Abstract
The presented study was conducted to investigate the effects of different doses of tramadol on the prenatal foetuses of rat at 20th day of gestation. The animals were divided into five groups; Control group (C), received saline orally; G1administered with (1/6 LD50; 50 mg/kg); G2 was given (1/10 of LD50; 30 mg/kg) and G3& G4 were treated with low doses of tramadol (1/50 of LD50; 6 mg/kg) and (1/100 of LD50; 3 mg/kg) respectively. Males and females were administered with tramadol for 7 days before mating, then they mate with each other and pregnant females continued treatment with tramadol to the 20th day of gestation. Tramadol significantly decreased body weight and length of foetuses and increased percentage of dead foetuses. Besides the early death of foetuscs which become resorbed during the gestation period, few foetuses died at the end of gestation period and remain as stillbirth. The percentage of mortality of resorbed foetuses and sillbirth is generally increased in the treated groups. Tramadol treatment caused retarded ossification of some bones and shortness of others. Numerous histopathological changes were detected in liver, kidneys, and lungs of the parentally treated foetuses rat tissues. Â
Highlights
Opioids are compounds that bind to opiate receptors
A significant decrease in body weight of foetuses (2.2 ± 0.18), (2.7 ± 0.17) (3.6 ± 0.18 and 4.2 ± 0.2) was observed in (1/6 LD50 (G1), G2, G3 and G4 respectively as compared to control group (5.4 ± 0.12).As well as a significant declined in the body length of foetuses in the different treated groups; (3.1 ± 0.17),G1; (3.5 ± 0.14),G2 ;(4.1 ± 0.16),G3 ; and ( 4.6 ± 0.3),G4, respectively as compared to control group (5.1 ± 0.2).Examining the gross morphology of foetuses of parentally –treated with Tramadol revealed the presence of pattern of congenital malformations including kyphotic body, kinky tail and presence of superficial haematomas in different parts of the body (Fig.2)
A significant decrease in the total number of foetuses in all treated groups with Tramadol; (38.3% and in alive foetuses by 53.3%), G1; (33.3% and alive fetuses by 46.6%), G2; G3 &G4 that were given low doses of tramadol displayed a notable decline in total number by (16.6% and 11.6%) and in alive foetuses by (23.3% and 16.6%) respectively, as compared to control group
Summary
Opioids are compounds that bind to opiate receptors. Opioids include alkaloid opioids, derived from the opium poppy, morphine and codeine. Opioid drugs are used for a range of conditions in pregnancy. Previous studies have demonstrated the harmful effects on the foetus/child of maternal abuse of opiates or opioids during pregnancy (Wendell, 2013). Women who were given analgesic medications during pregnancy (the first trimester) showed harmful effects in foetuses. Increased medical use of tramadol and the pharmacological properties of the drug make studies of its possible effect on malformation risk crucial. The present study aimed to investigate the adverse effects of the parentally treated foetuses of rat with high and low doses of tramadol. Tramadol is a synthetic opioid analogue of codeine first synthesized in 1962 by Grunenthal in an attempt to reduce common opioid adverse effects such as respiratory depression (Alvarado et al ., 2005). These effects include; edema, siderophages, pulmonary hemorrhage, pulmonary artery hypertrophy, bronchiolitis obliterans, panacinar emphysema, interstitial pneumonia and fibrosis (Karch & Stephens, 2000)
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