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Toxicon 193 (2021) 13–20

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Toxicon
journal homepage: http://www.elsevier.com/locate/toxicon

Hepatogenous photosensitization in ruminants and horses caused by the


ingestion of Chamaecrista serpens in Brazil
Múcio F.F. Mendonça a, Luciano A. Pimentel b, Paula V. Leal c, José C. Oliveira Filho b,
Lais G. Caymmi a, Antonio W.O. Silva a, Rubens S. Jesus b, Tiago C. Peixoto c, *
a
Postgraduate Program in Animal Science in the Tropics, Federal University of Bahia (UFBA), Av. Adhemar de Barros 500, Salvador, BA, 40170-110, Brazil
b
Veterinary Pathology Sector, Federal University of Recôncavo of Bahia (UFRB), Rua Rui Barbosa 710, Cruz Das Almas, BA, 44380-000, Brazil
c
Veterinary Pathology Laboratory, UFBA, Av. Adhemar de Barros 500, Salvador, BA, 40170-110, Brazil

A R T I C L E I N F O A B S T R A C T

Handling Editor: Kevin Welch This study aimed to describe the first reports of outbreaks of hepatogenous photosensitization in cattle, sheep,
and horses caused by spontaneous ingestion of Chamaecrista serpens, as well as to reproduce poisoning in sheep
Keywords: experimentally. Eleven photodermatitis outbreaks of unknown cause occurred in cattle, sheep and horses on nine
Chamaecrista serpens farms in the semiarid region of Bahia, northeastern Brazil, between July 2017 and July 2020. Cutaneous lesions
Hepatogenous photosensitization
of photosensitization initiated until one week after the animals were introduced in paddocks invaded by the plant
Hepatotoxic plants
at the beginning of the rainy season. The photosensitive skin lesions were progressive and consisted of hyper­
Photodermatitis
emia, edema, ulcerative-crusted lesions with necrosis, especially in non-pigmented skin areas. The lesions in
young animals were more severe. The animals avoided the sun and exhibited hyporexia, weight loss, restlessness,
irritability, and severe itching. An experimental study was made using seven sheep, and resulted in photo­
dermatitis, similar to that observed in the natural poisoning, seven days after the beginning of plant ingestion.
Two sheep were reserved for the control group. Serum biochemistry changes indicated liver injury caused by the
plant. Skin biopsies and liver biopsy guided by ultrasound were performed. The one sheep that had more pro­
nounced skin lesions was euthanized and necropsied. At the necropsy, the liver was enlarged, diffusely pale, and
firm, with an evident lobular pattern and an empty gallbladder. Histopathology revealed similar skin and liver
lesions in samples from biopsies and the necropsy. There was a marked disorganization of the cords of hepa­
tocytes associated with degenerative necrotic changes on the liver. The cutaneous injuries included orthoker­
atotic hyperkeratosis, hypergranulosis, acanthosis, and extensive areas of epidermic necrosis and ulceration.
Three sheep were protected from sunlight and the lesions regressed within 45 days after the plant’s consumption
ceased. In conclusion, C. serpens causes hepatogenous photosensitization in ruminants and horses, and should be
included in the list of differential diagnoses in cases of photosensitive dermatitis.

1. Introduction bovine congenital porphyria and bovine erythropoietic protoporphyria),


or secondary (resulting from the accumulation in subcutaneous capil­
Photosensitization is a skin disorder caused by long-wavelength ul­ laries of phytoporphyrin [phylloerythrin], a photodynamic metabolite
traviolet solar radiation or, less frequently, by visible light absorbed by of chlorophyll degradation, resulting from liver damage caused mainly
photodynamic compounds or by complexes of the latter with biological by toxic plants, mycotoxins, drugs, or infectious agents). Because liver
substrates in the skin (Hargis and Myers, 2017). In ruminants and damage is involved in the latter form, which is the most common type in
horses, photosensitization can be primary (due to the ingestion of pre­ herbivores, it is also referred to as hepatogenous photosensitization
formed photodynamic substances in plants or treatment with certain (Collett, 2019).
drugs), endogenous (due to aberrant heme pigment synthesis such as in In Brazil, cases of secondary photosensitization occur due to the

