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Copper (Cu) is an extensively used heavy metal and an indispensible micronutrient for living beings. However, Cu is also toxic and exerts multiple adverse health effects when humans are exposed to high levels of this metal. We have examined the effect of single acute oral dose of copper chloride (CuCl2) on parameters of oxidative stress, cellular metabolism, membrane and DNA damage in rat intestine. Adult male Wistar rats were divided into four groups and separately administered a single oral dose of 5, 15, 30 and 40 mg CuCl2/kg body weight. Rats not administered CuCl2 served as the control. Oral administration of CuCl2 led to significant alterations in the activities of metabolic and membrane-bound enzymes; brush border enzymes were inhibited by 45-75% relative to the control set. Inhibition of antioxidant enzymes diminished the metal-reducing and free radical quenching ability of the cells. Oxidative damage caused cellular oxidation of thiols, proteins and lipids. Diphenylamine and comet assays showed that CuCl2 treatment enhanced DNA damage while DNA-protein crosslinking was also increased in the intestinal cells. Examination of stained sections showed that CuCl2 treatment led to marked histological changes in the intestine. All the changes seen were in a CuCl2 dose-dependent manner with more prominent alterations at higher doses of CuCl2. These results clearly show that oral administration of CuCl2 results in oxidative damage to the intestine which can impair its digestive and absorptive functions.

The widespread use of sodium nitrite (NaNO2) as food preservative, rampant use of nitrogenous fertilizers for agricultural practices, and improper disposal of nitrogenous wastes have drastically increased human exposure to high nitrite levels causing various health disorders and death. In the present study, the protective effect of carnosine and N-acetylcysteine (NAC) against NaNO2-induced intestinal toxicity in rats was investigated. Animals were given a single acute oral dose of NaNO2 at 60 mg/kg body weight with or without prior administration of either carnosine at 100 mg/kg body weight/day for 7 days or NAC at 100 mg/kg body weight/day for 5 days. Rats were killed after 24 h, and intestinal preparations were used for the evaluation of biochemical alterations and histological abrasions. Administration of NaNO2 alone decreased the activities of intestinal brush border membrane and metabolic enzymes and significantly weakened the anti-oxidant defense system. DNA damage was also evident as observed by increased DNA-protein crosslinking and fragmentation. However, prior administration of carnosine or NAC significantly ameliorated NaNO2-induced damage in intestinal cells. Histological studies support these biochemical results, showing intestinal damage in NaNO2-treated animals and reduced tissue injury in the combination groups. The intrinsic anti-oxidant properties of carnosine and NAC must have contributed to the observed mitigation of nitrite-induced metabolic alterations and oxidative damage. Based on further validation from clinical trials, carnosine and NAC can potentially be used as chemo-preventive agents against NaNO2 toxicity.