effects of lantana camara
TRANSCRIPT
Effects of Lantana camara (Verbenaceae) on general reproductive
performance and teratology in rats
Fernanda B. Mello, Daniela Jacobus, Kelly Carvalho, Joao R.B. Mello*
Departamento de Farmacologia, Instituto de Ciencias Basicas da Saude (ICBS), Universidade Federal do Rio Grande do Sul,
UFRGS, Av. Sarmento Leite n. 500, sala 202, Porto Alegre, RS, 90046-900, Brazil
Received 23 July 2004; accepted 4 December 2004
Available online 2 February 2005
Abstract
Lantana camara L. (Verbenaceae) possesses several medicinal properties and it is used in folk medicine with antipyretic,
antimicrobial and antimutagenic properties. This plant is one of the 10 most noxious weeds in the world. Lantana poisoning
have caused severe economic losses and was the major cause of livestock mortality and morbidity. In this article we report the
effects of hydroalcoholic extract from Lantana camara var. aculeata leaves on fertility, general reproductive performance and
teratology in the rat. The data showed that the extract interfered in the frequency of fetal skeleton anomalies from dams treated
with the extract and induced embryotoxicity as indicated by post-implantation loss, without any signs of maternal toxicity. The
other parameters evaluated did not suggest modifications.
q 2004 Elsevier Ltd. All rights reserved.
Keywords: Lantana camara; Teratology; Reproductive toxicity; Fertility; Rats
1. Introduction
Lantana camara L. (Lantana, family Verbenaceae) is a
woody scrub plant with a number of flower colors: red,
white, yellow, pink, violet and it is one of the 10 most
noxious weeds in the world (Sharma et al., 1988). Lantana
possesses several medicinal properties and its used in folk
medicine with antipyretic, antimicrobial and antimutagenic
properties (Seawrigth, 1965; Sharma, 1984; Sharma et al.,
1988). These properties are attributed to lantadene A (Barre
et al., 1997). Capacity for poisoning is not necessarily
related to flower color (Seawrigth, 1963). Lantana is a wild
pest plant which causes sizeable economic losses in grazing
livestock in lantana infested regions in the world (Sharma
et al., 1989). Ingestion of leaves from Lantana camara, by
grazing animals produces photodermatitis, jaundice, liver
damage and death (Akther et al., 1990).
0041-0101/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.toxicon.2004.12.004
* Corresponding author. Tel.: C5551 3316 3569; fax: C5551
3316 3121.
E-mail address: [email protected] (J.R.B. Mello).
Although there are many investigations about economic
losses in lantana poisoning, and chemical investigations on
the nature of lantana constituents, there is no information
about female reproduction and teratology. The present study
was undertaken to evaluate the effects of hydroalcoholic
extract from Lantana camara var. aculeata leaves on
fertility, general reproduction and teratology in female rats.
It is part (the so-called Segment I and II study) of a more
comprehensive evaluation of the reproductive toxicity of
Lantana camara designed in three segments as rec-
ommended by guidelines of the Food and Drug Adminis-
tration (FDA), and of Organization for Economic
Cooperation and Development (OECD).
2. Materials and methods
2.1. Vegetal material
The vegetal material was collected in Viamao/RS/Brazil
district, dried to atmosphere temperature and mechanically
Toxicon 45 (2005) 459–466
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F.B. Mello et al. / Toxicon 45 (2005) 459–466460
triturated. Voucher specimens were identified (nZ114243)
by Prof. Rumi Kubo and deposited in the herbarium of the
Department of Botany, Institute of Bioscience of UFRGS.
The extract was obtained from 100 g of the dried and
triturated material in a hydroalcoholic solution (70:30 v/v),
during 24 h under eventual shaking. The resultant extract
was filtered. The filtered extract was then concentrated in a
rotary evaporator under reduced pressure at a temperature of
40 8C. The dried mass was stored in refrigerator and used as
the extract. The yield of the extract was 4.75% (w/w in terms
of dried material).