* Corresponding author.
E-mail addresses: mucinhoferraro@hotmail.com (M.F.F. Mendonça), lucianoanp@yahoo.com.br (L.A. Pimentel), paulavleal15@gmail.com (P.V. Leal),
jcoliveirafilho@ufrb.edu.br (J.C. Oliveira Filho), lais_caymmi@hotmail.com (L.G. Caymmi), antoniowesley_vet@hotmail.com (A.W.O. Silva), rubenssilva.agro@
gmail.com (R.S. Jesus), tcpeixoto@ufba.br (T.C. Peixoto).

https://doi.org/10.1016/j.toxicon.2021.01.013
Received 1 September 2020; Received in revised form 29 December 2020; Accepted 20 January 2021
Available online 28 January 2021
0041-0101/© 2021 Elsevier Ltd. All rights reserved.
M.F.F. Mendonça et al. Toxicon 193 (2021) 13–20

ingestion of Brachiaria spp. (Brum et al., 2009; Albernaz et al., 2010; trauma, erythema, edema, desquamation, necrosis, shedding of the
Souza et al., 2010; Faccin et al., 2014; Pupin et al., 2016), Enterolobium skin in the most affected parts, ulcerations, and crusting, as well as
contortisiliquum (Grecco et al., 2002; Olinda et al., 2015; Leal et al., restlessness, hyporexia, weight loss, and eventually death (Rowe, 1989;
2017), Stryphnodendron fissuratum (Ferreira et al., 2009; Lazaro et al., Tokarnia et al., 2012; Knupp et al., 2014; Constable et al., 2017).
2018), Lantana spp. (Rissi et al., 2007), Panicum spp. (Riet-Correa et al., In several municipalities of Bahia northeastern semiarid regions of
2009), and Crotalaria retusa (Lucena et al., 2010). Primary photosensi­ Brazil, farmers attribute cases of photosensitization in cattle, sheep,
tization is associated with poisoning from Ammi majus (Méndez et al., goats, and horses to spontaneous ingestion of Chamaecrista spp. How­
1991), Froelichia humboldtiana (Pimentel et al., 2007; Silva Filho et al., ever, until now, there has been no scientific proof of this plant’s toxicity.
2020), and recently, Malachra fasciata (Araújo et al., 2017). Chamaecrista serpens (L.) Greene is a subshrub of the Fabaceae fam­
Regardless of the cause, affected animals develop skin lesions pre­ ily, which is native to Brazil (Neto, 2010), occurring in most states apart
dominantly involving non-pigmented regions with less hair or wool from those in the west and south of the country (Souza and Bortoluzzi,
covering or those areas more exposed to the sun, such as the ears, face, 2015) (Fig. 1). Toxicity due to this plant has not been recorded before.
nostrils, teats, udder, vulva, and distal extremities of the limbs. Clini­ Therefore, the aim of this study was to describe the epidemiological
cally, dermatitis leads to intense itching with subsequent self-inflicted and clinicopathological findings of photosensitization outbreaks in

Fig. 1. Map of Brazil (bottom left) with the geographic distribution of Chamaecrista serpens highlighted in red. The larger map is of the square in the inset and shows
the four microregions in Bahia State, Northeastern Brazil (highlighted in green) where the eleven outbreaks of photosensitization occurred: Queimadas (1), Santaluz
(2), Araci (3), Tucano (4), Pé de Serra (5), Serra Preta (6), Santo Estêvão (7), and Cabaceiras do Paraguaçu (8). (For interpretation of the references to colour in this
figure legend, the reader is referred to the Web version of this article.)

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M.F.F. Mendonça et al. Toxicon 193 (2021) 13–20

cattle, sheep, and horses in Bahia, Northeast Brazil, caused by sponta­


neous ingestion of C. serpens, as well as to reproduce poisoning in sheep
experimentally.

