Effects of diclofenac sodium on renal parenchyma and prevention by vitamin-E in adult albino rats

To determine the preventive role of Vitamin E on renal parenchyma after given of Diclofenac Sodium in albino rats. Experimental Study This study was conducted in the Department of Anatomy Baqai Medical University and Muhammad Medical College, Mirpurkhas from June 2011 to November 2011, For this experimental study, 30 albino rats were taken. They were divided into three groups ; A, B and C. The animals in group-A given normal saline 10 ml/kg per day. Group-B received diclofenac sodium 2 mg/kg per day and group-C receives diclofenac sodium 2mg/kg/day dissolved in distilled water with vitamin-E 2 mg/kg/day dissolved in olive oil administered half an hour before the diclofenac sodium by feeding tube per day for 2 weeks. On day 15 all animals were sacrificed with deep ether anesthesia. Their kidneys were removed, fixed in 10% formalin. Representative blocks were taken and embedded in liquid paraffin. For routine histological examination 5 micro m thick section cut by microtome and stained with H and E, PAS and silver methenamine. Renal histology was done under light microscope to see the proximal and distal tubular diameter and count. No significant [P>0.05] changes were observed in the histopathology of kidney tissues of the groups A and C rats. The group B significantly [P<0.001] affected the histopathology of kidney. It may be concluded that diclofenac sodium produces changes in kidney, which may be attributed to ischaemia induced by inhibition of prostaglandin synthesis resulting in tubular necrosis in albino rats simultaneous administration of vitamin-E partially protect the morphological and histological changes induced by diclofenac sodium

Effect of endogenous hydrogen sulfide inhibition on structural and functional renal disturbances induced by gentamicin

Animal models of gentamicin nephrotoxicity present acute tubular necrosis associated with inflammation, which can contribute to intensify the renal damage. Hydrogen sulfide (H2S) is a signaling molecule involved in inflammation. We evaluated the effect of DL-propargylglycine (PAG), an inhibitor of endogenous H2S formation, on the renal damage induced by gentamicin. Male Wistar rats (N = 8) were injected with 40 mg/kg gentamicin (im) twice a day for 9 days, some of them also received PAG (N = 8, 10 mg·kg-1·day-1, ip). Control rats (N = 6) were treated with saline or PAG only (N = 4). Twenty-four-hour urine samples were collected one day after the end of these treatments, blood samples were collected, the animals were sacrificed, and the kidneys were removed for quantification of H2S formation and histological and immunohistochemical studies. Gentamicin-treated rats presented higher sodium and potassium fractional excretion, increased plasma creatinine [4.06 (3.00; 5.87) mg percent] and urea levels, a greater number of macrophages/monocytes, and a higher score for tubular interstitial lesions [3.50 (3.00; 4.00)] in the renal cortex. These changes were associated with increased H2S formation in the kidneys from gentamicin-treated rats (230.60 ± 38.62 µg·mg protein-1·h-1) compared to control (21.12 ± 1.63) and PAG (11.44 ± 3.08). Treatment with PAG reduced this increase (171.60 ± 18.34), the disturbances in plasma creatinine levels [2.20 (1.92; 4.60) mg percent], macrophage infiltration, and score for tubular interstitial lesions [2.00 (2.00; 3.00)]. However, PAG did not interfere with the increase in fractional sodium excretion provoked by gentamicin. The protective effect of PAG on gentamicin nephrotoxicity was related, at least in part, to decreased H2S formation.

Consumo de fumonisinas y daños a la salud humana / Fumonisin intake and human health

Las fumonisinas son una familia de micotoxinas que contaminan al maíz, alteran el metabolismo de los esfingolípidos y del folato, se asocian con defectos del tubo neural y están catalogadas por la Agencia Internacional de Investigación en Cáncer (IARC por sus siglas en inglés) como posibles carcinógenos humanos. Debido a que en México los derivados de maíz constituyen una parte importante de la dieta y existe alta prevalencia de población genéticamente susceptible a la deficiencia de folato, en este ensayo se presentan las evidencias mundiales y nacionales de la exposición a fumonisinas y la relevancia que para México representa la evaluación de esta exposición.

