Following a field outbreak of hepatogenous photosensitivity in sheep, an identical condition was reproduced experimentally by dosing 2 sheep with green, homogenized, Nidorella foetida material, collected from the camp where the outbreak occurred. This is a rare, unpalatable, aromatic shrub found in swampy places in the south-western Cape Province. The main lesion was a hepatosis, characterized by peripheral coagulative necrosis and midzonal degeneration in the 2 acute cases and mild bile duct proliferation and hepatic regeneration in the more chronic field case. Botanical, toxicological, clinical and pathological data are given.The articles have been scanned in colour with a HP Scanjet 5590; 600dpi. 
Adobe Acrobat XI Pro was used to OCR the text and also for the merging and conversion to the final presentation PDF-format.lmchunu2014mn201

Collett, M.G.

Green, Jennifer R.

Schneider, D.J.

The articles have been scanned in colour with a HP Scanjet 5590; 600dpi. 
Adobe Acrobat XI Pro was used to OCR the text and also for the merging and conversion to the final presentation PDF-format.Following a field outbreak of hepatogenous photosensitivity in sheep, an identical condition was reproduced experimentally by dosing 2 sheep with green, homogenized, Nidorella foetida material, collected from the camp where the outbreak occurred. This is a rare, unpalatable, aromatic shrub found in swampy places in the south-western Cape Province. The main lesion was a hepatosis, characterized by peripheral coagulative necrosis and midzonal degeneration in the 2 acute cases and mild bile duct proliferation and hepatic regeneration in the more chronic field case. Botanical, toxicological, clinical and pathological data are given.lmchunu2014mn201

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Onderstepoort J. vet. Res .• 54; 53-57 (1987) OVINE HEPATOGENOUS PHOTOSENSITIVITY CAUSED BY THE PLANT NIDORELLA FOETIDA (THUNB.) DC. (ASTERACEAE) D. J. SCHNEIDER<I), JENNIFER R. GREEN°> and M. G. COLLE1!<2> ABSTRACT SCHNEIDER, D. J., GREEN, JENNIFER R. & COLLE1T, M.G., 1987. Ovine hepatogenous photosen-sitivity caused by the plant Nidorellafoetida (lbunb.) DC (Asteraceae). Onderstepoort Journal of Veterinary Research, 54, 53-57 (1987) · , Following a field outbreak of hepatogenous photosensitivity in sheep, an identical condition was repro-duced experimentally by dosing 2 sheep with green, homogenized, Nidorella foetida material, collected from the camp where the outbreak occurred. This is a rare, unpalatable, aromatic shrub found in swampy places in the south-western Cape Province. The main lesion was a hepatosis, characterized by peripheral coagulative necrosis and midzonal degeneration in the 2 acute cases and mird bile duct proliferation and hepatic regeneration in the more chronic field case. Botanical, toxicological, clinical and pathological data are given. INTRODUCTION Many hapatotoxic plants, among them a fungus and an alga, are known to cause liver dama$e when ingested by sheep and cattle in South Africa. Potsonings by some of these hepatotoxic agents are frequently assoctated with photosensitivity, usually in less acute cases (Steyn 1949; Marasas, Adelaar, Kellerman, Mione, Van Rensburg & Burroughs, 1972; Kellerman, Basson, Naude, Van Rensburg & Weiman, 1973; Coetzer & Bergh, 1983; Kellerman, Coetzer, Schneider & Weiman, 198"3). Although the aetiotogies of most forms of hepatoge-nous intoxications are known, a few remain unresolved, and without identification the causative agents of the latter no rational control measures can be implemented in these cases. This is the first report of ovine hepatogenous photo-sensitivity caused by Nidorellafoetida. HISTORY OF THE FIELD OUTBREAK Ovine hepatogenous photosensitivity of unknown ae-tiology occurred during 1983 in a 30 ha camp on a farm in the Durbanville District near Cape Town. On 20 March 1985, 15 out of 300 South African Mut-ton Merino sheep from 9 months to 4 years of age were found to be photosensitive 5 days after having been placed in the camp. The grazing consisted of dry wheat stubble with Cynodon dactylon (L.) Pers. along the bor-ders. Apart from a few dry, well-known, unpalatable shrubs growing along one fence, a patch of green N. foetida shrubs was present in a localized moist area in a dry waterway. Most of the accessable Nidorella plants had been freshly grazed by the