Renal Diagnostics and Therapeutics Unit, National Institutes of Health, Bethesda, Maryland 20892-1268
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The
anti-inflammatory cytokines -melanocyte-stimulating hormone (MSH)
and interleukin (IL)-10 inhibit acute renal failure (ARF) after
ischemia or cisplatin administration; however, these agents
have not been tested in a pure nephrotoxic model of ARF. Therefore, we
examined the effects of
-MSH and IL-10 in HgCl2-induced ARF. Mice were injected subcutaneously with HgCl2 and then
given vehicle,
-MSH, or IL-10 by intravenous injection. Animals were killed to study serum creatinine, histology, and myeloperoxidase activity. Treatment with either
-MSH or IL-10 did not alter the increase in serum creatinine, tubular damage, or leukocyte accumulation at 48 h after HgCl2 injection. Because
-MSH and
IL-10 are active in other injury models that involve leukocytes, we
studied the time course of tubular damage and leukocyte accumulation to
investigate whether leukocytes caused the tubular damage or accumulated
in response to the tubular damage. Tubular damage was present in the
outer stripe 12 h after HgCl2 injection. In contrast,
the number of leukocytes and renal myleoperoxidase activity were normal at 12 h but were significantly increased at 24 and 48 h after injection. We conclude that neither
-MSH nor IL-10 altered the course of HgCl2-induced renal injury. Because the tubular
damage preceded leukocyte infiltration, the delayed leukocyte
accumulation may play a role in the removal of necrotic tissue and/or
tissue repair in HgCl2-induced ARF.
mercury; acute renal failure; leukocytes
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
HUMAN ACUTE RENAL FAILURE
(ARF) is caused by both ischemic and nephrotoxic insults
acting alone or in combination (33, 37). Because it is
often difficult to identify the cause of ARF, it would be useful to
have therapeutic agents that are effective in both ischemic and
nephrotoxic forms of ARF. We have recently shown that the
anti-inflammatory cytokines -melanocyte-stimulating hormone (MSH)
and interleukin (IL)-10 inhibit renal injury in both ischemia
and cisplatin models of ARF (3, 5, 6, 20, 21). They
inhibit renal injury even when started 1 (IL-10 in cisplatin-induced
ARF) or 6 h (
-MSH in ischemic ARF) after the injury
process is initiated (3, 5, 6). Both agents have multiple
effects; they inhibit the production of cytokines [tumor necrosis
factor (TNF)-
], chemokines (IL-8, monocyte chemoattractant protein-1), adhesion molecules [intracellular adhesion molecule (ICAM)-1], and inducible nitric oxide synthase (iNOS) (3, 5, 6).
-MSH also increases blood pressure after hemorrhagic
shock in rats and in healthy hemodialysis patients (1,
34).
There is evidence for vasoconstriction after HgCl2-induced
nephrotoxic ARF, because renal blood flow is reduced and because verapamil decreases HgCl2-induced renal injury (15,
38). However, the decrement in glomerular filtration rate is
much larger than the change in renal blood flow and remains when renal
blood flow is normalized by volume expansion (38).
Furthermore, verapamil has some antioxidant properties
(13). Therefore, recent work has focused on the role of
oxidant-induced renal injury in HgCl2-induced renal injury.
For example, HgCl2 increases the production of many endogenous oxidants, such as superoxide and hydrogen peroxide, and
causes depletion of protective glutathione (14, 27, 28). Indeed, some (12, 28), but not all (27),
studies showed that HgCl2-induced injury can be ameliorated
by superoxide dismutase or the antioxidants N-acetylcysteine
and melatonin. In contrast, the role of inflammation in the
HgCl2 model is controversial. Early studies by Solez et al.
(32) found decreased medullary blood flow and accumulation
of neutrophils in the vasa recta in rats treated with
HgCl2, suggesting a role for leukocyte-endothelial interactions. In more recent studies, Yanagisawa et al.
