Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction

http://if-pan.krakow.pl/pjp/pdf/2012/1_31.pdf

Animal models of acute renal failure

This review summarizes the latest advances in knowledge on the effects of flavonoids on renal function in health and disease. Flavonoids have antihypertensive, antidiabetic, and antiinflammatory effects, among other therapeutic activities. Many of them also exert renoprotective actions that may be of interest in diseases such as glomerulonephritis, diabetic nephropathy, and chemically-induced kidney insufficiency. They affect several renal factors that promote diuresis and natriuresis, which may contribute to their well-known antihypertensive effect. Flavonoids prevent or attenuate the renal injury associated with arterial hypertension, both by decreasing blood pressure and by acting directly on the renal parenchyma. These outcomes derive from their interference with multiple signaling pathways known to produce renal injury and are independent of their blood pressure-lowering effects. Oral administration of flavonoids prevents or ameliorates adverse effects on the kidney of elevated fructose consumption, high fat diet, and types I and 2 diabetes. These compounds attenuate the hyperglycemia-disrupted renal endothelial barrier function, urinary microalbumin excretion, and glomerular hyperfiltration that results from a reduction of podocyte injury, a determinant factor for albuminuria in diabetic nephropathy. Several flavonoids have shown renal protective effects against many nephrotoxic agents that frequently cause acute kidney injury (AKI) or chronic kidney disease (CKD), such as LPS, gentamycin, alcohol, nicotine, lead or cadmium. Flavonoids also improve cisplatin- or methotrexate-induced renal damage, demonstrating important actions in chemotherapy, anticancer and renoprotective effects. A beneficial prophylactic effect of flavonoids has been also observed against AKI induced by surgical procedures such as ischemia/reperfusion (I/R) or cardiopulmonary bypass. In several murine models of CKD, impaired kidney function was significantly improved by the administration of flavonoids from different sources, alone or in combination with stem cells. In humans, cocoa flavanols were found to have vasculoprotective effects in patients on hemodialysis. Moreover, flavonoids develop antitumor activity against renal carcinoma cells with no toxic effects on normal cells, suggesting a potential therapeutic role in patients with renal carcinoma.

/pdf/flavonoids-in-kidney-health-and-disease-23wlbmo7dw.pdf

Flavonoids in Kidney Health and Disease.

Kundur [Benincasa hispida (Thunb.) Cogn.]: A potential source for valuable nutrients and functional foods

Clinical application of cyclophosphamide (CP) as an anticancer drug is often limited due to its toxicity. CP is metabolized mainly in the liver by cytochrome P450 system into acrolein which is the proximate toxic metabolite. Many different natural antioxidants were found to alleviate the toxic effects of various toxic agents via different mechanisms. Therefore, the present study aimed at investigating the role of essential oils extracted from fennel, cumin and clove as natural antioxidants in the alleviation of hepatotoxicity induced by CP through assessment of hepatotoxicity biomarkers (AST, ALT, ALP), histopathology of liver tissues as well as other biochemical parameters involved in the metabolism of CP. The data of the present study showed that treatment of male mice with cyclophosphamide (2.5 mg/Kg BW) as repeated dose for 28 consecutive days was found to induce hepatotoxicity through the elevation in the activities of AST, ALT, and ALP. Combined administration of any of these oils with CP to mice partially normalized the altered hepatic biochemical markers caused by CP, whereas administration of fennel, clove or cumin essential oils alone couldn’t change liver function indices. Moreover, CP caused histological changes in livers of mice including swelling and dilation in sinusoidal space, inflammation in portal tract and hepatocytes, as well as, hyperplasia in Kuppfer cells. However, co-administration of any of the essential oils with CP alleviated to some extent the changes caused by CP but not as the normal liver. CP was also found to induce free radical levels (measured as thiobarbituric acid reactive substances) and inhibited the activities of superoxide dismutase, glutathione reductase, and catalase as well as activities and protein expressions of both glutathione S-transferase (GSTπ) and glutathione peroxidase. Essential oils restored changes in activities of antioxidant enzymes (SOD, CAT, GR, GST, and GPx) caused by CP to their normal levels compared to control group. In addition, treatment of mice with CP was found to induce the protein expression of CYP 3A4, 2B1/2, 2C6, 2C23. Moreover, the present study showed that essential oils reduced the expression of CYPs 2E1, 3A4 but could not restore the expression of CYP 2C6 and 2C23 compared to CP-treated mice. Interestingly, pretreatment of mice with essential oil of clove was found to restore activities of DMN-dI, AHH, and ECOD which were induced by CP to their normal control levels. It is concluded that EOs showed a marked hepatoprotective effect against hepatotoxicity induced by CP. In addition, co-administration of CP with any of these oils might be used as a new strategy for cancer treatment to alleviate the hepatotoxicity induced by CP.