2.2. Experimental animals
Male and female albino Wistar rats were kept under
constant conditions: a day/night cycle (lights on: 9:00–
21:00), a room temperature of 21G1 8C and 50G5%
relative humidity. The animals received a standard pelleted
diet (Nuvilab CR 1w, Parana, Brazil) and tape water
ad libitum during the experiment. All rats were adapted to
the conditions of our animal quarters for 3 weeks before
starting the experiment. Breeding, housing and experimental
procedures followed guidelines published in the NIH Guide
for Care and Use of Laboratory Animals and obeyed current
Brazilian laws.
2.3. Mating procedure
Males were housed single in a cage with wood shavings
as bedding. Three virgin females were placed into a cage of
one male for 2 h each day (7:00–9:00 h) and vaginal smears
were evaluated for sperm. The first 24-h period following
mating procedure was called day 0 of pregnancy if sperm
was detected in the smear. The mating procedure was
repeated every working day for 15 mating sessions
extending over 3 weeks.
2.4. Treatment of animals
The animals were divided in four experimental groups,
one control group (nZ56), that received vehicle and three
groups were treated with the extract in three doses, 1, 3 and
7 g kgK1, equivalent to dried and triturated plant, respect-
ively, LC 1 (nZ27), LC 3 (nZ28) and LC 7 (nZ24). All
experimental groups were treated by gavage every day. The
females were treated for 14 days prior the mating, during the
mating, extending over pregnancy (21 days) and lactation
period until day 21 after parturition. The males were treated
during 91 days (70 before the mating and 21 during the
mating).
2.5. Evaluation of the animals
All males and females were evaluated for weight
development, mortality, and signs of toxicity. Pregnant
females were also observed for weight gain, signs of
abortion, dystocia and prolonged duration of pregnancy.
2.6. Cesarean section
On day 21 of pregnancy half of the females per group
were anaesthetized by ethyl ether inhalation and killed by
decapitation. The gravid uterus was weighed with contents.
Resorptions as well as living and dead fetuses were counted.
The number of implantation sites was determined. All the
living fetuses were immediately weighed, numbered with
marker pen, examined for externally visible malformations
and fixed in a 5% formalin solution. All fetuses were
examined for skeletal anomalies after clearing with tripsin
and staining with alizarin red S (Taylor and Van Dyke,
1985). The degree of ossification was evaluated using
parameters proposed (Chahoud, 1996).
2.7. Postnatal development of the offspring
All the remaining pregnant females were allowed to give
birth to their offspring. From pregnancy day 20 the dam’s
cage were inspected for births and the day of birth was
designed as postnatal day 0. As soon as possible after birth
the numbers of viable and death newborns were recorded,
the pups were sexed and weighed. Any newborn death on
postnatal day 0 was considered to be a stillbirth. Weight gain
of the pups was recorded on postnatal days 0, 7, 14 and 21.
Each and every pup was examined for signs of physical
development and the days on which developmental land-
marks appeared were recorded as follows:
Ear unfolding: when both ears were unfolding;
Development of fur: the first detection of downy hair;
Incisor eruption: the first sign of eruption through the
gums of both the lower incisors;
Eye opening: total separation of the upper and lower eye
lids and complete opening of both eyes;
Testes decent, prepucial separation and vaginal opening.
At weaning (postnatal day 21) all dams were anaes-
thetized with ethyl ether, killed by decapitation and
subjected to postmortem examination. All major organs
were macroscopically inspected and weighed (liver, heart,
spleen, kidneys, ovaries and uterus). Livers were fixed in a
10% neutral buffered formalin solution for routine proces-
sing and light-microscopic evaluation of sections stained
with haematoxilin-eosin.