(40) found that HgCl2 increases renal mRNA
accumulation of TNF- and iNOS. They suggest that TNF-
and iNOS
cause injury rather than being associated with injury, because modest
protection was afforded by pretreatment with agents that inhibit
TNF-
or iNOS, such as the angiotensin II receptor antagonist
TCV-116, TNF-
antibody, or the iNOS inhibitor aminoguanidine
(40). The degree of protection with TNF-
antibody or
iNOS inhibition was rather modest, especially compared with more
complete projection in renal ischemia-reperfusion injury
(7, 23, 29). Furthermore, antibodies to the adhesion molecule ICAM-1 or lymphocyte function-associated antigens (LFA) did
not protect against HgCl2-induced injury (9);
in contrast, antibodies to ICAM-1 protected against ischemia-
and cisplatin-induced renal injury (8, 18, 19, 31).
Because of the only modest success of narrowly based anti-inflammatory
agents inhibiting renal damage after HgCl2 administration, we reasoned that the broad spectrum of action of -MSH or IL-10 (21, 26) might allow these agents to be effective in the
HgCl2 model of acute renal injury. As noted above,
-MSH
and IL-10 inhibit induction of both TNF-
and iNOS mRNA after both
ischemia and cisplatin administration (3, 5).
Furthermore, unlike ICAM-1 antibodies (18), delay of IL-10
treatment for 1 h after cisplatin still yields excellent
protection against cisplatin-induced injury (5).
Therefore, we tested IL-10 and
-MSH in a HgCl2 model of
acute renal injury.
![]() |
METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Animals. Male BALB/C mice, aged 6-7 wk, were purchased from the National Institutes of Health (NIH). All animals had free access to water and chow (NIH-07 Rodent Chow, Zeigler Bros., Gardners, PA) before surgery. Animal care followed NIH criteria for the care and use of laboratory animals in research.
Chemicals.
IL-10 was purchased from CN Biosciences (Boston, MA). -MSH was
purchased from Phoenix Pharmaceuticals (Mountain View, CA). All other
chemicals were purchased from Sigma (St. Louis, MO).
HgCl2 model of nephrotoxic ARF.
The mice were anesthetized with isoflurane (Baxter Healthcare,
Deerfield, IL) inhalation. The animals were given 6 mg/kg body wt of
HgCl2 (1 mg/ml) in normal saline by subcutaneous injection, and then either vehicle, 1 µg of IL-10, or 50 µg of -MSH
dissolved in 0.3 ml normal saline were given by intravenous injection.
The first dose of IL-10 or
-MSH was given immediately after the
HgCl2 injection. Additional doses of
-MSH were given
every 8 h. The animals were killed at 0.17, 0.5, 1, 2, 3, or 5 days after HgCl2 injection. At the time of death, blood was
collected for measurement of serum creatinine by an Astra 8 autoanalyzer (Beckman Instruments, Fullerton, CA) and both kidneys were
harvested for histological and other studies.
Histological examination. Parafolmaldehyde (4%)-fixed and paraffin-embedded kidney specimens were stained with periodic acid-Schiff reagent or naphthol AS-D chloroacetate esterase (kit no. 91-C, Sigma). Histological changes in the cortex and the outer stripe of the outer medulla (OSOM) were evaluated by semiquantitative measurements of tissue damage and leukocyte infiltration. Tubular damage, defined as tubular epithelial swelling, loss of brush border, vacuolar degeneration, necrotic tubules, and desquamation, was estimated by counting the percentage of damaged tubules in 10 high-power fields/section. Because the esterase stain identifies infiltrating neutrophils and macrophages (41), we use the term leukocytes. Leukocyte accumulation was evaluated by counting the number of esterase-positive cells in 10 high-power fields in the cortex and 10 high-power fields in the OSOM.
