Effects of Varied Oral Doses of Trimethoprimsulfamethoxazole Therapy on The Thyroid Glands, Hematology, Serum Chemistry And Sperm Count in Nigerian Local Dogs

Abstract

The effects of varied oral doses of trimethoprim-sulfamethoxazole therapy on the thyroid glands, haematology, serum chemistry and sperm count were evaluated in Nigerian local dogs. Twenty adult male dogs weighing between 4.5-10 kg were used for the study. The dogs were housed in metal cages in the Animal house of Department of Veterinary Parasitology and Entomology, University of Nigeria, Nsukka. The dogs were acclimatized for three weeks during which period they were vaccinated against rabies and screened for haemoparasites, helminthes and ectoparasites. The dogs were randomly assigned to four groups (A-D) of five dogs each. Baseline parameters were taken before the commencement of the experiment. Dogs in group B received 30mg/kg body weight (b.w) of trimethoprim- sulfamethoxazole (T/SMX) in drinking water. Dogs in group C received 60mg/kg b.w of T/SMX in drinking water whereas dogs in group D received 120mg/kg b.w of T/SMX in drinking water. Dogs in group A served as the control and received only clean drinking water. Treatment with T/SMX was at 12-hour intervals for a period of 21 days. About 5ml of blood was withdrawn weekly through the cephalic vein of all the dogs for haematology, serum enzyme assay and serum thyroid hormone assay. The rectal temperature, body weight, packed cell volume (PCV), haemoglobin concentration (HbC), red blood cell (RBC) count, total white blood cell (TWBC) count, serum enzymes-aspartate aminotransferase (AST), alanine amonotransferase (ALT) and alkaline phosphatise (ALP) activities, serum triiodothyronine (T3), thyroxine (T4), and serum thyrotropin (TSH) levels of all the dogs were assayed weekly. At the end of the 21-day treatment period, the dogs were humanely sacrificed. The thyroid glands, liver, testes and epididymis were dissected. Epididymal sperm count (ESC) was determined for each dog following standard procedures. Both the thyroid and liver were observed for gross pathological changes. Tissue sections were taken from both organs and processed histologically following standard procedures. They were observed for pathological changes under the light microscope. Data generated from this study were subjected to one-way analysis of variance. Variant means were separated using the least significant difference method. Significance was accepted at P < 0.05. The thyroid glands of groups C and D dogs showed petechial and ecchymotic haemorrhage grossly. At microscopy, follicular cell hypertrophy, colloid depletion and haemorrhage were observed in groups C and D dogs, while group B dogs showed only colloid depletion. The liver of groups B, C and D dogs showed multifocal areas of necrosis and widespread vacuolar degeneration. The PCV (%) of group D dogs (32.06 ± 3.90) was significantly (p < 0.05) lower than that of group A dogs (44.40 ± 4.14) on days 14 and 21 of treatment. The HbC (g/dl) of group D dogs (11.72 ± 0.13) was significantly (p < 0.05) lower than that of group A dogs (14.76 ± 0.32) on days 14 and 21 of treatment. The RBC counts (x106 cells/mm3 ) of groups B (6.00 ± 0.26), C (5.24 ± 0.37) and D dogs (4.37 ± 0.17) were significantly (p < 0.05) lower than that of group A dogs (7.38 ± 0.74) on days 14 and 21 of treatment. These suggested normocytic normochromic anaemia. The TWBC counts (x103 cells/mm3 ) of groups B (6.16 ± 0.81), C (8.22 ± 0.87) and D dogs (6.90 ± 1.20) were significantly (p < 0.05) lower than that of group A dogs (11.34 ± 1.08) on day 7. There were no significant (p > 0.05) variations in the serum AST activities across the groups. However, serum ALT activity (IU/L) of the group D dogs (16.73 ± 3.77) was significantly (p < 0.05) higher than that of group A dogs (8.98 ± 1.87) on days 14 to 21, while serum ALP activity (IU/L) of group D dogs (161.00 ± 19.42) was significantly (p < 0.05) higher than that of group A dogs (72.89 ± 5.96) on days 14 and 21 of treatment. Serum T3 levels (ng/dl) of group C dogs (0.32 ± 0.05) was significantly (p < 0.05) lower than that of group A dogs (0.63 ± 0.07) on day 21 of treatment. Serum T4 levels of groups B (0.16 ± 0.09), C (0.21 ± 0.01) and D (0.03 ± 0.03) dogs were significantly (p < 0.05) lower than that of group A dogs (0.36 ± 0.05) on days 14 and 21. Serum TSH (µIU/L) of group D dogs (0.64 ± 0.13) was significantly (p < 0.05) higher than that of group A dogs (0.09 ± 0.06) on day 21 of treatment. Serum testosterone (ng/ml) level of group D dogs (4.97 ± 0.80) was significantly (p < 0.05) higher than that of group A dogs (0.76 ± 0.64) on day 14 of 8 treatment. The ESC of groups B (0.88 ± 0.18) and C (0.47 ± 0.07) dogs were significantly higher than that of group A (0.40 ± 0.01), while that of group D dogs (0.06 ± 0.01) was significantly (p < 0.05) lower than that of group A. In conclusion, this study demonstrated that T/SMX therapy as used in this study severely affected thyroid morphology and function, suppressed erythropoiesis , caused mild leukopenia, caused hepatocyte necrosis and elevation of serum ALT and ALP activities and serum testosterone level and affected epididymal sperm count in Nigerian local dogs. Therefore prolonged use (for 21 days) of this drug at high doses should be discouraged. Male dogs treated with T/SMX for up to 21days may not be fit for breeding due to possible scrotal lesions and low sperm count. Treatment with T/SMX should be accompanied with folic acid and vitamin E to reduce the oxidative damage to tissues associated with its use.