To study the effect of chronic treatment with chaethomellic
acid (CA), a highly specific inhibitor of ras farnesyl-protein transferase,
on the renal function of rats with renal failure induced by renal mass
reduction.
Male Wistar rats were subjected to 5/6 nephrectomy
(RMR) or sham-operated (SO). One week after surgery, rats have
been placed in four experimental groups: RMR: rats without treat-
ment (n=13); RMR+CA: rats treated with CA (n=13); SO: rats
without treatment (n=13); SO+AC: rats treated with CA (n=13).
CA was intraperitoneally administered in a dose of 0.23  g/Kg
three times a week for 6 months. Creatinine, blood urea nitrogen
(BUN) and protein were measured in serum and/or urine by routine
laboratory techniques.
BUN, creatinine, and proteinuria were significantly lower and
creatinine clearance was significantly higher in SO and SO+AC groups
when compared with RMR and RMR+AC groups. There were no differ-
ences in creatinine, proteinuria and creatinine clearance between RMR
and RMR+AC groups. Anyway, RMR+AC group showed significant
lower BUN and lower creatinine and proteinuria, and higher creatinine
clearance than RMR group.
In a model of renal failure induced by RMR, 6 months
of treatment with CA may have some beneficial effect on renal
function

Colaço, Aura

Colaço, Bruno

Fonte, Elizabete

López-Novoa, Jose

Mega, Carmén

Nogueira, António José M.

Oliveira, Paula A.

Pires, Maria João

Virchows Archiv

To study the effect of chronic treatment with chaethomellic
acid (CA), a highly specific inhibitor of ras farnesyl-protein transferase,
on the renal function of rats with renal failure induced by renal mass
reduction.
Male Wistar rats were subjected to 5/6 nephrectomy
(RMR) or sham-operated (SO). One week after surgery, rats have
been placed in four experimental groups: RMR: rats without treat-
ment (n=13); RMR+CA: rats treated with CA (n=13); SO: rats
without treatment (n=13); SO+AC: rats treated with CA (n=13).
CA was intraperitoneally administered in a dose of 0.23  g/Kg
three times a week for 6 months. Creatinine, blood urea nitrogen
(BUN) and protein were measured in serum and/or urine by routine
laboratory techniques.
 BUN, creatinine, and proteinuria were significantly lower and
creatinine clearance was significantly higher in SO and SO+AC groups
when compared with RMR and RMR+AC groups. There were no differ-
ences in creatinine, proteinuria and creatinine clearance between RMR
and RMR+AC groups. Anyway, RMR+AC group showed significant
lower BUN and lower creatinine and proteinuria, and higher creatinine
clearance than RMR group.
In a model of renal failure induced by RMR, 6 months
of treatment with CA may have some beneficial effect on renal
function