sheep. All the sheep were taken out of the camp on 20 March 1985 and the 15 affected sheep were stabled. One large sack of fresh N. foetida plants was collected from the camp and taken to the Regional Veterinary Laboratory, Stellenbosch, for botanical identification and toxicity tri-als. The plant was identified by the Government Herbar-ium, Stellenbosch, as Nidorellafoetida (Thunb.) DC. DESCRIPTION, DISTRIBUTION AND EcOLOGY OF THE PLANT Family Asteraceae ( Compositae). Name Nidorellafoetida (Thunb.) DC. Description (Fig. l-3) Ol Regional Veterinary Laboratory, Private Bag X5020, Stellenbosch 7600 <2l Depanment of Pathology, Faculty of Veterinary Science, P.O. Box 12580, Onderstepoort 0110 Received 21 October 198&-Editor 53 A branched, erect, hairy perennial, slightly woody at the base. Height up to about 1 m. 'Leaves' bright-green, often tufted, linear-spathulate, obtuse, covered with short glands mingled with coarse hairs. 'Capitula' yel-lowish, rather small, densely corymbose. 'Involucral bracts' imbricate, oblong mucronate, raised and hairy in the middle and with a scarious, gland-fringed margin. The transition from marginal to central flowers gradual, the sterile central flowers having a more conspicuous corolla than the remainder. 'Flowering time' from January to October (Adamson & Salter, 1950; Weiman, Wilhelmina G., 1986. Botanical Research Institute, Pri-vateBagXlOl, PretoriaOOOl pers. com.) Distribution The plant is rather rare and is found only in the south-western Cape Province. There it has been found in Coastal Renosterveld and West Coast Strandveld and has been recorded in the following districts: Llandudno, Wynberg, Simon's Town, Camps Bay, Bredasdo~, Somerset Strand, Velddrif, Uilskraalmond and Hangkltp (Weiman, Wilhelmina G., 1986. Botanical Research Institute, Pretoria pers. com.) Eleven Nidorella spp. are described in South Africa (Gibbs Russell, G. E. and the staff of the National Her-barium, 1984) with 3 occurring in the winter rainfall area (Moffett, R. 0., Government Herbarium, P. 0. Box 4 71 , Stellenbosch 7600 pers. com.) Habitat N. foetida is usually found in full sun, near water, in marshy or seasonally marshy ground, often growing with reeds. It is found m a winter rainfall area, measuring 25~500 mm rain per annum, at an altitude between 3 and 170m. MATERIALS AND METHODS Field outbreak Blood samples for chemical pathological determi-nations (Table 2) were collected on 20 March 1985 from 4 of the 15 affected sheep. Eight days later another of the affected sheep (No. 8), 9 months old, was taken to the Regional Veterinary Laboratory, Stellenbosch. A blood sample was collected and the animal killed and autop-sied. Tissue specimens of liver, gall bladder, kidney, spleen, heart and affected skin were placed for fixation in 10 % buffered formalin and processed for light mi-croscopy. A representative pasture sample from this camp, mainly wheat stubble and C. dactylon, was collected and · examined for Pitlwmyces chartarum (Berk. & Curt.) M. B. Ellis, spores, as described by Di Menna & Bailey, 1973. OVINE HEPATOGENOUS PHOTOSENSITIVITY CAUSED BY THE PLANT NIDOREUA FOEflDA FIG. 1-3 NidorelWfoetida 3 Toxicity tests in sheep The green parts of theN. foetida plant material col-. lected during the outbreak were stripped off the woody stems, homogenized with water in a blender and dosed by stomach tube to 2 sheep (Nos. 1 and 2), as summa-rized in Table 1. The following routine chemical pathological deter-minations were done daily for the duration of the experi-ment on the sera of the 2 sheep that had received the plant material, as well as on I control sheep (No. 3): gamma-glutamyl transferase (GGT), aspartate transami-nase (AST) and total bilirubin (T Br). The 3 animals were young South African Mutton Merino sheep, kept in a camp containing green kikuyu grass (Pennisetum clan-destinum Hochst. ex chiov) pasture and were examined 3 times a day. No shade was present or provided in the camp, and during the day they were exposed to the maxi-mum sunlight. Autopsies on Sheep 1 and 2 were performed following death or euthanasia by exsanguination (Table 1). Se-lected tissue specimens of liver, kidney, heart and spleen TABLE I Toxicity of green homogenizedNidorellafoetida to sheep Age Mass Dose Sheep Sex No. (months) (kg) (glkg x n) I M 10 28 5 X 2 2 M 12 35 2,5 X l M= Male glkg x n = Dose x number of daily