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This research paper investigates the impact of repeated administration of ivermectin alone or in combination with vitamin c on the sexual hormones and fertility of female rabbits. The study reveals significant changes in estradiol, progesterone, follicular stimulating hormone (fsh), and luteinizing hormone (lh) levels, as well as the effect on pregnancy. The results suggest that ivermectin has adverse effects on female rabbit's reproductive efficacy, while vitamin c does not show significant beneficial effects.
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ABSTRACT This study was designed to investigate the effect of repeated administration of Ivermectin alone or with combination of vitamin C on sexual hormones.Besides, an attempt had been done to demonstrate the effect of ivermectinon fertility and pregnancy efficacy of female rabbits. Ninety sixmature female rabbits were used in this study and two experiment had been done. Each experiment were divided into8 groups of equal number(6) as fol- lows: group onewas administered 0.9% Nacl which act as control, Group two, three& fourwere administered (0.5mg/ Kg, 1mg/Kg, 2mg /Kg B.W Ivermectin)respectively, Group fivewas administered 50mg/Kg B.W vitamin C only, Group six, seven & eight were administered 50mg/Kg vitamin C in addition to Ivermectin (0.5mg, 1mg, 2mg respectively).The Ivermectin was given S/C weekly, while vitamin C was given daily P.O. for 8weeks. The results showed significant decrease (P˂ 0.05) in Estradiol level in 3rd , 4th , 6th , 7th& 8th groups, while proges- terone level clarified significant increase (P˂0.05) in 5th& 7th groups, the FSH level postulated significant increase (P˂0.05) in 4th , 5th& 6th groups, meanwhile, the LH level did not show significant difference in all treated groups as compared with the control group. The results of fertility study revealed adverse effect of ivermectin therapy on fertility and block the pregnancy in all treated group except the fifth group which administered vitamin C only as compared with control group and their effect persistent in second mating in intermediate dose(1mg/Kg Ivermectin) and high dose (2mg/Kg Ivermectin) groups alone and with combination with vitamin C. In conclusion: Ivermectin has adverse effects on reproductive efficacy on female rabbits, as well as, the vitamin C hasnot well emphasized beneficial effects on re- production.
Introduction Ivremectin is a semisynthetic macrocyclic lactone and acts as abroad spectrum antiparasitic drug against many in- ternal and external parasites (1). It consists of a mixture of two compound 22,23 dihydroavermectin B1a(H2B1a) and 22,23 dihydroavermectin B1b(H2B1b), Moreover, it contains no less than 80% H2B1a and no more than 20% H2B1b (2). Others studies has been used vitamin A and E in combination of ivermectin (3).The literature survey showed that ivermectin determined effect on the repro- ductive performance of ewe during the breeding season (4). However, many studies showed an adverse effects of ivermectin om male reproductive system such us on goat (5), bull (6), ram (7). little researches had been published on adverse effect of ivermectin on female reproduction, as well as, up to our knowledge no previous studies had been done on ivermectin with vitamin C combination, so it was deemed of interest to investigate the effect of re- peated administration of ivermectin on reproductive sys- tem of female rabbits and also to highlight whether the combination of vitamin C with ivermectin has ameliorative effect.
Materials and Methods The Ivermectin 10% purchased from local market (VET Product Office, KIPRO Company, Holland) and Vitamin C 500mg (AlShahba Labo, Syria).The FSH, LH & progester- one were done according to appropriate Elisa kit from Hu- man, GmbH Ltd. Germany, while Estradiol from Monobind Inc. lake Forest,CA92630, USA.
Animal housing Ninety six mature female rabbits ( Lepus cuniculus ), (1200- 2000gm) body weight and (8-12 months) of age were brought from local market in Basra Province/ Iraq. The rabbits were housed (6 rabbits / cage) in a wire silk cag- es measuring (100 X 50 X 50 cm) under controlled ani- mal house condition at temperature (25 ± 3 Co) and rela- tive humidity (50 ± 5 % ) in the animal house of Veterinary Medicine College in Basra University. The rabbits were kept under observation for one months. The animals were offered add libtium a rabbit’s diet, green leaves, alfalfa, and water.