2.8. Definition of terms used
Mating index: number of sperm positive females/number
of mated females!100
Pregnancy index: number of pregnant females/number of
sperm positive females!100
F.B. Mello et al. / Toxicon 45 (2005) 459–466 461
Tab
We
and
Day
lact
N:
1P
7P
14P
21P
1L
7L
14L
21L
We
D(d
D(d
Val
resp
Delivery index: number of females delivering/number of
pregnant females!100
Birth live index: number of live offspring/number of
offspring delivered!100
Viability index: number of live offspring at lactation day
4/number of live offspring delivered!100
Weanling index: number of live offspring at day
21/number of live offspring born!100
Post-implantation loss index: number of implantation
sites—number of live fetuses/number of implantation
sites!100.
2.9. Statistical analyses
Data were analyzed by one-way analysis of variance or,
alternatively, by the Kruskal–Wallis test whenever the data
did not fit a normal distribution. Using Tukey test tested
differences between groups. Proportions were analyzed by
the Chi-square test or, alternatively, by the Fischer exact
test. Statistical evaluation was performed using MINITAB
and EXCEL programs, and a difference was considered
statistically significant at P!0.05.
3. Results
3.1. Body weight changes and toxicity in female rats
No deaths were induced and no other signs of toxicity
were apparent in female rats treated orally with hydroalco-
holic extract from Lantana camara var. aculeata leaves with
three doses (1, 3 and 7 g kgK1) during premating, mating,
pregnancy and lactation. No statistically significant differ-
ences among control and Lantana camara treated groups
were found with regard to maternal and offspring weight
le 1
ight development of female rats orally treated with hydroalcoholic extr
7 g kgK1, respectively, LC 1, LC 3 and LC 7, during pregnancy and
s of pregnancy and
ation period:
Control LC 1
14 8
236.2G6.6 238.1G5.
249.8G6.8 245.1G5.
270.8G6.5 271.1G5.
325G7.1 329.1G8.
252.4G5.8 255.7G7.
267G9.8 265.3G7.
278.8G10.3 267.5G6.
272.9G11.7 273.5G7.
ight gain (g)
ay 21P–0P) 96.4G7.4 96.3G6.
ay 21L–1L) 20.6G5.9 17.79G0.
ues are given as meansGSE. Data were analyzed by ANOVA. Days of
ectively. No significant difference among groups was observed.
changes during the lactation period (Table 1). No adverse
effect of Lantana camara extract on pregnancy weight gain
was noted at any dose level (Table 1). There were no
difference in both absolute and relative organs weight
among the groups (Table 2).
3.2. Outcome of fertility tests
As can be seen in Table 3, the proportion of females
impregnated by male rats (mating index), and the ratio of
pregnant per sperm-positive females (pregnancy index) did
not differ between control and Lantana camara treated
groups. There was statistically difference among LC 3 and
LC 7 from control group in the post-implantation loss index.
In Table 4 are showed the other indexes (delivery index,
birth live index, viability index and weaning index). Neither
them showed difference statistically significant among the
groups.
3.3. Evaluation of embryo-fetotoxic effects
Body weight of Lantana camara treated fetuses did
not differ from that control group at any dose level (Tables 4
and 5). However, the two highest doses tested (3 and
7 g kgK1) produced an increase in the resorption rate and
parallel increase the post-implantation loss index (Table 3).
The effects of prenatal exposure to Lantana camara
hydroalcoholic extract on occurrence of fetal skeleton
abnormalities are shown in Table 6. There were differences
between the control and the treated groups. The frequency
of skeleton malformations was increased at 3 g kgK1.