Fumonisins are mycotoxins that contaminate maize, disrupt the folate and sphingolipid metabolism, are associated with neural tube defects, and are considered by the International Agency for Research on Cancer (IARC) as possible human carcinogens. Since maize-based foods are significant components of the Mexican diet and there is a high prevalence of genetic susceptibility for folate deficiency among Mexicans, this essay presents international and national evidence of fumonisin exposure and the relevance that such exposure represents for Mexico.

Therapeutic dose of acetaminophen with fatal hepatic necrosis and acute renal failure.

A 33-year-old woman without evidence of previous liver disease developed fulminant hepatic failure following the therapeutic dose of acetaminophen 3 days prior to admission. At admission, liver and renal function revealed hepatocellular injury with jaundice, and acute renal failure, total serum bilirubin 12.5 mg/ dL, direct serum bilirubin 8.1 mg/dL, aspartate aminotransferase 8460 IU/L, alanine aminotransferase 4640 IU/L, blood urea nitrogen 36 mg/dL, and serum creatinine 5.2 mg/dL. Two days later she developed multiorgan failure including hemodynamic disturbance with irreversible shock, and expired. Autopsy was performed, liver pathology showed severe centrilobular and midzonal necrosis, compatible with toxic hepatic necrosis, and renal pathology showed focal loss of tubular epithelial cells and partial occlusion of tubular lumen by cellular debris, compatible with acute tubular necrosis. Physicians should be aware of potential hepatotoxicity and nephrotoxicity of acetaminophen, even if given at therapeutic dosage in acute febrile illness.

Increased expression of p38 mitogen- activated protein kinase is related to the acute renal lesions induced by gentamicin

Mitogen-activated protein kinases (MAPK) may be involved in the pathogenesis of acute renal failure. This study investigated the expression of p-p38 MAPK and nuclear factor kappa B (NF-kappaB) in the renal cortex of rats treated with gentamicin. Twenty rats were injected with gentamicin, 40 mg/kg, im, twice a day for 9 days, 20 with gentamicin + pyrrolidine dithiocarbamate (PDTC, an NF-kappaB inhibitor), 14 with 0.15 M NaCl, im, twice a day for 9 days, and 14 with 0.15 M NaCl , im, twice a day for 9 days and PDTC, 50 mg kg-1 day-1, ip, twice a day for 15 days. The animals were killed 5 and 30 days after the last of the injections and the kidneys were removed for histological, immunohistochemical and Western blot analysis and for nitrate determination. The results of the immunohistochemical study were evaluated by counting the p-p38 MAPK-positive cells per area of renal cortex measuring 0.05 mm². Creatinine was measured by the Jaffé method in blood samples collected 5 and 30 days after the end of the treatments. Gentamicin-treated rats presented a transitory increase in plasma creatinine levels. In addition, animals killed 5 days after the end of gentamicin treatment presented acute tubular necrosis and increased nitrate levels in the renal cortex. Increased expression of p-p38 MAPK and NF-kappaB was also observed in the kidneys from these animals. The animals killed 30 days after gentamicin treatment showed residual areas of interstitial fibrosis in the renal cortex, although the expression of p-p38 MAPK in their kidneys did not differ from control. Treatment with PDTC reduced the functional and structural changes induced by gentamicin as well as the expression of p-p38 MAPK and NF-kappaB. The increased expression of p-p38 MAPK and NF-kappaB observed in these rats suggests that these signaling molecules may be involved in the pathogenesis of tubulointerstitial nephritis induced by gentamicin.