Experimental Design Two experiments had been done:
I-Hormonal Experiment Forty eight mature female rabbits were divided into eight groups (6 rabbits in each group). Each group was treated for 8week as follow: Group one :Injected (0.9 % NaCl) which acts as a control, Group two: Injected (0.5 mg/ kg B.W Ivermectin),Group three: Injected (1mg/kg B.W Ivermectin),Group four: Injected (2 mg/kg B.W Ivermectin), Group five : administered 50mg/ Kg B.W Vitamin C only, Group six : Injected (0.5 mg/Kg B.W Ivermectin +50mg/kg B.W Vit.C), Group seven: Injected (1mg/kg B.W Ivermectin + 50mg/Kg B.W Vit. C), and Group eight: Injected (2mg/ Kg B.W Ivermectin +50mg/kg B.W Vit. C).The Ivermectin were given subcutaneously and weekly, while vitamin C were giv- en daily and orally. At the end of experiment (8 Weeks), the blood samples were taken directly from the heart by using
INDIAN JOURNAL OF APPLIED RESEARCH X 71
disposable syringe and put in screw tube without anticoagu- lant then centrifuged at 4000 rpm for 10 minutes to get se- rum for hormonal assay (E2, Proges. FSH&LH).
II-Fertility Experiment Another Forty-eight mature female rabbits were similarly chosen randomly and divided into 8 groups of equal num- ber (6 rabbit/ group) and the treatment were also similar to the first experiments. After 8 week of treatment, a known fertile male rabbits (2 male/group) were mated with the female rabbits in each groups to estimate the pregnancy and number of offspring’s after one month, then the mat- ing was extended to another one months to study persis- tent the effect of treatment.
Statistical analysis The results were analysed by one- way ANOVA test. When significant differences were found, the means were com- pared using least significant difference (LSD). All statistical calculations were carried out by the aid of the statistical SPSS V. 22 (SPSS Inc.)
Results Experiment one Hormonal assay The effect of Ivermectin alone or with the combination of vitamin C on sexual hormones (Estradiol, proges- terone, Follicular stimulating hormone and luteinizing
hormone) of female rabbits after 8 weeks of treatment clarified in Table (1).The Estradiol (E2) level in the 3 rd^ , 4 th^ , 6 th^ , 7 th^ , and 8 th^ groups revealed significant decrease (p < 0.05) in Estradiol level as compared with control group. The progesterone level showed significant in- crease (p< 0.05) in 5 th^ and 7 th^ .The follicular stimulating hormone (FSH)in 4 th^ ,5 th^ and 6 th^ groups clarified signifi- cant increase (p < 0.05)in level in comparison with con- trol group. However, the luteinizing hormone (LH) in all treated groups showed no significant differences as compared with control group.
Experiment Two Fertility and pregnancy As illustrated on Table (2), after 8 weeks of treatment, in first mating there are absent of pregnancy in all treated groups except in control group which administered nor- mal saline and group which given 50mg/Kg B.W vitamin C daily.
At second mating there are notice pregnancy in second and sixth groups which injected 0.5mg/Kg B.W Ivermectin alone and group which injected 0.5mg/Kg B.W Ivermec- tin+ vitamin C, in addition to control group and group five which administered vitamin C only.
Table (1): Effect of ivermectin alone or with the combination of vitamin C on sexual hormone in female rabbits after 8 weeks of treatment. (Mean ±SE), n=6/ group
E ng/ml
Prog. ng/ml
ng/ml
ng/ml
1 st^ Group Control 0.9%Nacl
a
cd
b
2 nd^ Group (0.5mg/Kg IVM)
abc
bcd
bc
3 rd^ Group (1mg/Kg IVM)
c
bcd
bc
4 th^ Group (2mg/Kg IVM)
bc
ac
ac
5 th^ Group 50mg/Kg Vit.C
ac
ab
ac
6 th^ Group (0.5mg/Kg IVM) +(50mg/Kg Vit.C)
bc
d
ae
7 th^ Group (1mg/Kg IVM) + (50mg/Kg Vit.C)
bc
a
bc
8 th^ Group (2mg/Kg IVM)
bc
bcd
bc
Table (2): Effect of Ivermectin alone and with combination of vitamin C on fertility and pregnancy efficacy of female rabbits after 8 weeks of treatment. n=6/ group.
First mating Second mating NO. pregnant NO. offspring No. pregnant NO. offspring 1 st^ Group Control 0.9% Nacl 5 16 5 16 2 nd^ Group 0.5mg/Kg IVM 0 0 1 3 3 rdGroup 1mg/Kg IVM 0 0 0 0 4 thGroup 2mg/Kg IVM 0 0 0 0 5 thGroup 50mg/Kg Vit.C 6 20 6 20 6 thGroup 0.5mg/Kg IVM + 50mg/Kg Vit.C 0 0 2 6 7 thGroup 1mg/Kg IVM + 50mg/Kg Vit.C 0 0 0 0 8 thGroup 2mg/Kg IVM + 50mg/Kg Vit.C 0 0 0 0
INDIAN JOURNAL OF APPLIED RESEARCH X 73
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