Hematological effects in acute toxicity generated by the administration of honeybee (Apis mellifera L.) venom in European rabbit (Oryctolagus cuniculus)

Pavel, G.; Bratu, D.; Bejenariu, D.; Grădinaru, A.C.

doi:10.1590/1678-4162-13022

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Veterinary Medicine and Technology and Inspection of Animal Products • Arq. Bras. Med. Vet. Zootec. 75 (6) • Nov-Dec 2023 • https://doi.org/10.1590/1678-4162-13022 copy

Hematological effects in acute toxicity generated by the administration of honeybee (Apis mellifera L.) venom in European rabbit (Oryctolagus cuniculus)

[Efeitos hematológicos na toxicidade aguda gerada pela administração de veneno de abelha (Apis mellifera L.) em coelho europeu (Oryctolagus cuniculus)]

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Various studies demonstrated risks and benefits in the use of bee venom, a natural product characterized by a complex organic structure. In this study, we aimed to test the effects of bee venom administration in rabbits. Hematological investigations were carried out by determining specific blood indicators at different time intervals and at varying doses of venom. The obtained results showed a toxic action dependent on the dose and the daily cumulative effect; in the case of erythrocyte and platelet parameters, bee venom progressively generated the onset of thrombocytosis and reduced hemolysis for the short term. In the case of leukocytes, the administration of bee venom caused an increase of WBC count, segmented neutrophils and Ne/Lymph ratio, proportional to the dose and time of bee venom inoculation, but within the reference range; the average values of unsegmented neutrophils and basophils was above the upper limit of the normal range, with oscillating changes during the experiment; monocytosis and eosinophilia was also noted at different doses and times of venom inoculation. The investigations carried out 7 days after stopping the administration of bee venom revealed, in many cases, a progressive return to normal for the hematological parameters, except blood platelets.

Keywords:
bee venom; blood; toxicity; risk; benefits

Group	Time	RBC (x 10 ⁶ μL)	HGB (g/dL)	PCV (%)	MCH (pg)	MCHC (g/dL)	MCV (μm ³ )	PLT (x 10 ³ μL)
G₁	T₀	6.17±0.23	12.12±0.57	38.18±1.3	19.64±0.7	31.9±0.51	61.4±1.67	564.6±127.6
	T₁	5.99±0.22	11.64±0.31	36.88±0.8	19.42±0.69	31.26±0.96	61.6±1.52	519±125.1
	T₂	5.86±0.22	11.7±0.27	35.94±0.88	20±0.51	31.96±0.99	61.2±1.48	601.6±31.95
	T₃	5.86±0.3	12.12±0.48	36.16±1.28	20.68±0.59	33.1±0.8	61.8±1.92	710.6±91.05
	T₄	5.79±0.41	11.58±0.42	35.7±0.91	20.24±1.39	32.44±1.24	61.8±3.42	693±89.94

G₂	T₀	6.27±0.4	12.34±0.44	38.4±1.69	19.7±0.6	32.1±0.37	61.4±1.67	525.4±70.61
	T₁	5.97±0.18	11.6±0.26	36.52±0.92	19.44±0.38	31.3±0.81	60.8±1.48	568.6±76.84
	T₂	5.86±0.32	11.34±0.29	35.3±1.22	19.34±0.63	31.82±0.64	60.4±1.62	835.8±100.17
	T₃	6.15±0.49	12.34±0.71	37.98±2.16	20.08±0.59	32.5±0.98	61.8±1.79	813.4±123.29
	T₄	6.29±0.7	11.9±0.94	37.4±2.05	18.96±1.47	31.81±1.78	59.8±3.83	807.6±77.86
Reference values (Merck, 2008)		5-8	10-17	35-50	17-24	29-37	58-67	250-650