Colaço, Bruno Jorge

Biblioteca Digital do IPB

PS-21-022Losartan improves kidney function and decreases oxidative stressand tubular injury in spontaneously hypertensive rats during acuterenal failureJ. Markovic-Lipkovski*, M. Ivanov, Z. Miloradovic, N. Mihailovic-Stanojevic, J. Grujic-Milanovic, D. Jovovic, D. Karanovic, U. J. Vajic*University of Belgrade, Faculty of Medicine, Dept. of Pathology, SerbiaObjective:Acute renal failure (ARF) is a vicious illness, especially whenit is combined with arterial hypertension. We investigated effects oflosartan in spontaneously hypertensive rats (SHR) with ARF in order todetermine the role of angiotensine II.Method: The right kidney was removed and the renal ischemia wasperformed by clamping the left renal artery for 40 min. SHR groupsreceived losartan (competitive antagonist of type I angiotensine IIreceptor) or vehicle in the femoral vein 5 min during and 175 minafter the period of ischemia. All biochemical parameters weremeasured and kidney tissue was analysed morphologically andimmunomorphologically applying Bax and Bcl-2 antibodies 24 hafter ischemia.Results: Treatment with losartan induced significantly increased ureaclearance, decreased creatinine, improved oxidative stress parameters,increased HDL cholesterol and decreased tubular damages vs. ARF. Highexpression of pro-apoptotic Bax protein in proximal tubules of SHR withARF was lower in losartan-treated animals. Anti-apoptotic Bcl-2 proteinwas decreased in distal tubules of losartan-treated postischemic SHR,indicating lower degree of apoptotic damage in them.Conclusion: Treatment with losartan can improve kidney function, de-crease oxidative stress in SHRs with ARF. Angiotensine II receptorblockade may have beneficial effects on tubular injury of postischemicSHR.PS-21-023Effect of chaethomellic acid on renal function in rat model of chronicrenal failureA. Nogueira*, C. Mega, E. Fonte, P. Oliveira, B. Colaço, J. M. López-Novoa, A. Colaço, M. J. Pires*Dep of Veterinary Science, Center Study Animal Sciences, Vila Real,PortugalObjective: To study the effect of chronic treatment with chaethomellicacid (CA), a highly specific inhibitor of ras farnesyl-protein transferase,on the renal function of rats with renal failure induced by renal massreduction.Method: Male Wistar rats were subjected to 5/6 nephrectomy(RMR) or sham-operated (SO). One week after surgery, rats havebeen placed in four experimental groups: RMR: rats without treat-ment (n=13); RMR+CA: rats treated with CA (n=13); SO: ratswithout treatment (n=13); SO+AC: rats treated with CA (n=13).CA was intraperitoneally administered in a dose of 0.23 μg/Kgthree times a week for 6 months. Creatinine, blood urea nitrogen(BUN) and protein were measured in serum and/or urine by routinelaboratory techniques.Results: BUN, creatinine, and proteinuria were significantly lower andcreatinine clearance was significantly higher in SO and SO+AC groupswhen compared with RMR and RMR+AC groups. There were no differ-ences in creatinine, proteinuria and creatinine clearance between RMRand RMR+AC groups. Anyway, RMR+AC group showed significantlower BUN and lower creatinine and proteinuria, and higher creatinineclearance than RMR group.Conclusion: In a model of renal failure induced by RMR, 6 monthsof treatment with CA may have some beneficial effect on renalfunction.PS-21-024Apoptosis as a prognostic marker in prediction of renal injury, afteracute bleeding and volume replacement with HES 130/0.4 or Ringersolution, in a pig modelH. Vala*, R. Cruz, A. Machado, C. Venâncio, J. Mesquita, A. Silva, A.Liza ortiz, D. Ferreira*Escola Superior Agrária de Viseu, Instituto Politécnico de Viseu, PortugalObjective: The aim of this study is identify and quantify apoptosis inrenal tissue, using a biochemical marker (TUNEL) in a pig haemorrhagicmodel, after intravascular volume replacement with Ringer’s lactate orHydroxyethylstarch 130/0.4) solutions.Method: 18 Large White pigs underwent total intravenous anaes-thesia with propofol and remifentanil. 25 ml/kg of arterial bloodwere removed from the femoral artery. Volume was replaced, RL,in group1 (n=6) and HES 130/0.4, in group2 (n=6), 20 min afterbleeding. The control group did not face bleeding and volumereposition. One hour after volume replacement, pigs were eutha-nized with intravenous KCl, and renal fragments were taken forseveral studies, including immunohistochemically with TUNELmethod for apoptosis detection. ANOVA was used to compare databetween groups.Results: Apoptosis was, detected in all groups, mainly in epithelialtubular cells. The number of apoptotic cells per mm2 was lower in group1 (11.94cells/mm2), when compared with group 2 (67.94cells/mm2) andwith the control group (146.34cells/mm2). Levels of apoptosis weresignificantly lower in group1(RL), comparing with the controlgroup(P<0.05)Conclusion: The median apoptotic levels were significantly lowerin pigs, subjected to fluid replacement with RL, when comparedwith HES 130/0.4. Ringer lactate might promote better renal perfu-sion in the presence of severe hypovolaemia following acutehaemorrhage.PS-21-026Renal malakoplakia in a transplanted kidney: A case report andreview of the literatureE. Borg*, J. Degaetano*Mater Dei Hospital, Dept. of Histopathology, Msida, MaltaObjective: Malakoplakia is a rare chornic inflammatory conditionwhich is presumed to be due to impaired killing of bacteria bymacrophages. Renal malakoplakia in transplanted kidney is veryrare.Method: A 22 year old female on immunosuppressive therapy for atransplanted kidney presented with fever and rapid deterioration in renalfunction. Initial biopsy showed unremarkable looking renal parenchyma.In view of further clinical deterioration, nephrectomy of the transplantedkidney was performed.Results: The nephrectomy specimen showed numerous yellowish-white soft, well defined nodules. The rest of the kidney lookedunremarkable. The literature was searched for cases of renalmalakoplakia in transplanted kidneys. The data obtained was tabu-lated. Malakoplakia of a transplanted kidney is very rare. Only 14cases have been reported since 1977. All patients were on immu-nosuppressive therapy and experienced at least one preceding epi-sode of urinary tract infection. There was deterioration in renalfunction needing dialysis, and transplant nephrectomy in the major-ity of cases.Conclusion: Renal malakoplakia in kidney transplants is a very rarecondition and should be included in the differential diagnosis of unusualhistological features in post transplant biopsies.Virchows Arch (2013) 463:101–352 297