Nonetheless, the higher incidence of skeleton abnormalities
observed at this dose level seems to have been due, to a large
extent, to an increase in the occurrence of anomalies such as
forelimbs poorly ossified and sternebra with incomplete
act from Lantana camara var. aculeata leaves, with three doses 1, 3
lactation period
LC 3 LC 7
6 5
9 241.6G6.8 227.8G5.4
9 253G7.5 239.5G5.5
9 275G8.7 262G6.6
0 322G1.4 320G10.7
3 243G8.6 244.8G14.3
3 252G9.1 250G18.4
6 260G9.1 256.7G18.1
4 259G11 260.3G14.8
02 88.4G9.2 95.4G6.1
08 15.5G5.8 15.6G4.9
pregnancy and days of lactation are indicated by subscripts P and L
Table 2
Relative organs weight (%) from dams treated during premating, mating, pregnancy and lactation periods, with hydroalcoholic extract (70:30)
from Lantana camara var. aculeata
Relative organs weight (%) Control (nZ14) LC 1 (nZ8) LC 3 (nZ6) LC 7 (nZ5)
Heart 0.42G0.01 0.39G0.02 0.42G0.02 0.41G0.03
Spleen 0.19G0.01 0.17G0.01 0.17G0.01 0.19G0.02
Liver 5.78G0.24 6.15G0.25 4.83G0.08 4.99G0.24
Right kidney 0.42G0.01 0.42G0.004 0.41G0.02 0.36G0.01
Left kidney 0.55G0.16 0.39G0.01 0.38G0.02 0.36G0.01
Right ovary 0.03G0.002 0.02G0.002 0.02G0.003 0.02G0.003
Left ovary 0.03G0.002 0.02G0.002 0.02G0.002 0.02G0.003
Uterus 0.15G0.01 0.12G0.01 0.15G0.01 0.10G0.003
Data are given as meansGSE. Data were analyzed by ANOVA. No significant difference among groups was observed.
Table 3
Outcome of fertility tests in rats treated with hydroalcoholic extract from Lantana camara var. aculeata leaves
Outcome Control LC 1 LC 3 LC 7
Mated females (n) 42 20 21 18
Mated males (n) 14 7 7 6
Sperm-positive females (n) 31 14 12 10
Pregnant females (n) 25 13 11 10
Mating Index (%) 73.81 70 57.1 55.5
Pregnancy Index (%) 80.7 92.8 91.67 100
Post-implantation loss Index (%) 0.79 4.47 17.39a 12.7a
Data were analyzed by Chi-square test.a Significantly different (P!0.05) from control group.
Table 4
Reproductive index from dams treated with hydroalcoholic extract (70:30) from Lantana camara var. aculeata, to give birth.
Reproductive Index Control LC 1 LC 3 LC 7
No (dams) pups (14) 146 (8) 84 (6) 53 (5) 43
Number of pups per litter 10.1G0.38 10.4G0.75 8.8G1.32 7.5G1.26
Pups body weight (g) 6G0.06 6.1G0.06 6.1G0.07 5.62G0.22
Delivery index (%) 100 100 100 100
Birth live index (%) 98.9 100 98.9 100
Viability index (%) 98.7 98.8 95.2 97.7
Weanling index (%) 98.7 98.8 95.2 97.7
Data were given as meansGSE and proportions. Proportions were analyzed by Chi-square test. Data are given as meansGSE were analyzed by
ANOVA. No significant difference among groups was observed.
Table 5
Reproductive index from dams treated with hydroalcoholic extract (70:30) from Lantana camara var. aculeata leaves, and parameters evaluated
at the caesarian section performed on pregnancy day 21
Reproductive index Control LC 1 LC 2 LC 3
No (dams) pups (11) 106 (5) 44 (5) 33 (5) 57
Gravid uterus weight (g) 66.29G3.69 62.82G11.7 45.1G17.9 74.8G2.9
Litter size 10.36G0.59 8.8G1.82 11 11.4G0.24
Pups body weight (g) 4.68G0.05 5.04G0.05 4.79G0.05 4.83G0.07
No of pups with external malformations Zero Zero Zero Zero
Data are given as meanGSE. Data were analyzed by ANOVA. No significant difference among groups was observed.