2. Material and methods

2.1. Spontaneous field outbreaks

Eleven natural outbreaks of photosensitization of unknown cause


occurred in cattle, sheep and horses on nine farms in the semiarid region
of Bahia, northeastern Brazil between July 2017 and July 2020. The
eleven outbreaks in ruminants and horses occurred in eight municipal­
ities (Fig. 1): five in cattle [Tucano (10◦ 57′ 45.6′′ S 38◦ 47′ 27.7′′ W), San­
taluz (11◦ 15′ 21′′ S 39◦ 22′ 30′′ W), Pé de Serra (11◦ 50′ 02′′ S 39◦ 36′ 46′′ W),
Araci (11◦ 19′ 58′′ S 38◦ 58′ 01′′ W), and Santo Estêvão (12◦ 25′ 48′′ S
39◦ 15′ 03′′ W)]; four in sheep [Cabaceiras do Paraguaçu (12◦ 32′ 09′′ S Fig. 3. Close-up photograph of Chamaecrista serpens showing the leaflets, pods
39◦ 11′ 27′′ W), Queimadas (10◦ 58′ 40′′ S 39◦ 37′ 26′′ W), Santaluz, and Pé and yellow flowers. (For interpretation of the references to colour in this figure
de Serra]; and two in horses [Santaluz and Serra Preta legend, the reader is referred to the Web version of this article.)
(12◦ 09′ 37′′ S39◦ 19′ 54′′ W)]. Epidemiological histories and data were
obtained from producers through interviews during visits to farms 2.2. Experimental reproduction
where outbreaks occurred.
On these occasions, the pastures where the affected animals were This experiment was approved by the Animal Use Ethics Committee
kept were inspected. There was an overwhelming invasion of the native of the Federal University of Recôncavo of Bahia (protocol number
pastures by subshrubs that had yellow flowers (Fig. 2) and legume-like, 23007.013398/2012–21).
linear-oblong pods with rhomboid seeds, and spiked leaves, with up to Initially, with the intention of reproducing the intoxication, a pilot
13 pairs of leaflets (Fig. 3). The plant was named by the producers as experiment (PE), using a healthy, dewormed, black and white, crossbred
“sarninha” and/or “pela-égua”. Dorper ewe (Ov-0), was carried out between August and September
On three farms, producers attributed the disease to the natural 2017. Specimens of C. serpens were collected on a farm where photo­
consumption of this plant, and on the other six, it was mistakenly sensitization outbreaks of unknown cause had occurred in cattle in the
associated with an allergic process or parasitic disease (scabies). Sam­ municipality of Tucano, BA. The plants were stored in a cold chamber
ples of the plant suspected of causing the disease were collected from for 21 days. Ov-0 received feed that comprised concentrate and C. serp­
Tucano and Santaluz, Bahia (BA), and submitted to the Herbário da ens at amounts of 10 g/kg and 40 g/kg live weight (LW), respectively, for
Universidade Estadual de Feira de Santana (HUEFS) for botanical 21 days. After consuming the offered plant, Ov-0 was released into a
identification. The plants were identified as Chamaecrista serpens (L) massai grass (Panicum maximum) and transvala (Digitaria decunbens)
Greene (= Cassia serpens) (HUEFS-240995) and Chamaecrista sp. paddock, with sun exposure and water ad libitum, in the Veterinary
(HUEFS-249949), respectively. In other farms, Chamaecrista sp. was Pathology Sector of UFRB, Cruz das Almas, BA.
identified in the pastures during technical visits. On days zero (D0), 15 (D15), and 30 (D30) blood samples were
During inspection of the herds, ten cattle, six sheep, and two horses collected by puncture of the jugular vein using a vacuum system, in 10-
that showed more pronounced skin lesions were examined clinically and mL tubes, without an anticoagulant. This was to determine the serum
blood samples were drawn via jugular venipuncture for biochemical activities of GGT and AST, and the concentrations of total bilirubin,
analysis of gamma-glutamyl transferase (GGT), aspartate aminotrans­ direct bilirubin, indirect bilirubin, urea, and creatinine, using an auto­
ferase (AST), total bilirubin, direct bilirubin, indirect bilirubin, urea, and matic biochemical analyser, PKL 125®.
creatinine. Results showed a very slight elevation in GGT activities In the PE, clinical follow-up revealed that Ov-0 presented a slight
suggesting that liver damage, if any, was mild. photodermatitis in non-pigmented skin areas in the gluteal region that
initiated two weeks after the beginning of plant ingestion, in addition to
apathy and weight loss. The hematologic and leukocyte indices did not
show significant changes. However, serum biochemistry indicated liver
injury with elevation of GGT and AST activities, and direct bilirubin
concentrations (Table 1).
After successfully reproducing the photosensitization in this PE,

