Fish/flaxseed oil protect against nitric oxide-induced hepatotoxicity and cell death in the rat liver.

Sodium nitroprusside (SNP) is an antihypertensive drug with proven toxic effects attributed mainly to the production of nitric oxide (NO). Polyunsaturated fatty acids (PUFAs) are widely regarded as functional foods and have been shown to ameliorate the harmful effects of many toxicants. This study examined whether feeding of fish oil (FO)/flaxseed oil (FXO) would have any protective effect against SNP-induced hepatotoxicity and cell death. Male Wistar rats were fed either on normal diet or with 15% FO/FXO for 15 days, following which SNP (1.5 mg/kg body weight) was administered intraperitoneally for 7 days. Animals were killed after treatment, and livers were collected for further analysis. We observed that SNP significantly elevated tissue nitrite levels and lipid peroxidation (LPO) with concomitant perturbation in antioxidant defense systems accompanied with dysregulated glucose metabolism and pronounced cellular death. FO/FXO supplementation to SNP-treated rats caused reversal of tissue injury/cell death and markedly decreased LPO and improved antioxidant defense systems. FO/FXO appear to protect against SNP-induced hepatotoxicity by improving energy metabolism and antioxidant defense mechanism.

Protective effect of ω-3 polyunsaturated fatty acids (PUFAs) on sodium nitroprusside-induced nephrotoxicity and oxidative damage in rat kidney.

Sodium nitroprusside (SNP) a nitric oxide (NO) donor has proven toxic effects. Dietary ω-3 polyunsaturated fatty acid (PUFA) has been shown to reduce the severity of numerous ailments. Present study examined whether intake of fish oil (FO)/flaxseed oil (FXO, Omega Nutrition, St Vancouver, Canada) would have protective effect against SNP-induced toxicity. Male Wistar rats (150 ± 10 g) were used in this study. Initially animals were divided into two groups: one fed on normal diet and the other on 15% FO/FXO for 15 days. On the 16th day, SNP (1.5 mg/kg body weight) was administered intraperitoneally for 7 days daily. After 7 days animals were killed, kidneys were harvested for further analysis. SNP induced nephrotoxicity by increasing serum creatinine and blood urea nitrogen, SNP significantly decreased malate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase and malic enzyme but increased lactate dehydrogenase and glucose-6-phosphate dehydrogenase. Brush border membrane enzymes such as alkaline phosphatase, γ-glutamyl transpeptidase and leucine amino peptidase were also decreased. The activity of catalase and glutathione peroxidase decreased concomitantly with increased lipid peroxidation, indicating that the significant kidney damage has been inflicted by SNP. Feeding of FO and FXO with SNP ameliorated the changes in various parameters caused by SNP. The results of the present study suggest that ω-3 PUFA-enriched FO and FXO from seafoods and plant sources, respectively, are similarly effective in reducing SNP-induced nephrotoxicity and oxidative damage. Thus, vegetarians who cannot consume FO can have similar health benefits from plant-derived ω-3 PUFA.

Protective effect of ω-3 polyunsaturated fatty acids on L-arginine-induced nephrotoxicity and oxidative damage in rat kidney.

L-Arginine (ARG), an essential amino acid, is the endogenous source of the deleterious nitric oxide. Dietary ω-3 polyunsaturated fatty acid (PUFA)-enriched fish oil (FO) has been shown to reduce the severity of certain types of cancers, cardiovascular disease, and renal disease. Present study examined whether feeding of FO/flaxseed oil (FXO) would have protective effect against ARG-induced nephrotoxicity. ARG-induced nephrotoxicity was recorded by increased serum creatinine and blood urea nitrogen. ARG significantly altered the activities of metabolic and brush border membrane (BBM) enzymes. ARG caused significant imbalances in the antioxidant system. These alterations were associated with increased lipid peroxidation (LPO) and altered antioxidant enzyme activities. Feeding of FO and FXO with ARG ameliorated the changes in various parameters caused by ARG. Nephrotoxicity parameters lowered and enzyme activities of carbohydrate metabolism, BBM and inorganic phosphate (32Pi) transport were improved to near control values. ARG-induced LPO declined and antioxidant defense mechanism was strengthened by both FO and FXO alike. The results of the present study suggest that ω-3 PUFA-enriched FO and FXO from seafoods and plant sources, respectively, are similarly effective in reducing ARG-induced nephrotoxicity and oxidative damage. Thus, vegetarians who cannot consume FO can have similar health benefits from plant-derived ω-3 PUFA.