Parameters	G₁ T₀÷T₄ $\bar{X}$ ±σ_x; (4 df - degrees of freedom)	G₂ T₀÷T₄ $\bar{Y}$ ±σ_y (4 df - degrees of freedom)	G₁; G₂ $\bar{X}$ ±σ_x; $\bar{Y}$ ±σ_y (1 df - degree of freedom)
Parameters	G₁ T₀÷T₄ $\bar{X}$ ±σ_x; (4 df - degrees of freedom)	G₂ T₀÷T₄ $\bar{Y}$ ±σ_y (4 df - degrees of freedom)	T₀	T₁	T₂	T₃	T₄
RBC	p=0.275; p>0.05; ns	p=0.506; p>0.05; ns	p=0.641; p>0.05; ns	p=0.879; p>0.05; ns	p=0.964; p>0.05; ns	p=0.292; p>0.05; ns	p=0.202; p>0.05; ns
HGB	p=0.127; p>0.05; ns	p=0.049; p<0.05; s	p=0.514; p>0.05; ns	p=0.828; p>0.05; ns	p=0.051; p>0.05; ns	p=0.581; p>0.05; ns	p=0.505; p>0.05; ns
PCV	p=0.017; p<0.05; s	p=0.057; p>0.05; ns	p=0.817; p>0.05; ns	p=0.527; p>0.05; ns	p=0.368; p>0.05; ns	p=0.144; p>0.05; ns	p=0.129; p>0.05; ns
MCH	p=0.201; p>0.05; ns	p=0.311; p>0.05; ns	p=0.888; p>0.05; ns	p=0.956; p>0.05; ns	p=0.105; p>0.05; ns	p=0.143; p>0.05; ns	p=0.266; p>0.05; ns
MCHC	p=0.059; p>0.05; ns	p=0.478; p>0.05; ns	p=0.5; p>0.05; ns	p=0.945; p>0.05; ns	p=0.797; p>0.05; ns	p=0.318; p>0.05; ns	p=0.535; p>0.05; ns
MCV	p=0.989; p>0.05; ns	p=0.66; p>0.05; ns	p=1; p>0.05; ns	p=0.427; p>0.05; ns	p=0.447; p>0.05; ns	p=1; p>0.05; ns	p=0.409; p>0.05; ns
PLT	p=0.027; p<0.05; s	*p=0.00009; p<0.05; s*	p=0.564; p>0.05; ns	p=0.472; p>0.05; ns	p=0.001; p<0.05; s	p=0.172; p>0.05; ns	p=0.144; p>0.05; ns

Parameters	G₁ T₀÷T₄ $\bar{X}$ ±σ_x; (4 df - degrees of freedom)	T₀; T₁ $\bar{X}$ ±σ_x; $\bar{Y}$ ±σ_y (1 df - degree of freedom)	T₀; T₂ $\bar{X}$ ±σ_x; $\bar{Y}$ ±σ_y (1 df - degree of freedom)	T₀; T₃ $\bar{X}$ ±σ_x; $\bar{Y}$ ±σ_y (1 df - degree of freedom)	T₀; T₄ $\bar{X}$ ±σ_x; $\bar{Y}$ ±σ_y (1 df - degree of freedom)
PCV	p=0.017; p<0.05; s	p=0.136; p>0.05; ns	p=0.017; p<0.05; s	p=0.052; p>0.05; ns	p=0.011; p<0.05; s
PLT	p=0.027; p<0.05; s	p=0.584; p>0.05; ns	p=0.547; p>0.05; ns	p=0.071; p>0.05; ns	p=0.103; p>0.05; ns

Parameters	G₂ T₀÷T₄ $\bar{X}$ ±σ_x; (4 df - degrees of freedom)	T₀; T₁ $\bar{X}$ ±σ_x; $\bar{Y}$ ±σ_y (1 df - degree of freedom)	T₀; T₂ $\bar{X}$ ±σ_x; $\bar{Y}$ ±σ_y (1 df - degree of freedom)	T₀; T₃ $\bar{X}$ ±σ_x; $\bar{Y}$ ±σ_y (1 df - degree of freedom)	T₀; T₄ $\bar{X}$ ±σ_x; $\bar{Y}$ ±σ_y (1 df - degree of freedom)
HGB	p=0.049; p<0.05; s	p=0.012; p<0.05; s	p=0.003; p<0.05; s	p=1; p>0.05; ns	p=0.369; p>0.05; ns
PLT	p=0.00009; p<0.05; s	p=0.382; p>0.05; ns	p=0.0005; p<0.05; s	p=0.002; p<0.05; s	p=0.003; p<0.05; s