Renal tissue myeloperoxidase activity. Myeloperoxidase (MPO) activity, an indicator of leukocyte accumulation in tissues, was measured as described by Laight et al. (22). We used kidney tissues subjected to 40 min of ischemia and reperfused for 4 or 12 h as a positive control for the MPO assay (3). Kidney tissue was homogenized in a solution containing 0.5% (wt/vol) hexadecyltrimethylammonium bromide dissolved in 50 mM potassium phosphate buffer (pH 6.0) and centrifuged for 30 min at 20,000 g at 4°C. Samples were incubated at 60°C for 2 h in a water bath and then centrifuged at 4,000 g for 12 min. The supernatant (40 µl) was incubated with 160 µl of a reaction mixture containing 1.6 mM tetramethylbenzidine and 3 mM H2O2 diluted in 80 mM phosphate buffer (pH 5.4) in a 96-well microplate. The rate of change in absorbance at 630 nm was measured spectrophotometrically by using a SPECTRAmax 190 (Molecular Devices, Sunnyvale, CA). MPO activity was expressed as absorbance per minute per milligram of wet tissue.
Statistical analysis. All data are expressed as means ± SE. Differences between data sets were examined for statistical significance by using ANOVA with post hoc analysis (Bonferroni-Dunn or Dunnett tests; StatView 5.0, Berkeley, CA). A P value <0.05 was accepted as statistically significant.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
HgCl2-induced ARF.
In preliminary studies, we investigated the dose-response of
HgCl2 in mice by using serum creatinine at 48 h as the
end point. We found that 6 and 8 mg/kg body wt but not 2 and 4 mg/kg
body wt of HgCl2 induced a significant increase in serum
creatinine in male BALB/C mice (Fig.
1A). Therefore, we used 6 mg/kg body wt of HgCl2 in all subsequent
experiments. Injection of 6 mg/kg body wt of HgCl2 induced
a significant but transient increase in serum creatinine (Fig.
1B). The serum creatinine level significantly increased at
24 h (1.87 ± 0.35 mg/dl vs. day 0,
P < 0.01), peaked at 48 h (2.20 ± 0.53 mg/dl vs. day 0, P < 0.01), and then
gradually returned to the basal values by day 5. At 12 h after HgCl2 injection, histological examination of
periodic acid-Schiff stained sections revealed that tubular epithelial
swelling, loss of brush border, and vacuolar degeneration were limited
to the OSOM (see Fig. 3E). At 24-48 h after the
injection, extensive tubular damage and necrosis had spread to the
cortex (see Fig. 3A).
|
Effect of -MSH and IL-10 in HgCl2-induced ARF.
To evaluate the effects of
-MSH and IL-10 in
HgCl2-induced renal injury, we investigated serum
creatinine levels and histological changes at 48 h after
injection. Treatment with
-MSH or IL-10 did not decrease the level
of serum creatinine compared with vehicle-treated mice in
HgCl2-induced ARF at 48 h (
-MSH, 2.35 ± 0.07, vs. vehicle, 2.15 ± 0.23 mg/dl; IL-10, 2.10 ± 0.35, vs.
vehicle, 2.25 ± 0.32 mg/dl) or 72 h (Fig.
2). Similarly, tubular damage in
-MSH-
or IL-10-treated mice at 48 h was not significantly
different from that in vehicle-treated animals in either cortex
(
-MSH, 28.20 ± 5.57, vs. vehicle, 28.75 ± 1.31%; IL-10,
27.40 ± 2.41, vs. vehicle, 25.77 ± 3.16%) or the OSOM
(
-MSH, 38.63 ± 1.71, vs. vehicle, 38.00 ± 1.84%; IL-10,
37.75 ± 1.27, vs. vehicle, 33.38 ± 2.64%; Figs.
