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Biomedical subjects

D Appenroth

Publications and source records attributed to D Appenroth.

33 records · Page 2Linked to original sources
PubMed1990

Age dependent differences in the functional and morphological impairment of kidney following cisplatin administration.

In adult rats the clearance of inulin, urinary p-aminohippurate (PAH) excretion, TmPAH, as well as PAH accumulation in renal cortical slices were decreased 48-72 h following 0.6 mg cisplatin/100 g body mass (b.m.). Morphological investigations showed changes preferentially in proximal tubules. Reduced inulin clearance is discussed to be rather the consequence of inulin back leak in destroyed tubules than of a real decrease in glomerular function. The ultrastructure of glomeruli, distal tubules, and collecting ducts was not affected by cisplatin (CP) in 10- and 55-day-old rats. In 10-day-old rats, inulin clearance and urinary PAH excretion remained unaffected by CP, whereas TmPAH and PAH accumulation in vitro were significantly decreased following CP. Most significant ultrastructural changes occurring in mitochondria are discussed to cause decreased PAH accumulation following CP. The high portion of PAH filtered in young rats masked this impairment of active PAH secretion. Lower nephrotoxicity in young rats seems to be caused by low state of a differentiation of cell structure and transport function.

Age Factors↗
PubMed1989

Metyrapone decreases the glutathione concentration in liver and kidney.

A single dose of 7.5 mg/100 g b.wt. metyrapone, intraperitoneally, decreased the concentration of reduced (GSH) and oxidized (GSSG) glutathione in the liver and kidney of female Wistar rats for approximately 4-5 h. The ratio between GSSG and GSH was not affected in the kidney but is decreased in the liver.

Animals↗
PubMed1988

Age dependent differences in sodium dichromate nephrotoxicity in rats.

Investigations were performed on 10- and 55-day-old female Wistar rats. 1 or 2 mg sodium dichromate/100 g b. m. were administered subcutaneously. Urine was collected for 1 hour at different times after dichromate injection. Total urinary protein as well as some protein fractions (high and low molecular weight proteins as well as albumin) were determined. In adult rats dose dependence of nephrotoxicity was found concerning the extent and duration of renal damage. Separation of proteins gave an insight into the location of injury. At the beginning and in the recovery phase preferentially tubular damage was found. The peak of damage is characterized by additional glomerular disturbances. Young rats are much less susceptible to dichromate than adult rats are. Possible reasons are discussed.

Aging↗
PubMed1988

Nephrotoxicity and pharmacokinetics of cisplatinum in young and adult rats.

Wistar rats (10 and 55 days old) were administered a single dose of 0.6 mg cisplatinum (CP) 100 g body wt. intraperitoneally. Urinary volume, p-aminohippurate and total protein excretion were determined. Separation of urinary proteins was performed by sodium dodecylsulfate polyacrylamide gel electrophoresis. Significant symptoms of nephrotoxicity (oliguria, reduced PAH-excretion, heavy proteinuria, changes in urinary protein composition) were detected in adult rats 72 h after CP. At that time young rats did not show distinct signs of nephrotoxicity. Experiments on time dependence of nephrotoxicity showed that in young rats symptoms occurred already 6 h after CP-administration, and 72 h after CP the damage was nearly completely repaired. Pt-determination in serum, kidney tissue, and urine showed a shorter t1/2 in serum, lower concentrations in kidney tissue as well as higher Pt-concentrations in urine of young compared with adult rats.

Aging↗
PubMed1985

Effect of neonatal sympathectomy by 6-hydroxydopamine on renal hemodynamic parameters in adult rats.

Newborn rats were sympathectomized with 6-hydroxydopamine (6-OHDA) (10 mg/100 g b.w., once daily on the first 4 postnatal days). Hemodynamic parameters were determined at the 55th d of life. In comparison to non-sympathectomized control rats the blood pressure and total peripheral resistance of 6-OHDA treated animals were significantly diminished whereas the cardiac output was enhanced. In sympathectomized rats the resistance values of the whole kidney as well as of the cortex and outer medulla were lower than in control animals. No redistribution of renal blood flow was detectable. The results show a long lasting effect of neonatal denervation by 6-OHDA at least up to the 55th d of life.