Group	Time	WBC (total #)	Including (%):
Group	Time	WBC (total #)	unsNe	seNe	Eo	Ba	Mo	Lymph	Ne / Lymph
G₁	T₀	5.9±0.5	2.475±1	20.62±1.91	3±1.95	9.1±1.1	1.9±1.1	64.8±4.47	0.3±0.062
	T₁	8.52±1.1	3.3±0.43	31.32±3.23	2.74±0.87	10.64±1.71	1.24±0.57	50.43±4.99	0.63±0.13
	T₂	8.7±2.1	1.2±0.35	33.48±3.24	2.4±1.54	11.2±1.53	6.7±2.12	42.26±6.04	0.81±0.19
	T₃	10.84±2.17	1.5±0.3	26.94±6.91	3±0.21	8.46±2.96	2.04±0.57	58.2±7.63	0.48±0.2
	T₄	10.36±2.46	1.2±0.46	25.42±5.06	1.96±0.66	7.84±2.16	0.94±0.67	62.6±5.42	0.41±0.11

G₂	T₀	7.16±0.74	1.66±0.55	21.6±5.54	1.12±0.69	11.48±2.58	1.82±0.87	62.34±7.53	0.36±0.15
	T₁	7.36±0.7	2.62±0.69	43.96±11.54	1.62±0.7	2.62±0.8	4.1±3.55	44.88±11.61	1.07±0.49
	T₂	7.8±0.55	1.82±0.24	32.32±3.09	5.16±1.68	6.98±1.29	3.92±2.34	47.94±4.62	0.67±0.13
	T₃	9.32±0.72	2.34±0.8	26.04±9.2	1.92±0.28	7.9±1.44	1.1±0.26	60.68±10.07	0.45±0.22
	T₄	8.82±1.09	1.7±1.23	30.58±1.85	3.08±0.8	7.56±1.88	1.98±0.71	55.08±6.11	0.56±0.1
Reference values (Merck, 2008)		5÷12.5	0.02±0.1*	20÷75	1÷4	1÷7	1÷4	30÷85

Parameters	G₁ T₀÷T₄ $\bar{X}$ ±σ_x; (4 df - degrees of freedom	G₂ T₀÷T₄ $\bar{Y}$ ±σ_y (4 df - degrees of freedom	G₁; G₂ $\bar{X}$ ±σ_x; $\bar{Y}$ ±σ_y (1 df - degree of freedom)
Parameters	G₁ T₀÷T₄ $\bar{X}$ ±σ_x; (4 df - degrees of freedom	G₂ T₀÷T₄ $\bar{Y}$ ±σ_y (4 df - degrees of freedom	T₀	T₁	T₂	T₃	T₄
WBC	p=0.003; p<0.05; s	p=0.0009; p<0.05; s	p=0.014; p<0.05; s	p=0.081; p>0.05; ns	p=0.381; p>0.05; ns	p=0.175; p>0.05; ns	p=0.237; p>0.05; ns
unsNe	p=0.00003; p<0.05; s	p=0.23; p>0.05; ns	p=0.355; p>0.05; ns	p=0.099; p>0.05; ns	p=0.012; p<0.05; s	p=0.059; p>0.05; ns	p=0.419; p>0.05; ns
seNe	p=0.0015; p<0.05; s	p=0.0013; p<0.05; s	p=0.718; p>0.05; ns	p=0.046; p<0.05; s	p=0.578; p>0.05; ns	p=0.865; p>0.05; ns	p=0.064; p>0.05; ns
Eo	p=0.623; p>0.05; ns	p=0.00001; p<0.05; s	p=0.076; p>0.05; ns	p=0.055; p>0.05; ns	p=0.027; p<0.05; s	p=0.0001; p<0.05; s	p=0.043; p<0.05; s
Ba	p=0.073; p>0.05; ns	p=0.000003; p<0.05; s	p=0.146; p>0.05; ns	p=0.00001; p<0.05; s	p=0.015; p<0.05; s	p=0.714; p>0.05; ns	p=0.832; p>0.05; ns
Mo	p=0.000001; p<0.05; s	p=0.091; p>0.05; ns	p=0.208; p>0.05; ns	p=0.113; p>0.05; ns	p=0.088; p>0.05; ns	p=0.001; p<0.05; s	p=0.043; p<0.05; s
Lymph	p=0.00006; p<0.05; s	p=0.013; p<0.05; s	p=0.976; p>0.05; ns	p=0.355; p>0.05; ns	p=0.134; p>0.05; ns	p=0.672; p>0.05; ns	p=0.074; p>0.05; ns
Ne / Lymph	p=0.0004; p<0.05; s	p=0.003; p<0.05; s	p=0.722; p>0.05; ns	p=0.087; p>0.05; ns	p=0.214; p>0.05; ns	p=0.849; p>0.05; ns	p=0.054; p>0.05; ns

