Ochratoxin A and Citrinin Induced Nephrosis in Beagle Dogs I. Clinical and Clinicopathological Features

Abstract

Ind .A bs t rac t. O chrato xin A a nd cit rinin , bo th m ycot o xins , were give n se para te ly a nd co m bi ne d to yo ung Be agle d ogs for 14 days . O chra tox in A. 0 . 1 a nd 0 .2 mg/ kg , was give n by ca ps u le . a nd citr in in . 5 a nd 10 mg/ kg , was di ssol ved in e tha no l a nd give n by in tr ap erit on e a l inj e cti on . C lin ica l signs o f to xicosis in do gs g ive n 10 mg/k g citrin in a nd th e high er co mb ine d do se s included an o re xia . re tc hi ng . tene smus . wei ght lo ss . p ro stra tio n a nd d ea th. Sev e rit y o f the clinical di se ase a nd mo rt al ity were increase d wh e n the myco to xins were combin ed . w hich ind icat ed sy ne rgism . The cli n icop a th ol o gica l a h no rmali ties refl e cted ren al d a m age . in th a t gluta m ic o xa loace t ic tr a nsa mi na se a nd lacti c de hydroge nas e incre ased in the urine o f th e dogs w ith clin ical sig ns o f po iso ni ng . Se ru m lact ic deh yd ro gen a se wa s incr e ased in d ogs give n 10 mg/k g citrin in . Ce llula r a nd g ra n ula r cas ts . ket on e s . prot ei n a nd g lucose were in th e urin e of dogs give n la rge d oses of citrinin a lo ne o r co m bine d with ochra tox in A . Se r u m co nce ntra t io ns o f so d ium, pot a ssiu m a nd chlo ride decreased in th e dogs give n high do ses o f e ac h g ro u p . Natura lly oc cur r ing a nd expe rime n ta l a fla tox icosis ha ve be e n repo rte d in dogs a nd ca lle d he patit is " X " 13 , 3 3 , 34 , 39 J. Th e d ise ase a lso occ urs natu ra lly in swine a nd has be en re prod uce d ex peri me nta lly [9 , 11 , 28 ].D ogs a re ex tre me ly se ns itive to a flato xins a nd re cent reports ind ica te that yo ung dogs a re eve n mo re s us ce ptible to a no the r fu nga l toxin , oc h ratox in A [3 5J .O chra tox in A give n a t d o se s of 0.3-3 .0 mgjk g wa s primar ily ne ph ro to xic in t he do g a nd re na l da mage wa s refle cted by gran ula r ca st s , increa sed co nce nt ra tio ns of p rot ei n a nd gluc ose and e le va te d lact ic de hydrogen ase a nd gluta m ic o xa loace tic tra nsa m in ase in th e u rine [3 5J . The se ve rity o f ren a l lesio ns a p pea re d to be d ose re la ted .Ci tr in in , a no t he r mycot o xin , has be en fo u nd to xic to se ve ra l a nima l spe cies 11,2 ] a nd is a mod erat e nephroto xin wh en give n a t 20 a nd 40 mgjk g in th e d og , b ut not as potent as ochra tox in A [ 10 , 35 ]. Wh en citrin in was g ive n intrape ri ton e all y to yo ung Be ag le d ogs , ev ide nce o f ren a l d a m age included excess ive b loo d ur e a nitro gen , gluc os uria, pr o te in uri a , lo w uri nary spec ific gra vity , incr e a sed la ctic de hydroge na se , glu ta m ic o xa loace t ic tra nsa m inas e a nd iso citric d e hydrogen a se a nd g ran ula r ca sts in the urin a ry se d ime n t. T here were e mes is a nd int estin al intu ssus-154

Occurrence of mycotoxins in extruded commercial dog food

“…Several studies conducted in the past on Beagles showed that OTA was lethal in daily doses of 200 g/kg of BW for 2 weeks or in a single dose of 7.8 mg/kg of BW (Szczech et al, 1973). Symptoms such as anorexia, weight loss, vomiting, tenesmus, hemorrhagic diarrhea, dehydration and prostration have also been observed in dogs that had been exposed to this mycotoxin, again for 2 weeks, in doses of between 0.2 and 30 mg/kg of BW (Kitchen et al, 1977).…”

Outbreaks of Renal Failure Associated with Melamine and Cyanuric Acid in Dogs and Cats in 2004 and 2007

“…8 Although citrinin nephrotoxicity might involve the proximal and distal tubule in dogs, 8 citrinin is primarily a proximal tubular intoxicant 9 and has been associated with clinicopathologic evidence of hepatic injury. 7 The authors are not aware of any association of either of these toxins with the presence of unique intrarenal or urinary crystals or uroliths.…”

Ochratoxin A and Citrinin Induced Nephrosis in Beagle Dogs II. Pathology

“…Dogs given ochratoxin A had necrosis of lymphoid tissues in the spleen, tonsil, thymus, peripheral lymph nodes and lymph nodules of the ileum, colon and rectum. There was ulceration of the mucosa of the intestine in dogs given large combined doses of ochratoxin A and citrinin.The clinical and clinicopathologic features of the mycotoxicoses produced in Beagle dogs by administration of ochratoxin A and citrinin alone and in combination have been described [13]. Pathologic changes induced by ochratoxin A in several species including the rat [19, 20, 23, 24, 27, 281, pig [14][15][16] 251 [22, 271, chick [6, 10, 211 and hen [4] have been described.…”

“…The clinical and clinicopathologic features of the mycotoxicoses produced in Beagle dogs by administration of ochratoxin A and citrinin alone and in combination have been described [13]. Pathologic changes induced by ochratoxin A in several species including the rat [19, 20, 23, 24, 27, 281, pig [14][15][16]251, rainbow trout [9], dog [26], duckling [22, 271, chick [6,10,211 and hen [4] have been described.…”