F.B. Mello et al. / Toxicon 45 (2005) 459–466462
Table 6
Occurrence of skeleton abnormalities from dams treated orally with hydroalcoholic extract (70:30) from Lantana camara var. aculeata, with
three doses 1, 3 and 7 g kgK1, respectively, LC 1, LC 3 and LC 7, compared with a control group, during premating, mating and pregnancy
periods
Control LC 1 LC 3 LC 7
Fetuses examined (n) 106 44 33 57
Fetuses with skeleton abnormalities (%) 13.2 29.55a 39.4a 29.82a
Fetuses with anomalies in (%)
Forelimbs
Poorly ossified 0 2.27 12.13 0
Skull
Os interparietalis (incpl. ossif.) 0 0 0 7.01
Os interparietalis (disconnected) 0 0 0 1.75
Os parietalis (incpl. ossif.) 0 0 0 3.51
Os parietalis (additional ossif. Center) 0.94 0 0 0
Os supraoccipitalis (incpl. ossif.) 0 0 0 1.75
Os supraoccipitalis (disconnected) 0 0 0 1.75
Sternum
Sternebra (incpl. ossif.) 0.94 2.27 15.2 3.51
Sternebra (irreg. Shaped) 4.72 9.1 0 7.01
Additional ossification center 0.94 0 0 0
Ossification center absent 0 0 6.1 0
Thorax
Ribs (bent) 0 2.27 6.1 0
Additional ossification center 0 0 6.1 0
Vertebral column
Vertebral lateral (incpl. ossif.) 0 4.54 3.03 0
Thoracic
Additional ossification center 0 4.5 0 0
Lumbar
Irregular shaped (dumb-bell) 0.94 2.27 0 0
Additional ossification center 3.77 0 0 8.8
Ossification center bicentric 0.94 0 0 0
Incpl. ossif. 0 0 3.03 0
Cervical
Additional ossification center 0.94 0 0 0
All skeleton
Poorly ossified 0 9.1 0 0
Data were analyzed by the Chi-square test. Abbreviations: incpl. ossif, incomplete ossification.a Significantly different (P!0.05) from controls.
F.B. Mello et al. / Toxicon 45 (2005) 459–466 463
ossification. Anyhow, the higher incidence of skeleton
abnormalities as well as the embryolethal effect clearly
indicated that the doses 3 and 7 g kgK1 are embryotoxic to
rats.
3.4. Perinatal toxicity and postnatal development
of the exposed offspring
As shown in Table 1, duration of pregnancy was not
affected by treatment with Lantana camara hydroalcoholic
extract at any dose level. No adverse effect of Lantana
camara on labor was noted in this experiment, during
the entire lactation period, from postnatal day 1 through to
day 21 (Table 7). The peri- and postnatally exposed to
hydroalcoholic extract from Lantana camara var. aculeata
did not cause any signal of retardation on developmental
characteristics as: ear unfolding, development of fur, incisor
eruption, eye opening (Table 8), testes decent, prepucial
separation and vaginal opening (Table 9).
4. Discussion
Results suggested that the female fertility was not
affected by continuous treatment with hydroalcoholic
extract from Lantana camara var. aculeata, for 14 days
prior to mating and during the mating period. The
percentages of Lantana camara-treated females that copu-
lated (mating index) and were impregnated by males
(pregnancy index) did not differ from those obtained from
the control group at any dose level.
Data shows that the relative organs weight did not differ
among the groups. The livers from female rats treated with
extract during premating, mating, pregnancy and lactation
Table 7
Body weight gain of the pups (g), exposed to hydroalcoholic
(70:30) extract from Lantana camara var. aculeata leaves (1, 3 and
7 g kgK1) during the entire lactation period, from postnatal day 0
through to day 21
Day Control LC 1 LC 3 LC 7
0 6.23G0.05 6.11G0.06 6.14G0.07 5.65G0.22
7 12.52G0.15 13.1G0.14 13.2G0.25 12.09G0.32
14 22.2G0.23 21.6G0.23 21.8G0.54 20.54G0.49
21 31.8G0.4 32.17G0.58 30.6G0.95 30.28G0.69
Data were analyzed by ANOVA. Values are given as meanGSE.
No significant difference among groups was observed.
F.B. Mello et al. / Toxicon 45 (2005) 459–466464
periods, showed some degenerative lesions like as already
described (Sharma et al., 1981; Frisch et al., 1984; Munyua
et al., 1990).
