Cases of karyomegaly were described by Sclare30 and by Mihatch31 in patients affected with tubular-interstitial nephropathy. The Karyomegalic cells showed enlarged nuclei with accumulation of genetic material. No aetiology was suggested.
Our study of rats experimentally intoxicated by ochratoxin A, a well-known nephrotoxic compound, indicates the presence of karyomegaly with alteration of the tubular tissue. In control animals no karyomegalic cells were detected. These observations suggest that karyomegaly with megacytosis may be caused by the nephrotoxic ochratoxin A in the kidney.
In addition abnormal mitosis together with karyomegalic cells were observed at an earlier stage of the intoxication (30 days) suggesting possible regeneration if the OTA insults are stopped.
After 90 days of treatment, the degeneration increased and only karyomegalic and apoptotic-like cells were observed indicating that the regeneration no longer occurs and that the degeneration becomes irreversible.
Van der Merwe KJ et al. A toxic metabolite produced by Aspergillus ochraceus . Nature1965; 205: 1112-1113 .
2.
Bauer J , Gareis M . Ochratoxin A in the food chain . Z. Veterinärmed. B. 1987; 34: 613-627 .
3.
Krogh P . Ochratoxins in food, In: P. Krogh (Ed.), Mycotoxin in food. New York: Academic Press . 1987, pp 97-121.
4.
Kuiper-Goodman T , Scott PM . Risk assessment of the mycotoxin ochratoxin A . Biomed. Environ. Sci. 1989; 2: 179-248 .
5.
Breitholtz A , Olsen M , Dahlback A , Hult K . Plasma ochratoxin A levels in three Swedish populations surveyed using an ion-pair HPLC technique . Food Add. Cont. 1991; 8/2: 183-192 .
6.
CreppyEE et al. Etude de l'ochratoxicose humaine dans trois régions de France: Alsace, Aquitaine, Rhône-Alpes, In: Creppy EE , Castegnaro M , Dirheimer G (Eds.). Human ochratoxicosis and its pathologies, INSERM/John Libbey EUROTEXT, Paris , 1993; pp 147-158.
7.
Hadidane R et al. Correlation between alimentary mycotoxin contamination and specific diseases . Hum. Toxicol. 1985; 4: 491-511 .
8.
BachaH et al. In: Creppy EE , Castegnaro M , Dirheimer G (Eds.). Human ochratoxicosis and its pathologies, INSERM/John Libbey EUROTEXT, Paris , 1993; pp 111-121.
9.
Maaroufi K et al. Ochratoxins in human blood and nephropathy in Tunisia . Human Exp. Toxicol. 1995; 14: 609-615 .
10.
Krogh P et al. Experimental porcine nephropathy changes of renal function and structure induced by Ochratoxin A-contaminated feed . Acta Pathol. Microbiol. Scand., section A, Suppl. 1974; 246: 1-21 .
11.
Kane A , Creppy EE , Röschenthaler R , Dirheimer G . Changes in urinary and renal tubular enzymes caused by subchronic administration of ochratoxin Ainrats . Toxicology1986; 42: 233-243 .
12.
Boorman G. NTP technical Report on the Toxicology and Carcinogenesis Studies of ochratoxin A (CAS No 303-47-9) In F 344/N Rats (Gavage Studies), US. Department of Health and Human Services, National Institutes of Health, Research Triangle Park, NC, NIH Publication 89/ 2813 1989.
13.
Krogh P , Hald B , Plestina R , Ceovic S . Balkan Endemic Nephropathy and foodborn ochratoxin A: preliminary results of survey of foodstuffs . Acta. Pathol. Microbiol. Scand. 1977; 85: 238-240 .
14.
Chernozemsky IN et al. Geographic correlation between the occurrence of endemic nephropathy and urinary tract tumours in Vratza district . Bulgaria J. Cancer. 1977; 19: 1-11 .
15.