Table 1
Serum biochemistry results for the pilot experiment where Ov-0 received Cha­
maecrista serpens plant material in the diet for 21 days.
Biochemical parameters D0 D15 D30 Ref. intervalsa
b
GGT (IU/L) 44 – 679 20–52
ASTc (IU/L) 90 349 982 60–280
TBd (mg/dL) 0,2 0,3 1,9 0,1–0,4
DBe (mg/dL) 0,1 0,2 1,1 0-0,27
IBf (mg/dL) 0,05 0,1 0,8 0-0,12
a
Reference intervals by Kaneko et al. (2008).
b
Gamma-glutamyl transferase.
c
Aspartate aminotransferase.
d
Total bilirubin.
e
Fig. 2. Pasture invaded by Chamaecrista serpens in the municipality of Santaluz, Direct bilirubin.
f
Bahia State, Northeastern Brazil. Indirect bilirubin.

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M.F.F. Mendonça et al. Toxicon 193 (2021) 13–20

further experimentation proceeded (the second experimental study). Thirty days after the beginning of the experiment, the EG animals
Four healthy, crossbred sheep, comprising two adult light brown ewes were removed from the pasture. Ov-1, which had more pronounced skin
(Ov-1 and Ov-2), one five-month-old black ram lamb with a white right lesions, was euthanized and necropsied. During the necropsy, fragments
foot (Ov-3), and one five-month-old white and black spotted ewe lamb of skin from different regions (with and without lesions), organs from
(Ov-4), constituted the experimental group (EG). In order to prove the the abdominal and thoracic cavities, and the brain were collected. The
toxicity of C. serpens in loco, the sheep were introduced into a native Ov-0, Ov-2, Ov-3, Ov-4, Ov-5, and Ov-6 sheep were subjected to skin
pasture where C. serpens was the dominant plant. It appeared highly biopsies. This material was fixed in 10% formalin, processed by routine
palatable for the sheep. This native pasture was on the Santaluz farm histological techniques, stained with hematoxylin-eosin (HE), and
(Fig. 2), where there had been outbreaks of photosensitization in cattle, evaluated under an light microscope.
sheep, and horses 10 years previously. No known photosensitizing After they were removed from the pasture, the EG animals were kept
plants had been found on this property. Two adult light brown ewes (Ov- in shaded paddocks without C. serpens, fed exclusively with Pennisetum
5 and Ov-6), kept on a C. serpens-free pasture on the same farm, served as purpureum and concentrate feed at 1% of live weight and water ad
a control group (CG). The sheep were observed daily for 30 days. All libitum for 45 days, with physical examinations and blood collections
sheep had direct exposure to solar radiation and had water ad libitum. being performed every 15 days (D45, D60, and D75) to assess their
The experiment took place during the end of the rain/winter season, recovery.
between August and September 2019. Rainfall ranged from 12 to 25 mm
during this time (Inmet, 2019). 3. Results
On D0, D15, and D30, the sheep from EG and CG were weighed and
subjected to a comprehensive clinical examination with emphasis on the 3.1. Spontaneous field outbreak
skin. On these occasions, blood samples were collected by puncture of
the jugular vein similar to that performed in the PE. The data provided It was found that, in general, the animals avoided the sun (remaining
by Kaneko et al. (2008) for serum enzyme activities and analyte con­ in the shade), grazed mainly at night (periods of mild temperature), and
centrations were taken as a reference, as well as the individual values of exhibited hyporexia, weight loss, restlessness, irritability, and severe
each sheep obtained on D0. This way, the EG sheep served as their itching with self-inflicted trauma. The photosensitive skin lesions varied
control, which prevented the occurrence of possible individual in relation to their distribution, size, intensity, and appearance
variations. (Figs. 4–6). Generally, the photodermatitis was progressive and con­
All sheep in the PE, EG, and CG were subjected to liver evaluation by sisted of skin hyperemia, edema, ulcerative-crusted lesions with necro­
percutaneous liver biopsy guided by ultrasound with catheter no. 14 on sis, especially in non-pigmented skin areas, with loss of epidermis
D0 and repeated on D30. The technique described by Néspoli et al. (extensive dry areas, which were mummified in appearance with cracks
(2010) was adapted. The animals were kept standing, with the catheter and ulcerations). In addition, the lesions in young animals were more
inserted in the 11th intercostal space, after local wool was shaved (10 severe, and there was no sex predilection. In horses, where the outbreak
cm2), surgical antisepsis, and local anesthetic button block with 5 mL of occurred in Santaluz, affecting a mare with a creamy coat, the head was
2% lidocaine hydrochloride (Dorfin®), in the intercostal muscle, with at severely affected by crusty and ulcerative lesions that bleed easily, and
least three liver samples being collected from each animal. the whole body was compromised by scabs (Fig. 6). Other clinical signs

Fig. 4. Cattle naturally intoxicated with Chamaecrista serpens in Bahia State, Northeastern Brazil showing a variety of focal to multifocal photosensitive skin lesions
(A–F). Note itching (C), and bleeding on face due to intense itching (E).