administrations 2 4 FIG. 4 Very early stage of photosensitivity in Sheep 2 from both, as well as skin and gall bladder from S~eep 2, were collected, fixed in 10 % buffered formahn and processed for microscopy . Clinical signs Field outbreak REsULTS The 15 affected sheep examined on 20 March 1985 all had swollen ears, eyehds and lips, with serious exuda-tion on the skin of some of the most severely affected areas. Icteric mucous membranes and coronites, as manifested by hyperaemia of the skin of the coronet, was seen in most of these animals. The sheep were placed in a stable, fed oat and lucerne hay and examined again 8 days later. Although they all survived, there was a marked drop in body mass. The swellings had subsided, but dark-brown scabs and crusts covered the affected skin areas (Fig. 5) and icterus was no longer visible in the mucous membranes of the live animals. Period Total Duration Signs of of dosed dose experiment photo- Fate days g (days) sensitivity I 280 I - Died 5 437,5 5 + Killed - = No signs of photosensitivity + = Photosensitivity present 54 FIG. 5 Sheep from field outbreak (Sheep 8) 9 days after initial signs of photosensitivity were seen FIG. 7 Yellowish-brown liver with accentuated lobulation and a few small haemorrhages of Sheep 2 TABLE 2 Chemical pathological findings in the blood of 5 sheep from the field outbreak Sheep No. Date GGT AST Total bilirubin 4 85/03/20 112 Not available 137,6 5 85/03/20 103 Not available 84,0 6 85/03120 150 Not available 59,6 7 85/03120 86 Not available 132,8 8• 85/03128 128 137 29,3 • This blood specimen was collected from 1 sheep from a field out-break and brought to the laboratory for autopsy 8 days after the sheep had been taken out of the toxic camp TABLE 3 Chemical pathological changes in the blood of sheep dosed with green Nidorel/afoetida plant material Sheep Days after GGT AST Total Date be~inning of ip.J€ at ip.J€ at bilirubin No. dosmg regime 25•c 25•c JLmoV€ 1 85103/21 - 28 43 4,6 85/03/22 1 73 178 111 ,0 2 85/03/25 - 25 20 1,9 85/03/26 1 92 178 28,4 85/03/27 2 97 178 75,4 85/03/28 3 92 178 84,6 85/03/29 4 77 178 90,0 3• 85/03/26 31 38 4,2 85103/27 30 10 6,5 85/03/28 28 46 1,7 85/03/29 27 27 2,0 • Control sheep 55 D. I. SCHNEIDER, JENNIFER R. GREEN & M.G. COLLETI FIG. 6 Pale-brown, swollen liver with disseminated haemorrhages of Sheep 1 FIG. 8 Peripheral coagulative necrosis with severe midzonal degener-ation in the liver of Sheep 1 No P. charta rum spores were found during spore counting of pasture samples from the toxic camp. Toxicity tests Sheep 1 became listless, refused food and suffered from ruminal stasis and paresis 20 h after having re-ceived 2 doses of 5 glkg plant material on Day 1. The sheep's condition deteriorated rapidly and it died 26 h after having received the ftrst dose. Sheep 2 received 5 daily doses of 2,5 g!kg of the plant. On the 4th day, at midday, the sheep became restless, sought the shade of a comer post and developed a marked swelling of the ears, eyelids and face (Fig. 4). On the 5th day, the swelling had increased, the eyes were almost closed and visible mucous membranes had a yellowish tinge. The sheep was autopsied on Day 5. Sheep 3 was kept on the pasture for 4 weeks without developing any abnormal clinical signs. During the course of the experiment the weather was ftne, hot and sunny. Chemical pathology Field outbreak In the fteld outbreak, the T Br and GGT levels of the serum of the 4 sheep tested on 20 March 1985 were found to be markedly elevated (Table 2). AST was not tested. The serum levels ofT Br, AST and GGT of the sheep (No. 8) bled 8 days later were elevated, although that of the T Br was markedly lower than those tested at the earlier stage of the disease. OVINE HEPATOGENOUS PHOTOSENSITIVITY CAUSED BY THE PLANT NIDOREUA FOEIIDA FIG. 9 Accentuated lobulation caused bf peripheral haemorrhage and prominent bile duct proliferation m the liver of Sheep 2 Toxicity tests In the case of Sheep 1 and 2, T Br, AST and GGT serum levels were found to be markedly elevated 24 h after having received the initial dose (Table 3). These serum values of Sheep 3 (control) remained within nor-mal limits. Pathology Field outbreak The subcutaneous swelling of the affected areas of the head and face had dissapeared by the time the animal was autopsied, but these areas were covered by dark-brown crusts on the point of becoming detached