Studies on the protective effect of dietary fish oil on uranyl-nitrate-induced nephrotoxicity and oxidative damage in rat kidney.

Human and animal exposure demonstrates that uranium is nephrotoxic. However, attempts to reduce it were not found suitable for clinical use. Dietary fish oil (FO) enriched in omega-3 fatty acids reduces the severity of cardiovascular and renal diseases. Present study investigates the protective effect of FO on uranyl nitrate (UN)-induced renal damage. Rats prefed with experimental diets for 15 days, given single nephrotoxic dose of UN (0.5mg/kg body weight) intraperitoneally. After 5d of UN treatment, serum/urine parameters, enzymes of carbohydrate metabolism, brush border membrane (BBM), oxidative stress and phosphate transport were analyzed in rat kidney. UN nephrotoxicity was characterized by increased serum creatinine and blood urea nitrogen. UN increased the activity of lactate dehydrogenase and NADP-malic enzyme whereas decreased malate, isocitrate and glucose-6-phophate dehydrogenases; glucose-6-phophatase, fructose-1, 6-bisphosphatase and BBM enzyme activities. UN caused oxidant/antioxidant imbalances as reflected by increased lipid peroxidation, activities of superoxide dismutase, glutathione peroxidase and decreased catalase activity. Feeding FO alone increased activities of enzymes of glucose metabolism, BBM, oxidative stress and Pi transport. UN-elicited alterations were prevented by FO feeding. However, corn oil had no such effects and was not similarly effective. In conclusion, FO appears to protect against UN-induced nephrotoxicity by improving energy metabolism and antioxidant defense mechanism.

Effect of trichloroethylene (TCE) toxicity on the enzymes of carbohydrate metabolism, brush border membrane and oxidative stress in kidney and other rat tissues.

Trichloroethylene (TCE), an industrial solvent, is a major environmental contaminant. Histopathological examinations revealed that TCE caused liver and kidney toxicity and carcinogenicity. However, biochemical mechanism and tissue response to toxic insult are not completely elucidated. We hypothesized that TCE induces oxidative stress to various rat tissues and alters their metabolic functions. Male Wistar rats were given TCE (1000 mg/kg/day) in corn oil orally for 25 d. Blood and tissues were collected and analyzed for various biochemical and enzymatic parameters. TCE administration increased blood urea nitrogen, serum creatinine, cholesterol and alkaline phosphatase but decreased serum glucose, inorganic phosphate and phospholipids indicating kidney and liver toxicity. Activity of hexokinase, lactate dehydrogenase increased in the intestine and liver whereas decreased in renal tissues. Malate dehydrogenase and glucose-6-phosphatase and fructose-1, 6-bisphosphatase decreased in all tissues whereas increased in medulla. Glucose-6-phosphate dehydrogenase increased but NADP-malic enzyme decreased in all tissues except in medulla. The activity of BBM enzymes decreased but renal Na/Pi transport increased. Superoxide dismutase and catalase activities variably declined whereas lipid peroxidation significantly enhanced in all tissues. The present results indicate that TCE caused severe damage to kidney, intestine, liver and brain; altered carbohydrate metabolism and suppressed antioxidant defense system.

Studies on the protective effect of dietary fish oil on gentamicin-induced nephrotoxicity and oxidative damage in rat kidney.

