Effects of varenicline on lung tissue in the animal model

A total of 34 rats were randomly allocated into study (varenicline) and control groups. The rats were divided into two groups (i) control group, (ii) varenicline group. Then, the rats in the each group were sub-divided equally in turn as acute (C1; V1) and chronic (C2; V2) ; all rats of acute and chronic groups were sacrificed under the anesthesia on the 45th day for acute group [C1 (n=5) and V1 (n=12)] and the 90th day for chronic group [C2 (n=5) and V2 (n=12)], respectively. Thus, biochemical and histopathological analysis were carried out.

Results

Thirty four rats completed the study, 24 were in varenicline group and 10 were in control group. In chronic exposure to varenicline, oxidant levels comprising of malondialdehyde (MDA), and myeloperoxidase (MPO) increased and superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GPx) levels, named as antioxidants, decreased significantly when compared to the control group. MDA and MPO levels were also significantly higher and SOD, CAT, GPx, GSH levels were also significantly lower in chronic varenicline group when compared to acute varenicline group. These findings were also supported by histopathological observations.

Conclusion

This is the first study, which evaluated pulmonary effects of varenicline experimentally on an animal model. It was observed that chronic varenicline treatments cause inflammation and lung cell injury.

Keywords:
Varenicline; Lung tissue; Oxidative stress; Pulmonary toxicity

Groups	C1 (n=5)	V1 (n=12)	C2 (n=5)	V2 (n=12)
Lung injury score	0 (0-1)	6 (5-7)^a a p =0.001 vs C1;	0 (0-1)	7 (6-8)^b b p =0.001 vs C2; ^,^c c p =0.001 vs V1.

		MDA nmol/g tissue	SOD U/g protein	CAT K/g protein	GPx U/mg protein	GSH µmol/g tissue	MPO U/g protein
Acute	Control Group (n=5)	7.37 (6.39-9.12)	46.99 (36.64-50.49)	14.17 (10.82-17.75)	4.28 (2.76-5.66)	0.47 (0.43-0.55)	31.32 (24.69-37.78)
Acute	Varenicline Group (n=12)	7.09 (4.62-15.90)	44.40 (32.15-59.05)	13.34 (18.83-7.73)	3.93 (2.05-6.96)	0.46 (0.28-0.67)	31.65 (22.14-40.26)
Chronic	Control Group (n=5)	7.12 (6.44-8.02)	45.01 (34.12-54.29)	13.20 (8.14-21.81)	3.98 (2.90-4.65)	0.46 (0.41-0.50)	30.90 (20.71-35.43)
Chronic	Varenicline Group (n=12)	18.75 (11.19-21.60)^a a Significantly different compared with both control groups (p≤0.05); ^,^b b Significantly different compared with acute varenicline group (p≤0.05).	14.89 (6.04-18.15)^a,b	4.87 (3.15-5.12)^a,b	1.11 (0.7-1.92)^a,b	0.15 (0.10-0.20)^a,b	90.78 (70.46-109.12)^a,b

		Lung Weight (g)	Body Weight (g)
Acute	Control Group (n=5)	20.1±1.62	300±10
Acute	Varenicline Group (n=12)	18.8±2.81	295±12
Chronic	Control Group (n=5)	19.0±1.47	310±8
Chronic	Varenicline Group (n=12)	19.4±2.90	318±12

Sociedade Brasileira de Pneumologia e Tisiologia SCS Quadra 1, Bl. K salas 203/204, 70398-900 - Brasília - DF - Brasil, Fone/Fax: 0800 61 6218 ramal 211, (55 61)3245-1030/6218 ramal 211 - São Paulo - SP - Brazil
E-mail: jbp@sbpt.org.br

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[1] Correspondence to: Hilal Ermis, Department of Pulmonary Medicine, Faculty of Medicine, Turgut Ozal Medical Center, Inonu University, 44280, Malatya, Turkey. Tel.: + 90 422 341 0660-3806. Telefax: + 90 422 341 0728. E-mail: hilalermis3@gmail.com