Toxic effects of the non-steroidal anti-inflammatory drug diclofenac. Part II: cytological effects in liver, kidney, gills and intestine of rainbow trout (Oncorhynchus mykiss).

In the present study, cytopathology was investigated in the liver, kidney, gills and gut of rainbow trout (Oncorhynchus mykiss) exposed to five different concentrations (1, 5, 20, 100 and 500 microg/L) of the anti-inflammatory drug diclofenac under laboratory conditions. The lowest observed effect concentration (LOEC) for cytological alterations in liver, kidney and gills was 1 microg/L. In the gut, however, no diclofenac-induced cytopathology occurred. As the most prominent reactions induced by diclofenac (1) in the kidney, a severe accumulation of protein in the tubular cells (so called hyaline droplet degeneration), macrophage infiltration and structural alterations (dilation, vesiculation) of the endoplasmic reticulum (ER) in the proximal and distal renal tubules were observed. Furthermore, shortening of podocytes and their retraction from the basal lamina, a thickening of the basal lamina, the formation of desmosomes, and necrosis of endothelial cells in the renal corpuscles occurred; (2) in the liver, the most striking reactions were the collapse of the cellular compartmentation as well as the glycogen depletion of hepatocytes; (3) in the gills, pillar cell necrosis, hypertrophy of chloride cells, and epithelium lifting became evident in the secondary lamellae.

[1]  F. Wrestler,et al.  Diclofenac-associated hepatitis. , 1999, Southern medical journal.

[2]  T. Braunbeck.  Cytological alterations in fish hepatocytes following in vivo and in vitro sublethal exposure to xenobiotics — structural biomarkers of environmental contamination , 1998 .

[3]  Aleem Ahmed Khan,et al.  Diclofenac residues as the cause of vulture population decline in Pakistan , 2004, Nature.

[4]  R. Negele,et al.  Morphological effects of acute and chronic atrazine exposure in rainbow trout (Oncorhynchus mykiss) , 1991, Archives of environmental contamination and toxicology.

[5]  T. Révai,et al.  Nephrotic syndrome and acute interstitial nephritis associated with the use of diclofenac. , 1999, Wiener Klinische Wochenschrift.

[6]  T. Ternes,et al.  Pharmaceuticals and personal care products in the environment: agents of subtle change? , 1999, Environmental health perspectives.

[7]  R. Triebskorn,et al.  Brown trout Salmo trutta f. Fario liver ultrastructure as a biomarker for assessment of small stream pollution. , 1998 .

[8]  T. Braunbeck,et al.  Cytopathology of liver and kidney in rainbow trout Oncorhynchus mykiss after long-term exposure to sublethal concentrations of linuron , 1995 .

[9]  S. Adams,et al.  Induction of heat shock proteins, changes in liver ultrastructure, and alterations of fish behavior: are these biomarkers related and are they useful to reflect the state of pollution in the field? , 1997 .

[10]  H. R. Triebskorn.  Assessment of the cytotoxic impact of heavy metals on soil invertebrates using a protocol integrating qualitative and quantitative components. , 1998, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[11]  T. Ternes.  Vorkommen von Pharmaka in Gewässern , 2001 .

[12]  I. Singh.  A MODIFICATION OF THE MASSON-HAMPERL METHOD FOR STAINING OF ARGENTAFFIN CELLS. , 1964, Anatomischer Anzeiger.

[13]  R. Triebskorn,et al.  Ultrastructural changes in fish gills as biomarker to assess small stream pollution. , 1998, Tissue & cell.

[14]  T. Miyazaki,et al.  Gill lamellar pillar cell necrosis, a new birnavirus disease in Japanese eels. , 1999, Diseases of aquatic organisms.

[15]  R. Flower.  Non-steroidal anti-inflammatory drugs: back to the future. , 1999, Rheumatology.

[16]  E. Reynolds.  THE USE OF LEAD CITRATE AT HIGH pH AS AN ELECTRON-OPAQUE STAIN IN ELECTRON MICROSCOPY , 1963, The Journal of cell biology.

[17]  T. Ternes.  Occurrence of drugs in German sewage treatment plants and rivers 1 Dedicated to Professor Dr. Klaus , 1998 .

[18]  T. Braunbeck,et al.  Sex-specific reaction of liver ultrastructure in zebra fish (Brachydanio rerio) after prolonged sublethal exposure to 4-nitrophenol , 1989 .

[19]  J. Vane,et al.  Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. , 1971, Nature: New biology.

[20]  H. Segner,et al.  Nutrition-related histopathology of the intestine of milkfish Chanos chanos fry , 1986 .

[21]  J. Mallatt.  Fish Gill Structural Changes Induced by Toxicants and Other Irritants: A Statistical Review , 1985 .

[22]  K. Kümmerer.  Pharmaceuticals in the Environment , 2001 .

[23]  R. Hofer,et al.  The effects of treated domestic sewage on three organs (gills, kidney, liver) of brown trout (Salmo trutta) , 1993 .

[24]  H. Köhler,et al.  Plasticity of the endoplasmic reticulum in three cell types of slugs poisoned by molluscicides , 1992, Protoplasma.

[25]  J. Schwaiger,et al.  Toxic effects of the non-steroidal anti-inflammatory drug diclofenac. Part I: histopathological alterations and bioaccumulation in rainbow trout. , 2004, Aquatic toxicology.

[26]  F. Sacher,et al.  Pharmaceuticals in groundwaters analytical methods and results of a monitoring program in Baden-Württemberg, Germany. , 2001, Journal of chromatography. A.

[27]  R. Triebskorn,et al.  Ultrastructural biomarkers as tools to characterize the health status of fish in contaminated streams , 2001 .

[28]  T. Heberer,et al.  Occurrence and Distribution of Organic Contaminants in the Aquatic System in Berlin. Part I: Drug Residues and other Polar Contaminants in Berlin Surface and Groundwater , 1998 .