Aijaz Ahmed Khan

Protective effect of dietary flaxseed oil on arsenic-induced nephrotoxicity and oxidative damage in rat kidney.

Arsenic, a naturally occurring metalloid, is capable of causing acute renal failure as well as chronic renal insufficiency. Arsenic is known to exert its toxicity through oxidative stress by generating reactive oxygen species (ROS). Flaxseed, richest plant based dietary source of ω-3 polyunsaturated fatty acids (PUFAs) and lignans have shown numerous health benefits. Present study investigates the protective effect of flaxseed oil (FXO) on sodium arsenate (NaAs) induced renal damage. Rats prefed with experimental diets (Normal/FXO diet) for 14days, were administered NaAs (20mg/kg body weight i.p.) once daily for 4days while still on the experimental diets. NaAs nephrotoxicity was characterized by increased serum creatinine and blood urea nitrogen. Administration of NaAs led to a significant decline in the specific activities of brush border membrane (BBM) enzymes both in kidney tissue homogenates and in the isolated membrane vesicles. Lipid peroxidation and total sulfhydryl groups were altered upon NaAs treatment, indicating the generation of oxidative stress. NaAs also decreased the activities of metabolic enzymes and antioxidant defence system. Histopathological studies supported the biochemical findings showing extensive damage to the kidney by NaAs. In contrast, dietary supplementation of FXO prior to and alongwith NaAs treatment significantly attenuated the NaAs-induced changes.

Protective effect of Nigella sativa oil on cisplatin induced nephrotoxicity and oxidative damage in rat kidney

BACKGROUND Nephrotoxicity is a severe complication in patients undergoing cisplatin (CP) chemotherapy. Previous studies in our lab have shown that administration of a single dose of CP results in decrease in the activities of brush border membrane (BBM) and free radical scavenging enzymes and induces oxidative stress in rat kidney. Nigella sativa, is one of the most revered medicinal plant known for its numerous health benefits. Nigella sativa seed/oil has been shown to improve kidney functions in animal models of acute kidney injury. OBJECTIVE The present study was undertaken to investigate whether Nigella sativa oil (NSO) can prevent the CP-induced nephrotoxic effects. RESULTS The effect of NSO was determined on CP induced alterations in various serum parameters and on enzymes of carbohydrate metabolism, BBM and antioxidant defense system in renal cortex and medulla. Administration of NSO (2ml/kg bwt. orally), prior to and following a single dose CP treatment (6mg/kg bwt. i.p), significantly attenuated the CP induced increase in serum creatinine (Scr) and blood urea nitrogen (BUN) and decrease in the activities of BBM enzymes in renal cortical and medullary homogenates as well as in isolated BBM vesicles (BBMV). NSO administration also precluded CP induced alterations in the activities of carbohydrate metabolism enzymes and in the enzymatic and non-enzymatic antioxidant parameters. Histopathological observations showed extensive kidney damage in CP treated animals and remarkably reduced renal injury in CP and NSO co-treated group. CONCLUSION The biochemical and histological data suggest a protective effect of NSO against CP-induced acute kidney injury.

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.

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.

Oral administration of Nigella sativa oil ameliorates the effect of cisplatin on membrane enzymes, carbohydrate metabolism and oxidative damage in rat liver

Highlights • NSO improves the endogenous antioxidant status and metabolic activity of liver.• NSO protects the liver against CP generated free radical attack.• Oral administration of NSO ameliorates the hepatotoxicity induced by CP treatment.

Wallerian Degeneration in the Optic Nerve of the Rabbit

Progressive anterograde axonal degeneration is known to follow after transection of the axon from the soma, which to some extent correlates with the passage of time after the lesion. However, the minimum time required for such changes to begin remains unresolved. In this study, 20 young adult rabbits of either sex underwent experimental monocular enucleation (left eye) under general anaesthesia. Left optic nerves from such animals were treated as experimental and those from either side of non-operated animals served as controls. Animals were sacrificed postoperatively at periods ranging from 12 h to 3 months. Brains were fixed with 10% formalin and Karnovsky fixatives by an intracardiac perfusion method. Light microscopy of 8-µm paraffin sections and 0.5-µm araldite sections from the optic nerves did not reveal any changes at 12 h. At 24 h, focal minute cavities appeared across the optic nerves. Those nerves from late postoperative stages revealed such cavities with increasing dimensions, disarray of fascicular organization, fragmentation, ovoid formation and finally dissolution of the myelin sheaths. There was an appreciable increase in the number, size and aggregation of glia cells. The debris of degeneration remained prominent even 3 months after enucleation. Electron microscopy revealed splitting of myelin, intramyelinic and periaxonal oedema and occurrence of amorphous and electron-dense materials in the degenerating nerve fibres. It was concluded that while the optic nerve showed degenerative changes as early as 24 h after enucleation, debris of degeneration was only partly removed even after 3 months.

