Deneysel gentamisin nefrotoksisitesinde üriner enzim aktivitelerinin önemi
Küçük Resim Yok
Tarih
1994
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Trakya Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Bu araştırmada, akut renal yetmezliğe bir model olarak oluşturulan deneysel gentamisin nefrotoksisitesinde, üriner enzim aktiviteleri ve enzim/kreatinin oranı gibi yeni diyagnostik ve prognostik prosedürlerin teşhis ve prognozdaki önemleri araştırıldı. Ayrıca bu parametrelerin rutin teşhiste kullanılan diğer metotlarla karşılaştırmaları yapıldı. Araştırmada 2'si kontrol, 7'si deneme grubu olmak üzere toplam 9 köpek kullanıldı. Deneme grubunu oluşturan köpeklere nefrotoksisite oluşturmak amacıyla, 10 mg/kg dozunda ve 8 saat aralıklarla, günde 3 kez (8.00, 16.00, 24.00) olmak üzere, 10 gün süreyle Gentamisin sülfat enjeksiyonları yapıldı. idrar ve kan örnekleri, deneme öncesi 2 ve deneme boyunca 9 kez olmak üzere, gün aşın periyotlarda alındı. İdrar örnekleri ultrason kontrolündeki sitosentezis yoluyla, kan örnekleri vakumlu tüpler kullanılarak alındı. İdrar örneklerinde N-asetil-B-D- glukozaminidaz (NAG), $- glutamil-transferaz (GGT) ve Alkalen fosfataz (ALP) enzim aktiviteleri, kreatinin (ÎKR), protein (İPr), glikoz (İGLU) ve elektrolit (İCa++, İP+, İNa+, İK+) konsantrasyonları ölçüldü. İdrar dip stik ve sedimentin mikroskobik muayeneleri yapıldı. Kan örneklerinde kan üre nitrojen (BUN), serum kreatinin (SKR), total protein (TP), albumin (ALB), glikoz (GLU) ve elektrolit (Ca++, P+ Na+, K+) konsantrasyonları ölçüldü. İdrar protein/kreatinin (İPr/İKR) oranı ve günlük protein kayıpları (Gün.K) hesaplandı. İdrar ve serumda ölçülen elektrolit konsantrasyonları ve glikozun fraksiyonel klirensleri belirlendi. Deneme öncesi 2 kez, deneme boyunca da 3. kez olmak üzere 5 defa sodyum sulfanilat klirensi ölçüldü. Deneme boyunca tüm köpeklerde günlük klinik muayeneler yapıldı. Denemenin 11. gününde l'ikontol 2'si deneme grubundan olan 3 köpeğin, 12. günde üremik koma nedeniyle uyutulan 2 köpeğin ve deneme sonunda da kalan 4 köpeğin otopsileri ve histopatolojik incelemeleri yapıldı. Tüm köpekler denemenin 7. gününde başlayan ve giderek artan şekilde gentamisin nefrotoksisitesinin klinik belirtilerini (anoreksi, halsizlik, kusma, abdominal ağrı, kanlı diyare) gösterdiler. Denemenin 12. gününde, 2 köpekte üremik koma belirtileri (salivasyon, kusma, sık soluma, nöbetler ve diyare) tesbit edildi. Denemenin 8. gününde tüm köpeklerde hematuri, proteinuri, glikozuri ve idrar sedimentinde granular kastların varlığı tesbit edildi. BUN, SKR ve P+ ve K+ konsantrasyonlarında sırasıyla denemenin 3, 9 ve 13. günlerinde çok önemli (p<0.01) artışlar, ALB konsantrasyonunda denemenin 7. gününde, Na+'da ise 9. günde çok önemli (p<0.01) azalma gözlendi. İdrar kreatinin ve idrar İNa+ konsantrasyonlarında54 çok önemli (p<0.01) ve ÎK+ konsantrasyonunda denemenin 1. gününde önemli (p<0.05) düşme, İPr ve ÎGLU konsantrasyonlannda da sırasıyla. denemenin 7 ve 9. günlerinde çok önemli (p<0.01) artışlar tesbit edildi. îdrar protein/kreatinin oranı denemenin 9. gününde çok önemli (p<0.01) artış gösterdi. Sodyum sulfanilat klirensi denemenin 1. gününden başlayarak artış gösterdi ve SS retensiyonundaki artış deneme boyunca devam etti. îdrar GGT akti vitesinde denemenin 7. "gününde çok önemli (p<0.01) artış belirlenirken, NAG ve ALP aktivitelerinde önemli farklılık gözlenmedi. GGT/KR (p<0.01), NAG/KR (p<0.01) ve ALP/KR (p<0.01) oranlannda ise sırasıyla denemenin 7. ve 13. günlerinde önemli artışlar gözlendi. Fosfor, Ca++, K+ ve Na+'un fraksiyonel klirenslerinde de sırasıyla denemenin 7., 9. ve 13. günlerinde çok önemli (p<0.01) artışlar tesbit edildi. Otopside, böbrekler ve perikapsüler dokuların solgun ve ödemli olduğu, bazı vakalarda böbrek kapsulasında yapışmalar ve böbrek etrafındaki yağ dokusunda jelatinöz atrofi tesbit edildi. Denemenin 11. günündeki histopatolojik incelemelerde, proksimal tubullerin nekroze olduğu ve hücrelerin sınırlan ile çekirdeklerinin tamamen ortadan kalktığı, tubuluslann şekilsiz, eozinofılik küçük granular yapıda kitlelerle dolu olduğu görüldü. Denemenin 12 ve 16. günlerindeki incelemelerde de benzer ve bazı vakalarda daha şiddetli histopatolojik bulgular gözlendi. Sonuç olarak, bu araştırmada gentamisin nefrotoksisitesinde meydana gelen tubuler hasarın belirlenmesinde en duyarlı indikatörün idrar GGT/KR oranı olduğu ve bunun çeşitli nedenlerden kaynaklanabilen tubuler hasarın belirlenmesinde kullanılabileceği kanısına varıldı.
