Repeated Administration of Clinically Relevant Doses of the Prescription Opioids Tramadol and Tapentadol Causes Lung, Cardiac, and Brain Toxicity in Wistar Rats.

摘要: Tramadol and tapentadol, two structurally related synthetic opioid analgesics, are widely prescribed due to the enhanced therapeutic profiles resulting from synergistic combination between μ-opioid receptor (MOR) activation monoamine reuptake inhibition. However, number of adverse reactions has been growing along with their increasing use misuse. The potential toxicological mechanisms for these drugs not completely understood, especially owing its shorter market history. Therefore, in present study, we aimed comparatively assess putative lung, cardiac, brain cortex damage elicited by repeated exposure doses both prescription opioids. To this purpose, male Wistar rats were intraperitoneally injected single daily 10, 25, 50 mg/kg tramadol or corresponding a standard analgesic dose, an intermediate maximum recommended respectively, 14 consecutive days. Such treatment was found lead mainly lipid peroxidation inflammation lung tissues, as shown through augmented thiobarbituric acid reactive substances (TBARS), well increased serum biomarkers, such C protein (CRP) tumor necrosis factor-α (TNF-α). Cardiomyocyte integrity also be affected, since opioids incremented lactate dehydrogenase (LDH) α-hydroxybutyrate (α-HBDH) activities, while tapentadol associated creatine kinase muscle (CK-MB) isoform activity. In turn, analysis metabolic parameters tissue revealed concentration upon drugs, LDH (CK) activities following treatment. addition, pneumo- cardiotoxicity biomarkers quantified at gene level, neurotoxicity levels; changes expression correlate oxidative stress, inflammatory, metabolic, histopathological that detected. Hematoxylin eosin (H & E) staining several alterations, including alveolar collapse destruction sections, inflammatory infiltrates, altered cardiomyocytes loss striation heart degenerated neurons, accumulation glial microglial cells sections. Masson's trichrome confirmed fibrous deposition cardiac tissue. Taken whole, results show administration extends dose range which injury is observed lower doses. They reinforce previous assumptions devoid risk even clinical