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Toxicological evaluation of flumequine in pubertal male rats after oral administration for six weeks

JeongWoo Kang
JeongWoo Kang
, 
Md Akil Hossain
Md Akil Hossain
, 
Byungkook Choi
Byungkook Choi
, 
Joon-Hyoung Cho
Joon-Hyoung Cho
, 
Seok-Jin Kang
Seok-Jin Kang
, 
Hyun-Ok Ku
Hyun-Ok Ku
, 
Sang-Hee Jeong
Sang-Hee Jeong
 y 
Hwan-Goo Kang
Hwan-Goo Kang
   | 30 mar 2018
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Publicado en línea: 30 mar 2018
Páginas: 87 - 96
Recibido: 03 ago 2017
Aceptado: 20 feb 2018
DOI: https://doi.org/10.2478/jvetres-2018-0012
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© 2018 J. W. Kang et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Fig. 1

Body weight changes in pubertal male Wistar rats treated with corn oil (control) or with flumequine (FLU) at doses of 53, 200 and 750 mg/kg for six weeks. Values are mean ±SD for seven rats in each group. ∗ P < 0.05, ∗∗ P < 0.01
Body weight changes in pubertal male Wistar rats treated with corn oil (control) or with flumequine (FLU) at doses of 53, 200 and 750 mg/kg for six weeks. Values are mean ±SD for seven rats in each group. ∗ P < 0.05, ∗∗ P < 0.01

Fig. 2

Relative organ weights in pubertal male Wistar rats treated with corn oil (control) or with flumequine (FLU) at doses of 53, 200 and 750 mg/kg for six weeks. Values are mean ±SD for seven rats per treatment group. ∗ P < 0.05, ∗∗ P < 0.01
Relative organ weights in pubertal male Wistar rats treated with corn oil (control) or with flumequine (FLU) at doses of 53, 200 and 750 mg/kg for six weeks. Values are mean ±SD for seven rats per treatment group. ∗ P < 0.05, ∗∗ P < 0.01

Fig. 3

Serum biochemical parameters of pubertal male Wistar rats treated with corn oil (control) or flumequine (FLU) for six weeks Values are mean ±SD of seven rats in each group. ∗ P < 0.05; ∗∗ P < 0.01
Serum biochemical parameters of pubertal male Wistar rats treated with corn oil (control) or flumequine (FLU) for six weeks Values are mean ±SD of seven rats in each group. ∗ P < 0.05; ∗∗ P < 0.01

Fig. 4

Changes in serum immunoglobulins in Wistar male rats of control group and flumequine (FLU) 53, 200, and 750 groups. Values are mean ±SD of seven rats in each group. ∗ P < 0.05; ∗∗ P < 0.01
Changes in serum immunoglobulins in Wistar male rats of control group and flumequine (FLU) 53, 200, and 750 groups. Values are mean ±SD of seven rats in each group. ∗ P < 0.05; ∗∗ P < 0.01

Fig. 5

Changes in plasma cytokines in Wistar male rats treated with corn oil (control) or flumequine (FLU) 53, 200, and 750 mg/kg for six weeks. IL-10 – interleukin-10; IL-6 – interleukin-6; TNF-α – tumour necrosis factor-α; IFN-γ – interferon-γ; GM-CSF – granulocyte-macrophage colony-stimulating factor; IL-1β – interleukin-1β; IL-2 – interleukin-2. Values are mean ±SD for seven rats in each group. ∗ P < 0.05; ∗∗ P < 0.01
Changes in plasma cytokines in Wistar male rats treated with corn oil (control) or flumequine (FLU) 53, 200, and 750 mg/kg for six weeks. IL-10 – interleukin-10; IL-6 – interleukin-6; TNF-α – tumour necrosis factor-α; IFN-γ – interferon-γ; GM-CSF – granulocyte-macrophage colony-stimulating factor; IL-1β – interleukin-1β; IL-2 – interleukin-2. Values are mean ±SD for seven rats in each group. ∗ P < 0.05; ∗∗ P < 0.01

