The effect of tilmicosin on fetal development in pregnant female rats was investigated in this study. Forty pregnant female rats were divided into four groups (each of 10 female rats). Rats in the 1st, 2nd and 3rd groups were received tilmicosin at a dose of 20, 100, 200 mg/kg ·b ·wt/day orally from the 6th to 15th day of gestation respectively, while the 4th group received 0.5 ml distilled water orally for the same period of gestation and was used as control group. All the pregnant female rats were sacrificed on the 20th day of gestation and their fetuses were subjected to morphological, visceral and skeletal examinations. Tilmicosin at a dose 100, 200 mg/kg ·b ·wt significantly decreased the number of viable fetuses; the number of resorbed fetuses was increased, and induced retardation in growth of viable fetuses; some skeletal and visceral defects in these fetuses were observed and these effects were dose dependant. It could be concluded that tilmicosin caused some abnormalities and fetal defects, so it is recommended to avoid using pregnancy.
Macrolide antibiotics are frequently used for presumed or documented Gram-positive lower and upper respiratory infections, Helicobacter pylori-related peptic ulcer and soft tissue infections. Moreover, for the treatment of chlamydia and other selected infections in pregnancy [
Most therapeutic agents cross placental barrier and enter the circulation of fetus. Every drug given during pregnancy has tendency to produce some sort of structural abnormalities in the neonate [
The study of abnormal prenatal development and congenital malformations caused by physical agents or exogenous chemical is a growing area of medical research in the quest for the eradication of preventable birth defects. Defects of birth are known to occur in large numbers; roughly 7% to 10% of all children require an extensive health care to diagnose or treat a birth defect; this compromises the quality of life of millions of people worldwide [
Tilmicosin (TILMI 25% ®) in the form of water solution contains tilmicosin as tilmicosin phosphate 250 mg/ml, manufactured by KEPRO B.V, Holland.
The experiment was carried out on forty mature healthy female Wister albino rats. The used rats were 8 - 10 months and 210 - 250 gm, obtained from animal mouse colony of faculty of Veterinary Medicine Benha University. Animals were kept under hygienic conditions and fed on balanced ration and water ad libitum. Female rats were examined periodically using vaginal smear test to ensure that they were always in a regular estrous cycle [
The pregnant rats were divided into four groups each of 10 rats. Rats were given timicosin orally from the 6th to 15th days of gestation.
1) The 1st group received timicosin orally at a dose of 20 mg/kg∙b∙wt/day.
2) The 2nd group received timicosin orally at a dose of 100 mg/kg∙b∙wt/day.
3) The 3rd group received timicosin orally at a dose of 200 mg/kg∙b∙wt/day.
4) The 4th group received 0.5 ml of distilled water orally for the same period, behaved as control group.
All females were killed on the 20th day of pregnancy and their uteri were dissected in order to examine the position and number of viable, resorbed, or dead fetuses. The surviving fetuses were weighed and the length from crown to rump was measured and examined for any external gross malformations, while others were stained by alizarin red for skeletal examination [
The obtained results from the experiment were expressed as mean ± SEM and were analyzed by using SPSS program (one way ANOVA). Differences were declared significant at P < 0.05.
The obtained results indicated that oral administration of tilmicosin from the 6th to 15th day of pregnancy produced significant decrease in number of viable fetuses; fetal body weight and length were shown in
Fetal body length (cm) X ± S.E | Fetal body weight (g) X ± S.E | Number of dead fetuses X ± S.E | Number of resorbed fetuses X ± S.E | Number of viable fetuses X ± S.E | Animal group |
---|---|---|---|---|---|
3.48 ± 0.053* | 4.70 ± 0.052* | - | - | 9.30 ± 0.300 | 1st group |
3.56 ± 0.052* | 3.93 ± 0.019* | - | - | 7.40 ± 0.699* | 2nd group |
2.81 ±0.047* | 3.09 ± 0.054* | - | 2.1 ± 0.6 | 3.30 ± 0.948* | 3rd group |
4.45 ± 0.062 | 4.98 ± 0.047 | - | - | 9.2 ± 0.326 | 4th group |
*P < 0.05.
Parameters | 1st group | 2nd group | 3rd group | 4th group |
---|---|---|---|---|
Number of examined fetuses | 24 | 24 | 24 | 24 |
Lung hypoplasia | - | 3 (12.5%) | 5 (20.83%) | - |
Heart enlargement | - | 4 (16.66%) | 6 (25%) | - |
Brain diverticulum | - | 6 (25%) | 6 (25%) | - |
Thymus hypoplasia | - | 5 (20.83%) | 7 (29.16%) | - |
%: percent of total abnormalities in relation to the number of examined fetuses.
poplasia with cardiac enlargement
Oral administration of tilmicosin in doses (100 and 200 mg/kg∙b∙wt) to female pregnant rats induced significant decrease in the number of viable fetuses/mother when compared with control group without any fetal death. Significant decrease in number of feti/mother might be attributed to the lack of oval production or of the basic cell constituent as a result of drug administration [
Significant increase in the number of resorbed fetuses in the present study might be attributed to the interference of tilmicosin with the placental transmission of leucin amino acid and magnesium as deficiency of leucin or magnesium produced high incidence of fetal resorptions [
Administration of tilmicosin to female pregnant rats during the period of organogenesis produced significant decrease in both weight and length of fetuses. This result was consistent with [
Parameters | 1st group | 2nd group | 3rd group | 4th group |
---|---|---|---|---|
Number of examined fetuses | 24 | 24 | 24 | 24 |
Skull | - | 2 (8.33%) | 3 (12.5%) | - |
Sternbrea | - | 2 (8.33%) | 4 (16.66%) | - |
Ribs | - | - | 1 (4.16%) | - |
Digital bone | - | 1 (4.16%) | 3 (12.5%) | - |
Caudal vertebrae | - | 2 (8.33%) | 3 (12.5%) | - |
%: percent of total abnormalities in relation to the number of examined fetuses.
Administration of tilmicosin at a dose 100, 200 mg/kg∙b∙wt to female pregnant rats during the period of organogenesis induced many fetal visceral abnormalities as diverticulum dilatation in the brain of fetuses. The obtained result was consistent with [
Pulmonary hypoplasia with cardiac enlargement due to tilmicosin administration at a dose of 100, 200 mg which was a dose dependent may be attributed to disturbance of the metabolism of arginine in fetus [
Oral administration of tilmicosin at a dose 100, 200 mg/kg∙b∙wt to female pregnant rats resulted in hypoplasia of thymus gland which was a dose dependent. Tacrolimus might impair thymic microenvironment and disturb the thymocyte maturation [
Impaired ossification of skull, absence of sternbrae, reduction or absence of caudalvertebrae, absence of digit’s bone of fore and hind limb and absence of some metacarpal and metatarsal bone after administration of tilmicosin at dose 100 and 200 mg/kg∙b∙wt might be attributed to the disturbance in metabolism of some minerals as magnesium and zinc in fetus, or to the interference of the drug to the placental transmission of magnesium and zinc from the mother to the fetus [
Because of the negative relationship between Mg and PTH [
Administration of tilmicosin during period of organogenesis especially at high doses could induce some fetal defects and abnormalities, so it is advisable to avoid using during pregnancy.
The authors declare that there are no conflicts of interest.
Seham Abo-Kora,Amany El-Meleh,Mohamd Aboubakr, (2016) Effect of Tilmicosin on Fetal Developments in Pregnant Female Albino Rats. Pharmacology & Pharmacy,07,147-152. doi: 10.4236/pp.2016.74019