3, A-C, and
4).
|
|
Time course of tubular damage and leukocyte accumulation. We studied the time course of tubular damage and leukocyte accumulation in the kidney to investigate whether leukocytes caused the tubular damage or accumulated in response to the tubular damage after HgCl2 administration. Esterase-positive cells were found only occasionally in both control kidneys and at 12 h after HgCl2 injection (0.21 ± 0.15 cells/mm2). The number of esterase-positive cells in the OSOM were significantly increased at 24 h (10.10 ± 2.73 cells/mm2 vs. day 0, P < 0.05) and then rapidly increased and reached a maximum at 48 h after HgCl2 injection (31.10 ± 6.26 cells/mm2 vs. day 0, P < 0.01; Fig. 5A). In the cortex, esterase-positive cells were only sporadically present even at 48 h (3.15 ± 1.31 cells/mm2). Most of the esterase-positive cells were exclusively located around necrotic tubules, not normal or degenerated tubules, which were located mainly in the OSOM (Fig. 3D).
In contrast to the delayed entry of leukocytes, tubular damage was present in the OSOM as early as 12 h after HgCl2 injection (16.19 ± 2.75% vs. day 0, P < 0.05; Figs. 3E and 5). The majority of necrotic tubules disappeared by day 5, and some denuded basement membranes were covered with flattened regenerating epithelial cells. Hyperproliferative cells occasionally could be seen in some proximal tubules on day 5 (Fig. 3F). However, we could still observe some casts in damaged tubular lumens.MPO activity in HgCl2-induced acute renal injury.
The time course of leukocyte accumulation in the kidney was also
determined by renal tissue MPO assay. The basal level of MPO activity
was 2.67 ± 0.22 absorbance · min1 · 100 mg
tissue
1. MPO activity remained unchanged by 12 h
after exposure to HgCl2. MPO activity significantly
increased at 24 h after HgCl2 injection (5.28 ± 0.56 absorbance · min
1 · 100 mg
tissue
1 vs. day 0, P < 0.01)
and then peaked at 48 h (8.77 ± 0.13 absorbance · min
1 · 100 mg
tissue
1 vs. day 0, P < 0.01;
Fig. 5B). These results were consistent with the number of
esterase-positive cells detected by histological analysis. However,
increased kidney tissue MPO activity in HgCl2-induced acute
renal injury was much less than that in ischemia- or
reperfusion-injured kidney tissues (24.98 ± 2.86 absorbance · min
1 · 100 mg
tissue
1 at 4 h and 46.29 ± 16.39 absorbance · min
1 · 100 mg
tissue
1 at 24 h after reperfusion; Fig.
5B).
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
In contrast to their effects in ischemic and cisplatin
models of renal injury, neither -MSH nor IL-10 inhibited injury in the HgCl2 model. Because the role of leukocytes is unknown,
we investigated the role of leukocytes in the HgCl2 model.
Lack of effect of -MSH or IL-10.
Because many therapeutic agents have a golden window of opportunity, we
first investigated the minimal dose of HgCl2 that would
produce consistent renal injury (Fig. 1). Most previous studies of
HgCl2 ARF had been performed in rats, generally by using
1-7.5 mg/kg of HgCl2 (for example, see Refs.