Achour A et al.Néphropathies interstitielles chroniques. Approches cliniques et étiologiques: Ochratoxine A, In: Creppy EE , Castegnaro M and Dirheimer G (Eds.), Human ochratoxicosis and its pathologies. INSERM/John Libbey EUROTEXT, Paris , 1993 pp 227-234.
16.
Maaroufi K et al. Foodstuffs and human blood contamination by the mycotoxin ochratoxin A: correlation with chronic interstitial nephropathy in Tunisia . Arch. Toxicol. 1995; 69: 552-558 .
17.
Krogh P , Hald B , Plestina R , Ceovic S . Balkan endemic nephropathy and foodborn ochratoxin A: Preliminary results of survey of foodstuffs . Acta Pathol. Microbiol. Scand. Sect. B1985; 85: 238-240 .
18.
Creppy EE et al. Genotoxicity of ochratoxin A in mice: DNA single-strand break evaluation in spleen, liver and kidney . Toxicol. Letters1985; 28: 29-35 .
19.
Kane A et al. Distribution of the [3H]-label from low doses of radioactive ochratoxin A ingested by rats, and evidence for DNA single-strand breaks caused in liver and kidneys . Arch. Toxicol. 1986; 58: 219-224 .
20.
Pfohl-Leszkowicz A et al. Differential DNA-adduct formation and disappearance in three mice tissues after treatment by the mycotoxin ochratoxin A . Mutat. Res. 1993; 289: 265-273 .
21.
Maaroufi K et al. Génotoxicité de l'ochratoxine A, relation avec la tumeur rénale . Archives de l'Institut Pasteur1994; 71: 21-31 .
22.
Seegers JC et al. A comparative study of ochratoxin A-induced apoptosis in Hamster Kidney and Hela cells . Toxicol. Applied Pharmacol. 1994; 129: 1-11 .
23.
Baudrimont I. Variation de la néphrotoxicitéde l'ochratoxine A sous l'effet de facteurs métaboliques et non métaboliques. PhD Thesis (No 2) 1995, University Bordeaux 2, France.
24.
Godin M et al. Karyomegalic interstitial nephritis . Am.J.KidneyDis. 1996; 27: 166-166 .
25.
Mantle PG et al. Penicillium aurantiogriseuminduced, persistent renal histopathological changes in rats; an experimental model for Balkan Endemic Nephropathy competitive with ochratoxin A. In: Castegnaro M , Plestina R , Dirheimer G , Chernozemsky IN , Bartsch H (Eds.), Mycotoxins, Endemic Nephropathy and Urinary tract tumours, IARC Scientific Publications vol. 115, Lyon , 1991; pp 119-127.
26.
Hard GC , Greig JB . Comparative acute nephrotoxicity of Penicillium aurantiogriseum in rats and hamsters, In: Castegnaro M , Plestina R , Dirheimer G , Chernozemsky IN , Bartsch H (Eds.), Mycotoxins, Endemic Nephropathy and Urinary tract tumours, IARC Scientific Publications vol. 115, Lyon , 1991; pp 113-117.
27.
Gad SC , Neil CS . Statistic for toxicologists. In: Principles and Methods of Toxicology, 1982; pp 273-279.
28.
Baudrimont I et al. Effect of superoxide dismutase and catalase on the nephrotoxicity induced by subchronical administration of ochratoxin A in rats . Toxicology1994; 89: 101-111 .
29.
Harwig J , Kuiper-Goodman T , Scott PM . Microbial food toxicants, In: Rechcigl M (Ed.), Ochratoxins, Handbook of Food-borne Diseases of Biological Origin, Boca Raton, CRC Press , 1983; pp 193-238.
30.
Sclare G . A case of unexplained karyomegaly . Beitr. Pathol. 1976; 157: 301-306 .
31.
Mihatsch MJ et al. Systemic karyomegaly associated with chronic interstitial nephritis. A new disease entity?Clin. Nephrol. 1979; 12: 54-62 .
32.
Spoendlin M et al. Karyomegalic Interstitial Nephritis: further support for a distinct entity and evidence for a genetic defect . Am. J. Kidney Dis. 1995; 25: 242-252 .
