Differential Effects of Cisplatin on the Production of NADH-Dependent Superoxide and the Activity of Antioxidant Enzymes in Rat Renal Cortical Slices in vitro

1996 ◽  
Vol 79 (4) ◽  
pp. 191-198 ◽  
Author(s):  
Jin-Gang Zhang ◽  
W. Edward Lindup
1976 ◽  
Vol 231 (1) ◽  
pp. 14-19 ◽  
Author(s):  
M Barac-Nieto

Rat renal cortical slices were incubated with [1-(14)C]palmitate bound to 2.5% albumin. The following effects were found: a)1 mM palmitate utilization or oxidation to CO(2) varied according to the concentration of lactate in the media, it increased at 0.8 and 3.2 mM, was unchanged at 8 mM, and decreased at 16 mM. Esterification was stimulated at 3.2 mM lactate. b) Addition of glutamine (0.1 mM) instead of lactate stimulated incomplete and complete oxidation of palmitate (1 mM), whereas high medium glutamine (10 mM) inhibited palmitate (1 mM) utilization, esterification, and oxidation to CO(2) but increased its incomplete oxidation. The low rate of exogenous palmitate oxidation observed in this study and the finding that exogenous palmitate oxidation is only partially inhibited at very high concentrations of exogenous lactate or glutamine are consistent with the view that these exogenous substrates contribute little to the oxidative metabolism of rat renal cortex in vitro, which probably depends on the supply of substrates endogenous to the tissue.


1994 ◽  
Vol 13 (2) ◽  
pp. 89-93 ◽  
Author(s):  
J.G. Zhang ◽  
L.F. Zhong ◽  
M. Zhang ◽  
X.L. Ma ◽  
Y.X. Xia ◽  
...  

1 The protective effects of dithiothreitol (DTT) on cisplatin-induced nephrotoxicity were investigated with rat renal cortical slices. 2 The nephrotoxic effects of cisplatin (2 mmol l-1) were manifested in several ways: the Na+ and water content were increased while K+ was decreased. The malondiadehyde (MDA) concentration in the slices and the lactate dehydrogenase (LDH) released into the medium were increased. The uptake of p-aminohippurate (PAH), the synthesis of glucose and the glutathione (GSH) concentration in the slices were all decreased. 3 Despite a DTT-related increase in platinum (Pt) uptake by the slices, DTT (0.5-2 mmol I-1 ) ameliorated all these toxic effects of cisplatin in a concentration related manner. 4 The results suggest that the protective mechanism of DTT is its antioxidative action, DTT is also a metal chelator, however, and so a protective effect via chelation of Pt by DTT cannot be excluded.


1997 ◽  
Vol 11 (5) ◽  
pp. 723-729 ◽  
Author(s):  
M. Blackmore ◽  
J.C. Richardson ◽  
S.A. Rhodes ◽  
L. Patterson ◽  
A.J. Spencer ◽  
...  

1986 ◽  
Vol 251 (1) ◽  
pp. E98-E103 ◽  
Author(s):  
W. L. Henrich ◽  
W. B. Campbell

The sequence of intracellular events that lead to renin release is incompletely defined. Accordingly, we examined the interrelationship of two important factors in the process: renin release coupled to cAMP and renin release related to a decrease in intracellular calcium activity (Cai). Rat renal cortical slices were used to study these relationships in vitro. In the initial studies, cAMP-coupled renin release was established for isoproterenol (10(-5) M), prostacyclin (PGI2; 10(-6) M), and forskolin (10(-5) M). Each agent caused an increase in renin release and tissue cAMP levels, which were inhibited by the addition of the adenyl cyclase inhibitor 2',5'-dideoxyadenosine (DDA, 10(-5) M) to the media. Diltiazem (10(-4) M) and 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8; 0.6 X 10(-4) M) are believed to decrease Cai by different mechanisms; each of these agents caused a significant increase in renin release. Renin release stimulated by diltiazem, and TMB-8 was not inhibited by either DDA or indomethacin. The calcium ionophore A23187 (17 X 10(-6) M) and vanadate (10(-3) M) were next added to produce an increase in Cai. Both of these agents blunted renin release produced by isoproterenol, PGI2, and forskolin. These results provide strong indirect support for an inverse relationship between Cai and renin release in the juxtaglomerular cell. The results also imply that changes in Cai occupy a step that is distal to cAMP-coupled events in the sequence of intracellular events which culminate in renin release.