Animals↗
PubMed1984

Age differences in cisplatinum nephrotoxicity.

Male and female Wistar rats (5-105-day-old) were administered 3 different doses of cisplatinum (CP) (0.15, 0.3 or 0.6 mg/100 g body wt, intraperitoneally) After 3 days the renal excretory functions were investigated. There were no sex differences in nephrotoxicity. In rats of all age groups a dose dependent decrease in body weight appeared. In 5- and 33-105-day-old rats the 2 lower doses did not or only mildly influence renal function. 0.6 mg CP/100 g body wt in these age groups lead to a significant reduction in urine volume. The excretion of osmotically active substances and p-aminohippurate were reduced. There is a statistically significant proteinuria. In 10- and 15-day-old rats the 2 lower doses were without any pathologic consequences, but 0.6 mg CP/100 g body wt was followed by a significant increase in the protein excretion of 15-day-old rats. Consequently, regarding the parameters measured 10-15-day-old rats seemed to be less susceptible to CP-nephrotoxicity.

Aging↗
PubMed1983

[Inhibition of the renal excretion of PAH by probenecid homologs].

The authors studied the effects of probenecid and five of its homologues on the renal excretion of p-amino-hippuric acid (PAH). All the compounds under study inhibited the excretion of PAH. Probenecid and its homologues were injected 15 min before the administration of PAH. With all the substances tested, the inhibition of the excretion of PAH was most marked during the first 30 min of the diuresis experiment. The extent of efficiency increases within the homologous series up to the diethyl compound; after that, the inhibitory effect decreases with the increase in chain length. In the dosage range under study, the probenecid homologues show linear dose-response relationships. With due regard to toxicity and efficiency, the authors conclude from the results obtained that the diethyl compound is the most potent substance; probenecid itself is less efficient, being twice as toxic.

Aminohippuric Acids↗
PubMed1981

[Stimulation of the renal excretion of p-aminohippuric acid by probenecid homologues (author's transl)].

Probenecid and five of its homologues showed increased lipophilicity with increasing chain length of the substituents. Parallel to this, the toxicity increased about 30 times. All the probenecide homologues under study stimulated the excretion of p-aminohippuric acid (PAH) when applied repeatedly. If a threshold dose is exceeded, an increase of the pretreatment dose will not result in a further increase in PAH excretion. As compared to non-pretreated control animals, the highest possible increase in PAH excretion lies between 40 and 80% independently of the structure of the respective probenecide homologue. Due to their more favourable therapeutic range (LD50 divided by D40-50), the probenecide homologues with shorter chains are better suited to stimulate the excretion of PAH, though the extent of stimulation is the same with all the probenicide homologues under study.

Aminohippuric Acids↗
PubMed1981

Effect of sympathectomy with 6-hydroxydopamine on the renal excretion of water and electrolytes in developing rats.

The influence of sympathectomy (SE) by s.c. administration of 6-hydroxydopamine (10 mg/100 g b.m. daily from the 1st up to the 4th day of life) on the age dependent development of the renal excretion of water and electrolytes was tested by means of diuresis experiments in conscious rats. Immediately after SE natriuresis occurs as a consequence of denervation. Already on the 10th day of life this denervation diuresis disappears due to several compensatory mechanisms and 10 to 55 day old rats excrete less sodium than control animals of the same age. The potassium excretion is also diminished in 20 to 55 day old rats. The results show -- that the typical age course of water and electrolyte excretion is not altered by SE, -- that adrenergic influences are of importance for the renal function in rats, and -- that the consequences of the sympathectomy can be fully compensated in the kidney too.

Animals↗
PubMed1976

[Cytogenetic studies after contact with juvenile blastic leukemias].

Persons with long professionell contact to acute childhood leukemia and first-degree relatives had a higher tendency of chromosome bursting off in the metaphases from cultivated lymphocytes. Since persons with contact and relatives for one thing and controls for another showed significant differences in the degree of hurtibility of metaphases, cultivation ane preparation could not be responsible for themselves. It is discussed whether the contact to childhood leukemia may lead to any reaction between peripheral lymphocytes and an infectious agent. This reaction itself leads to a higher susceptibility of metaphases from peripheral lymphocytes to the injuring laboratory conditions.