Fig. 6

Changes in serum hormones in Wistar male rats treated with corn oil (control) or flumequine (FLU) 53, 200, and 750 mg/kg for six weeks TSH – thyroid stimulating hormone; FSH – follicle stimulating hormone; LH – luteinising hormone; fT4 – free T4; fT3 – free T3; tT4 – total thyroxine; tT3 – total triiodothyronine. Values are mean ±SD for seven rats in each group ∗ P < 0.05; ∗∗ P < 0.01
Changes in serum hormones in Wistar male rats treated with corn oil (control) or flumequine (FLU) 53, 200, and 750 mg/kg for six weeks TSH – thyroid stimulating hormone; FSH – follicle stimulating hormone; LH – luteinising hormone; fT4 – free T4; fT3 – free T3; tT4 – total thyroxine; tT3 – total triiodothyronine. Values are mean ±SD for seven rats in each group ∗ P < 0.05; ∗∗ P < 0.01

Fig. 7

Histopathological findings in thyroid glands from Wistar male rats treated with corn oil (control) or flumequine (FLU) in a dose of 750 mg/kg for six weeks. Degeneration and depletion of thyroid follicular epithelial cells are present
Histopathological findings in thyroid glands from Wistar male rats treated with corn oil (control) or flumequine (FLU) in a dose of 750 mg/kg for six weeks. Degeneration and depletion of thyroid follicular epithelial cells are present

Fig. 8

Expression of 8-hydroxydeoxyguanosine (8-OHdG), cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1), cyclooxygenase-2 (COX-2) and interleukin-1β (IL-1β) in Wistar male rats treated with corn oil (control), or flumequine (FLU) in a dose of 53, 200, and 750 mg/kg for six weeks. Values are mean ±SD of seven rats in each group. ∗ P < 0.05; ∗∗ P < 0.01
Expression of 8-hydroxydeoxyguanosine (8-OHdG), cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1), cyclooxygenase-2 (COX-2) and interleukin-1β (IL-1β) in Wistar male rats treated with corn oil (control), or flumequine (FLU) in a dose of 53, 200, and 750 mg/kg for six weeks. Values are mean ±SD of seven rats in each group. ∗ P < 0.05; ∗∗ P < 0.01

Sperm motility parameters, sperm numbers, and preputial time of pubertal male Wistar rats exposed to FLU for six weeks

Parameter Corn oil 53 mg/kg 200 mg/kg 750 mg/kg
Motility (%) 73.84 ± 18.89 75.21 ± 7.62 67.38 ± 17.19 75.1 ± 10.98
HYP (%) 34.85 ± 11.11 33.08 ± 11.04 39.4 ± 9.41 38.69 ± 15.38
VCL (m/s) 114.5 ± 15.46 98.84 ± 33 97.62 ± 24.97 116.7 ± 26.85
VSL (m/s) 49.56 ± 22.86 42.48 ± 25.36 29.96 ± 26.22 43.73 ± 28.57
VAP (m/s) 65.62 ± 20.37 53.06 ± 28.43 47.12 ± 23.86 65.53 ± 27.4
LIN 42.14 ± 14.8 32.16 ± 16.43 27.47 ± 19.59 39.84 ± 17.03
STR 72.73 ± 12.25 59.82 ± 18.36 53.54 ± 27.14 70.76 ± 16.49
BCF (Hz) 11.22 ± 1.148 10.64 ± 2.02 10.4 ± 1.63 11.05 ± 1.09
MAD (degree) 4.85 ± 1.9 4.05 ± 1.8 3.35 ± 1.82 4.21 ± 2.07
WOB 56.3 ± 10.95 48.6 ± 14.12 46.77 ± 12.18 54.26 ± 12.15
DNC 1152.16 ± 185.66 1081.74 ± 387.94 966.36 ± 359.05 1263.49 ± 416.64
DNM (μm) 27.59 ± 12.16 39.65 ± 17.03 30.22 ± 9.39 32.79 ± 16.04
ALH (μm) 10.03 ± 0.76 9.40 ± 1.81 9.35 ± 1.54 10.56 ± 1.521
Sperm numbers (×104)+ 38 ± 9 48 ± 10 44 ± 8 35 ± 9
Preputial time (days) 40 ± 1.5 39 ± 1.2 39 ± 1.8 40 ± 1