9, 11, 12, 15,
24, 28, 40), whereas studies in
mice have used 3-7 mg/kg of HgCl2 (16, 17,
36). For example, Tanaka-Kagawa et al. (36) found
differences in sensitivity to Hg-induced ARF among mouse strains by
using 5.4 mg/kg of HgCl2; however, they did not study
BALB/C mice. In BALB/C mice, we found that neither 2 nor 4 mg/kg of
HgCl2 caused sufficient renal injury. Because 6 mg/kg of
HgCl2 caused consistent renal injury, this dose was selected for subsequent studies. We then used doses and dose schedules for
-MSH and IL-10 that this laboratory had previously shown to be
effective in ischemia- and cisplatin-induced ARF (3, 5). Despite the use of optimal doses and dose schedules, we found that neither
-MSH nor IL-10 had a statistically significant effect on either creatinine (Fig. 2) or renal histology (Figs. 3 and
4). The lack of effect of
-MSH and IL-10 is similar to the lack of
effect of other anti-inflammatory strategies, including antibodies to
LFA and ICAM-1 (11) or CD8 cell depletion
(9). In contrast, Yanagisawa et al. (40)
found that HgCl2 increased renal TNF-
and iNOS and that
pretreatment with TNF-
antibody or the iNOS inhibitor aminoguanidine
inhibits renal damage. However, the degree of protection with TNF-
antibody or iNOS inhibition was rather modest, especially compared with
more complete protection in the renal ischemia or reperfusion
injury model (7, 23, 29). Most of the agents that
substantially inhibit HgCl2-induced ARF, such as superoxide
dismutase, N-acetylcysteine, and melatonin, likely inhibit
oxidant-induced cell injury (12, 14, 28), although some
controversy remains (27). For example,
N-acetylcysteine reduced lipid peroxidation
(12), and melatonin increased the renal content of
malandialdehyde and glutathione after HgCl2
(28). Therefore, the inability of
-MSH to inhibit renal
injury after HgCl2 administration is less surprising.
Although Yanagisawa et al. (40) found that pretreatment
with anti-TNF-
antibody or the iNOS inhibitor aminoguanidine was
modestly protective, there are differences between our model and
Yanagisawa's model that might be significant, including species
differences (mice vs. rats), route of HgCl2 administration
(subcutaneous vs. intraperitoneal), and perhaps most importantly, the
length of pretreatment (none vs. 1-5 days). Which of these
factors, if any, is important is unknown.
|
Role of inflammation in HgCl2-induced ARF.
Electron microscopic studies by Solez et al. (32) found
neutrophils in the vasa recta after HgCl2 administration to
rats. More recent studies by Ghielli et al. (11) also
found renal accumulation of macrophages and CD8+ and
CD4+ T cells after Hg administration. Yanagisawa et al.
(40) found induction of the proinflammatory cytokine
TNF-. The importance of these leukocytes in tissue injury and repair
is not known. Previous studies have not correlated histological changes
with leukocyte accumulation soon after Hg administration. The lack of
effect of
-MSH, IL-10, LFA, and ICAM-1, and only modest effect of
anti-TNF-
antibodies caused us to reappraise the role of leukocytes in HgCl2-induced ARF. In the present study, leukocyte
accumulation was measured by two independent methods: direct counting
and MPO assay. We found evidence of tubular damage at 12 h,
without any increase in leukocyte accumulation. Previous studies by
Zalme and colleagues (25, 42) also found early renal
damage to the proximal straight tubule as early as 6 h after Hg
administration. In contrast, we first detected both leukocyte and MPO
accumulation at 24 h after HgCl2 administration (Figs.
5 and 6). Thus in the HgCl2 model, tubular damage preceded
leukocyte accumulation. In the renal ischemia model, in
contrast, leukocyte accumulation occurs much earlier, starting
~2-4 h after injury, and either precedes or occurs at the same
time as evidence of tubular injury assessed by routine histological
methods (3, 4, 22, 39). Therefore, the leukocyte
accumulation after Hg administration is more likely to be in response
to tissue damage, whereas in the ischemia-reperfusion model,
there is emerging evidence that early accumulation of macrophages and T
cells may precede and perhaps cause the tubular damage (2, 4, 10,
30, 41). Leukocytes, measured by either esterase staining or MPO
assay, are only transiently found in the kidney (Fig. 5), which is
similar to previous findings in the uranyl acetate model, where
ED-1-positive cells transiently emigrate to the region of injury and
then gradually disappear after the tubules have regenerated
(35). Strategies that inhibit inflammation would not be
expected to decrease renal damage, and might even increase tubular
damage, in the HgCl2 model.
|
Conclusion.
We conclude that -MSH and IL-10 do not reduce renal injury after
HgCl2 administration. Leukocytes accumulate in renal
tissues in response to the HgCl2-induced nephrotoxic
injury. Strategies that inhibit leukocyte-endothelial interactions are
either only modestly effective or fail to protect against
HgCl2-induced injury.