" The Importance of Urinary Enzyme Activities in Dogs With Experimentally Induced Gentamicin Nephrotoxicity. " In this study, the importance of urinary enzyme activities and enzyme- creatinine rate which are the new diagnostic and prognostic procedures of acute renal diseases were investigated in the dogs with experimentally induced gentamicin nephrotoxicity using as a model of acute renal failure and, these parameters were compared with the other parameters which have been using in the diagnosis of renal diseases. Totally nine healthy and mature dogs were used in the study. Two of which were served as controls and remaining seven dogs were assigned to experimental group. Gentamicin sulphate was given to induce nephrotoxicity at the dose of 10 mg/kg body weight every 8 hours for 10 consecutive days. The samples of blood and urine were taken twice before the experiment and every other day during gentamicin injection and for 5 days after gentamicin injection was ceased. The samples of urine were taken by ultrasound guided cytocentesis, the samples of blood were taken by vacotainer tube. The N-acetyl-B-D-glocosaminidase (NAG), ^-glutamyl transterase (GGT) and Alkaline phosphatase (ALP) and creatinine (CR), total protein (TP), glucose (GLU) and electrolyte (Ca4-1", P+, Na+, K+) concentrations in the urine samples and blood urea nitrogen (BUN), total protein (TP), albumin (ALB), creatinine (SCR), glucose and electrolytes (C&++, P+, Na+, K+) concentrations in the blood samples were measured. Urine dip stick and microscopic examination of urine sediment were performed. Urine protein-creatinine rate and daily protein loss in urine were calculated. The fractionel clearences of electrolytes (Ca++, P+, Na+, K+) and glucose were determined. Sodium sulphanilate clearence was measured twice before the experiment and three times during the experiment. Daily clinical examination of all dogs were performed during the experiment. Autopsy and histopatologic examinations were performed in three dogs (1 control, 2 experimental group) on the 11th day of the experiment, two dogs were euthenasied due to uremic coma on the 12th day of the experiment and remaining dogs were necropsied at the end of the experiment. All dogs became ill on the 7th day and showed clinical symptoms of gentamicin nephrotoxicity (anorexia, lethargy, apathy, vomiting, abdominal pain and bloody diarrhea). These symptoms developed more severely by the time of the56 experiment. Two dogs showed the symptoms of uremic coma (salivation, vomiting, hyperpnea, seizure and diarrhea) on the 12th day of the experiment and were necropsied. Haematuria, proteinuria, glucosuria and granular casts in the microscopic examination of urine sediment were determined for the first time on the 8th day of the experiment. BUN, serum creatinine and P+ and K+ concentrations were significantly (p<0.01) increased on the 3rd, 9th and 13th days of the experiment respectively. Significant decreaments (p<0.01) in the serum albumin and Na+ concentrations were respectively determined on the 7th and 9th days of the experiment. Significant decreaments in urine CR (p<0.01), Na+ (p<0.01) and K+ (p<0.05) concenterations were observed on the 1st day of the experiment. Urine protein and glucose concentrations were significantly (p<0.01) increased on the 7th and 9th days of the experiment, respectively. Urine protein-creatinine (UP/UCR) rate was significantly (p<0.01) increased on the 9th day of the experiment. The sodium sulfanilate (SS) clearance increased from the 1st day of the experiment and S S retention increased by the time during the experiment. Significant increaments in the fractional clearances of P+, Ca"4-1", K+, and Na+ were respectively determined on the 7th, 9th and 1 3th days of the experiment. Wherease, urine GGT activities were found to be increased (p<0.01) on the 7th day of the experiment, urine NAG and ALP activities did not significantly increase. Significant increaments in the GGT/CR (p<0.01), NAG/CR (p<0.01) and ALP/CR (p<0.05) rates were observed respectively on the 7th and 13th days of the experiment. The kidneys and pericapsular tissues were pale and edematous at the necropsy. Adhesions and jelatinous atrophy around the renal capsule were determined in the some cases. Histological examination showed necrosis of proximal tubular epithelium with the disappearance of the nuclei and the tubular cell on the 1 1th day of the experiment. Tubules bizarre and filled with small eosinophilic granul formations. Similar and sometimes more severe lesions were evident on the 12th and 16th days of the experiment. In conclusion,GGT/CR rate wasfound to be the most sensitive and reliable indicator in the determination of renal tubular damage associated with gentamicin nephrotoxicity.
