High Doses of PDE5 inhibitors and tramadol reversibly alters haematological parameters in rats

Abstract

This study examined the effect of chronic administration of PDE5 inhibitors and tramadol on haematological indices because of their reported high incidence of abuse. Additionally, the possibility of reversal of negative effects following withdrawal of treatment was examined. Fifty male rats (180 -200g body weight) were grouped into five (n = 10), namely: control, sildenafil, tadalafil, tramadol and sildenafil+tramadol group. The different groups were orally treated with 0.2mL normal saline, sildenafil (1 mg/100gb.w.), tadalafil (1 mg/100gb.w.), tramadol (2 mg/100g b.w.) and sildenafil + tramadol (1 &2 mg/100gb.w. respectively). Treatment was done thrice a week, for 8 weeks and the animals were allowed access to feed and water ad libitum. Five animals were sacrificed per group, while the remaining 5/group continued for another 8 weeks without drug administration (recovery test).Blood samples were collected from each animal via cardiac puncture at the end of both phases for assessment of haematological parameters. Red blood cells (RBC) count, haemoglobin (Hb) concentration, packed cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), red cell distribution wide standard deviation (RDW-SD), white blood cells (WBCs) count, platelets count, mean platelets volume (MPV) and platelets large cell ratio (P-LCR) were significantly reduced in all the treated groups compared with the control. Following withdrawal of treatment, RBC count, Hb concentration, PCV and red cell absolute values were significantly increased in all recovery groups compared with their respective treated groups. Haematological alterations were reversed following withdrawal of treatment. However, platelet indices were poorly reversed in sildenafil and tramadol recovery groups.

Effect of material tramadol on some blood components of laboratory rats

“…These results are in agreement with each 15 and Owoade et al, 2019. The reason may be that the decrease in these blood components, due to the inhibitory effect of tramadol on the morphological differentiation of red blood cells, will affect the rest of the blood components, such as hemoglobin concentration and platelet count.…”

“…Or it may be due to the adverse effect of the mechanism of blood clotting in the body. In addition, it causes the use of various analgesics such as tramadol, which many studies in this field 8,15,18,19,21 have confirmed.…”

“…The group one (G1 ), the average weight of rats was 153.78 g, served as control and injection doses of saline solution for 10 days. In group two ( G2 ), the average weight of rats was 140 g, and in group three (G3 ), the average weight of rats was 142.5 g, and in group four (G4 ) average weight of rats was 142.9 g. These rats were injected with tramadol HCl at concentrations of 20 mg, 40 mg, and 80 mg/100 g body weight/day for 10 days, respectively 14,15 .…”

“…will decrease 15,16,[18][19][20][21] . Or it may be due to the adverse effect of the mechanism of blood clotting in the body.…”

“…The The reason for the decrease in the volume of HCT may be due to the effect of this substance tramadol on the decrease in the activity or function of the sympathetic nerve during blood circulation in the spleen and thus will affect the volume of HCT 15,19,22,23 . In addition to a decrease in hemoglobin concentration, this will lead to the inhibition of the biosynthesis of iron in the bone marrow, and this will subsequently affect MCH and MCHC 8,15,18,19 or because when the animal is injected with tramadol, HCT will decrease due to the transfer of bodily fluids from parts outside the blood vessels to the inside of the blood vessels, and many studies confirmed this in this field 8,15,21,22 Or it could be the reason raised anti-diuretic hormone and aldosterone secretion with resulting water and salt retention causes the expansion of the extracellular fluid leading to hemodilution and drop in HCT 6 .…”