have been reported in drinking water across the globe [1,4,5]. Exposure to NaNO 2 has been associated with several adverse health effects ranging from respiratory tract impairment, birth defects, neurological damage, and oxidative stress [1], to carcinogenicity and mutagenicity [6,7].…”

Carnosine and N‐acetyl cysteine protect against sodium nitrite‐induced oxidative stress in rat blood

“…The doses of CAR and NAC were selected on the basis of earlier reported animal studies with these antioxidants (Gallant et al, 2000;Nishikawa-Ogawa et al, 2006). The dose of NaNO 2 (60 mg/ kg body weight) was inferred from our previous experiment; at this dose significant alterations in biochemical parameters were observed (Ansari et al, 2017). No animal died during the entire treatment procedure.…”