Haematological parameters of male Wistar rats exposed to FLU for six weeks

Parameters Control 53 mg/kg 200 mg/kg 750 mg/kg
RBC (×106 cells/mL) 7.58 ± 0.2 7.43 ± 0.31 6.72 ± 1.24 7.07 ± 0.31
HGB (g/dL) 13.9 ± 0.50 13.9 ± 0.59 12.62 ± 2.35 13.5 ± 0.49
HCT (%) 41.6 ± 2.10 41.5 ± 1.55 38.1 ± 8.1 41.2 ± 1.23
MCV (fL) 54.73 ± 1.64 55.9 ± 1.63 56.32 ± 2.12 58.8 ± 0.4
MCH (pg) 18.3 ± 0.43 18.7 ± 0.39 18.72 ± 0.13 19.1 ± 0.32

P < 0.05
MCHC (g/dL) 33.43 ± 0.4 33.5 ± 0.76 33.3 ± 1.07 32.8 ± 0.34
CHCM (g/dL) 33.64 ± 0.52 34 ± 0.96 33.61 ± 0.86 33.3 ± 0.93
CH (pg) 18.4 ± 0.5 19 ± 0.38 18.88 ± 0.51 19.4 ± 0.55

P < 0.01
RDW (%) 11.4 ± 0.43 11.5 ± 0.5 11.34 ± 0.64 12 ± 0.45
HDW (g/dL) 2.40 ± 0.08 2.48 ± 0.18 2.30 ± 0.14 2.42 ± 0.15
PLT (×103 cells/mL) 1315± 271 1264± 223 737.4 ± 655 1356 ± 81.23
MPV (fL) 7.17 ± 0.28 7.13 ± 0.27 10 ± 4.77 7.36 ± 0.15
WBC (×103 cells/mL) 5.75 ± 1.34 5.75 ± 2.41 6.91 ± 3.9 9.21 ± 2.49

P < 0.05
NE (×103 cells/mL) 16.39 ± 2.92 18.4 ± 3.95 15.82 ± 3.29 19.2 ± 3.92
LY (×103 cells/mL) 79.59 ± 3.18 77.3 ± 4.04 80.3 ± 3.23 75.7 ± 4.87
MO (×103 cells/mL) 1.32 ± 0.39 1.53 ± 0.37 1.72 ± 0.68 2.34 ± 1.07

P < 0.05
EO (×103 cells/mL) 1.72 ± 0.63 1.77 ± 0.65 1.34 ± 0.89 1.9 ± 0.36
BA (×103 cells/mL) 0.25 ± 0.21 0.29 ± 0.16 0.12 ± 0.13 0.2 ± 0.07
LUC (×103 cells/mL) 0.65 ± 0.39 0.69 ± 0.25 2.16 ± 3.27 0.74 ± 0.23

Serum biochemical parameters of pubertal male Wistar rats exposed to FLU for six weeks

Parameter Control 53 mg/kg 200 mg/kg 750 mg/kg
ALT (U/l) 20.1 ± 2.9 19.8 ± 3.7 20.7 ± 8.1 24.3 ± 7.6
AST (U/l) 61.2 ± 6.4 60.8 ± 4.8 65.6 ± 5.6 60.1 ± 7.4
ALP (U/l) 127.3 ± 27.6 140.8 ± 35.7 151.6 ± 50.4 141.1 ± 37.8
LDH (U/l) 188.8 ± 56.6 264.9 ± 110.4 470.6 ± 254.2

P < 0.01

 352.8 ± 146.7

P < 0.05
CK (U/l) 134.0 ± 35.1 162.4 ± 57.3 220.4 ± 99.4 326.0 ± 194.1

P < 0.05
Alb (mg/dl) 3.33 ± 0.13 3.27 ± 0.12 3.34 ± 0.13 3.30 ± 0.13
BUN (mg/dl) 12.1 ± 1.9 12.8 ± 1.4 11.2 ± 4.8 11.9 ± 3.3
Glu (mg/dl) 145.86 ± 12.2 145.5 ± 15.4 136.6 ± 12.1 109.7 ± 13.5

P < 0.01
TG (mg/dl) 92.2 ± 32.9 72.1 ± 16.2 74.3 ± 20.2 71.41 ± 17.8
Ca (mg/dl) 10.58 ± 0.1 10.23 ± 0.4 8.95 ± 3.7 10.38 ± 0.5
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