The maternal deaths as well as the decrease in overall
weight gain during pregnancy, are indications that there was
maternal toxicity. These maternally toxic doses of any
substance also proved to be embryofeto-toxic as revealed by
three outcomes evaluated: embryolethality, prenatal growth
retardation and fetal malformations (Souza et al., 1997).
The dams did not present any sign of toxicity and neither
decrease in maternal weight gain, which is an indirect
evaluation of toxicity, did not differ significantly between
the treated groups and the control.
The preimplatation period of pregnancy is considered to
be ‘all-or-none’ period, the period during which maternal
exposure to exogenous agents may cause either embryo
lethality or normal development of the embryo with a
normal fetus at delivery (Lemonica et al., 1996). Some
investigators have reported an increase in the number of
Table 8
Physical signs of postnatal development of offspring of rats treated oral
aculeata leaves (1, 3 and 7 g kgK1) during the pregnancy and lactation pe
Postnatal
day
Ear unfolding (%) Development of fur (%)
C LC1 LC3 LC7 C LC1 LC3 LC7
2 52.4 54.2 71.4 54.8 – – – –
3 90.4 81.9 100 100 – – – –
4 98.6 97.6 – – – – – –
5 100 100 – – – – – –
6 – – – – 6.9 – 90.6 –
7 – – – – 99.3 26.5 100 16,7
8 – – – – 100 100 – 100
9 – – – – – – – –
10 – – – – – – – –
11 – – – – – – – –
12 – – – – – – – –
13 – – – – – – – –
14 – – – – – – – –
15 – – – – – – – –
16 – – – – – – – –
17 – – – – – – – –
18 – – – – – – – –
Data were analyzed by the Chi-square test.
anomalies in fetuses whose mothers received chemical
agents during this period (Giavini et al., 1990).
It is generally accepted that prenatal growth retardation
and an increase resorption rate can be secondary to
substance-induced maternal toxicity (Manson and Kang,
1994).
According to this study, the increase of post-implan-
tation loss index was statistically different from the control
and LC 3 and LC 7 groups, suggesting that the extract
induced embryotoxicity in these groups, without any sign of
maternal toxicity. The tendency to an increase in the post-
implantation loss reported here, may have occurred due to a
toxic effect of the extract on the embryo.
The role of maternal toxicity in causing fetal malfor-
mations, however, is still a matter of controversy. Published
data and the relationship between maternal toxicity,
malformations and embryotoxicity were reviewed (Khera,
1984 and 1985). In the mouse, even malformations as severe
as neural tube defects, fused or missing ribs, and fused or
scrambled sternebrae could be caused by maternal toxicity
(Khera, 1984). On the other hand, in rats and rabbits,
maternal toxicity was associated with gross structural
anomalies such as fused, supernumerary, missing or wavy
ribs; fused, missing or split vertebrae, and fused, missing or
non-aligned sternebrae (Khera, 1985). Although most
authors do not agree with the conclusion that major
malformations (exencephaly and open eyes) can be
secondary to maternal toxicity, it is generally accepted
that some variations and reversible minor structural
anomalies (extra or wavy ribs) could result from maternal
toxic effects. An increased frequency of variations and
minor malformations found only at maternally toxic doses
ly with hydroalcoholic (70:30) extract from Lantana camara var.