Riñón y medicamentos / Kidney and drugs

El riñón tiene un rol muy importante en la excreción de los medicamentos y de sus metabolitos, muchos de los cuales provocan alteraciones de la función renal o daño de sus diversas estructuras (glomérulos, túbulos, intersticio). las alteraciones producidas pueden ser agudos y reversibles o crónicas. Los medicamentos que tienen más efectos adversos sobre el riñón son los analgésicos (paracetamol) y antiinflamatorios, los medios de contraste yodados, los inhibidores de la enzima de conversión de la angiotensina, los aminoglicósidos (gentamicina), la ciclosporina y las sales de oro. La administración de estos medicamentos, potencialmente nefrotóxicos requiere de prudencia, especialmente en los ancianos y portadores de daños renales previos (diabéticos, hipertensos, etc.) y de controles seriados de orina y creatininemia

Renal dysfunction in patients of kala azar treated with sodium antimony gluconate.

We studied 27 patients presenting with renal dysfunction after Stibamate therapy. Eighteen patients were proved cases of Kala Azar, others of PUO. Out of 10 cases in whom Kidney biopsy was done, 6 had tubular necrosis, one had mild mesangial proliferation and 3 had normal picture.

Clinicopathological study of acute renal failure following viperine snake bite.

Fifty patients of acute renal failure following Viperine snake bite were studied. Oliguria (100%), local swelling (48%) and bleeding tendencies (42%) were the predominant clinical features encountered. Of the 25 patients in whom detailed coagulation studies were done, 24 patients had disseminated intravascular coagulation (DIC) and 1 had primary fibrinolysis. DIC was commoner with Russell's viper bite (62%) in comparison to Echis carinatus bites (40%). Renal histology obtained in 29 cases revealed tubular necrosis (35%), cortical necrosis (24%) tubular degeneration (17%) and glomerular changes (17%). Ballooning of glomerular capillaries (59%), splitting of glomerular basement membrane (40.7%), swelling of endothelial cells (29.6%), and focal proliferation of mesangial cells (17%) were the significant glomerular changes encountered. 20 (40%) patients succumbed, DIC (50%), irreversible shock (30%) and septicaemia (20%) being the immediate causes of death. Development of oliguria within 24 hours of snake bite and cortical necrosis were associated with higher mortality.

Uranyl Nitrate Induced Polyuric Acute Tubular Necrosis in Rats

We investigated the pathobiological course of uranyl nitrate (UN) induced polyuric acute tubular necrosis (ATN) in male Sprague Dawley rats. UN (5mg/kg 15mg/kg and 3Omg/kg) in 5% NaHCO3 induced weight loss, polydipsia, and polyuria 24 hrs after injection when compared to the controls which were treated with 5% NaHCO3 only. Twenty four hours following the injection of UN, serum creatinine and blood urea nitrogen levels had increased. These changes continued for at least 72 hours, although the concentration of uranium had decreased. Light microscopic studies conducted 24 hours after injection, revealed partial degeneration and necrosis of the proximal tubules and many casts m the distal convoluted tubules. These changes progressed for 72 hours. Despite this tubular damage, the glomeruli were relatively intact. 5 days after injection, the epithelial cells lining the proximal tubules displayed regenerative activities; these findings were more prominent after 10 days. Through electron microscopic examination, we observed the destruction of mitochondria in the proximal tubular cells, a possible cause of polyuria. Ten days post injection regenerative activities in the proximal tubular cells showed that the maturation of intracellular organelles followed the proliferation of the premature cells.

Studies on djenkol bean poisoning (djenkolism) in experimental animals.

Djenkolic acid was extracted from djenkol beans with 70% ethanol and water and was quantitatively determined by paper chromatography. Djenkol beans contained 0.3-1.3 gm% djenkolic acid and about 93% of this acid occurred in the free state. The toxicity of djenkol beans was studied in 5 rhesus monkeys, 9 albino rats and 22 mice fed with 70% ethanol extracts. The total urinary output decreased. There was an increase in specific gravity of the urine during the period of feeding monkeys with djenkol beans. Urinary samples of the experimental animals were turbid and contained some red cells, white cells, epithelial cells, albumin and amorphous particles. One of 22 mice excreted sharp needle-shaped crystals in the urine on day 3 after feeding. Histological examination of kidneys of rats and mice showed mild to severe acute tubular necrosis with some glomerular cell necrosis.