Acute oral dose of sodium nitrite causes redox imbalance and DNA damage in rat kidney

Sodium nitrite (NaNO2) is widely used as a food additive and preservative in fish and meat products. We have evaluated the effect of a single acute oral dose of NaNO2 on oxidative stress parameters, antioxidant capacity, and DNA in rat kidney. Male Wistar rats were divided into four groups and given single oral dose of NaNO2 at 20, 40, 60, and 75 mg/kg body weight; untreated rats served as the control group. All animals in NaNO2‐treated groups showed marked alterations in various parameters of oxidative stress as compared to the control group. This included increase in lipid peroxidation, protein oxidation, hydrogen peroxide levels, and decrease in reduced glutathione content and antioxidant capacity. Administration of NaNO2 also increased DNA damage as evident from release of free nucleotides and confirmed by comet assay. It also led to greater cross‐linking of DNA to proteins. Histological analysis showed marked morphological changes in the kidney of NaNO2‐treated animals. These alterations could be due to increased free radical generation or direct chemical modification by reaction intermediates. Our results suggest that nitrite‐induced nephrotoxicity is mediated through redox imbalance and results in DNA damage.

Histomorphometry of Preterm and Term Human Placentas

La existencia intrauterina del feto depende de la placenta, el mayor organo de nutricion y homeostasis. El estudio se llevo a cabo para comparar los cambios morfometricos e histologicos de la placenta humana de termino y pretermino. Ochenta placentas fueron obtenidas del Departamento de Obstetricia y Ginecologia, JNMCH, AMU, Aligarh y se dividieron en grupos, el primer grupo de placentas de pretermino hasta 36 semanas (n = 30) y el segundo grupo de placentas de termino, de 37 a 40 semanas (n = 50 ). Las muestras fueron fijadas en solucion de formol-salina al 10%. Se estudiaron las variables morfologicas macroscopicas de las placentas. Hubo un aumento significativo en el peso de la placenta, el area de decidua y el diametro del cordon umbilical de la placenta a termino en comparacion con la de los prematuros. De cada placenta se tomaron y se procesaron bloques de tejido para incluirlos en parafina. Cortes de 5 µm fueron tenidos con HE y Van Gieson para microscopia optica. De cada muestra fueron estudiadas 200 vellosidades, bajo campo de alta resolucion y la aparicion de diferentes caracteristicas se expreso como porcentajes para cada parametro. La aparicion de las microvellosidades y brote sincitial en el sincitio estaban casi ausente en las vellosidades de las placentas de termino. Se puede concluir que al aumentar la edad gestacional hubo un aumento gradual en el numero de capilares en las vellosidades de la placenta de termino. Existe un aumento significativo en el recuento de nudo sincitial, necrosis fibrinoide, membrana vasculosincisial y disminucion en el porcentaje de las vellosidades que muestran celulas citotrofoblastica y numero de celulas de Hofbauer en las placentas del termino de grupo en comparacion con el grupo de pretermino.

Ameliorative effect of carnosine and N-acetylcysteine against sodium nitrite induced nephrotoxicity in rats: ANSARI et al.

The widespread use of sodium nitrite (NaNO2) for various industrial purposes has increased human exposure to alarmingly high levels of nitrate/nitrite. Because NaNO 2 is a strong oxidizing agent, induction of oxidative stress is one of the mechanisms by which it can exert toxicity in humans and animals. We have investigated the possible protection offered by carnosine (CAR) and N‐acetylcysteine (NAC) against NaNO 2‐induced nephrotoxicity in rats. Animals orally received CAR at 100 mg/kg body weight/d for seven days or NAC at 100 mg/kg body weight/d for five days followed by a single oral dose of NaNO 2 at 60 mg/kg body weight. The rats were killed after 24 hours, and the kidneys were removed and processed for various analyses. NaNO 2 induced oxidative stress in kidneys, as shown by the decreased activities of antioxidant defense, brush border membrane, and metabolic enzymes. DNA‐protein crosslinking and DNA fragmentation were also observed. CAR/NAC pretreatment significantly protected the kidney against these biochemical alterations. Histological studies supported these findings, showing kidney damage in NaNO 2‐treated animals and reduced tissue impairment in the combination groups. The protection offered by CAR and NAC against NaNO 2‐induced damage, and their nontoxic nature, makes them potential therapeutic agents against nitrite‐induced nephrotoxicity.

Acute renal toxicity of sodium chlorate: Redox imbalance, enhanced DNA damage, metabolic alterations and inhibition of brush border membrane enzymes in rats

Sodium chlorate (NaClO3) is widely used in paper and pulp industries and as a non‐selective herbicide. Humans can be exposed to NaClO3 through contaminated drinking water due to its improper and unchecked usage in industries and as herbicide. NaClO3 is also present as a major stable by‐product in drinking water that has been disinfected with chlorine dioxide. In this study, we have investigated the effect of a single acute oral dose of NaClO3 on rat kidney. Adult male Wistar rats were divided into one control and four NaClO3 treated groups that were orally given different doses of NaClO3 and euthanized 24 hr after the treatment. Oral administration of NaClO3 resulted in increased hydrogen peroxide levels, lipid, and protein oxidation while thiol and glutathione content and activities of brush border membrane enzymes were decreased in kidney in a NaClO3 dose‐dependent manner. Significant alterations in the activities of enzymes involved in carbohydrate metabolism and antioxidant defense were also observed. Administration of NaClO3 induced DNA fragmentation and increased DNA–protein cross‐linking. Histological studies showed marked damage in kidney from NaClO3 treated animals. These results strongly suggest that NaClO3 induces nephrotoxicity via redox imbalance that results in DNA and membrane damage, metabolic alterations and brush border membrane enzyme dysfunction.