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M.F.F. Mendonça et al. Toxicon 193 (2021) 13–20

Fig. 5. Sheep naturally poisoned by Chamaecrista serpens in Bahia State, Northeastern Brazil showing focally extensive photosensitive skin lesions on the flank and
lateral abdomen (A), and on the back (B).

Fig. 6. Horses naturally poisoned by Chamaecrista serpens in Bahia State, Northeastern Brazil showing photosensitive skin lesions characterized by ulceration and
crusts around the lips, nostrils, muzzle and periorbital regions.

observed in horses were apathy and drowsiness. In the outbreak at Serra hyporexia, irritability, with intense photophobia and moderate to severe
Preta, approximately 50% of the mares showed photosensitive lesions in dermatitis that evolved into scaly ulcerative skin lesions (Fig. 7). The
non-pigmented areas of the body, such as the face and limbs, in addition main clinical signs and outcome observed in sheep experimentally
to body irritation and itching. poisoning by C. serpens are described in Table 2.
Outbreaks of natural poisoning by C. serpens occurred approximately Regarding serum biochemistry, there was a progressive increase in
one week after the animals were introduced to paddocks invaded by the GGT activity in the four sheep of the EG between D0, D15, and D30,
plant at the beginning of the rainy season, when there is great growth of which suggested liver injury caused by the plant. The two control sheep
the plants in the pastures (it is one of the first plants to sprout leaves after showed no variation in GGT levels. Following the removal of the sheep
the first rains). from the pastures on D30, GGT activities steadily decreased on D45 and
The incidence of photosensitization in the spontaneous outbreaks in D60 until recovery on D75 (Fig. 8). There were no notable changes in
cattle and sheep varied between 6% and more than 60%. AST activities or in the concentrations of the other measured analytes.
Ov-1 showed more severe photosensitization, characterized by ul­
3.2. Experimental reproduction cerative and necrotizing dermatitis, with hyperemia, alopecia, desqua­
mation, and subsequent dermal healing and thickening. These lesions
Pruritus and photophobia were first noticed a few days after sheep in were bilateral and were mainly located on the face, ears, sides of the
the EG began consumption of C. serpens. The clinical signs progressively chest, axillae, flank, pelvis, and back, where they were more extensive
worsened with the animals remaining in the shade, and showing and accentuated. After euthanasia, Ov-1 was necropsied. In addition to

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M.F.F. Mendonça et al. Toxicon 193 (2021) 13–20

Fig. 8. Serum activities of gamma-glutamyl transferase (GGT) in experimental


poisoning by Chamaecrista serpens in four sheep.

