Mir Kaisar Ahmad

Chemoprotective Effect of Taurine on Potassium Bromate-Induced DNA Damage, DNA-Protein Cross-Linking and Oxidative Stress in Rat Intestine

Potassium bromate (KBrO3) is widely used as a food additive and is a major water disinfection by-product. It induces multiple organ toxicity in humans and experimental animals and is a probable human carcinogen. The present study reports the protective effect of dietary antioxidant taurine on KBrO3-induced damage to the rat intestine. Animals were randomly divided into four groups: control, KBrO3 alone, taurine alone and taurine+ KBrO3. Administration of KBrO3 alone led to decrease in the activities of intestinal brush border membrane enzymes while those of antioxidant defence and carbohydrate metabolism were also severely altered. There was increase in DNA damage and DNA-protein cross-linking. Treatment with taurine, prior to administration of KBrO3, resulted in significant attenuation in all these parameters but the administration of taurine alone had no effect. Histological studies supported these biochemical results showing extensive intestinal damage in KBrO3-treated animals and greatly reduced tissue injury in the taurine+ KBrO3 group. These results show that taurine ameliorates bromate induced tissue toxicity and oxidative damage by improving the antioxidant defence, tissue integrity and energy metabolism. Taurine can, therefore, be potentially used as a therapeutic/protective agent against toxicity of KBrO3 and related compounds.

Oral administration of a nephrotoxic dose of potassium bromate, a food additive, alters renal redox and metabolic status and inhibits brush border membrane enzymes in rats

The time dependent effect of orally administered KBrO(3) on redox status and enzymes of brush border membrane (BBM) and carbohydrate metabolism has been studied in rat kidney. Animals were given a single oral dose of KBrO(3) (100mg/kg body weight) and sacrificed at different times after this treatment; control animals were not given KBrO(3). The administration of KBrO(3) resulted in nephrotoxicity, a decline in the specific activities of several BBM marker enzymes and also induced oxidative stress in kidney. The specific activities of enzymes of carbohydrate metabolism were also altered and suggest a shift in energy metabolism from the aerobic to anaerobic mode. The renal effects of single oral dose of KBrO(3) appeared to be reversible; maximum changes in all the parameters were 48 h after administration of KBrO(3) after which recovery took place, in many cases almost to control values, after 168 h. These results suggest that the administration of a single nephrotoxic dose of KBrO(3) inhibits brush border membrane enzymes, induces oxidative stress and alters energy metabolism of the renal system in a reversible manner.

Potassium bromate causes cell lysis and induces oxidative stress in human erythrocytes

In the present study, we have studied the effect of KBrO3 on human erythrocytes under in vitro conditions. Erythrocytes were isolated from the blood of healthy nonsmoking volunteers and incubated with different concentrations of KBrO3 at 37°C for 60 min. This resulted in marked hemolysis in a KBrO3‐concentration dependent manner. Lysates were prepared from KBrO3‐treated and control erythrocytes and assayed for various parameters. KBrO3 treatment caused significant increase in protein oxidation, lipid peroxidation, hydrogen peroxide levels, and decrease in total sulfhydryl content, which indicates induction of oxidative stress in human erythrocytes. Methemoglobin levels and methemoglobin reductase activity were significantly increased while the total antioxidant power of lysates was greatly reduced upon KBrO3 treatment. Intracellular production of reactive oxygen species increased in a dose dependent manner. Exposure of erythrocytes to KBrO3 also caused decrease in the activities of catalase, glutathione peroxidase, thioredoxin reductase, glucose 6‐phosphate dehydrogenase and glutathione reductase whereas the activities of Cu‐Zn superoxide dismutase and glutathione‐S‐transferase were increased. These results show that KBrO3 induces oxidative stress in human erythrocytes through the generation of reactive oxygen species and alters the cellular antioxidant defense system.

Cr(VI) Induces Lipid Peroxidation, Protein Oxidation and Alters the Activities of Antioxidant Enzymes in Human Erythrocytes

The effect of potassium dichromate (K2Cr2O7), a hexavalent chromium compound, on human erythrocytes was studied under in vitro conditions. Incubation of erythrocytes with different concentrations of K2Cr2O7 resulted in marked hemolysis in a concentration-dependent manner. K2Cr2O7 treatment also caused significant increase in protein oxidation, lipid peroxidation and decrease in total sulfhydryl content, indicating that it causes oxidative stress in human erythrocytes. However, there was no concomitant nitrosative stress as the nitric oxide levels in hemolysates from K2Cr2O7-treated erythrocytes were lower than in control. Exposure of erythrocytes to K2Cr2O7 decreased the activities of catalase, glutathione peroxidase, thioredoxin reductase, glucose-6-phosphate dehydrogenase, and glutathione reductase, whereas the activities of Cu–Zn superoxide dismutase and glutathione S-transferase were increased. These results show that K2Cr2O7 induces oxidative stress and alters the antioxidant defense mechanism of human erythrocytes.