Acute Disease↗
PubMedDate not supplied

Ontogenetic aspects of thallium-induced nephrotoxicity in rats.

The effect of Tl2SO4 (Tl, 20 mg kg-1 body wt.) on renal function was investigated in 10- and 20-day-old rats. Nephrotoxic effects were evaluated by the determination of glomerular filtration rate, urinary volume, electrolyte and protein excretion, as well as by morphological investigations. In contrast to adult rats there were no morphological destructions in 10- and 20-day-old rats. Changes in renal function seemed to be less expressed in 10- and 20-day-old than in adult rats. The smaller nephrotoxicity in 10-day-old rats may be caused by lower Tl concentration in renal tissue, whereas in 20-day-old rats decreased nephrotoxicity cannot be explained in this way. The activity of Na+/K(+)-ATPase in rat renal tissues was found to be involved in the mechanisms of Tl enrichment in renal tissue, being an indirect determinant of Tl nephrotoxicity.

Animals↗
PubMedDate not supplied

Protective effects of methimazole against cisplatin-induced nephrotoxicity in rats.

In adult rats 6 mg kg-1 body wt. cisplatin given i.p. was nephrotoxic. Four days of i.p. treatment with 40 mg kg-1 body wt. methimazole, which started 1 day before CP, prevented increases in blood urea nitrogen and in the renal excretion of proteins. Furthermore, methimazole treatment reduced the oliguric effect of cisplatin and the depression of renal sodium excretion. However, it had no effect on the increased formation of lipid peroxides in cisplatin-damaged kidneys, although repeated treatment with methimazole enhanced the renal glutathione content. Methimazole acts as a radical scavenger, maintaining the glutathione pool in the kidney.

Animals↗
PubMedDate not supplied

Is thallium-induced nephrotoxicity in rats connected with riboflavin and/or GSH?--reconsideration of hypotheses on the mechanism of thallium toxicity.

Adult female Wistar rats (Han:Wist) were injected with 2 mg of Tl2SO4 per 100 g body weight. Parameters of nephrotoxicity were urinary volume and protein excretion as well as blood urea nitrogen concentration. Thallium concentrations were determined in renal cortex and medulla. There was no effect of different schedules of vitamin B2 (riboflavin) treatment on thallium nephrotoxicity. Glutathione (GSH) concentration was not decreased by thallium in renal cortex or in medulla. The increase of GSH concentration in renal tissue by N-acetylcysteine pretreatment did not influence thallium nephrotoxicity. Buthionine sulphoximine diminished thallium nephrotoxicity by a significant decrease of thallium concentration in renal medulla, which was caused by enhanced urinary excretion of thallium. From our investigations we conclude that there is no relation between thallium-induced nephrotoxicity and riboflavin and/or GSH.

Acetylcysteine↗
PubMedDate not supplied

Beneficial effect of acetylcysteine on cisplatin nephrotoxicity in rats.

The influence of acetylcysteine (ac-cys) on cisplatin (CP) nephrotoxicity was investigated in female Wistar rats. Administration of 0.6 mg CP 100 g-1 body wt. was followed by oliguria and proteinuria, as well as a significant increase of blood urea nitrogen concentration. The i.p. administration of 0.6 mg CP 100 g-1 body wt. concomitantly with 100 mg ac-cys 100 g-1 body wt. s.c. completely abolished the nephrotoxic effects of CP. However, following this, the Pt concentration in kidney was decreased significantly by ac-cys treatment. This was caused by the enhanced urinary excretion of Pt. The same effect on CP nephrotoxicity appeared when CP and ac-cys were dissolved together in solution prior to injection. It could be shown that in this solution a ligand exchange reaction of CP by ac-cys started immediately, resulting in increased renal excretion and decreased Pt concentration in kidney. From our results we concluded that the protective effect of ac-cys on CP nephrotoxicity is based on the formation of a complex unsuitable for tubular reabsorption.

Acetylcysteine↗