Parameters	G₁ T₀÷T₄ $\bar{X}$ ±σ_x; (4 df - degrees of freedom	T₀; T₁ $\bar{X}$ ±σ_x; $\bar{Y}$ ±σ_y (1 df - degree of freedom)	T₀; T₂ $\bar{X}$ ±σ_x; $\bar{Y}$ ±σ_y (1 df - degree of freedom)	T₀; T₃ $\bar{X}$ ±σ_x; $\bar{Y}$ ±σ_y (1 df - degree of freedom)	T₀; T₄ $\bar{X}$ ±σ_x; $\bar{Y}$ ±σ_y (1 df - degree of freedom)
WBC	p=0.003; p<0.05; s	p=0.001; p<0.05; s	p=0.002; p<0.05; s	p=0.001; p<0.05; s	p=0.004; p<0.05; s
unsNe	p=0.00003; p<0.05; s	p=0.047; p<0.05; s	p=0.077; p>0.05; ns	p=0.195; p>0.05; ns	p=0.087; p>0.05; ns
seNe	p=0.0015; p<0.05; s	p=0.0002; p<0.05; s	p=0.00006; p<0.05; s	p=0.084; p>0.05; ns	p=0.082; p>0.05; ns
Mo	p=0.000001; p<0.05; s	p=0.032; p<0.05; s	p=0.0058; p<0.05; s	p=0.282; p>0.05; ns	p=0.017; p<0.05; s
Lymph	p=0.00006; p<0.05; s	p=0.004; p<0.05; s	p=0.0003; p<0.05; s	p=0.339; p>0.05; ns	p=0.907; p>0.05; ns
Ne / Lymph	p=0.0004; p<0.05; s	p=0.002; p<0.05; s	p=0.0006; p<0.05; s	p=0.146; p>0.05; ns	p=0.174; p>0.05; ns

Parameters	G₂ T₀÷T₄ $\bar{Y}$ ±σ_y (4 df - degrees of freedom	T₀; T₁ $\bar{X}$ ±σ_x; $\bar{Y}$ ±σ_y (1 df - degree of freedom)	T₀; T₂ $\bar{X}$ ±σ_x; $\bar{Y}$ ±σ_y (1 df - degree of freedom)	T₀; T₃ $\bar{X}$ ±σ_x; $\bar{Y}$ ±σ_y (1 df - degree of freedom)	T₀; T₄ $\bar{X}$ ±σ_x; $\bar{Y}$ ±σ_y (1 df - degree of freedom)
WBC	p=0.0009; p<0.05; s	p=0.673; p>0.05; ns	p=0.156; p>0.05; ns	p=0.002; p<0.05; s	p=0.023; p<0.05; s
seNe	p=0.0013; p<0.05; s	p=0.005; p<0.05; s	p=0.005; p<0.05; s	p=0.382; p>0.05; ns	p=0.009; p<0.05; s
Eo	p=0.00001; p<0.05; s	p=0.289; p>0.05; ns	p=0.001; p<0.05; s	p=0.044; p<0.05; s	p=0.003; p<0.05; s
Ba	p=0.000003; p<0.05; s	p=0.00008; p<0.05; s	p=0.008; p<0.05; s	p=0.027; p<0.05; s	p=0.025; p<0.05; s
Lymph	p=0.013; p<0.05; s	p=0.022; p<0.05; s	p=0.007; p<0.05; s	p=0.775; p>0.05; ns	p=0.133; p>0.05; ns
Ne / Lymph	p=0.003; p<0.05; s	p=0.015; p<0.05; s	p=0.007; p<0.05; s	p=0.427; p>0.05; ns	p=0.033; p<0.05; s

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[1] *Corresponding authors: gpavel@uaiasi.ro; a.c.gradinaru@uaiasi.ro