-MSH (and perhaps IL-10) is more
effective when the injury pathway involves leukocyte-endothelial
interactions (ischemia) rather than direct tubular toxicity
(HgCl2).
![]() |
ACKNOWLEDGEMENTS |
---|
This study was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases.
![]() |
FOOTNOTES |
---|
Address for reprint requests and other correspondence: R. A. Star, Rm. 3N108, Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Dr., Bethesda, MD 20892-1268 (E-mail Robert_Star{at}nih.gov).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
First published January 2, 2002;10.1152/ajprenal.00203.2001
Received 2 July 2001; accepted in final form 29 November 2001.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Bertolini, A,
Guarini S,
Rompianesi E,
and
Ferrari W.
-MSH and other ACTH fragments improve cardiovascular function and survival in experimental hemorrhagic shock.
Eur J Pharmacol
130:
19-26,
1986[ISI][Medline].
2.
Chamoun, F,
Burne M,
O'Donnell M,
and
Rabb H.
Pathophysiologic role of selectins and their ligands in ischemia reperfusion injury.
Front Biosci
5:
E103-E109,
2000[ISI][Medline].
3.
Chiao, H,
Kohda Y,
McLeroy P,
Craig L,
Housini I,
and
Star RA.
-Melanocyte-stimulating hormone protects against renal injury after ischemia in mice and rats.
J Clin Invest
99:
1165-1172,
1997
4.
De Greef, KE,
Ysebaert DK,
Dauwe S,
Persy V,
Vercauteren SR,
Mey D,
and
De Broe ME.
Anti-B7-1 blocks mononuclear cell adherence in vasa recta after ischemia.
Kidney Int
60:
1415-1427,
2001[ISI][Medline].
5.
Deng, J,
Chiao H,
Kohda Y,
and
Star RA.
IL-10 inhibits ischemic and nephrotoxic renal injury (Abstract).
J Am Soc Nephrol
12:
800A,
2001.
6.
Deng, J,
Kohda Y,
Chiao H,
and
Star RA.
MSH acts in part via IL-10 to inhibit ischemic and nephroxic ARF (Abstract).
J Am Soc Nephrol
12:
800A,
2001.
7.
Donnahoo, KK,
Shames BD,
Harken AH,
and
Meldrum DR.
The role of tumor necrosis factor in renal ischemia-reperfusion injury.
J Urol
162:
196-203,
1999[ISI][Medline].
8.
Dragun, D,
Tullius SG,
Park JK,
Maasch C,
Lukitsch I,
Lippoldt A,
Gross V,
Luft FC,
and
Haller H.
ICAM-1 antisense oligodesoxynucleotides prevent reperfusion injury and enhance immediate graft function in renal transplantation.
Kidney Int
54:
590-602,
1998[ISI][Medline].
9.
Ghielli, M,
Verstrepen WA,
Dauwe S,
Nouwen EJ,
and
De Broe ME.
Selective depletion of CD8-positive leukocytes does not alter mercuric chloride induced acute renal failure in the rat.
Exp Nephrol
5:
69-81,
1997[ISI][Medline].
10.
Ghielli, M,
Verstrepen W,
De Greef K,
Vercauteren S,
Ysebaert D,
Nouwen E,
and
De Broe M.
Inflammatory cells in renal pathology.
Nephrologie
19:
59-67,
1998[ISI][Medline].
11.
Ghielli, M,
Verstrepen WA,
De Greef KE,
Helbert MH,
Ysebaert DK,
Nouwen EJ,
and
De Broe ME.
Antibodies to both ICAM-1 and LFA-1 do not protect the kidney against toxic (HgCl2) injury.
Kidney Int
58:
1121-1134,
2000[ISI][Medline].
12.
Girardi, G,
and
Elias MM.
Effectiveness of N-acetylcysteine in protecting against mercuric chloride-induced nephrotoxicity.