Effect of chaethomellic acid on renal function in rat model of chronic renal failure

EFFECT OF CHAETHOMELLIC ACID ON RENAL FUNCTION IN A RAT MODEL OF CHRONIC RENAL FAILURENogueira AJ1, Fonte ME1, Oliveira PA1, Colaço B2, López-Novoa JM3, Mega C4, Colaço A1, Pires MJ11Department of Veterinary Science, Center for the Study of Animal Sciences, ECAV, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal2Department of Zootecnia, Center for the Study of Animal Sciences, ECAV, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal3Renal and Cardiovascular Physiopathology Unit, Reina Sofía Institute for Renal Research, Department of Physiology and Pharmacology, University of Salamanca, Biomedical Research Institute of Salamanca, Salamanca, Spain4Department of Animal Science, Rural Engineering and Veterinary Science, Agrarian Superior School of Polytechnic Institute of Viseu, Viseu, PortugalRESULTSRenal function parameters are shown in table 1. BUN (figure 1), creatinine (figure 2) and urinary protein excretion (figure 3)were significantly lower and creatinine clearance (figure 4) was significantly higher in the SO and SO+AC groups whencompared with the RMR and RMR+AC groups. There were no significantly differences in creatinine, urinary proteinexcretion and creatinine clearance between the RMR and RMR+AC groups. However, the RMR+AC group showedsignificantly lower BUN and lower creatinine and urinary protein excretion, and higher creatinine clearance than the RMRgroup.Universidade de Trás-os-Montes e Alto DouroMATERIALS AND METHODSAnimal care and treatment were conducted in conformity with institutional guidelines that are in compliance withinternational laws and politics. Male Wistar rats were subjected to 5/6 nephrectomy (RMR) or sham-operated (SO). Oneweek after surgery, rats have been randomized and placed in four experimental groups: RMR: RMR rats without treatment(n=13); RMR+AC: RMR rats treated with AC (n=13); SO: SO rats without treatment (n=13); SO+AC: SO rats treated with AC(n=13). AC was intraperitoneally administered in a dose of 0.23 µg/Kg three times a week for six months. Creatinine, bloodurea nitrogen (BUN), electrolytes and protein were measured in serum and/or urine by routine laboratory techniques. Thedifferences between groups were evaluated by one-way analysis of variance (ANOVA) followed by Bonferroni post hoctests. All data are presented as the mean ± SD and were considered significant at p<0.05.INTRODUCTIONChaethomellic acid (AC) is a highly specific inhibitor of ras farnesyl-protein transferase. The aim of this study has been toevaluate the effect of chronic treatment with chaethomellic acid (CA) on the renal function of rats with renal failure inducedby renal mass reduction.CONCLUSIONSThese results suggest that in a model of renal failure induced by RMR, six months of treatment with chaethomellic acidmay have some beneficial effect on renal function.  Universidade de Trás-os-Montes e Alto DouroTable 1: Effect of chaethomellic acid on renal function parameters after renal mass reduction.Parameters SO(n = 13)SO+AC(n = 13)RMR(n = 12)RMR+AC(n = 8) ANOVA POST HOC (1)Urinary Flow (µl/min.)Md = 0,010M = 0,011SD = 0,002Md = 0,009M = 0,009SD = 0,003Md = 0,027M = 0,029SD = 0,008Md = 0,023M = 0,025SD = 0,009F(3,42) = 34,729p < .001SO vs. RMR**SO vs. RMR+AC**SO+AC vs. RMR**SO+AC vs. RMR+AC**Sodium (mmol/l)Md = 144,600M = 145,170SD = 1,831Md = 143,960M = 142,299SD = 6,784Md = 145,735M = 146,957SD = 4,218Md = 147,245M = 146,388SD = 3,569F(3,42) = 2,497p = .073Potassium (mmol/l)Md = 4,810M = 