and nuclear pyknosis of individual or random groups of hepatocytes


(coagulative necrosis) (Fig. 9), in addition to mild focal to mild multi­
focal lymphoplasmacytic pericholangitis.
The cutaneous histological changes included, in general, irregular
superficial orthokeratotic hyperkeratosis, marked hypergranulosis and
Fig. 7. This sheep had been introduced to a paddock invaded by Chamaecrista pseudoepitheliomatous hyperplasia (acanthosis), multifocal keratino­
serpens 30 days previously and shows multifocal photodermatitis characterized cyte vacuolization, and extensive areas of epidermal necrosis with ul­
by crusting, ulcerative-necrotic lesions. The inset shows focally extensive ceration, serocellular crusts, and intralesional bacterial colonies
photosensitive skin lesions on the side of the chest. (secondary infection). In the superficial and deep dermis, there was
marked angiogenesis and intense diffuse proliferation of fibroblasts and
disorganized collagen fibers (Fig. 10), as well as mild to moderate
Table 2
multifocal mononuclear periadnexitis and sweat gland ectasia. The
Experimental poisoning by Chamaecrista serpens in sheep. Main clinical changes
sheep in the CG showed no skin and liver changes.
and outcome.
Ov-1 Ov-2 Ov-3 Ov-4 4. Discussion
Day 7 Itching, Itching Itching Itching
regions of The diagnosis of hepatogenous photosensitization associated with
alopecia and
the natural intake of C. serpens in cattle, sheep, and horses raised
erythemaa
Day 15 Crusted Itching, Itching, Itching, extensively in the state in Bahia, Northeast Brazil, was carried out. The
lesions irritability irritability irritability evaluation was based on the history, presence, and consumption of the
spread and and and
throughout hyporexia hyporexia hyporexia
the bodya,
irritation,
itching and
hyporexia
Day 30 Reddish Reddish Reddish Reddish
mucosa, mucosa, mucosa, mucosa,
ulcerative regionsa crusted lesion in
and crusted with hairy lesion in the ventral
lesions on rarefaction the region region of
the bodya, and some of the distal the neck
including areas of pelvic limb involving
the labial crusted involving non-
commissure lesion, and non- pigmented
(similar to ↑ GGT pigmented areas, and
the burn), areas, and ↑ GGT
and ↑ GGT ↑ GGT
Photossensitization Yes Yes Yes Yes
Outcome Euthanasia Recovered Recovered Recovered
a
Head, ears, neck, back, side, axillae, groins, and hips.

the skin lesions already described, the liver was enlarged, diffusely pale,
and firm, with an evident lobular pattern and an empty gallbladder.
Additionally, there was moderate irregularity in the visceral face of the
left lateral hepatic lobe.
Microscopic evaluation revealed skin and liver changes in the PE and Fig. 9. Photomicrograph of the liver of a sheep experimental poisoned by
EG. In the liver, there was a marked disorganization of the cords of Chamecrista serpens. There is loss of organization of hepatocyte cords, intra­
hepatocytes associated with amphophilic intracytoplasmic micro- and cytoplasmic vacuoles, multifocal nuclear pyknosis (arrow), moderate multifocal
macrovacuoles (moderate steatosis), cytoplasmic hypereosinophilia, coagulative necrosis, in addition to the focal area of fibrosis near the periportal
region (PR) (arrowhead) and diffuse increase in eosinophilia. Ov-1. HE. 400x.

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M.F.F. Mendonça et al. Toxicon 193 (2021) 13–20

