Muhammad Furqan Akhtar1, Sobia Younas1, Ammara Saleem2, Mirza Muhammad Faran Ashraf Baig3, Ali Sharif4, Mohamed M Abdel-Daim5,6, Azhar Rasul7, Mohammad Saleem8. 1. Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore Campus, Lahore, Pakistan. 2. Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan. 3. Research and Biomedical Engineering for Novel Biofunctional, and Pharmaceutical Nanomaterials, Faculty of Dentistry, Prince Philip Dental Hospital, The University of Hong Kong, Hong Kong, China. 4. Institute of Pharmacy, Faculty of Pharmaceutical and Allied Health Sciences, Lahore College for Women University, Lahore, Pakistan. 5. Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, Jeddah, Saudi Arabia. 6. Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt. 7. Department of Zoology, Government College University Faisalabad, Faisalabad, Pakistan. 8. Department of Pharmacology, Punjab University College of Pharmacy, University of the Punjab, Lahore, Pakistan.
Abstract
OBJECTIVES: Tramadol, an atypical opioid, is clinically efficacious in treating moderate to severe pain. The aim of current study was to find out the toxicological effects of tramadol exposure to pregnant rats and fetuses during the late phase of pregnancy. METHODS: Wistar pregnant rats were exposed to 1.25, 2.5, or 5 mg/kg/day tramadol from 14th to 20th day of pregnancy. The same therapy was given to nonpregnant rats for 7 days. The body weight, oral glucose and lipid tolerance tests, and effect on complete blood parameters in both pregnant and nonpregnant rats were determined. On 20th day, maternal placentas were excised and weighed while fetuses were observed for any deformity and growth retardation. Oxidative stress biomarkers were estimated in the liver and kidney tissue homogenates of the pregnant and nonpregnant rats while the whole fetus homogenate was processed for the same. Moreover, histopathology of the liver and kidney of pregnant and nonpregnant rats were carried out. RESULTS: Tramadol administration did not significantly alter the area under curve of the blood glucose and triglyceride levels in both the pregnant and nonpregnant rats. It reduced the live fetuses, placental weights, fetal length, and fetal weights. Tramadol treated pregnant rats showed significantly (p < .05) reduced red blood cells, hematocrit, hemoglobin, and platelets with reference to control group. Similarly, structural abnormalities and malfunctioning of the liver and kidney of pregnant rats were instituted; however, it did not affect the structural integrity of nonpregnant rats. A substantial (p < .001-.0001) altered glutathione and malondialdehyde levels in the fetuses, pregnant, and nonpregnant animals (tissue homogenates) at all dosage levels were indicative of tramadol induced oxidative stress. Furthermore, tramadol exposure resulted in more significant (p < .01-.001) alteration of lipid profile in the pregnant than the nonpregnant animals. CONCLUSION: Acquired results suggested the maternotoxic and fetotoxic effects of tramadol exposure during the late gestation period.
OBJECTIVES: Tramadol, an atypical opioid, is clinically efficacious in treating moderate to severe pain. The aim of current study was to find out the toxicological effects of tramadol exposure to pregnant rats and fetuses during the late phase of pregnancy. METHODS: Wistar pregnant rats were exposed to 1.25, 2.5, or 5 mg/kg/day tramadol from 14th to 20th day of pregnancy. The same therapy was given to nonpregnant rats for 7 days. The body weight, oral glucose and lipid tolerance tests, and effect on complete blood parameters in both pregnant and nonpregnant rats were determined. On 20th day, maternal placentas were excised and weighed while fetuses were observed for any deformity and growth retardation. Oxidative stress biomarkers were estimated in the liver and kidney tissue homogenates of the pregnant and nonpregnant rats while the whole fetus homogenate was processed for the same. Moreover, histopathology of the liver and kidney of pregnant and nonpregnant rats were carried out. RESULTS: Tramadol administration did not significantly alter the area under curve of the blood glucose and triglyceride levels in both the pregnant and nonpregnant rats. It reduced the live fetuses, placental weights, fetal length, and fetal weights. Tramadol treated pregnant rats showed significantly (p < .05) reduced red blood cells, hematocrit, hemoglobin, and platelets with reference to control group. Similarly, structural abnormalities and malfunctioning of the liver and kidney of pregnant rats were instituted; however, it did not affect the structural integrity of nonpregnant rats. A substantial (p < .001-.0001) altered glutathione and malondialdehyde levels in the fetuses, pregnant, and nonpregnant animals (tissue homogenates) at all dosage levels were indicative of tramadol induced oxidative stress. Furthermore, tramadol exposure resulted in more significant (p < .01-.001) alteration of lipid profile in the pregnant than the nonpregnant animals. CONCLUSION: Acquired results suggested the maternotoxic and fetotoxic effects of tramadol exposure during the late gestation period.