/pdf/protective-effects-of-essential-oils-as-natural-antioxidants-3ipqrud83w.pdf

Protective Effects of Essential Oils as Natural Antioxidants against Hepatotoxicity Induced by Cyclophosphamide in Mice.

Introduction. Evidence suggests that reactive oxygen species play a role in the pathophysiology of renal ischemia/reperfusion (I/R) injury. This study was designed to investigate the renoprotective activity of methanolic fruit extract of Benincasa cerifera in I/Rinduced kidney failure in rats. Materials and Methods. Renal pedicles of 12 rats were occluded for 60 minutes followed by 24 hours of reperfusion. Six days prior to induction of I/R, 6 of the rats received Benincasa cerifera, 500 mg/kg, orally. Serum creatinine, urea, and uric acid levels were measured after the operation. At the end of reperfusion period, the rats were sacrificed. Superoxide dismutage, catalase, reduced glutathione, and renal malondialdehyde content were determined in the renal tissues. Results were compared with a group of rats with sham operation. Results. Renal I/R caused significant impairment of kidney function. Six-day administration of Benincasa cerifera, however, minimized this effect. Rats with renal I/R only showed significantly decreased activity of superoxide dismutage, catalase, and reduced glutathione compared with the sham-operated rats. These declining trends were significantly less in the group treated with Benincasa cerifera compared with those in the I/R-only group (P = .008, P = .07, and P < .001, respectively). Renal I/R produced a significant increase in malondialdehyde level, while pretreatment with Benincasa cerifera was associated with a significantly lower malondialdehyde level (P < .001). Conclusions. These findings imply that reactive oxygen species play a crucial role in I/R-induced kidney injury and Benincasa cerifera exerts renoprotective activity probably by the radical scavenging activity.

http://www.ijkd.org/index.php/ijkd/article/viewFile/111/94

Renoprotective activity of benincasa cerifera fruit extract on ischemia/reperfusion-induced renal damage in rat

The present study investigated the protective effects of Syzygium cumini extract (SCE; 100 and 200 mg/kg) against genotoxicity and oxidative stress (OS) induced by cyclophosphamide (CP) in mice. Animals were received 14 days pretreatment (oral) of SCE, followed by induction of genotoxicity by CP (40 mg/kg), 24 hours before sacrifice. Mice bone marrow chromosomal aberration assay, micronucleus assay, and sperm abnormality assay were employed for the study. Activities of hepatic antioxidant enzymes were also investigated. Phytochemical investigation was done to determine total phenolic and flavonoid content in SCE. Results showed that CP produced a significant increase in average percentage of aberrant metaphases and chromosomal aberrations (CAs) excluding gap, and micronuclei (MN) formation in polychromatic erythrocytes produced cytotoxicity in mouse bone marrow cells and induced abnormal sperms in a male germ line. CP also markedly inhibited the activities of superoxide dismutase (SOD), catalase (...

Investigation of antigenotoxic potential of Syzygium cumini extract (SCE) on cyclophosphamide-induced genotoxicity and oxidative stress in mice.

Objectives: Lithium is a drug of choice in maniac disorder. Lithium
inhibits the glycogen synthase kinase-3 (GSK-3), an enzyme involved in
the insulin signalling pathway. Elevated levels of GSK-3 were found in
diabetic rats and humans. We aimed to determine the effect of lithium
chloride in diabetes and associated vascular complications in diabetic
rats. Materials and Methods: Type 2 diabetes was induced by high fat
diet and low dose of streptozotocin. Diabetic rats were divided into
diabetic control and lithium chloride treatment groups. Lithium
chloride was used as a GSK-3 inhibitor. The treatment was given for 4
weeks. Various biochemical parameters were measured before initiation
and the end of treatment. Systolic blood pressure was measured by the
non-invasive tail-cuff method, while various biochemical and tissue
parameters were estimated for efficacy. Vasoreactivity was performed by
taking the contractile response of H 2 O 2 (10 -6 M to 10 -3 M) and
angiotensin II (10 -11 to 10 -7 M) in rat thoracic aortas of different
groups. Statistical comparisons between all groups were performed by
using two tailed one-way ANOVA followed by the Dunnett test. P-values
<0.05 were considered statistically significant. Results: Treatment
with lithium chloride significantly reduced the augmented systolic
blood pressure, various biochemical parameters, and antioxidant
parameters in diabetic-treated rats. Treatment also showed the decrease
in augmented responses of H 2 O 2 and angiotensin II in rat thoracic
aortas of treated rats. Conclusions: We can conclude that lithium
chloride treatment reduces the diabetic state as well as
diabetes-induced vascular dysfunction.

Nilesh R. Kanzariya

Papers

Renoprotective activity of benincasa cerifera fruit extract on ischemia/reperfusion-induced renal damage in rat

Investigation of antigenotoxic potential of Syzygium cumini extract (SCE) on cyclophosphamide-induced genotoxicity and oxidative stress in mice.

Antidiabetic and vasoprotective activity of lithium: Role of glycogen synthase kinase-3