riod
Incisor eruption (%) Eye opening (%)
C LC1 LC3 LC7 C LC1 LC3 LC7
– – – – – – – –
– – – – – – – –
– – – – – – – –
– – – – – – – –
– – – – – – – –
– – – – – – – –
7.2 21.9 66 7,5 – – – –
96.3 37.2 100 42,5 – – – –
100 100 – 100 – – – –
– – – – – – – –
– – – – – – – –
– – – – 27.7 43.4 35.8 38.7
– – – – 65.4 57.9 64.1 71
– – – – 85.4 83.2 98.1 100
– – – – 100 96.4 100 –
– – – – – 100 – –
– – – – – – – –
Table 9
Sexual signs of postnatal development of offspring of rats treated orally with hydroalcoholic (70:30) extract from Lantana camara var. aculeata
leaves (1, 3 and 7 g kgK1) during the pregnancy and lactation period
Postnatal
day
Testes decent (%) Prepucial separation (%) Vaginal opening (%)
C LC1 LC3 LC7 C LC1 LC3 LC7 C LC1 LC3 LC7
14 2.8 2.6 18.5 – – – – – – – – –
15 31.2 38.5 22.2 81.3 – – – – – – – –
16 59.6 82.1 81.5 100 – – – – – – – –
17 71.8 100 100 – – – – – – – – –
18 96.1 – – – – – – – – – – –
19 100 – – – – – – – – – – –
20 – – – – 4.3 71.8 51.8 – – – – –
21 – – – – 11.4 74.3 66.7 – – – – –
22 – – – – 12.9 82 77.8 – – – – –
23 – – – – 82.9 97.4 88.9 25 – – – –
24 – – – – 100 97.4 100 93.6 – – – –
25 – – – – – 100 – 100 – – – –
26 – – – – – – – – – – – –
27 – – – – – – – – – – – –
28 – – – – – – – – – – – –
29 – – – – – – – – – – – –
30 – – – – – – – – – – – –
31 – – – – – – – – – – – –
32 – – – – – – – – – – – –
33 – – – – – – – – – – – –
34 – – – – – – – – 11.3 2.3 23.1 19
35 – – – – – – – – 21 11.4 30.8 28.5
36 – – – – – – – – 33.9 13.7 35 38
37 – – – – – – – – 42 16 38.4 57
38 – – – – – – – – 67.8 25.1 50 57
39 – – – – – – – – 75.9 27.4 65,4 57
40 – – – – – – – – 90.4 31.9 69.2 76
41 – – – – – – – – 95 41 73.1 80.8
42 – – – – – – – – 100 72 80.8 90.3
43 – – – – – – – – – 100 100 100
Data were analyzed by the Chi-square test.
F.B. Mello et al. / Toxicon 45 (2005) 459–466 465
does not necessarily reflect the teratogenic potential of the
test substance (Souza et al., 1997).
The groups that received the plant extract showed a
significant increase in number of malformations or
anomalies.
The examinations of the skeleton of fetuses are carried
out within the terms of reference of the tests of chemical
substances for embryotoxicity (Lorke, 1977). This author
classify deviations from normal found on the skeleton as
follows: individual variations of normal, developmental
retardation of the skeleton (retardation effects) and
malformations.
The skeleton alterations found on the three groups
treated with Lantana camara hydroalcoholic extract, are
developmental retardation of the skeleton (retardation
effects).
According to the results, it is possible to suggest that the
constituents fromLantanacamaravar.aculeata: lantadeneA,
lantadene B, lantadene C, lantadene D, reduced lantadene
A and reduced lantadene B, are responsible to cause these
alterations on the fetuses skeleton.
A relationship between Lantana camara active
principles and teratogenic effects was establish for the first
time.
The importance of these findings are relevant because
the extensive use of Lantana camara in folk medicine with
repercussion in human health. Animals could also consume
this plant during the pregnancy period, producing terato-
genic alterations in their offspring.
The possibility that the exposure of the embryo to certain
chemical substances can lead to physical and behavioral
disturbances is known from human and animal epidemio-
logical studies (Gerenutti et al., 1992).
The development of fur, ear unfolding, incisor eruption
and eye openings, did not differ among the groups. There
were no difference of testicle descent, vaginal opening and
prepucial separation of experimental and control groups,
suggesting that the Lantana camara hydroalcoholic extract
F.B. Mello et al. / Toxicon 45 (2005) 459–466466
did not interfere in the development of the hypothalamic-
pituitary-gonadal axis.
Acknowledgements
This work was supported by the Conselho Nacional de
Desenvolvimento Cientıfico e Tecnologico (CNPq), the
Fundacao de Amparo a Pesquisa do Rio Grande do Sul, and
Pro-Reitoria de Pesquisa da UFRGS.
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