Toxicology
67:
155-164,
1991[ISI][Medline].
13.
Girardi, G,
and
Elias MM.
Evidence for renal ischaemia as a cause of mercuric chloride nephrotoxicity.
Arch Toxicol
69:
603-607,
1995[ISI][Medline].
14.
Girardi, G,
and
Elias MM.
Mercuric chloride effects on rat renal redox enzymes activities: SOD protection.
Free Radic Biol Med
18:
61-66,
1995[ISI][Medline].
15.
Girardi, G,
and
Elias MM.
Verapamil protection against mercuric chloride-induced renal glomerular injury in rats.
Toxicol Appl Pharmacol
152:
360-365,
1998[ISI][Medline].
16.
Hultman, P,
Enestrom S,
and
von Schenck H.
Renal handling of inorganic mercury in mice. The early excretion phase following a single intravenous injection of mercuric chloride studied by the Silver Amplification method.
Virchows Arch
49:
209-224,
1985.
17.
Kawaida, K,
Matsumoto K,
Shimazu H,
and
Nakamura T.
Hepatocyte growth factor prevents acute renal failure and accelerates renal regeneration in mice.
Proc Natl Acad Sci USA
91:
4357-4361,
1994[Abstract].
18.
Kelly, KJ,
Meehan SM,
Colvin RB,
Williams WW,
and
Bonventre JV.
Protection from toxicant-mediated renal injury in the rat with anti-CD54 antibody.
Kidney Int
56:
922-931,
1999[ISI][Medline].
19.
Kelly, KJ,
Williams WW, Jr,
Colvin RB,
and
Bonventre JV.
Antibody to intercellular adhesion molecule 1 protects the kidney against ischemic injury.
PNAS USA
91:
812-816,
1994[Abstract].
20.
Kohda, Y,
Chiao H,
McLeroy P,
Craig L,
and
Star RA.
Anti-inflammatory cascade protects against renal ischemia-reperfusion injury (Abstract).
J Am Soc Nephrol
9:
580A,
1998.
21.
Kohda, Y,
Chiao H,
and
Star RA.
-Melanocyte-stimulating hormone and acute renal failure.
Curr Opin Nephrol Hypertens
7:
413-417,
1998[ISI][Medline].
22.
Laight, DW,
Lad N,
Woodward B,
and
Waterfall JF.
Assessment of myeloperoxidase activity in renal tissue after ischemia/reperfusion.
Eur J Pharmacol
292:
81-88,
1994[Medline].
23.
Ling, H,
Edelstein C,
Gengaro P,
Meng XH,
Lucia S,
Knotek M,
Wangsiripaisan A,
Shi YX,
and
Schrier R.
Attenuation of renal ischemia-reperfusion injury in inducible nitric oxide synthase knockout mice.
Am J Physiol Renal Physiol
277:
F383-F390,
1999
24.
Lux, SE,
John KM,
Kopito RR,
and
Lodish HF.
Cloning and characterization of band 3, the human erythrocyte anion-exchange protein (AE1).
Proc Natl Acad Sci USA
86:
9089-9093,
1989[Abstract].
25.
McDowell, EM,
Nagle RB,
Zalme RC,
McNeil JS,
Flamenbaum W,
and
Trump BF.
Studies on the pathophysiology of acute renal failure. I. Correlation of ultrastructure and function in the proximal tubule of the rat following administration of mercuric chloride.
Virchows Arch
22:
173-196,
1976.
26.
Moore, KW,
de Waal MR,
Coffman RL,
and
O'Garra A.
Interleukin-10 and the interleukin-10 receptor.
Annu Rev Immunol
19:
683-765,
2001[ISI][Medline].
27.
Nath, KA,
Croatt AJ,
Likely S,
Behrens TW,
and
Warden D.
Renal oxidant injury and oxidant response induced by mercury.
Kidney Int
50:
1032-1043,
1996[ISI][Medline].