from the un<!erlying skin. Slight icterus was apparent in the sub-cutis. The liver was yellowish-brown, i.e. slightly more yellow than normal. Histopathologically, there was a mild heJ?atosis with hepatocellular unrest. This was more promment in the peripheral zones of the lobules and was characterized by hepatocytic anisonucleosis and by occasional binucleate hepatocytes. There was mild degeneration and necrosis of the hepatocytes in the midzonal and peripheral zones. Th~re was a mild portal bile duct proliferation and a mild penportal mononuclear cell infiltration. A mild periphe-ral fa!!f degeneration and mild bile stasis were also pre-sent (Ftg. 10). The gall-bladder wall was oedematous, and there was mild nephrosis characterized by cloudy swelling and hy-dropic degeneration in the proximal tubules. A fibrinopurulent exudate had formed a crust on the skin of the macroscopically affected areas. A severe hy-peraemia, oedema, lymphatic dilatation, focal minerali-zation and a mild neotrophil infiltration of the dermis was also present. No other lesions considered to be of significance were encountered in the other organs exam-ined microscopically. Toxicity tests Sheep} The liver was slightly swollen, friable and pale-brown, having many disseminated haemorrhages vary-ing in size from pin.:point to 4 mm in diameter (Fig. 6). The gall-bladder wall was slightly oedematous. The car-cass was distincly icteric, and there was a mild hydrotho-rax, hydropericardium and ascites, the fluid being more yellow than normal. Other changes observed were severe end?Card~al hae~orrhages of the right ventricle and gas-tro-mtestmal stasts. 56 FIG. 10 Hepatocellular unrest with mild bile duct proliferation seen in the regenerating liver of Sheep 8 A severe hepatosis, found on histopathological exami-nation, was characterized by peripheral coagulative ne-crosis of hepatocytes and severe midzonal degeneration. In addition, in several lobules there was early coagula-tive necrosis in the midzonal areas (Fig. 8). In these areas, there were also small haemorrhages. Small foci of hepatocytic lysis, frequently situated around the central vem, were also encountered. There was hydropic dege-neration and early coagulative necrosis of the proximal tubules in the kidney. No lesions of significance were noticed in the other organs examined. Sheep2 The liver was yellowish-brown with distinct lobula-tion. A few pin-point- to pin-head-sized disseminated haemorrhages were present (Fig. 7). The wall of the gall-bladder was slightly oedematous. Moderate icterus could be seen macroscoptcally. On histopathological examination, the liver lesions were found to be less severe than those in Sheep 1. The lobulation in the liver was accentuated by the peripheral haemorrhage present in most lobules, and intralobular bile duct proliferation was prominent (Fig. 9). Relatively numerous necrotic or dividing and regenerating hepato-cytes were encountered, particularly in the peripheral zones of lobules. The hepatocytes in paracentral and central zones showed mild hydropic degeneration with occasional binucleate and regenerating cells. Small foci of degeneration were evident in the epithe-lial layer of the gall-bladder, with aggregation of neutro-phils m these areas. Mild nephrosis, as manifested by the mild hydropic degeneration of the proximal tubules, occurred. The skin was moderately oedematous. The other organs examined did not reveal any significant changes from the normal. DISCUSSION This is the first report of a Nidorella sp. causing toxic-ity in animals. Although this study has shown N. foetida to be highly toxic to sheep, it is not of major economic importance in South Africa because of its localized dis-tribution. A knowledge of its hepatotoxicity and resultant photo-sensitivity, however, is important in elucidating the ae-tiology of other outbreaks of hepatogenous photosensi-tivity of unknown cause; for instance, "Stellenbosch photosensitivity", which occurs in the same area. This knowled~e might also be valuable in the investigation of the posstble toxicity of other more common Nidorella spp. occurring in other parts of South Africa. It is evident that N. foetida, like Athanasia trifurcata L. (Kellerman et al., 1983) and numerous other toxic . plants, is unpalatable and consequently not normally grazed by stock. In certain circumstances, however, (e.g. acute