Protective effect of taurine against potassium bromate-induced hemoglobin oxidation, oxidative stress, and impairment of antioxidant defense system in blood

Potassium bromate (KBrO3) is widely used as a food‐additive and is a major water disinfection by‐product. KBrO3 causes severe toxicity in humans and experimental animals. Bromate is considered a probable human carcinogen and a complete carcinogen in animals. We have investigated the potential role of taurine in protecting against KBrO3‐induced oxidative stress in rat blood. Animals were given taurine for 5 days prior to KBrO3 and then sacrificed. Blood was collected and used to prepare hemolysates and plasma, which were then used for the analysis of several biochemical parameters. Administration of single oral dose of KBrO3 alone induced hepato‐ and nephro‐toxicity as evident by elevated marker levels in plasma. Lipid peroxidation and protein oxidation were increased both in plasma and erythrocytes, suggesting the induction of oxidative stress. KBrO3 increased methemoglobin, nitric oxide, and hydrogen peroxide levels. It also altered the activities of the major antioxidant enzymes and lowered the antioxidant power of blood. Administration of taurine, prior to treatment with KBrO3, resulted in significant attenuation in all these parameters but the administration of taurine alone had no effect. These results show that taurine is effective in mitigating the oxidative insult induced in rat blood by KBrO3.

Oral administration of potassium bromate, a major water disinfection by-product, induces oxidative stress and impairs the antioxidant power of rat blood

Potassium bromate (KBrO(3)) is a widely used food additive, a water disinfection by-product and a known nephrotoxic agent. The effect of KBrO(3) on rat blood, especially on the anti-oxidant defense system, was studied in this work. Animals were given a single oral dose of KBrO(3) (100 mg/kg body weight) and sacrificed 12, 24, 48, 96 and 168 h after this treatment. Blood was collected from the animals and separated into plasma and erythrocytes. KBrO(3) administration resulted in increased lipid peroxidation, protein oxidation, hydrogen peroxide levels and decreased the reduced glutathione content indicating the induction of oxidative stress in blood. Methemoglobin levels and methemoglobin reductase activity were significantly increased while the total anti-oxidant power was greatly reduced upon KBrO(3) treatment. Nitric oxide levels were enhanced while vitamin C concentration decreased in KBrO(3) treated animals. The activities of major anti-oxidant enzymes were also altered upon KBrO(3) treatment. The maximum changes in all these parameters were 48 h after the administration of KBrO(3) and then recovery took place. These results show for the first time that KBrO(3) induces oxidative stress in blood and impairs the anti-oxidant defense system. Thus impairment in the anti-oxidant power and alterations in the activities of major anti-oxidant enzymes may play an important role in mediating the toxic effects of KBrO(3) in the rat blood. The study of such biochemical events in blood will help elucidate the molecular mechanism of action of KBrO(3) and also for devising methods to overcome its toxic effects.

Alterations in brush border membrane enzymes, carbohydrate metabolism and oxidative damage to rat intestine by potassium bromate.

The acute toxicity of potassium bromate (KBrO(3)) on rat small intestine was studied in this work. Animals were given a single oral dose of KBrO(3) (100 mg/kg body weight) and sacrificed 12, 24, 48, 96 and 168 h after the treatment; control animals were not given KBrO(3). The administration of KBrO(3) resulted in a reversible decline in the specific activities of several BBM enzymes. Lipid peroxidation, protein oxidation and hydrogen peroxide levels increased while total sulfhydryl groups and reduced glutathione decreased in KBrO(3)-treated rats indicating induction of oxidative stress in the intestinal mucosa. The activities of anti-oxidant and carbohydrate metabolic enzymes were also altered upon KBrO(3) treatment. The maximum changes in all the parameters were 48 h after administration of KBrO(3) after which recovery took place, in many cases almost to control values after 168 h. Histopathological studies supported the biochemical findings showing extensive damage to the intestine at 48 h and recovery at 168 h. These results show that a single oral dose of KBrO(3) causes reversible oxidative damage to the intestine.

DNA damage and DNA–protein cross-linking induced in rat intestine by the water disinfection by-product potassium bromate

The genotoxic effects of potassium bromate (KBrO3), a food additive and water disinfection by-product, on the small intestine of rats are reported here. Adult male rats were given a single oral dose of KBrO3 (100 mg kg(-1) body weight) and sacrificed 12, 24, 48, 96 and 168 h after this treatment while control animals were not given KBrO3. Administration of KBrO3 caused a significant increase in DNA damage when analyzed by the comet assay which suggests the induction of DNA strand breaks. This was also shown by colorimetric assay of nucleotides formed upon DNA degradation. KBrO3 treatment also resulted in increased formation of DNA-protein cross-links in the intestine. The maximum changes in these parameters were 48 h after administration of KBrO3 after which recovery took place. Thus, a single oral dose of KBrO3 exerts genotoxic effects in the intestine of rats, possibly through the mechanism of oxidative DNA damage.