4,808SD = 0,355Md = 4,710M = 4,511SD = 0,662Md = 5,230M = 5,275SD = 0,472Md = 4,820M = 4,849SD = 0,408F(3,42) = 4,964p = .005 SO+AC vs. RMR**Chloride (mmol/l)Md = 101,190M = 102,522SD = 4,268Md = 101,340M = 99,715SD = 7,811Md = 104,535M = 105,264SD = 5,276Md = 108,670M = 107,284SD = 6,241F(3,42) = 3,186p = .033 SO+AC vs. RMR+AC*Calcium (mg/dl)Md = 10,530M = 10,533SD = 0,366Md = 10,830M = 10,476SD = 0,882Md = 11,460M = 11,397SD = 0,475Md = 11,435M = 11,333SD = 0,602F(3,42) = 7,477p < .001SO vs. RMR**SO vs. RMR+AC*SO+AC vs. RMR**SO+AC vs. RMR+AC*Phosphorus (mg/dl)Md = 6,420M = 6,392SD = 1,010Md = 6,210M = 6,073SD = 0,998Md = 7,670M = 8,209SD = 1,707Md = 7,165M = 7,481SD = 1,363F(3,42) = 7,140p = .001SO vs. RMR**SO+AC vs. RMR**BUN (mg/dl)Md = 39,800M = 40,433SD = 6,866Md = 45,200M = 45,654SD = 7,138Md = 118,750M = 147,167SD = 69,824Md = 87,125M = 95,894SD = 40,221F(3,42) = 19,440p < .001SO vs. RMR**SO vs. RMR+AC*SO+AC vs. RMR**SO+AC vs. RMR+AC**RMR vs. RMR+AC*Creatinine (mg/dl)Md = 0,730M = 0,739SD = 0,069Md = 0,700M = 0,755SD = 0,170Md = 1,430M = 1,691SD = 0,799Md = 1,085M = 1,274SD = 0,519F(3,42) = 11,532p < .001SO vs. RMR**SO+AC vs. RMR**Urinary Protein Excretion (g/day)Md = 1,606M = 1,517SD = 0,310Md = 1,729M = 1,667SD = 0,412Md = 51,494M = 45,603SD = 20,440Md = 22,598M = 35,524SD = 30,890F(3,42) = 23,034p < .001SO vs. RMR**SO vs. RMR+AC**SO+AC vs. RMR**SO+AC vs. RMR+AC**Creatinine Clearance (ml/min.)Md = 1,600M = 1,585SD = 0,238Md = 1,400M = 1,462SD = 0,301Md = 0,700M = 0,733SD = 0,355Md = 0,900M = 0,950 SD = 0,366F(3,42) = 20,214p < .001SO vs. RMR**SO vs. RMR+AC**SO+AC vs. RMR**SO+AC vs. RMR+AC**SO: sham-operated untreated animals; SO+AC: sham-operated animals treated with chaethomellic acid; RMR: renal mass reduction untreated animals; RMR+AC: renal mass reductionanimals treated with chaethomellic acid; Md: Median; M: Mean; SD: Standard Deviation; F: statistic from ANOVA; p: significant value from ANOVA test; (1): Bonferroni post hoc test; pairsof groups with statistically significant differences: *p < .05 and **p < .01.Figure 1: Effect of chaethomellic acid on BUN (mg/dl) after renal mass reduction. SO: sham-operateduntreated animals; SO+AC: sham-operated animals treated with chaethomellic acid; RMR: renal massreduction untreated animals; RMR+AC: renal mass reduction animals treated with chaethomellic acid.Figure 3: Effect of chaethomellic acid on urinary protein excretion (g/day) after renal massreduction. SO: sham-operated untreated animals; SO+AC: sham-operated animals treated withchaethomellic acid; RMR: renal mass reduction untreated animals; RMR+AC: renal mass reductionanimals treated with chaethomellic acid.Figure 2: Effect of chaethomellic acid on creatinine(mg/dl) after renal mass reduction. SO: sham-operateduntreated animals; SO+AC: sham-operated animals treated with chaethomellic acid; RMR: renal massreduction untreated animals; RMR+AC: renal mass reduction animals treated with chaethomellic acid.Figure 4: Effect of chaethomellic acid on creatinine clearance (ml/min.)) after renal mass reduction. SO:sham-operated untreated animals; SO+AC: sham-operated animals treated with chaethomellic acid;RMR: renal mass reduction untreated animals; RMR+AC: renal mass reduction animals treated withchaethomellic acid.

Effect of chaethomellic acid on renal function in a rat model of chronic renal failure

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Effect of chaethomellic acid on renal function in a rat model of chronic renal failure

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