1989 ◽  
Vol 256 (6) ◽  
pp. E798-E804 ◽  
Author(s):  
S. Kim ◽  
M. Hosoi ◽  
M. Hiruma ◽  
F. Ikemoto ◽  
K. Yamamoto

Concanavalin A (con A) chromatography of rat plasma revealed the presence of three differently glycosylated forms of renin, including the con A unbound form (renin C), the loosely bound form (renin A), and the tightly bound form (renin B). Rat renal cortical slices in vitro secreted all these forms. They had a different half-life in the plasma after ligation of both renal artery and vein (half-life of 21 +/- 1, 14 +/- 3, and 35 +/- 4 min for renin A, B, and C, respectively). Thus differently glycosylated forms of renin are released from the kidney into the blood circulation and disappear, with a different half-life. Rats were sodium-depleted and captopril-treated (40-60 mg.kg-1.day-1) for 2 wk, and the effects of these treatments on relative proportions of renin A, B, and C were investigated. These treatments elevated plasma renin concentration approximately 60-fold (from 24 +/- 3 to 1,406 +/- 128 ng angiotensin I.h-1.ml-1; P less than 0.01), in association with an increase in the relative percent of renin C in the plasma from 22 +/- 2 to 39 +/- 3% (P less than 0.01). Moreover, the relative proportion of renin C released from the renal cortical slices was significantly higher in the treated than in the control rats (42 +/- 9 vs. 16 +/- 3% of secreted renin, respectively; P less than 0.02). These results show that the predominant release of renin C, with the longest half-life (35 min) in the plasma, contributes to the increased plasma renin concentration in sodium-depleted and captopril-treated rats.


Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 272
Author(s):  
Chuan Xu ◽  
Annie Wang ◽  
Eileen R. Hoskin ◽  
Carla Cugini ◽  
Kenneth Markowitz ◽  
...  

Severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) is detectable in saliva from asymptomatic individuals, suggesting a potential benefit from the use of mouth rinses to suppress viral load and reduce virus spread. Published studies on the reduction of SARS-CoV-2-induced cytotoxic effects by mouth rinses do not exclude antiseptic mouth rinse-associated cytotoxicity. Here, we determined the effect of commercially available mouth rinses and antiseptic povidone-iodine on the infectivity of replication-competent SARS-CoV-2 viruses and of pseudotyped SARS-CoV-2 viruses. We first determined the effect of mouth rinses on cell viability to ensure that antiviral activity was not a consequence of mouth rinse-induced cytotoxicity. Colgate Peroxyl (hydrogen peroxide) exhibited the most cytotoxicity, followed by povidone-iodine, chlorhexidine gluconate (CHG), and Listerine (essential oils and alcohol). The potent antiviral activities of Colgate Peroxyl mouth rinse and povidone-iodine were the consequence of rinse-mediated cellular damage when the products were present during infection. The potency of CHG was greater when the product was not washed off after virus attachment, suggesting that the prolonged effect of mouth rinses on cells impacts the antiviral outcome. To minimalize mouth rinse-associated cytotoxicity, mouth rinse was largely removed from treated viruses by centrifugation prior to infection of cells. A 5% (v/v) dilution of Colgate Peroxyl or povidone-iodine completely blocked viral infectivity. A similar 5% (v/v) dilution of Listerine or CHG had a moderate suppressive effect on the virus, but a 50% (v/v) dilution of Listerine or CHG blocked viral infectivity completely. Mouth rinses inactivated the virus without prolonged incubation. The new infectivity assay, with limited impacts of mouth rinse-associated cytotoxicity, showed the differential effects of mouth rinses on SARS-CoV-2 infection. Our results indicate that mouth rinses can significantly reduce virus infectivity, suggesting a potential benefit for reducing SARS-CoV-2 spread.


2021 ◽  
Vol 22 (13) ◽  
pp. 6647
Author(s):  
Radka Podlipná ◽  
Martina Navrátilová ◽  
Lucie Raisová Stuchlíková ◽  
Kateřina Moťková ◽  
Lenka Langhansová ◽  
...  

Although manure is an important source of minerals and organic compounds it represents a certain risk of spreading the veterinary drugs in the farmland and their permeation to human food. We tested the uptake of the anthelmintic drug fenbendazole (FBZ) by soybean, a common crop plant, from the soil and its biotransformation and accumulation in different soybean organs, including beans. Soybeans were cultivated in vitro or grown in a greenhouse in pots. FBZ was extensively metabolized in roots of in vitro seedlings, where sixteen metabolites were identified, and less in leaves, where only two metabolites were found. The soybeans in greenhouse absorbed FBZ by roots and translocated it to the leaves, pods, and beans. In roots, leaves, and pods two metabolites were identified. In beans, FBZ and one metabolite was found. FBZ exposure did not affect the plant fitness or yield, but reduced activities of some antioxidant enzymes and isoflavonoids content in the beans. In conclusion, manure or biosolids containing FBZ and its metabolites represent a significant risk of these pharmaceuticals entering food consumed by humans or animal feed. In addition, the presence of these drugs in plants can affect plant metabolism, including the production of isoflavonoids.


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