food shortage, a craving for green plants when the animals are on dry grazing or requiring roug-hage when on lush, young, green pasture) stock may ingest sufficient quantities of these unpalatable plants to cause intoxication. The first 2 factors undoubtedly played a role in this outbreak. In Sheep 1 , which manifested an acute severe hepato-sis involvmg the entire lobule to some degree, a zonal necrosis involving the periphery of the lobule was a par-ticularly prominent feature. Although the hepatosis in Sheep 2 and the field case was less severe, the haemor-. rhages found in the peripheral zone followed the same pattern. It is evident from this investigation that inN. foetida toxicity the insult is directed at the hepatocytes, as is also the case in poisoning caused by A. trifurcata (Kellerman et al., 1983), Asaemia axillaris (Thunb.) Harv. ex Jack-son (Coetzer & Bergh, 1983) and Lasiospermum bipin-natum (Thunb.) Druce (Kellerman et al., 1973). Some evidence of a zonal necrosis is usually also found with these 3 hepatotoxic plants. In comparing the histopathological changes in the liver caused by different hepatotoxic components, the duration of toxin ingestion, the dosage, the period be-tween the last dose of toxic material and death or eutha-nasia must be taken into account. In this particular inves-tigation, there was a marked difference m the pattern of Nidorella ingestion in the 3 sheep that were autopsied. Sheep I died 26 h after having received 2 doses of 5 glk:g of plant material on 1 day; Sheep 2 was killed 4 days after 5 daily doses of 2,5 glkg, and the "field sheep" was killed 8 days after being taken out ofthe "toxic" land where it has been for 5 days. Sheep 2 would pro-bably have survived if more plant material had not been , admmistered. 57 D. J. SCHNEIDER, JENNIFER R. GREEN & M. G. COLLEIT ACKNOWLEDGEMENTS The authors wish to thank Mr R. 0. Moffett and Mrs A. Fellingham of the State Herbarium, Stellenbosch, and Miss W. Weiman of the Botanical Research Institute, Pretoria, for identification of the Nidorella sp. and for supplying botanical information. Thanks are also due to Mr E. W. P. Heine and Miss A. M. D. Kriel of the Regional Veterinary Laboratory, Stellenbosch, for their excellent technical assistance, to Mr P. van der Merwe of the Fruit and Fruit Technology Research Institute, Stellenbosch, for the photographs of the sections, and to Mr D. G. du Toit for co-operahon on the farm. We are grateful to the Directorate of Veterinary Ser-vices, Pretoria, for permission to publish this article. REFERENCES ADAMSON, R. S. & SALTER, T. M., 1950. Flora of the Cape Peninsula. Cape Town: Juta. COE1ZER, J. A. W. & BERGH, T., 1983. Photosensitivity in South Africa. IV. Pathological changes in the liver in ovine sensitivity caused by the plant Asaemia axillaris (Thunb.) Harv. ex Jackson. Onderstepoort JourMl ofVeteriMry Research, 50, 55-58. Dr MENNA, MARGARET E. & BAILEY, J. R., 1973. Pithomyces charta-rum spore counts in pasture. New Zealand Journal of Agricultural Research, 16, 343-351. GIBBS RUSSELL, G. E. and the staff of the National Herbarium, 1984. Memoirs of the Botanical Survey of South Africa, No. 48. KELl.ERMAN, T. S., BASSON, P. A., NAUDE, T. W., VAN RENSBURG, I. B. R. & WELMAN, Wn.HELMINA G., 1973. Photosensitivity in South Africa. I. A comparative study of Asaemia axillaris (Thunb.) ex Jackson and Lasiospermum bipifiii(Jtum (Thunb.) Druce poison-ing in sheep. Onderstepoort Journal of Veterinary Research, 40, 115-126. KELl.ERMAN, T. S., COE1ZER, J. A. W., SCHNEIDER, D. J. & WELMAN, Wn.HELMINA G. , 1983. Photosensitivity in South Africa. m. Ovine hepatogenous photosensitivity caused by the ytant At~­nasia trifurcata L. (Asteraceae). Onderstepoort Journa of Veteri-nary Research, 50,45-53. MARASAS, W. F. 0 . , ADELAAR, T. F., KELLERMAN, T. S., MINNE, J. A., VAN RENSBURG, I. B. J. & BURROUGHS, G. W., 1972. First report of facial eczema in sheep in South Africa. Onderstepoort JourMl ofVeteriMry Research, 39, 107-112. STEYN, D. G., 1949. Vergiftiging van mens en dier. Pretoria: Van Schaik. 

Ovine hepatogenous photosensitivity caused by the plant Nidorella foetida (Thunb.) DC. (Asteraceae)

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Ovine hepatogenous photosensitivity caused by the plant Nidorella foetida (Thunb.) DC. (Asteraceae)

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