Background: Tilmicosin is a macrolide antibiotic used mainly for controlling respiratory infections in animals.
Tilmicosin therapy, like that with other macrolide members, may be associated with various adverse effects on different
organ functions that remain a controversial matter. Therefore, the object of the present study was to investigate
the adverse effects of tilmicosin, a relatively new macrolide, on biochemical and haematological parameters as
well as histological structure in mice in a trial to evaluate its safety after administration of a small and larger doses
subcutaneously.
Materials, Methods & Results: Forty male Swiss albino mice were assigned randomly to four groups; the first
group was untreated while the other three were treated with escalating doses of tilmicosin (20, 40 & 60 mg/Kg, SC).
Tilmicosin caused tender swellings at the site of injection and animals received a dose 60 mg/kg of body weight died
shortly postadministration. Animals received smaller doses, 20 & 40 mg/kg of body weight survived and blood, plasma
and tissue samples showed marked dose-dependent alterations. Tilmicosin significantly decreased all (but not MCV)
erythrocytic parameters and indices including, RBC count, HCT, HGB, MCH and MCHC. Additionally, lymphocytes
exhibited significant decrease, while granulocytes exhibited significant increase compared to control. Hepatorenal
function markers including, ALP, ALT, AST, urea and creatinine showed significant increases, compared to control,
particularly post-administrating 40 mg/kg of body weight dose. Cardiac function marker, CK, showed significant
increase after both doses of tilmicosin. Significant decreases in TP, ALB and GLB concentrations compared to control;
and, on contrary, significant increases in CHOL, TAG and GLU were also recorded. Parallel dose-dependent
degenerative changes were also observed in liver, kidney, heart and spleen tissue samples picked from treated groups.
Discussion: The subnormal levels of erythrocytic parameters and indices recorded from treated groups in this study
may indicate that tilmicosin administration caused acute anemia in a dose-dependent manner. Low number of RBCs
and decreased percentage of its haematocrit value indicates bone marrow dyfunction that might be caused by tilmicosin
in this study. Tilmicosin-induced renal dysfunction was proved in the present study indicated by high levels of
creatinine and urea. Renal dysfunction may result in decreased erythropoietin production, a key hormone in RBC
synthesis. Recorded effects of tilmicosin on leukocytic counts could be related to tilmicosin-induced “stress” of the
treated animals. Increased ALP, ALT and AST activity from one hand and urea and creatinine from the other hand
may indicate that tilmicosin at the tested doses caused significant changes in hepatic and renal tissues, respectively.
Higher CK activity in the treated groups indicate cardiotoxicity of tilmicosin. Histopathological findings were parallel
to the biochemical ones and supportive to them. Hepatorenal dysfunction caused what is well-known as “metabolic
syndrome” that was associated with adverse effects on metabolic parameters towards the negative side in tilmicosintreated
mice. These data indicate that tilmicosin, especially in large but-tolerated doses, may cause adverse effects
on blood and organ functions and structures; and thus particular care and monitoring programs should be followed
if it is used in therapy. |