Gentamicin (GM)-induced nephrotoxicity limits its long-term clinical use. Several agents/strategies were attempted to prevent GM nephrotoxicity but were not found suitable for clinical practice. Dietary fish oil (FO) retard the progression of certain types of cancers, cardiovascular and renal disorders. We aimed to evaluate protective effect of FO on GM-induced renal proximal tubular damage. The rats were pre-fed experimental diets for 10 days and then received GM (80 mg/kg body weight/day) treatment for 10 days while still on diet. Serum/urine parameters, enzymes of carbohydrate metabolism, brush border membrane (BBM), oxidative stress and phosphate transport in rat kidney were analyzed. GM nephrotoxicity was recorded by increased serum creatinine and blood urea nitrogen. GM increased the activities of lactate and glucose-6-phosphate dehydrogenases whereas decreased malate, isocitrate dehydrogenases; glucose-6 and fructose-1,6-bisphosphatases; superoxide dismutase, catalase, glutathione peroxidase and BBM enzymes. In contrast, FO alone increased enzyme activities of carbohydrate metabolism, BBM and oxidative stress. FO feeding to GM treated rats markedly enhanced resistance to GM elicited deleterious effects and prevented GM-induced decrease in 32Pi uptake across BBM. Dietary FO supplementation ameliorated GM-induced specific metabolic alterations and oxidative damage due to its intrinsic biochemical/antioxidant properties.

Time dependent effect of gentamicin on enzymes of carbohydrate metabolism and terminal digestion in rat intestine.

Gentamicin (GM) is an aminoglycoside antibiotic commonly used against life threatening gram negative bacterial infections, however, nephrotoxicity remains the major concern for its long term use. Although its effects on kidney are well characterized but there have been no studies regarding its effects on intestine. We hypothesize that GM causes adaptive coordinated effect on enzymes of carbohydrate metabolism and terminal digestion/ absorption in rat intestine. Rats were administered a nephrotoxic dose of GM (80 mg /kg body weight) daily for 15 days and a time dependent effect was observed on various enzyme activities. Activities of lactate (LDH), malate (MDH) and isocitrate (ICDH) dehydrogenases, significantly increased and peaked at different time intervals of GM treatment. Whereas LDH activity remained higher, MDH and ICDH activity slowly declined from their peak values. Activities of fructose-1,6-bisphosphatase, glucose-6-phosphatase and glucose-6-phosphate dehydrogenase increased but malic enzyme decreased in a time dependent manner. Activity of alkaline phosphatase and sucrase significantly increased but gamma-glutamyl transpeptidase activity decreased. GM administration increased lipid peroxidation, glutathione peroxidase but decreased superoxide dismutase and catalase activities. The results indicate that GM treatment selectively upregulated certain enzymes of carbohydrate metabolism and terminal digestion/absorption and perturbed antioxidant defenses.

Effect of potassium dichromate on renal brush border membrane enzymes and phosphate transport in rats.

Chromium is widely used in industry but exposure to chromium compounds in the workplace can result in nephrotoxicity. Various nephrotoxicants affect the brush border membrane (BBM) lining the epithelial cells of the proximal tubule, but there have been no studies regarding the effect of potassium dichromate (K2Cr2O7), a hexavalent chromium compound, on renal BBM. In the present work, the effect of administering a single intraperitoneal dose (15 mg/kg body weight) of K2Cr2O7 on rat renal BBM enzymes and inorganic phosphate (Pi) transport was studied. The animals were administered normal saline (control) or K2Cr2O7 and sacrificed 1, 2, 4 and 8 days after treatment. K2Cr2O7 induced reversible damage to the rat kidney function as indicated by serum creatinine (Scr) and urea nitrogen levels. The activities of BBM marker enzymes were significantly decreased in isolated BBM vesicles (BBMV) and homogenates of cortex and medulla on 1, 2 and 4 days after administration of K2Cr2O7 with complete recovery to control values after 8 days. The decrease in the activities of the enzymes was mainly due to changes in maximum velocity (V(max)) values, while the Michaelis constant (Km) remained unchanged. The sodium dependent Pi transport across BBMV was reduced by 50% after treatment with K2Cr2O7. Thus, the administration of a single dose of K2Cr2O7 leads to impairment in the functions of renal BBM. These results suggest that the nephrotoxicity of K2Cr2O7 may be mediated, at least in part, by its effect on renal BBM.