lesions in EG sheep, this behavior was exacerbated. Therefore, the


consumption of leguminous plants in the field tends to decrease, as
occurred on the outbreaks reported here. Although the GGT activities of
the EG sheep were not as high, baseline conditions returned after being
removed from the paddocks invaded by the plant, considering that these
animals at the beginning of the experiment were healthy. Similar find­
ings have been described in the experimental reproduction of hep­
atogenous photosensitization (Faccin et al., 2014; Pupin et al., 2016;
Leal et al., 2017). These enzymatic activity changes were not observed in
cases of primary photosensitization (Tokarnia et al., 2012). New ex­
periments should be carried out in order to assess the dose dependent
effect.
No popular name records were found for C. serpens; however, C.
nictans is popularly known as “peninha,” “mata pasto,” “falsa sensitiva,”
and “falsa dormideira” (Lorenzi, 2008). Conversely, in properties where
the photosensitization outbreaks occurred, it was popularly known as
“sarninha” and/or “pela-égua.” This name was attributed by the pro­
ducers due to the common observation of dermatitis cases (clinically like
scabies) after the introduction of the animals to pastures invaded by
C. serpens. However, from our experience in the field, the term “scabies”
Fig. 10. Photomicrograph of the skin of a sheep experimental poisoned by is a common designation and used in a generic way among ranchers to
Chamecrista serpens. There is marked hyperkeratosis and pseudoepitheliomatous define any apparent skin lesions in animals. Extrapolating the use of the
hyperplasia. Note marked angiogenesis and diffuse proliferation of fibroblasts term “scabies” to other causes of skin lesions, other than those caused by
and disorganized collagen fibers. Ov-1. HE. 100x. mites, causes confusion and should be avoided.
It is important to mention that in the northeastern semiarid regions
plant in pastures, clinical signs, and laboratory (serum biochemistry) of Brazil, other plants that cause primary or hepatogenous photosensi­
and pathological findings. The toxicity of the plant was proven by the tization in farm animals can also be found. These include
experimental reproduction of sheep intoxication. F. humboldtiana, M. fasciata, Brachiaria spp., S. fissuratum,
Experimentally, the time of appearance of the first clinical signs is E. contortisiliquum, and C. retusa (Tokarnia et al., 2012). The possibility
compatible with historical and field observations, being noticed seven of a synergistic action between different plant species should be
days after the beginning of C. serpens consumption (introduction of the considered. However, in nine farms where the 11 outbreaks described
animals to pastures intensely invaded by the plant). here occurred (five in cattle, four in sheep, and two in horses), no known
Initially, it was suggested that the photosensitization was primary, toxic photosensitizing plants were found.
since the onset of the first cutaneous lesions appeared within a few days The toxic principle of C. serpens is not known; however, further
after the introduction into pastures (acute poisoning) with C. serpens studies must be carried out to determine the toxic principle, establish the
predominance. However, this hypothesis was ruled out by the detection toxic dose of C. serpens, and understand the pathogenesis of the lesions,
of liver damage as shown by changes in serum biochemistry (GGT, AST, as well as the ways of intoxication control and prophylaxis. The removal
and bilirubin), as well as the histological liver lesions. of animals from pastures invaded by the plant is recommended as a
The changes in serum GGT described here corroborate those of prophylactic measure.
Mendonça et al. (2009), Olinda et al. (2015), and Leal et al. (2017), who It has been proven for the first time that photodermatitis of unknown
demonstrated hepatogenous photosensitization by elevated activities. etiology observed in farm animals from northeast semiarid is caused by
The failure to observe an elevation in AST activities in the EG may be the consumption of C. serpens, and that this intoxication progresses with
explained by the fact that AST is an enzyme of acute injury, which may a picture of hepatogenous photosensitization (experimentally proven).
increase within 24–48 h, reaching its peak during the first five days post- Outbreaks of C. serpens poisoning occur spontaneously in ruminants and
injury (Hoffmann and Solter, 2008). As the experimental reproduction horses that have free access to pastures invaded by the plant at the
in loco only allowed blood testing every 15 days, this alteration could beginning of the rainy season and can achieve high incidence. Thus,
not be observed. Another important factor is that in the animals that C. serpens should be considered as a toxic plant of ruminants and horses
were removed from the pasture and kept in the shade, there was an and included in the list of differential diagnoses in cases of photosensi­
average 37.66% reduction in GGT activities, returning to normality. tive dermatitis.
This is not observed in primary photosensitization cases (Méndez et al.,
1991; Pimentel et al., 2007; Tokarnia et al., 2012). There were no sig­ Credit author statement
nificant changes in urea or creatinine concentrations.
On the other hand, the sheep from the PE had a huge increase in AST Múcio F.F. Mendonça, Conceptualization, Investigation, Validation.
and GGT activities, while in those from the EG, GGT increases were Luciano A. Pimentel, Conceptualization, Methodology, Writing – orig­
particularly subtle. This fact could possibly be explained by the plant inal draft. Paula V. Leal, Methodology, Writing – original draft and
dose ingested. In PE, the ingested dose of C. serpens was 40 g/kg on the Review & editing. José C. Oliveira Filho, Resources. Lais G. Caymmi,
period of 21 days, which represent a high dose for many toxic plants Investigation, Validation. Antonio W.O. Silva, Investigation, Validation,
(Tokarnia et al., 2012). However in the EG, the dose of ingested plant Formal analysis. Rubens S. Jesus, Investigation. Tiago C. Peixoto, Project
cannot be quantified as it is impossible to know if or how much of the administration, Supervision, Methodology, Writing – original draft and
plant was ingested daily. Furthermore, pastured sheep ingest less plant Review & editing.
volume than confined sheep. For example, the consumption of the
legume (Arachis pintoi cv. Amarillo) varies between 25 g/kg LW and 55 Declaration of competing interest
g/kg LW for grazing and confined sheep, respectively (Dal-Pizzol et al.,
2019). Pastured sheep also tend to avoid grazing during the hottest The authors declare that they have no known competing financial
hours of the day (Resende et al., 2008; Paula et al., 2009). Thus due to interests or personal relationships that could have appeared to influence
photophobia and irritability in consequence of photosensitive skin the work reported in this paper.

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M.F.F. Mendonça et al. Toxicon 193 (2021) 13–20

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