" The Importance of Urinary Enzyme Activities in Dogs With Experimentally Induced Gentamicin Nephrotoxicity. " In this study, the importance of urinary enzyme activities and enzyme- creatinine rate which are the new diagnostic and prognostic procedures of acute renal diseases were investigated in the dogs with experimentally induced gentamicin nephrotoxicity using as a model of acute renal failure and, these parameters were compared with the other parameters which have been using in the diagnosis of renal diseases. Totally nine healthy and mature dogs were used in the study. Two of which were served as controls and remaining seven dogs were assigned to experimental group. Gentamicin sulphate was given to induce nephrotoxicity at the dose of 10 mg/kg body weight every 8 hours for 10 consecutive days. The samples of blood and urine were taken twice before the experiment and every other day during gentamicin injection and for 5 days after gentamicin injection was ceased. The samples of urine were taken by ultrasound guided cytocentesis, the samples of blood were taken by vacotainer tube. The N-acetyl-B-D-glocosaminidase (NAG), ^-glutamyl transterase (GGT) and Alkaline phosphatase (ALP) and creatinine (CR), total protein (TP), glucose (GLU) and electrolyte (Ca4-1", P+, Na+, K+) concentrations in the urine samples and blood urea nitrogen (BUN), total protein (TP), albumin (ALB), creatinine (SCR), glucose and electrolytes (C&++, P+, Na+, K+) concentrations in the blood samples were measured. Urine dip stick and microscopic examination of urine sediment were performed. Urine protein-creatinine rate and daily protein loss in urine were calculated. The fractionel clearences of electrolytes (Ca++, P+, Na+, K+) and glucose were determined. Sodium sulphanilate clearence was measured twice before the experiment and three times during the experiment. Daily clinical examination of all dogs were performed during the experiment. Autopsy and histopatologic examinations were performed in three dogs (1 control, 2 experimental group) on the 11th day of the experiment, two dogs were euthenasied due to uremic coma on the 12th day of the experiment and remaining dogs were necropsied at the end of the experiment. All dogs became ill on the 7th day and showed clinical symptoms of gentamicin nephrotoxicity (anorexia, lethargy, apathy, vomiting, abdominal pain and bloody diarrhea). These symptoms developed more severely by the time of the56 experiment. Two dogs showed the symptoms of uremic coma (salivation, vomiting, hyperpnea, seizure and diarrhea) on the 12th day of the experiment and were necropsied. Haematuria, proteinuria, glucosuria and granular casts in the microscopic examination of urine sediment were determined for the first time on the 8th day of the experiment. BUN, serum creatinine and P+ and K+ concentrations were significantly (p<0.01) increased on the 3rd, 9th and 13th days of the experiment respectively. Significant decreaments (p<0.01) in the serum albumin and Na+ concentrations were respectively determined on the 7th and 9th days of the experiment. Significant decreaments in urine CR (p<0.01), Na+ (p<0.01) and K+ (p<0.05) concenterations were observed on the 1st day of the experiment. Urine protein and glucose concentrations were significantly (p<0.01) increased on the 7th and 9th days of the experiment, respectively. Urine protein-creatinine (UP/UCR) rate was significantly (p<0.01) increased on the 9th day of the experiment. The sodium sulfanilate (SS) clearance increased from the 1st day of the experiment and S S retention increased by the time during the experiment. Significant increaments in the fractional clearances of P+, Ca"4-1", K+, and Na+ were respectively determined on the 7th, 9th and 1 3th days of the experiment. Wherease, urine GGT activities were found to be increased (p<0.01) on the 7th day of the experiment, urine NAG and ALP activities did not significantly increase. Significant increaments in the GGT/CR (p<0.01), NAG/CR (p<0.01) and ALP/CR (p<0.05) rates were observed respectively on the 7th and 13th days of the experiment. The kidneys and pericapsular tissues were pale and edematous at the necropsy. Adhesions and jelatinous atrophy around the renal capsule were determined in the some cases. Histological examination showed necrosis of proximal tubular epithelium with the disappearance of the nuclei and the tubular cell on the 1 1th day of the experiment. Tubules bizarre and filled with small eosinophilic granul formations. Similar and sometimes more severe lesions were evident on the 12th and 16th days of the experiment. In conclusion,GGT/CR rate wasfound to be the most sensitive and reliable indicator in the determination of renal tubular damage associated with gentamicin nephrotoxicity.
Açıklama
Doktora
Anahtar Kelimeler
Veteriner Hekimliği, Veterinary Medicine