28.
Nava, M,
Romero F,
Quiroz Y,
Parra G,
Bonet L,
and
Rodriguez-Iturbe B.
Melatonin attenuates acute renal failure and oxidative stress induced by mercuric chloride in rats.
Am J Physiol Renal Physiol
279:
F910-F918,
2000
29.
Noiri, E,
Peresleni T,
Miller F,
and
Goligorsky MS.
In vivo targeting of inducible NO synthase with oligodeoxynucleotides protects rat kidney against ischemia.
J Clin Invest
97:
2377-2383,
1996
30.
Rabb, H,
Daniels F,
O'Donnell M,
Haq M,
Saba SR,
Keane W,
and
Tang WW.
Pathophysiological role of T lymphocytes in renal ischemia-reperfusion injury in mice.
Am J Physiol Renal Physiol
279:
F525-F531,
2000
31.
Rabb, H,
Mendiola CC,
Saba SR,
Dietz JR,
Smith CW,
Bonventre JV,
and
Ramirez G.
Antibodies to ICAM-1 protect kidneys in severe ischemic reperfusion injury.
Biochem Biophys Res Commun
211:
67-73,
1995[ISI][Medline].
32.
Solez, K,
Kramer EC,
Fox JA,
and
Heptinstall RH.
Medullary plasma flow and intravascular leukocyte accumulation in acute renal failure.
Kidney Int
6:
24-37,
1974[ISI][Medline].
33.
Star, RA.
Treatment of acute renal failure.
Kidney Int
54:
1817-1831,
1998[ISI][Medline].
34.
Star, RA,
Haynes S,
and
Middelton JP.
Phase 1 trial of -melanocyte stimulating hormone (Abstract).
J Am Soc Nephrol
9:
161A,
1998.
35.
Sun, DF,
Fujigaki Y,
Fujimoto T,
Yonemura K,
and
Hishida A.
Possible involvement of myofibroblasts in cellular recovery of uranyl acetate-induced acute renal failure in rats.
Am J Pathol
157:
1321-1335,
2000
36.
Tanaka-Kagawa, T,
Suzuki M,
Naganuma A,
Yamanaka N,
and
Imura N.
Strain difference in sensitivity of mice to renal toxicity of inorganic mercury.
J Pharmacol Exp Ther
285:
335-341,
1998
37.
Thadhani, R,
Pascual M,
and
Bonventre JV.
Medical progress-acute renal failure.
N Engl J Med
334:
1448-1460,
1996
38.
Vanholder, RC,
Praet MM,
Pattyn PA,
Leusen IR,
and
Lameire NH.
Dissociation of glomerular filtration and renal blood flow in HgCl2-induced acute renal failure.
Kidney Int
22:
162-170,
1982[ISI][Medline].
39.
Willinger, CC,
Schramek H,
Pfaller K,
and
Pfaller W.
Tissue distribution of neutrophils in postischemic acute renal failure.
Virchows Arch
62:
237-243,
1992.
40.
Yanagisawa, H,
Nodera M,
Umemori Y,
Shimoguchi Y,
and
Wada O.
Role of angiotensin II, endothelin-1, and nitric oxide in HgCl2-induced acute renal failure.
Toxicol Appl Pharmacol
152:
315-326,
1998[ISI][Medline].
41.
Ysebaert, DK,
De Greef KE,
Vercauteren SR,
Ghielli M,
Verpooten GA,
Eyskens EJ,
and
De Broe ME.
Identification and kinetics of leukocytes after severe ischaemia/reperfusion renal injury.
Nephrol Dial Transplant
15:
1562-1574,
2000
42.
Zalme, RC,
McDowell EM,
Nagle RB,
McNeil JS,
Flamenbaum W,
and
Trump BF.
Studies on the pathophysiology of acute renal failure. II. A histochemical study of the proximal tubule of the rat following administration of mercuric chloride.
Virchows Arch
22:
197-216,
1976.